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Genotyping Console 4.0 User Manual

1. wamom oann a tural eanna n ee 1i mare wr Figure Out ol borde tue lagged C Table for Axiom Data detsut vem page 74 Note The ligation nucleotide la the nucleotide at the 3 end o a solution probe which is the nucleotide ligated to tne array probe The AT channel la the optical channel In which signal rom ligated A UT nucleotides are detected The GC channel ie the channe whieh signal rm gated or nucleotides are deleted The AT probes are hose control probes that correspond o genomie posi ons tor whieh te expected igation nucleotide i A or T The Ge probes Ea naat cnt probes hl argon ona amare te witen ihe pected igation nucleotide is G or C E Note The ligation nucleotide is the nucleotide at the end Solution probe which is the nociealide tha i gated tthe probe The AT channe is ihe fected The GC channal is the plica channel in which signal rom A or T nucleotides are tcs channel in which signal trom gated or C nucleotides are detected The AT probes are those Control probes that correspond to nom plymorphie genomie postons lor whieh the expected ligation mucleotide A or T Te GC probes are hose control probes that correspond 10 non genomie positions lr which the expected ligation nucleotide ls G o C menaly QC Table for SNP Data defau
2. Fire 8 2 Selected array tles paired by enzyme set and sampleeerence satus Copy Number QC Summary Table for 100K 500K The Copy Number QC Surmenary Tabie displays QC intormation about the copy number and LOH analyses Use he GTC Browser page 248 to view Copy Number LOH and CN Segments data in a genomie context Thi table plays OC formation for Numer anys Tha Copy Nimmer QC Summary Table uses table oplons as described in Tabie Features To open the OC Summary table fhe Copy arte OH Res se of redi and select Show Copy Nr Sunny From tne Workspace menu select Copy Number LOH Results gt Show Copy Number QC Summary C Summary table opens H cu MEC M CM M MC Figur 2 Copy Number QC Report tor 100K arrays The flowing lomo is displayed fr Human Mapping arrays Fle Fie name Mets Gehe Coracle Ue Hart Bounds in or out of QC bounds See Sting QC Thresholds page 257 fer more information IOR tor all chromosomes range average tor al chromosomes IOR tor J chromosomes interquartile rangs for each individuasi chromosome Fle Date Date le was crestea range OR of he smoothe CN is splayed for each sample The OR values are displayed tor each cromosoma wel as tor tne wcle sample In a pared analysis he values are reported each alele independent Tho
3. See LOH Es ie Ero lo mai Fire 103 Copy Number Analysts Options dialog box Configuration dropdown ist ferent coniguaton trom e dropdown st poop 4 Gk te See Reference otel Fie As buton The Save dag box opens tt Corsi Ue Hart re Fire 104 Sev dialog box Chek Save nthe Save dag ho T Select a diferent annotation Note The Netty ants regional C correction ion nie must be ot NAZ6 1 or higher version contlguration Nies are with configuration fes are without regional GC correction the can be of NAZS higher version tered in dialogue window Annotations or other array platforms or custom annotation fee will not be Mered I OK in the Select Annotation Fle dialog box Miei Gesch Coracle Ue at Fire 105 Select annotation box Select Output Root pan Thi changes the locaton where CNLOH tles chk Sect Output Root Pa rouse tunon E Tae Tea Stem rte Delete im B In e Browse tr Foder dalog box at appears select anew estn or he data tles and cick Miet Gehe Coracle Uwer Hart Il ED ous Ero Figure 184 Browse for Folder alg bos Select CNLOH Bach Name elon changes he nam
4. only Computed Gander Corte gender Fer mora detala ne Aspen E Gender Cale page 307 Meis Gehe Coracle User Mant Tne Human SNP Array 6 0 contains SNPs and CN probe sets iom wo enzyme sets Nap and S Some SNPs and CN proba els are orly present on fragment generaled by one af e enzymes ue ther SNPs CN probe ses are present on agents generaled ether enzymes reete There san where sample may work proper wi one enzyme set bul not wth he oar Contsst OC broken down by enzyme set for these arrays to heo you evaluate data for hese issues Intensity QC Table for Human Mapping 100K 500K amp SNP 5 0 Data default view The Intensity QC Table contis he re See Tabie Festures for more on te abe iow By dea he colonna d be degayat pos bra cfc hehe CEL met the speci OC Ur ae call Rate Cameutnd OC Cat Rats fr al QC Computed Gender Campin ponder more detain on Append E Gender Calg page 307 Human SNP Ara 52 contains SNPs and CN prebe sets iom wo enzyme sela Nap and Some SNPs and CN probe sts wok ih one ate enzyme ses wh ther SNPs work mih bob There sans store sample may work proper wit on enzyme set bul not wth he oer Tha OC Cal tate is broken down by enzyme set for hese araya to help you evaluate e data fr hese sues Custom Groups of I
5. Toremove he Data Sat ht ck on Data Set and slat Remove Data Set s wll remove al data Tes for al Dala Sel tom he Werte Figure 16 Shortcut menu Remove Data Set Not Removing sli data or sub sets data trom a workspace or data set does not delete the fl dom the system jast he pointers tothe data used by GTC In Genotyping Console individual or set of data tes can be removed tom he Workspace The allowing sectons iso now io Remove Sample Fies tom a Data Set Remove Intensity Fes tom a Data Set page 57 Remove Genotyping Copy Number or Number Variation Results tarn a Dala Set page 58 Ta remove Sampie ies pen the Sample Tale the rowa ARROL Nes to be Nght eik and sees Remove Selected Dala Data Set tyr Canace User ana esate trong youto cote he eto Tte ehe ARR es wl be removed om IE Note t here associated CEL andor CHP fles wit these ARR fles they wil not be removed trom the Data Set Remove Intensity Fils trom Data Set mansay EL b apen te ay QG Tave gh eo o CEI tles t be mie Camas Emane Earran m tes QU SENS Nab 3 wwoesesswe cet in om a 2 2n 29 2m Er 0 Ej t prompt youl contem e eto The hehe CE esl be removet hom e E Mote N there are
6. Figure 20 Seeing a workspace package to unpack 2 Select workspace package you wish 1o unzip and cick Open The Unpack Location dag box opens ty Genotyping Corsi User Har Figur 29 Select fer to unpack the workspace Browse one fider whare you wish to vno o Fes n he workspace package and ich OK The Unoacing Progress indicator appears naag sana ecu o aa er Wak ge tace pe b His eg rm gure 0 Unpacking progress indicator hene unpacking operto te progress disappears You can now open yt Gente Coracle er Har Chapter 6 Quality Control for Genotyping Analysis To hei reseechersesabah processes for genotyping analyses Afyetix has developed vera cna teatres Researcher are encouraged mentor ese conis on regulat ba assess sss dla quay These features neue Metrics tke QC Cal Rate Contas QC and Dish QC SNPs genotype cals The flowing sections in tis chapter ete Modiyeg OC Ties Contrast OC page 69 OC Cat Rate page Custom Groups of ney QC Fies page 74 gt Graphing OC Rest page 78 Signature SNPs page 8 Modify QC Thresholds Genotyping Console maintains detaut aids for QC mats nd wll gott in e intensity QC tables the merce whic are cud f e value You can most esos as needed 1 To mosty be QC opos clk on e QC Thres
7. distribution of the Gender rai tor aer 1200 mol Bs nd 1500 female rd ples ng 2n cram a chow har oct ot the owe cul fed ne nd upper ea town and goce tentem m prati pode crei Fel UR The gender method produces Unknow gender cals far poor samples However in tema cases whee sample has ossental irat the danda cal be rale Suc a asiy ont by evening t QC Cala The en probe gender method casses genders conside oriy wo possible cases maie XY and Tene XX However unusual such at 000 XO XXY and XYY aio rate in poplatons X chromosome Rosa a vara loser gain of ine X eeomosone Rh 1a happen Vivo ad in ines To a detect dent eae una genders our addtional gender columns can ne GHP Sansa Tabie by selecting Show Da The fou columns ae xot const gender chx he rate gentjpes of SNP on he X chromosome chiot gender mean he average probe ana utanstomed of X chromosome nonglymorphie probes gender mean he average probe ion ot Y chromosome nonglymorphie probes gender rato Gender rao YX gender mean gender mean tt Cosi User Hart Note SNP CHP tes created with GTC
8. Figure 1030 LOH parametere The LOH quite erent between SNP 6 0 and 00K 100K stead of using HMM the rnm simol aoe runa of homazygocs SNP eae taking no overal het rl and Ie ay orae n caina HET call Error Rate tt Genagrirg Corsi User Hart The Genotyping perform wet in context of signal tom SNPs wih very low eror However hen signal artes ron SNP the genotyping eno rate e ghar he case of LOM sociated wah CN 1 region ona singl X dvomesome witout speci eaten b genotyping hen we wu exact o hets lo be caled n pracoe win curent atl SNEED genotyping parameter usual ose around S9 hal cal depending on sample qua Lower resul in a higher het cale rate The agri het cal error rate in the cae LOM being cated as par of a reference model generaton and defaut no cal vested Las fef genotyping used anm adusta ht cal ups 1nacecsoy depending tne observed n ca genotyping rale Inl oer cases e he cal error teras ne in he The het cal errato tuned tor LOH in hemizygous dees Le alos ot a porton ol 1 chromosome oto In fact sma regne of Copy LOM are very common ey arse rom pto of pared Eomosomes tat ean pe ace tough diferent nas of decent back to sage ancestor and eso regions idea end
9. Gente Cora User ana indi Gata can be shared by simply he ies to locaton and generating a Workspace te you decide simply move he dala tes andlor o Workspace Genotyping Conse wil ask you locate the rising fies See Missing Data for more norton Using Zip Workspace Top a workspace 1 From th menu select Zip Workspace Tre Select name ol package to save dialog box opens om 9 landi ae Peme mE x Ce P OEE Figure 526 Select package box 2 Select a name tor the workspace you wish lo save trom the Fio name dropdown Box Use o dialog ox to secta location for me packed workspace 4 Chek Save The Workspace 2p progress ncaa appears UCL epe pet eg Mcr Fire 27 Progress bar progress indicator provides n estimate ot me n needed to fish the packing When packing is Hohe package appear e locaton spocted and con be or shared wih another user Te unzip workspace package 1 From menu select Unzip Workspace Select Workspace Package dialog box opens iecore pr Mfr Street Donc M rd e s Netcom tore Fenne Nav anacak perpe Peek
10. range is a measure of dispersion or pred Lis he difference between me 75 percent oen lied Q3 Sed quante and he 25 percent 01 The or equae range erre OS Shoe ma OR represent canal 50 o e data t not aed by outers or extreme values and hence robust metne measure o person In general the vd IOR ecl be comparatio othe Chromosomal OI or te uen compa An observed tn 3 chromosoma cosevon polenta y oe change Changing Algorithm Configurations for Human Mapping 100K 500K Analysis You can change parameter tor he number and LOM ant or Human Mapping 100KISDOK aan To open the Contiguratons dialog box 1 Fem the Edit menu select Copy Number Configurations New Configuration The Select Probe Array Type dialog box opens fresh Genotyping Corse Uter Marat Select proba ray tpe Figs 88 Soci Pre Array Type log box 2 Select MapplngtO0K or MappingSO0K the tat and cick Select Te Copy Number options dio tox opens Copy Number LOH Configuration Options east Reta sen Pape Sies Rng Omanie Cy unin Paane Serene Sota ar me Gee ie Geese Ce Coe Figure 20 Basie Canfgurlon Options ter Muman Mapping 10K 00K arrays Entar vos for contigution Options The parameters are desorbed in Mme Cosi User ana
11. CHP tes are reared sted he OH analyst done ih th genotype cats made on the BRL Note You can pertorm single sample analysis on more than one CEL at a ime single sample meen that each CEL Ne s compared reterence model Notes on Selecting Files against a Previously Created Reference Model File Ayo recommends not using ony female samples against a Reference Model Fle previously created wih any male samples when nunning ana See Apendix A Aportes page 292 tor references to he BRLMM P To CNILOH analysis with a previously crested Reference Model File 1 Open he Workspace and select the Data Set wily the data or ani Fem e Workspace menu select Intensity Data gt Copy NumberOH Analysis or Miei Gesch Coracle Ue Mant on the Intensity Data fle set an select Perorm NumberiLOH Analysis a popup Cree Copy Number OH Arai buton ZE he otra select Perform Co RATE ane Te Copy Number Anais Options dialog box opens Copy Number LOH Analysis Options For Reference Model File Creation and Analysis Uam misiles Cony ake Serta Cort xm 1 ls Seed DULDH Ba ane pe Figure 104 Copy MumberLOM Analysts Options 4e he Advanced tton to review analysis contguraton parameters You can cha
12. Fire 11 22 Stow Copy Number Segments The Slat Copy Number Segments log box appears Figur 11 23 Select Copy Number Segments dialog box 2 Selec Copy Number Segment tes cn segments iom Io lat Cek OK tt Coa User Hans The Segment Reports fr al chosen tles open in a single lati e diia IE Segment report infomation can also be viewed in the GTC Browser See Loading Dats into the GTC Browser page 249 The Copy Number Segments Report able content changes i you using a custom map in e Copy Number Report Starting GTC 3 0 1 CNV a win the SONY enter eal rom te custom map and CNV Amolaten a replated th vanatore names rom he custom map of me segment dala sean GTC table view oniy Semple CNCHP name Copy Humber State per marker CN as emat by ha HM nemer me Copy number change s decrease or increase tom normal valo ew Chromosome where me segment located Cytoband Star Pos wa ich a Number change Segment gin Cytoband End Pos Tha band within ich a Copy Number change Size of tha segment ol Copy Number change Makers Number of SNPs markers segment pm ied number as encompassed by Over Peter of marters ina segment ora te tous Start Linear Pos base posto
13. in a Plus agorir wie p as ctas ar now represented as 2 dmensional gausians and resistance to non gaussian cluster behavior hes bean improved A usual dala hasbeen used 1o generale made rapesen he ater proper earned or each marker Urbe Plus arien is designed 1o ca in angle sample made bout adiping to iv data he default penawar to use dame cusenng 10 adapt cr 10 Pa Although sample can be run by el more samples allow more leri of any sii fom he valning Fray the key sdvance in preprocessing is an aat reduc layer that a dene 1o use infomation tated on retested probes to reduce Impact sal flats wen sometimes occur The method operates onthe raw prabe data amo satay probes detect usual diirences repeats intensies Standard age processing vanslormatons ae use to etc of n were deviations occuring in boh channe cust seating a polenta acad act Once regions are market as unbusted due 1o potentat aiat intensies lom ed ae sed ta replace unustad teates or genetypin poss In he case where e maed usted fora en probe he behavior ao ane and alow he memod to lade hha compatte win nau reprocessing proves Seeing oe iier ae vr
14. CNV names f CNY data avallabie SNP or CN probe set 1D win Logarato The log ratios displayed in the status bar may not exactly match the ratios tor in the CNCHP ties The values in CHCHP are converted into a olor value used forthe heat display tis color value ls hen translated int he log ratio value used forthe stas bar display CAV region ID I CNVCHP les are loaded vi Miei Gehe Cora Ue Note recommends that you do not use long names for the CEL and CHP tes since hese long names can cause dispay problems n ie Heat Map Viewer The status bar in he Heat Wil not be abla to display the information he and CHVCH names derived ine SEC names ae o long eda can ces e sie te Map on ihe screen by dragging the vertical window Figure in Status bar Navigating the Heat Map The Heat Map provida several options for selecting dat of interest seeing Chromosome Selecting Regions Selecting the Chromosome for Display The claplaya tha dala tor one at a me When lls frst opens t displays al of chromosome 1 iri Cvamosore Map and Heat Map Select he Chromosome f interest rom the Chromosome dropdown Fire 1317 Chamero at You can seal tough chromosomes by dein he Chromosome dropdown let and Usi me mouse whe
15. workapace tet fie has been moved dead Console prompt you upate i locations or ignore e ming fe Options include Lacate the new directory which contains tis tio Ignore tis and apen e workspace depone al missing ties ito ignore coton selected he fes wl be Ragged as missing in he software unti they are eher deleted om he wonapaco or th path ia corrected lables may fest The laloning sections describe he Directory Search and File Search tyr Canace User ana pe gure 22 Workspace moved hastens e CLOSED NEP ART O Che O bee O wed ate peace a declan sh ei Tha cn ae CEDE Figure 29 Pind lle notice Mote ta workspace is already opened go to Workspace Verily File Locations pertorm hia check Directory Search When ying to ese moved or missing Nes Hh directory search option chosen you must browse to he contra te missing He tyr Corsi User ana m nator imn Honc pn d can 2 G cnma come trem Figure 24 For Fler dialog bos El Not Genotyping Console wl ook for the mis dom the Workspace inia new dir inde in that directory t there are additional nies 1 Ihe path wi lo be updat Wen t
16. Figure 121 CW Genotyping Options 4 Select he Cip Root Path orte CNUCHP esl sel important always save your results folders with diferent batch name and location to make sure you can td your data ater t you don t change te output rot path GTC wil use the previous te Bath whieh can belong to another dala se or another hard disk S Change the Base Batch and ade name I Seed 8 Notes and a progress bar psy te progress of ne analysis Patra iy Mant ater dni S DE po Fire 122 CV notice men he analysis complete te resus aro dlaglayad in the Table ee bel Te CNY cal data con so be viewed in the Haat Map viewer il you have n Copy Number Anyi Same CEL os you canot vew CNVCHP data CNCHP cai Mine Cosi User ana CNV Table Display The CNY Resula tabe displaya te Cal Cal Contdence Sono and sample tibtes with A Column View ter sach delned CNV Region selected Somos ltd by CNVCHP and CNV Region 10 To open the CNV Tabie Double on the CNV batch older ol trat or Right click on Number OH Rast ath folder of interest and select Show Copy Number Variation Resta Table or From he Workspace menu select Copy Number Variation Results gt Show Copy Number Variation exits Tabie Toe ble opens and displays the rest tor Chromosome 1 Fire 123 CAV Renta table Slat iw When you frst open he aie displays he Deut view y
17. iredhso Genie vini STO O Sin svo Fue 1031 Smoothing Signal Graph Output Smoothing Gaussian Window The log rat i the raw estat of iog of CN signal compared to an expected state of CN 2 or each marker These raw simata can be using Gaussian tower noise to improve Mote ao at he enpense of ng boundares where CN alate changes For each marter Io smooth af gerame dance ton Bat Gassan iom has Sander Devon Song Casson I ual signat s gt lom a8 Sening is value to O wil resuttin no smoothing Smoothing Sigma Multiplier n principie tne Gaussian smooth uses al markera In practice sumcundag tar tom any particular have nner reac onthe fa value The Sradting Sigma Mulier parameter number o Standart Deviatons on the gen marker where maar i b nuded in e oon Noe at ager values wil resul tease compute ras rhe Sening mis value to O wi enu no smoothing Smoothing Parameters options Smooth ratio to CN Checking mis option Smooth ratio to the HMM metn parameters tor diferant CN states and vene Te smoothed flo to Number So s value nthe smoothed 2 ao wil became 2 aner vedin Ibe HIM mean comspondg CN sas a V
18. decia to snow mute windows Select Windows ET Se poe Meaty display to tie the windows sie by de Select Wow aye Tie Vor Tre wo SNP graphe for Cases and Contos wi be splayed side by side Ma a ed Cunenty each cluster graph must be dependently Future versions of Genotyping Corsi wit tegat is tt Corsi User ana Appendix D Annotation Definitions Conn tame Descrip Tre Ae argue tol of probes ue dtc par She iet NP pron on Tre Antic argu tol of ros wed dtc a pear Aspen ot fhe pesos ta Canter mr NC teme mani red ven inom singe victae palmer he sma che rc The QUE anced andi SNP d aa gren a he Ten norton ese Seip Set mn ou SNP poe Chromosome St peste tase sart poster whare th SNP end The gee guen ar donde cure arte varaion d Oy sh as gnome bae onse potere aan eaten ol he SNP tom he SNP phyla reso bar posed oy UES Svana ve icu wher he SNP ore rame rrr an SNP GNP praba teen marker mag i ather PAR regions Prove count Tre etal nuanta af prabe w be prob ow fe acie GNP be bati
19. edn pi Dre Technical Support provides technical support o al scans users pone or contaci Ayeti Technical AFFYMETRIX Contra Expressway ania Clara USA 88S ONA CH Fax 1408 T3 susporQaymetis AFFYMETRIX UK Lid Voyage Mercry Pak Wycombe Lane Green tt Genagrirg Canale Un ana gh Wycombe HP 10 oH ted Kingdom UK and Others t 0 1628 552550 Germany Tet o1s03001334 Fax saa 0 1825 552555 AFFYMETRIX JAPAN KK Ms NN Big Tonyo 082014 Japan sesjapangatymetric com tt Corsi Ue Hart Chapter2 Working with Genotyping Console Genotyping Consol stand alone t can be on computers mat have Sytem OCOS sore Command Conto AGC suave o ether C Note you are using GCOS es Ayer recommends that you anser dats out of GCOS using he Data Tranter available at Aymetibccom and use Ine File option In order to retain Sample atributes Tabie 2 1 and Table 22 show he opertng syste hat Genotyping has been vested on and h eeommendad maium requremerts The larger dala aize wit Genome Vis Human SNP D Arraya should be lakan to account when caste the necessary aviae dk
20. Corsi Ue Hart Contrast QC min BB Peak BB Valley AA Peak AA Valley 10K Random Contrast CES sinh k 4 B A B ysinh Adjust Value to Zero if Abs QC_StyOnly QC Nsponly gt 2 E ane mo al Spe rao automa GW SPs where Contrast values fa wiin neti Const PETRA end d a i ur pte totg e it open Cave lyric pep rl wage p The Contast QC is agus to zero f aba Contra QC Nsp Contrast QC gt 2 tt Corsi Ue Hart Appendix G Best Practices SNP 6 0 Analysis Workflow 1 study Design Where posite randomiate ot cases and contol across sample plates usualy qood In studies involving s usualy good to o ensure members ot a ore on he Sane same piate 2 Sample Cali Check Reprocess samples wth Contrast QC 04 4 Genotyping Custer Samples win Cluster by or csteratlogelher according which process is most convenient for the b wor Esch duster should contain mimm 48 samples Wa leas 15 ome samples 5 Genotyping Post Custer Sample Quay Check Reet samples wi cute low Brdeeed Calrstes Reet samples wih excess predicted heterozygosiy 8 Genotyping Post Genotyping SNP Fitton ltr or SNPs with high SNP cites over sangles in he study somewhere a the range of 90 95 Tae exception Y chr SNPs which are always NC tor Female samples May also want to reject based on deviation t
21. PAIRS B G mayr mto Figure 25 igh clk manin table The soci dala is copied too clipboard and can be paste inb i Winen you expr te tom he CNV Results table you export the CNV data tor displayed chromosome an or al daplsyad CNVCH Nes To save the table as s tabled text le 1 From e Table manu sect Save Table or ih ck the table and select Save Table to Flle ftom he popup menu or ck he Save Table to File buton The Save As dialog box opens Att Gehe Corsi User ana 24 Save As dlog box 2 Select a location enter a nama for he text fle and cick Save Tre ie saved in the specie ication The contains a tst ot me fies chromosome regions and samle abut intormation in abe play data oniy fer cvtmosome gure 127 Tex displayed in spreadsheet stare Exporting trom the Batch Results Ifyou export data trom the CNV baten you create an individua texi e for each CNVCHP exported The fe tete formation abou he CNV regions tor every chromosome in each CNVCHP ie in he results set To export CNV trom the Results set 1 Select he Results set at you eh to export in the Dala Tree tt Canace User Hart 2 From me Workspace select Copy Number Varlation Result gt Export Copy Number Variation aut or NECS Fight on the Numer OH data set and select Export Copy Number Var
22. to both versions However given the additional constant onthe it Bz deed 92 ta more Hely than to ether correct abe th clusters or set genotypes lo No Calls IE Mote For Birdseed or Birdseed v2 chromosome X and Y pertormance within esch gender wil be ntuenced by the numberof samples ofthat gender In the clustering For example clustering a aingle emale with males wil yield typical high perlrmance on autosomal SNPs for all samples but perfomance onthe X ehromasome lor female may be poor For good perlormance on X In mates recommended tha st eas 15 female samples be included in he clustering ru For X or Y in males there la minimum requirement Mime Gente Cora User ana te genotyping nalis inated several vindoss wil be splayed showing he progress of the orte Penne pvt etant um gre dog boxes or Genome Wide Human SNP 5 0 gure 1 Note The status messages window siso displays information regarding the algorithm process Note For tastest run tine y mee recommends performing genotypin red local ysl wth a important On the recommended workstation batches of 80 CEL files Axiom Genome Wide Human Array have been successful run Wen he sort completes he CHP Summary Table ibe automate tr Gesch Coracle Ue Hart Tae ae al
23. together according to which proces is most convenient oc he lab Post Custer Sample Quay Check Reet samples wth clustering cal rates ies than 97 Reject samples with exces predicted heterozygosl What exse consttutes an outer wl depend on e popaton Vs ofen useful piot tne hetemzygosiy against 1e sale cal rate ater Samples have unusual cat fatatetzygeal combinations Note deo a because Consol NX markara general have Sy higher on males 5 Piate tevel quay heck For each plate check the overa sample ale rate nd the of perlormance DOC amp eal rata Tor ase samples Any piate wih an urs high amber of lure ra sue at lcs sa specie subset Ol experimen 6 Genotyping fal ound Repeat genotype clustering rejection f any cur sales in he pre minary round ot hen T Post Genotyping SNP Exclude SNPs wih low SNP cat rats ated over al passing samples in me study somewhere in ne range o 90255 Theexepton is Y chr SNPs whieh are always NoCals for Female samples You may also wart to reject based on deviation tom HW n controls reroducibty and Mendatan herane re poesi and appropiate Post Asocion Study Anshsis tt Corsi User Hart rapsctchatar plots for al candidate SNPs to ensure hal here nothing unusual about the Ge
24. IC You cannot change the annotation les in this analysis once a specie reference mode tie is chosen The annotation les used o create Reference are automatically selected Note The Neff annotation files must be of NA26 1o higher version configuration tles are with regionai GC correction I he contiguration es are without regional GC correction Neth les can be ot MASS or higher version 1 Set apt os pan tna changes ha con whare ie CNA OH eae cet Rooi Pah owe tn secret Etat Crete 15 Inthe Browse tar Folder dialog box hat opes select a new location tar tho data and pe Mies Gesch Cora Ue Hart wart PES Ero Born Shem gure 1011 Browse for Folder dialog bor Thi changes me name of he fider in whic the CNCHP are plac C Note This tolder is the location where the dierent Data Results ni feider rough Windows Explore to view report ties e kept You can access the CTE Asa utc tthe CHCHP tles to help you ak them TEE 10 The Select Fes dialog box opes ti Gehe Coracle Ue Hart co oe Figure 1012 Select Fles dilog box Cic he adet E to ad dala to me sample or reference tat cick he Remove buon Z to remove data trom a ist 12 cirok Ater generating me Copy CNS enc Nes you can Generale Segme
25. See he Motion tor intormaton on gore Axiom Algorithm The Aion GT method genotyping procedure delivered in Genotyping Console 4 0 or use with he Genome nde Human The pray maiodcioial change as been a incorporate Process ivo he APT Supr e sasay Aem GTI and im te rca and calling over BRL P whlch a used Genome Wide SNP 50 ses SNP 50 art Many ofthe improvements in genotyp cain were developed or e Pus product 2 dimension cluster ouer detectan Preprocessing hss been proved by educ ayer win reduces Impact ol arttacts on genotyping Together ese changes aw lor ood ray pertormanee on ne gan Saeed assay tt Cora User Hart Muthaneel processing lows e use of bol vaditonai il in whieh two diferent probes io the seme jon cf sequence and dtnguah alleles a wel as dye based ll detectan n wich esame probe s maged m more han clan deg alles BAN hese words are handed Consola 42 ranspareniy othe user bath pes f prone are used on Ie Aon p he second area ot mgrovement is in te genotype custo and Many o he improvements were developed inna course of ta Ple produ
26. and SNP ls aval la you during a session of he solar E Fire 29 Workspace wih dala and SNP at should cota oniy related data example belonging a one pray investigate or ne research Be tute Yo open ape tole Be de Db cater Same se af CEL es utin tuo workspaces i no recommended Tne workspace fle stores he lacatons of me data Nes not a f he Nes themselves Slat Workspace gt Properties gt Show information gt Show Locations or press Convo o vew d Ter istoc wih a workspace and ne comet e pams ront cio dta setin e diecoy Wee nd cec Show Fie ocstons on e harc menu rure 2 10 Miei Gesch Corale Uer Hart Figure 210 Workspace shortcut menu Aye Genotyping Corde User arust I Inet Dat Fee te Sot 11 ecient ane mane em ities Roc ime c EET poco ee pio DET pe ur uu pore c PU peces Ru ea pore oer p E peso e o SE SNAM nube FE TT poc o puc puc or LU Fire 211 Location ata sets Esch workspace can have dats sets A dta set manages a group of ARRXML CEL CHP CNCHP landi LOHCHP and CNVCHP a singe of aray or aray aet e Human Mapping 100K or 300K Arraya Genome SNP 50
27. path and name atiibute information for CNCHP and CNVCHP ties f valla The Toolbar provides quick acces toe of the Hest Mme Cosi Ue EEE Ce WC Hen a ota em d p overt p p isi E fal i i i H i H ex Rog RO al Can only be sat before looting data mod Many ot hese clone also be accessed using Heat Map menu when the Heat map open Some can aesae by nthe Map and using popup men CNV Map The CNV Map dep regions i the loaded CNV Map for me selected chromosome Chromosome Coordinate scale paying e chromosome potione for CNV ragns that contains SNPs and N probe seta deployed in Heat Nap ote ol me SNP and CN probe sets doped in he He on the section of chromosome nthe Figure 1210 CNV Mo Since SNP and CN probe sets are not unforiy along the corosorme me relatonstip between the Teat map and he cromosoma map a not ineat tt Gearing Coracle User Hart Figure 1311 SNPICH Probe set n with genomic position in CNV Map Heat Map intensity values are displayed the hofzontal range wih he rests hes sac vray J Hap the values fo te SNPs and CN probe sets using heat range scale Figure 12 12 CNV map Heat map histogram The initis order is by m
28. tyr Gein Canace User Man chia egal dala se tha dala to generata the SE cer a corsa eng fe Genome ie amar ey 20 ista opin x ar BOK Aya BA and a Gene iar uren NP hay 6 Lay nd regni o Gene de Han Ama Fr ame istis se Chater Export Each CHP file to a Separate Text File Export al results to single opion i not selected the flowing output text wi result The nae is ihe CHP name wih 3 TXT entension The haser of ne txt wi ideale source CHP locaton aod rare he eseculon GUID which genotyping batch run Iis was generated and the Shihan t c ae fed cl nt gai vare edd ey wba Note Three dashes 7 represent no call For Axlom results two dashes in boin alles represent deletion p Fiir 15 Exported gonatype res Genome Wide SNP D array deed tt tyr Corsi User ana T s ame Export Data to One File 1 me Export al results to single option is selected te folowing output text fiefs wl result The name is ane Expert Fie Name bo Tha cli a Probe Seti CHPlename Expertes For example in Figure 755 the exports rss ect codes and ondes tt Genet Corsi User ana mem EL D z z Figure 7 55 Export al data to single le Export the Combined Results of an
29. Cup Sut add to dique output fle names Tha Select Fies dialog box opens Miei Gehe Coracle Ue Hart s ecu Fire Select es tor Paired sample Select he Enzyme Set shared atribute hom Ie Enzyme Set Shared drop Tre ies are sorted by Enzyme Set Atte tt Corsi Ue Hart Fl ene NEU em AS REN TEE rra rr ces made ae NATUR Mm nae porum ey EL Stns ar ma nce NATI Me Mey vae NASIE BED ACE Erie pui Er Nata nae LY a EEL eed ian e EL NAME Meroe nse Sese me Ro EE NATA vas ABER Avi Se moe Fire 34 zortea by Enzyme Set 11 Select he Sample vs Reference tom the drop down ist ans oh Hy Seals Her yaa ETT EN gt siye rne Mieres dot The tles are sorted by he samplaeeranca tute Miet Gehe Cora Uer Hart pu IT NEL CONES IL a Ear ele lane Dorn 59 ESSE Summe por qu ra RESCUE dius E Hm TIO LIE EDITI EA oT D oT oT HM ET ET pop UD EIE Lor Ir Fire Sorted by Eneyme Set and Sampie Reterence abuts
30. More Mapping soo yam oe OM arin ase ase Demi oe OM arin DOC we iy caer a Only samples thet meet OC resold should be genotyped Lote tis recommended tnat samples not meeting these specilicalions be or rescanned Note The QC rate ta wellcorelated with clustering perormance and is etlective single sample meli or deciding what samples shouldbe used in dawnstream clustering However the coran between GC call ate and genotyping performance Is not perfec and there wl occasionally be imple tat passes the call fate Dt which sub optimal genotyping peormance Review he Genotyping Resulls page 95 for recommendations additonal per sample QC to aller clustering analysis east 96 and an accuracy a at least 55 with average performance signiicanty higher when analyzed with Genotyping Console a Mies Corale Ue Mant E The majority ot the Genome Wide HumonSNP 6 0 samples ilie genotyping ca rte otat nas 9P and an accuracy a Bertomence sgniieany when analyzed wiih Genotyping Consti at can be automate itd upon inport of CEL les by selecting At OC tena Fies option 5 Mang a Data Set Gender analyal also perlormed dusing me QC provides a gender cal mat wil be used to select mode Tarte X end Y chromosomes dung gentyping Diferent process are us forte pender cal dap
31. PAD Ma The ot a stor ec riam aralar ek O dala a ing natn maias n ba Sore scri SNP Sorry tate e sow and IG ere caeco yl eii metere uate To mankes E SNP EM tt Gente Coracle Ue Har Gentes anal tod tema me paar ale all To eating Carel oll per andthe EE Sent aray ype Conten et oa prre d tea opera OC antler Gere Sony rure ate eto le seston Go i Fe seater eee Aye Genotyping User Mart
32. a smoothed rato wih a value ot 58 wii be CN ihe Smoothing Gaussan Window a 0 or ire Seating Sigma he and inersion 10 CN vas witout ny rang Smooth Log Ratio tt Corsi User Hart Checking mis option rests he smoothed 2 ratios ony any smoothing Checking mis option wll prevent smoothed og ratios being and inude in ha CNCHP te Sap Mies Genotyping Cane Uter Marat Chapter 11 Common Functions for Copy Number LOH Analyses Thi chapter covers the number functions tat are common obo Human Mapping 100K S0OK arrays and the Genome Wide Human SNP Array 50 These eos ince Usi e Segment Reporting amp Custom Regine page 227 Landing Data into me GTC Browser page 240 Export Copy Number OH dala page 251 Seting QC Thresholds page 257 Using the Segment Reporting Tool amp Custom Regions rn span Pera Ta neh e SPUN EMEN MU eem Eze pene emen munnan sepre sone Rt Note The SAT requires annotation files annoLdb to version of annotation Mes depending on Ine annotation version generated the CNCHP te Introduction 3 Detect al CN Segments that meet inii tter requirements 2 Fier Segments using a designated CNV Map to remove Segments tat overtag wih known CNV Regions apioa Generate Custom Region Repo
33. cals 2 fre AA Cul 105 488 Cate feta cals 05 8AB Cas eio cate Treaty Wore pas Proctor Aye Genotyping Cane User Mart rr etc arate NBN steps rara a ned Semen iw a ner ge roce reris Sa la wane nei parle pte sete mosses TEC ed Seer Ne tree woe Pye aston ahr gare nay see pe a The th SII rat When me alate Asa ein Te rearing ENS mere alaa s Sosed on he sequen simon SNP Sines emerson te ec a dien E OM ll cia SNP ali prr hal dor When org edi ere cl fe alte coron Meet m eranen i dee ha he ence era sar tows tervenar samed en he sone rng ne tque sarang SNP ee You can display sddiional annotations by selecting the Al Columns View For complete descriplons on all avatable annotations columna inthe SNP Summary able see Appendix D See he Pec Genotyping Anais page GT secon for more on performing genotyping analyses Ste Tale and Graph Features page Me lor mor on customizing ba taba ve Custom Groups of Genotyping Results Genotyping Console alos tor custom grouping of genolyping esl To make a custom group o genotyping results 1 Select he rowla tom an apen CHP Summary table to be added
34. Sample va Reference atte shouid be designated for the Nes At Sampie tes should be assigned one trt vale an a erence should assigned dierent vake Miet Gehe Coracle Uer Hart force und Abi 3 SEES P 1 A Deum 00 2 NOSAR A E omi 3 OLMA E unm Des VENDER Y NALAN Dress A Noms a eat araara TT n nampan and gt 0 rand F_UN 1 Ti Over ani Dress 15 Deme Deme MONE Y 15 NAZLA E Dmm Desas UO VDO Y Y NANDA E lod Hemd WATST Y Noms Pa chams awa Fire 2 Sample ve Rlerence rb Example ere doing pated raison cles tve patents A Weve uso Human Mapping 500K arraya we have to run each sample Diseased or Norma on Ino array hi ges a Toll of 20 araya to math up boh or enzyme se and a sargaelrence ana Miet Gehe Cora Uer Hart e TE Toe eene pap oyara 2 Wo married enam em
35. Select he expr options OK Table 710 PLINK enor optiona tem Cereris brea fl iod and Table 711 Fler by SN Lit Chone opto oriy he SNPs spoofed a usenet SNP et 4 In te next dialog box select an anaolaton fle and cick OK sia Geet Cora Ur ana Chapter8 Table amp Graph Features Cors esr several ropes whieh are monto abes and graphs The folowing Genotyping Data Tabi 146 Table Features page 146 Graph Features page 151 IE Noe The use o the GTC Copy Number to view Copy NumberLOH dats ls described in tne GTC Browser anusi Genotyping Data Tables In Genotyping Consi here are several ttis which pay dola Sample page 55 QC page 76 CAP Table page 91 SNP Summary Tate page 98 IE tote For Human Mapping 100K 500K or Axioms Genome Wide Human arrays the CHP Summar SS Sry data ler een ary poe WA e played i ditt oes wit den Table Features common tatio acess through o shoteuts on the table toolbar E Ero PE sie gure Table toolbar Meis Gehe Coracle Uer Mant apy Clipboard or Descending Shaw Une Graph Each lable in Genotyping Consi has a detsut set ot layed UE Ie im E To creste custom views 1 Select he New View norat C
36. Data sep The owing sections descrive how to o AMA CHP tes pape 53 1t you chaose to import Sample andlor ens and QC flos you wi be asked t select the fles ta be imported selecting fe ciek he Open tution Mies Gesch Coracle Ue Mant BUR aE canto iini du ETT O CU SES EETCNEE cor mum 5 Bones cade Becas ue per Hosan swe oa Becas Mores De Me Hips o Serenus ankim D aerie ant Fire 12 Select ties toad to the set The selected ARRIXMLICELIGOC fies wil adiac to th sel only f hey are fo From same array asis used bythe dala st f Notley n he dala st E When loading a large sto lea ti recommended that you use the Select Directory option oad all contained ana then optionally remove undesired es ate impart Windows has that nite how many tes be returned to the appliestion using te Select Fies option A possible to select more tnan he Windows butter causing only a subset of the les to be The maximum number ot varies an example when ying o BDO ARR and C tothe Data Ser Ime although al les could be selected oniy a subset are tally adde tothe Workapace itte you selected Aui QC nent Fles and required rar Hes are
37. Genotyping Console 4 0 User Manual Not tor use in diagnosti procedures yer Cana Commmand Conse Poured by Mme Genah compatta Cae MET an ar vere Aya eA Ores he prey le radars are propery other respectus amor contain frm te Coin Mandelan eran Man OME tte ich has SS ied rors ts ep eo Tes sons es een inte Licenze ati aman arden that govem your uze of Met occ Me ants te ie Aba pt cpm cess we an rn ature pve oy ah ape sues expt ne Ait te ard carat bas rer ane rior cer rail pcp edo ence Apts cone red Myre poss pirum oe 2 comedet ngs ue his pesos ombre AO pone pec recommended debere producte may ba covered by one or more of the ann potent US Patent Nos 5753129 5 785716 597 104 os at eset eis OS 12T OZAN SA 80 EADE o BABA t os sero son 0 312462 b Db GAOT BB 0202 ard oer S org pmi Copia mets ne At Rights Reserved Contents QC Tame Fon H Gere Cane Uter Marat Miner Gere Core Uter Manat Geneen Cus Fees cn Mur Nae misi SNP Racer BO ren Gere Cane Uter Mant Miet Gesch Coracle
38. Sos Gol ais aan niom signal contrast AT Stn atom signal contest AT S 108 conor 5 atom signal conan GC siom signal contrast signal mean siom signal contrast T mean fresh Gener Corse Uter Marat Decr sigra cort AT_S JOR Asam srt oriant AT S Aner sro content AT_B Atom E nna nt Aera Rom en Ares amon Mea dl a cn A be cw raisin e AT huma A E Mean of he C poe a enter GC p nds ricis er eraran mony Mea con AT pote aw neni rien PEG nomen Seine d GC rte sies o pr peer ers coe GC TOR Sa en rule ange of coruri GC probe rentes igrat dia nt GC corral ej Mean ot cool GC probe iral ntenetiee tm cool pee nr te ion etm com tere erate uan venta GEJ ng ners rat o ona niu roses am s n choad aE aon a whe nar aer d GC abo a ea sce aun ay Log Ditererce OC meri des a Feel SER Cg AT SR ctl pres er pl sro ttn htt pet QC CV AT tc enor omet tt eint For mare intormaton on displaying data e CHP Table see Table and Greg page 148 In adaton to the tabular ol he malis the CHP rests can be displayed in a ine graph To opena ine graph the ine graph shot on the CHP
39. he neni tte I you want to see al lale etic sw 10 A Columna View ithe Tabie before opening P ne ren ty Genagrirg Cora User ana Intensity QC test ll sorted by Bounds Nvv 4 y E OT 3 le B Fire amp 11 by bounde numeric metic can be in ine graph To change the Y or X anis meti or add addtional meis othe roh sie om the Y roc drop down fes ETT BI E Figur amp 12 Select a meti forte X or Vis For moreinormaton see Graph Features page 150 Note Values displayed in tables or exported to a text are only done with certain number ot digi ater ie decimal Fiering i perlormed using he ul precision stored In the SNP statisties Te export the graph data Select he Save Data to File shart on te graph toota Coracle User ant At data libe exported a text From the exemple above Ine label hound QC Cat Rale td OC Cal Rate Nap are al exported he pected For mare intormaton see Tabie amp Graph Features Table amp Graph Features Figure 1 Exported het Genotyping Console during the stap a s t of SNPs are genotyped using a show in the lube below These SNPs can be usad to vaniy a sample deny by comperi e genoly casa rent denn or genotyping by PCR of ot
40. Genome Nude SNP 60 or Ax Wide Human Araya ty Gente Corsi Un Hart EAD Mate O Penate EL Pear arate ner Fire 212 ata et Adela set manages Sample struts ARR or XML tles dala CEL and GOC fes grouped dung QC into Note tles are not avaliable CEL fles QC din GTC 46 The QC information is stored in Me GEL e Custom CEL groupa assembled by you I Noe You ean create custom lats of intensity and genotyping d Groups of QC Pos page 79 lt Genotype Rasus CHP ties These re grouped it genotype esl therm rect anal or import Custam CHP groups asserraied by you Copy Number CH Rasus Analysis les Copy nuer Narber Segments and Copy Number Custom Regiona Copy Number Variation Ress Nes These re grouped int Bath Copy Number Variation resus elmer trom direct analysis or import tyr Cora User Har Reports Concordance repons data sel information can be displayed in tables and graphs an exporting Sample tomato Signa SNP genotypes CHP and SNP summary data SNP itor raps Copy QC information number segment and custom region data nt for Genome Wide ron SNP 50 or Genome ide Human Aray Copy Number Vatatonresuts Copy Number OH dola can be layed in the GTC Browser See the GTC Br
41. OK to save o new copy namber QC valves ir Costing Cora Ue Manat Chapter 12 Copy Number Variation Analysis Copy hamber variation CNV Analysis uses tho Canary alor to make CN state call 1 2 3 4 for previ regiona win varaton inne genome uses repan wih a egion cn SNP probe etn We an oregon wh cen copy nune varaton can CONAN 2 Note CNV is only available for Genome Wide Human SNP Array 6 dats it does not work with other amy forming Copy Number Variation Analysis important Always save your results folders with a dierent batch name and location to make sure You ean ind your iater t you don t change the output rol path GTC wil use the previous tle ath which can belong to another data set or another hard disk For more deals on hard diak apace quiemens see Appendix 3 page S18 To perform CNV analysis 1 Open he workspace and selec the data set withthe dala ranas 2 Select ers dala set to dala vee 3 rer the workspace menu select Intensity Data gt Perform Copy Number Variation Analysis ots pe meet st Neset ana select Copy Number Van Ani Pom Pe o ke Prom Copy Number Variation Any buton E n me ota The Copy Number Anais Options dialog box opens Miei Gehe Coracle Uer Hart Arist rao men E po Came Canna achine
42. OWS_CCNS CHOP et ve sp eng IN GM CHE CHCHP IS GV Een once ETE GI CORE CHOP EWE canot nc ARR rc CCHE RTT SALE car ITE TE apace CONS CNC Mz o cma nc a 8987 8 0v APOS GELE CNE CHOP trn Camp cnc EEE pet NASA M CONS Gui C cna anre 08 NATOS SM CHE lam can IRE Tt NADIOSS OWS CONS CHOMP omer TE Tres pe Figure 12 4 Seeing Fia asocatlons tor ipe CRYCH 4 Use he CNCNV Association dialog bor select CNV fles to be played wih te CNCHP tes in the Hes Yau can select al CNVCHP tles om given bach using the Select CNV Bath Gop dow and manly your bleh choice Tor any a chosen fea Tha CNY dala automaticaly cade if available and CNV map associated win ese fl wit oos GWE E CTE CENE jain Gut ew venom I ri GM CCHSCCHP RU crar lem IHRE DE E al Fire 125 Selecting CNV batch 5 and progress bats pay he progress of lang he data The Heat Map opens loss he resus Tha CHV dala automaticaly loaded if available and he CNV map associated wih CNVCHP ias ie ake aulorateat oed tt Genagrirg Cora User Har nen notes you of the number of number an copy number variation 1 iai es aded Cick OK
43. Tre rote appears If none of he copy number data es nad any Segments ammo cies esata rerata aperti bottle str pure Figure V o Segmente Rests notice Tre nace appears t one ol he copy number data Hes had Segments ar Mou ick OK in he notice above Gente Cora User aa Sepou ta wan Figure 113 View Segment CNLON ce ik Yes to pia ttes In he GTC Browser Selecting CNV Map tor Filing Segments The SRT atowe you to Mer e detected copy number segments against a CNV Map of known number ation regions by a spa percentage The SRT uses Ine Toronto CNV map he dal map fo ana You can choose oiher ENV mape Braad CNV mao or user detned map nthe SRT Fiers di br A CNV map template Custom Regions c eons bed la provided in bran feider When SNP and CN probe sets lose genoma postions due to an annotation update ase SNP and CN probe we nan inde n SRT o calculate ona EZE O tman Figure 1 30 CN ap optione The CNV Map use he BED format To select a custom CNY map The dialog box opens tt Genet Corsi User ana Figure 11 11 Open CHV Fi dialog box Select he CNV Map trom the lst displayed in the dialog box ad cick Open Selecting Fers You can Mesh tor tne segment sze and of markers requred to define segments
44. be mer ac Dese Ede stented andi tum t etnia n ragione saecu Coni ot resa CEL ne se at pe sree ads CEL aie daa Conia senare he eset OC Saye tonne tr are acer CEL Eure 2 Not Genotyping Console wil only add tles to tne data set that use he same array type as he data Next browse to the drat fies to ba imported and select he data tles tyr Canace User ana BUR aE canto iini du ETT ue puc emos Eun EFE E ances Wem Bern Boons per Base oi Beuzeg aon orones Scu cos Fire S11 Select ties toad the set Not When loading a large set ot es ti recommended that all contained les and then optionally remove undesired te The maximum number of les varies As an example when eying o add 800 ARR and CEL to the Data Set sone Ue although al es could be selected oniy a subset actual added tothe Workapace Noe Based on the type s ot dta the Sample Attribute Table the Intensity C Table andlor CHP Summary lon about he existing and added The Status Message Pane wil report any problema with the
45. combination ot Nap Sy below Mappng250K Nsp sy The Segment Report Tool a ater Copy Number analysis Ifyou wish to run CN number andor LOH analysis on both array types al he same tme you need have Enzyme Slabs setup fo he fios You can use Enzyme and Sample Reference ables o make soring ana paring up e easier Algorithm CHA pets paired and unpaired CN analysis Pared CN Anais Ped CH Analysis usd to compare for example to samples from he same Individual to look lor copy ferences dierent yee o lesus orania out Tumor Normal or ested Ped analysis that genotyping batch analysis be on the dta o be analyzed trst CN Anas Ungaed CN Analysis used compare samel fies sel of reference tt Cora User ana analysis requires that genotyping batch ans be on he data 1o be analyzed Copy data is output wah the sux analysis can be run at he same time as copy number analysis orin a separate step nunning the number analy Huren tapping copy number and LOH data output in separate fles and Gioco ies mente segment reports can be run on Human Mapping 1000500 array CN dala ro gender cats re made by the Reporting Tet Copy Number LOH Analysis for Human Mapping 100K 500K Arrays This descr
46. the Custom input Regions file can be loaded into the GTC Browser lows you to view your Custom Regions in a genome context Running the Segment Reports Tool Tha basic operation of he Segment Reporting Tool is described bow You can select tom several opens tor using he Segment Reporting Tool Selecting CNV Map page 235 Piters page 256 Ou segments hat overlap with known CNV regions oplona age 22 Adding the Segment Report Fle page237 Create Segment Summary Report Fle page 237 Usi a Custom Regios Fle page 238 Crate Custom Regon Summary Raport page 240 To creste a segment report 1 Select the resus set you wish to generale report or 2 From the Workspace mena select Copy Results gt Run Segre Reporting Tool or tt Cosi User Har socks nb Cay Mune Rese stan ee Run Segment Tea one pop nen ke Run Segment Reporting Yoo btn le ba 9 per eee terit Soucy arb Say Tae Son nope Ie E Rete naa po eerta urbes tenis Gg ano copy tundra tanks orem Figure Y Popup menu E W you have selected a data set with no copy number ies aaah pear the following notice nu Fire 112 Waring Ifyou see is cick OK and then select a dala set with copy number dala 1 you have selecte
47. 1 0 wil not contain these data columns one must fles again using GTC 20 above lor hem lo be calculated Scat of en cstar eh ha const gender eX ht rate gander ortam wo main clusters o points one for ales nd Tor females win unus gender are pectet lal outside of e two ran uses ical positi devons fum normal ser copy ante Tho teow shows tha selef piat Tor ba 270 apap Sampie NATOBSA and cule of tne sca gender work has demonstrated Wat NATOSS4 8 known t Nave onitan degree af X mosaiciam BMC Baers 2006 725 and sample NATESAD rae x Store nna an rp see oer A m ant 79275200 Male see FOI APP Cr contrast Fire D 2 Genter Metres tor 270 sampler on SNP 60 Gen r Calls Female or Male in Copy Number Analysis SNP 6 0 only number arai o SNP 50 dala provides an actusi gender cal eae Male Tha gender la using te same rod as in tn SNP 60 genotyping gender cal process described Stove using te rao of et renplyrrpi probes CN Segment Report SNP 6 0 only For SNP 6 0 Arrays he Segment Reporting Tool makes a gender determination for me sample based on he ruber a or he X and Y chromosomes Normal males n fetales are expacad o aye Copy Mamer State or auiosemes 2 Females a
48. 2 Inthe dao box hat appears select a SNP Lis and ciek OK no SNP List is avaable generate a SNP Jat For ore etis Creste a SNP Lit or importa SNP Lit tt Corsi Ue Hart Fir 126 Selecta SHO Lit IE Note Depending on the number ot CHP tles in the Genotyping Results bach and the number ot Sites nthe SNP generating the SNP Closer Graph can tke several mines in te next dialog box select an anaolaton fle and cick OK tt Corsi Ue Hart amio a v rare Ses e Fora mpm j Le Figure 127 Select an annotation tle BRL ara SRL hats prs in tread cnt 728 Se the BRLMM P white paper for mare detalls transformation applied tome contrast For seed clustering a performed n a two dimensional A versus B space Figure 7 20 For the Alam QTY atr cem le perenna Lg rato wea seth apace gue 3 Log Log ato slot Hog B Strength Aog tt Gearing Corsi User Hart Aye Genotyping User Mart 3 mm SNP A 4253484 20090500134344 SNP UET n m E ora Yd 3 T H H i Li CIT mese 904 siparo m gure 7 29 SNP Cluster Graph algorithm ty Genet Cele Ue Hart in oc y H T 1 Fir 120 SNP Cluster Graph GT
49. Array Set re gre sutton pe araye oan aray fer enamate Hunan Hopping 25K Neg an 250 Siy eat be combined and spore io one L Note Sample tles ARR are required for the genotype resulta that you want to combine and export 1 quera Genotype Ress group and se Export Mee Genotype Rests on estat en Faure 156 tt Coracle Un ana IT sense chter ee Fusion pores Fi Eget Tle Paros TTG p Figure 14 Select genotype results to merge tor export 2 In the dialog box hat appears select he samples to export and ick OK Figure 7 57 tt Corsi User Hart Fire 157 Sect samples tor merged export nhe nex dialog box select a destination and ena a name o he results Figure 7 58 Select a sample matching optan using one user fom ARR for hese samples Select an export option Export orward strand base eslls with dbSNP RS ID Choose this pon to include te forward sand Base call AT CG AG TE nthe tte On probe stew USN RS 1D cade Export cali codes with Probe Set ID Choose tis option o include he cal codes AA AS er Bejn heted fe tt Genet Corsi User ana o Figure 1 Export options 4 Select sonolaton and cick OK Figure 7 59 Figure 7 60 shows an example of merged Aye Genotyping User Mart Fir 0 Example merged rents wilh one sample par row Expo
50. Basic Optone Advanced 4 Save me changes tthe coniguatn To seve as new contiguraton Ck Save Seve ul configuration Ck Default To edita previously crested Contiguration 1 om De Ed men select Copy Number Configurations Open Contiguaion The Open cistog box opens dne Ep Figur 9 1 Open dog box 2 Select me canfguation and lick Open The Base Options dialog box opena Ener values lor confguralon Options The parameters Basie Oplons vanced Onions Att User Har Basic Options The basic se dieplayed when lg box fest opens Copy Humber LOH Configuration Options Wapping po Resmi anais SNPs an Figment Rena von Omane Clm Fase E Seno Sec Cay Nunta Tenet Gee Ce Ce Figure Basie Configuration Options The Basle Optons alow you to change parameters for Fragment Sat Copy Number Parameters Restrict by Fragment Size erties ean be patie on oniy SAPs bases on he agmen se where tre Fyne Sos Rang ite im v Fire 23 Restrict by Fragment size To enable this option 1 Check me box nent to Analysis to SNPS on Fragment Sizes Ranging 2 Entar te size of tagments hal you want to be nad in the tt Genagrirg Corsi er ana enatesspeceston
51. Chapter4 Library amp Annotation Files Genotyping Consol requires information stored in ibrary fies lo analyze the CEL generated by GCOS ar yma Genes Command Conse sotware These fes ee hom NelAs can be ourioaded utin Genotyping Gentypeg ony ase tray Tes eque fm Nat tor anise bu tase aro vot wih GCOS or Command Consdl and are Suro scan ama Gencypg Console uses SQL annotation ies annat db to display and export about the SNP and probe sts such as Chromosome Physical Posto BSN RS 10 ete as wel a or certain dy You se tan son e GIC A babe fies mas ae SOL The owing sections in tis chapter indue Serge Litany Pam Obtaining rary amp Annotation Fes page 34 Setting the Library Path 1 Genotyping Consol tna on workstaton wth Command Console me ibrary path ia Suomi sete ray path used by Command Console If Comman Corea s nol lale and a pal apecined Genotyping Cenacle prompta you to see a ocato or to ary path You can sel the any wout tenting he reram any open wolagaces mst b caet Ate Usera must have we scenas t herr ole iake sare ta o te ry Nes lor use Ye location for the e ies em NN erat Er io d etes erected cum err bee CIL Figure 41 path nolo To change an existing ibrary path 1 an
52. GC correction edn Hato Motel rar GC comen mist SNP EO wi changes este ETT rne Ud 79 E 9 15 02 02 Fire 1027 parametere Copy Number Parameters Parameters witout regional GC correction In contiguraton tho regiona GC correcto 1e same Hidden Markov Mode HMM suse SNP 6 0 and iso mapping arraya as mat usec in GNAT 4 wih me ong nelatie excepto for SNP 8051 ratas pror 1o using tbe not possis and 2 in og ats Tor SNP marnes le and 3 summary is not pose Accordingly omer han smoothing Ine Same parameters NAT 4 exposed as advanced These parameters af used 1 data how ihe Cauta per marker Number rom faga ratos ty Gehe Corsi Ue ana ders Er EE pm aLa sin 02 aall aal az Teeketes Figure 1021 partes State represents the posse values tat 1e HMM can The M locks for CN states 0 1 2 3 an ar reser CN state ofS ore a represented as CN Siale 4 A Saat Hidden Markos HMM s apple tor smoothing an segmenting ne CN Gata The priors and decay ar wo user unable The HUM hs 5 poss states Ed The delau or sach state is 0 2 indicating that each SNP nas equal prior probably of beig i ay one ot he 5 S
53. Group Samp yt User Har To pertorm Pared copy number andior LOH analys 1 Open he Workspace and select Data Set wth data or anal 2 Select ie ensty Data io set Fem te Workspace menu select Intensity Data gt Pertorm Copy NumberLOH Analyst or Fight kon the Intensity Data set and select Perorm NumberiLOH Analysis trom the popup ck he Perlorm Copy Number Analysis buton nthe tata The Select Analysis Type dialog box opens mm 7 O Urwanie Anai O Lave Newser maun oe Figure 81 Select Anaya dialog bor 4 Selec Paired Sample Analysis tor Sample ype 5 Select he analysis ype CN LOH or botn Tha Copy Number Anis dialog box opens tt Corsi Ue Hart Samet rape Cait p site A gn pn lt Ca Number Opa ah connor cearo See LOM Ea am if See Bk rs mem ak Figure 82 Copy Number Analyala Options diag T Review anti contguraton parameters select new analysis configuration desee See Changing Algor Contguratons fr Human Mapping 1004800K page 79 for more matan on Seating a rale Change e loving dase Output Foot Path location of he Results Group tke Note This tolder a the location where the dierent Data Results te are kept You can access the alder rough Windows Explore lo view report es
54. SNP cal rale range iom 0 10 35 Consider removing SNPs w h minor tequency MAF below certain 1 Depending on ckaunstances consider removing SNPs sity oul ot Hardy cases andor conois wave in ange of 10 a vae nce he genotyping rests aro generated you can SNP Summary Table page Custom Groups of Genotyping Results page 101 Crete SNP Lists page 103 impo SNP Liste pape 107 SNP Cluster Graph page 109 Sae ALSNP Custer Grape PDF Fle page 118 SNP summary Table AD important you cannot display the SNP Summary Tabie unti you have created a SNP SNP List page 103 for mare Information The SNP Summary Table SNP level stasis based on the batch o CHP ties r ntcick on a batch and select Show SNP Surimary Table tt Corsi Ue Hart ES po neve Bl Scie Shs hte cor pnt cert ests at retype est Pk p p Fire 1 Show SNP Summary Table Genotyping Consola store SNP summary ination a binary whieh la generated dung genotyping a env Cree ca oro qa d eaa rct e e escis Genotype Rest CHP tjes were not generated by Genotyping Canoe but ino ine workspace the rame he Summary bea generated Genalyping onsale wi prompt 1o save he summary stai Ts message w
55. Sample terence cick he Ad bution E o sad data to me Sample Fes ist or Reference Files list cack the Remove buton E o remove data trom a ust ithe les a he Fies lst hated you wit not be o em to he Sample or Reference ts ntl you have selected a festa group ore ue mue BESE IES Figure 814 Highlighted reed to select Res Group See Selecting Results Groups pape 169 for mors formaton cick me Up A Doun V tons to change tns fies poston and ign arrays by enzyme set ion ia not important mae samples may be Used in information se the Aymetr website forthe while paper Humber and Los of etronygotyEstinaon Agri forthe GeneChip Human Mapping Ay You can also change the sort order olumn headers nthe Rat Mme Coa User ana For more information shoul using shared atributas par flet by enzyme vat or sarmglalralarence group see Using Shared Atrtutes to Group Samples page 172 pr IMPORTANT The Copy Number and output fles vill be named using the Enzyme Set attribute the arrays progress windows open as he raya proceeds generating me Copy Number andlor LOH tes you can Generale Segment Report CNLOHCN Segment data inthe GTC Browser Export dala to her stare Tre te omat deserte in Copy Nnbert OH Format tor Hanan Copy
56. Segantoverapping a agen Seres one row in e tie Redon wah neo Segre soe ara represanta ge Fow inthe talle vite Loss Gai olan nol Segment for Human have e CNA custom regens Custom Regiona Segment Data tor he Genome Wide Human SNP Array 60 have he CNS custom regions entension Custom Regions table in GTC To View A Custom Region Reportin Genotyping Console 1 Genotyping Console data ree select a Copy OH Resulte group for ich you have generis Custom Regen uang he Segment Reporting Tao Todo his Right icing on a Copy Number OH Results rop and choose Show Copy Number Custom Regions tt Corsi Ue Hart Figure 126 Sene Custom Regione 2 Select Copy Number Custom Regions cust regions om tl Fire 1127 Select Copy Number Custom Region Fes Custom Regions for al selected fles opens in a aingie tat and displays he folowing Inlormmalon tt Canace User Han Se overlap ot region by Segment eng overlap ot segment by region f markers in region Segment size kb Segment size markers DistBetweentlarkers t Chromosome Cytoband End Pos pm End Linear Postion Custom Regions regt name Region name trom Custom Input Regions Percentage of ovetap of Custom Regio
57. Summary table taba The aviae features tar hls graph are the same as in he Graphing QC Rests seen page 78 Review the Genotyping Results Betere conduci downstsam analysis of genctyping result te essentia to theraugh OC ol beth SNPE ad samples Thare i no single test way odo QC Dut some sop ht are generaly ange are old blo 1 Persample QC teng Precision serie taling per chip QC metie shoutd be excluded prior o chat as described in Chapter aly Contol t Genatyaing Ani page 67 Semele swaps wich may have occured during handing should be identite and rescued or removed ne way todos ito generate by typing samples on a dazen or more wich wi tba SNPs reported in he Signature SNPs B Anoher 1o use town pedigree infomation re appropl t contem expected relatedness pan Poster Remove samples wih cuir dusting ca rates or heterozygosy ich wl tend be ow peeing Samples at escaped QC eati rate e Depending on he downstream ana lote appl any yp eatedness and fated campis Depending on he downstream analysis o be appe consider controling or population siructure Bol be removing Saree ha are ceany om dite pops fom ihe buco tyr Coa User Hart Remove SNPs wih per SNP cal rates sometines rere as completeness less than some threshold values ora por
58. To case versus contro SNP cuter pert ne folowing stepe Step 1 Make custom groups o CHP les one for the Cases and one tor the Control samples 1 Select ross tom an open CHP Summary table which contains te cose sangle right click and sect Add Selected Rows 1o Group Note Selecting e appropriate les is dramatically implied our sample les contain an tribute Sistah yos oer rom contol tbe sulle Cute cred cusam viu ar splays arbe and sort on I 2 Entar a name tor his data group e g Cases and select OK The new groue wili be dlaplayed in he Bee Custom groups are by wit Aye Genotyping Career Mart p trary ot Er fx ui y Repeal stapt 2 forte conl Step 2 Import he SNPs to be displayed in the cluster graphs In association studies SNPs wth poor cluster properties can te source of alse posiives Ater enin your todo teal evaluate he top SNP his plor additonal analys 4 elk on the SNP Lists icon in he ee and select Import SNP List li s Note SNP Lists can information be generated in Genotyping Console See Create SNP List section for more 5 Brosse tob locaton of e of your tap SNP his and entar a noma tar tne new SNP List Erter ral SF Tp Hema Tel Tha naw SNP ist wli be displayed in the data
59. User Hart Cal values fore CNV regions curent played i he Heat Map rore man one CNV region is present hen me average of CNV cl rane ENV regen used tor he CNV cla some CNCHP Hes do not have CNVCHP data ese fies wi be displayed at the olor of he Heat Map afer on CNV Cal values Mar soring you can export a ist ot me es in her new sorted order Toson 1 Zoom in on e regien you wish to 2 Selec he sort option trom he Hast map men or ciek he button for te apn Figure 1223 Sorted by median Export List o Files in Sorted Order Te exporta lst ot es in their sorted order 1 From te Heat Map menu select Export Ordered File Names or ugh eka te heat map and select Export Ordered Flle Names om the popup menu tt Gehe Coracle User ana reip Figure 1324 Ment Map shortcut menu The Save As dialog box opens Figur 1825 ve As dialog box 3 Chek Save in te Save As dialog box A text fle crested win he CNCHP and CNVCHE f available path and names tt Genet Corsi User ana E o asini SR dii m 21 im Fire 336 ot sorted estet ormat ICNLOH and CNV om he viewer You can use the export uncon in GTC lodo this See Sporn CRY Dat age 204 tr more maton spo a view of he Heat Map for use in a orto show oer users proiden several ways Port te Het Map Viewer ou Expor
60. a Segnet Summary Repon bete enl Fire 1 20 Custom Regions Summary Report in Exes Tne Fie contains Custom Regiona Segment nformati organized Regan Name with he oration anregins as i De Segment Report Loading Data into the GTC Browser tote Upon running Segment Reporting Tool you are given the option to open the new in the Browser Notez t you generated Custom Re Using the Files Open mena in n he Chromosome Vie na you can load the en Input regions bed le Into the Browser ows to se your regna epa Displaying copy number data in the GTC browser 1 In he Genotyping Console dta ree select number you ah ody tyr Genagrirg Cora User ana qo Inset aj pte Panse pee Burns cay orbes tenis noe Cnr urbe ran Figure 1120 Selecting resulte in the GTC 2 on he Results Group and select View Results in Browser oo he content sete or From the Workspace menu select Copy NumberiLOH Results gt Results In Browser or lone toolbar lek the View Results in Browser buton The Select Copy Number Resula dialog box opens tt Corsi Ue Hart qe 3c t pr aa po GEF p o Figure 1130 Select Copy Number Rest dog box Tha dialog box pays a othe resuts dta in o selected Results set You can select me lowing type
61. associated ARRIXML andlor CHP fles with these CEL les they wll not be removed rom the Data Set ty Genagrirg Coa User aa Remove Genotyping Copy NumberiLOM or Copy Number Variation Results from a Data Set Ta remove Genotyping Copy NumberLOH CHPICNCHPILOHCHP or Copy Nunber Varaton CNVCHP los icio onte Beto resula end sec Remove Bate Result The tare wil prompt You conim i gopra Ti ata vn FT Pre TOE 2 e Mamme s emmssrm pi Sortie d q Namaz GWE CCEL i am 3 aem Sese nen Vene v SHE a qw um ee 49 foes Go Nar ld 2 as ae Figur 9 Remove Copy MumberLOM results group kJ tote in Genotyping Console individua CHP fles cannot be removed entire batch results can be emoved are are associated andor CEL Mes wih these CHP es they wi not be Temoved rom the set Edit Sample Attributes In Console sae only AGCC sample les ARR can be ete To make tul use of me features in Genotype Conse da shout be in e Command Console format provides Data Exchange Console sofware DEC to conver our GCOS dala 1o Command Canale Tha conversion 1o me new ral wil bed a unique i enter at i used to a
62. atu required by GTC software to dote EN grin o un carey she pared ornate rae o araya sre atch up araya for pared trom the same patient Th SanpieFterence pal ng sors out he list and is therefore helplul bu opal and is not required by e agori a an wey Using shared touts slows you to sort tles for easier selection and norms you you have made cran miss in paring Enzyme Set Shared Attribute Funcional required in all paired and enzyme set unpaired Copy Number LOH analysis Tha Human Mapping 100K and 500K arrays use two diferent physical avaya to cover entra set of SNPs Haman mapping 100 Mappings Mappingsox_Hins240 Human mapping soo Mapping250k o Mappingzsok Sy Running tne some biological boh arrays in a stis necessary o completly cover genome You can group analis resta trom me wo arrays for one sample into one number dala CNCHP fle using Set Shared o group araya ie necessary to match enzyme sts wth he Enzyme Set whether you are gerlorming paired or To set les up for using enzyme set attributes Pate Sample cel and Genotyping ehe les for botn array ln e some dola 2 necessary abuts for Enzyme Set in Sample fles Tis shoud be done during ial sample Aion b you cn add and edi estas vang GCOS or AGCC Isler on ach paro
63. cick he Ad bution E o data to me Sample Fes ist or Reference Files ist cick the Remove button E o remove data trom a ust ithe es a ihe Fies lst hated you wit ol be abi o hem to he Sample or Reference unti you have selected a festa group re TEE TETAS Fire need to select Results Graup See Selecting Results Groupe page 169 or more cick me Up A Doun Y nutans to change tne fie s positon and arrays by enzyme set and Semprelrenceatutes Tre analya compe te at samo mth lat he et ilrence CEL CHP second seme CEL CHP win he second reerence and s0 Note You change the sort order of the Sample and Reference fles list by clicking on t column headers nie Jal For more information shoul using shared ates pair tles by enzyme set or group see ing Shared Ros to Greu Sanies age Vr Miei Gehe Cora Ue Hart pem aen Fant CEL Fens Fer Site Pr aen stk ae ok Bose SEL or fami SVE Mond MATZEN CEL pucr Nama pore Nama porca MESTRE Nome Mx uei NEED NACE Mama porc Figure 87 Fle paired by enzyme st and sampeeerenc 14 When De are paired by enzyme set and sam
64. dant e age lr kd aye Surman Axiom GTI andes mulichanel data incorporates improvements n cust and alg hal nave occured e development ol ater producta and noduces n alat reducto sagen pregrocessing These changes have Been ned 1o provide hgh on ie gio assay Based lying alton and tror Bot adapto ofthe medo poss Copy NumboriLOH 00K S00K CNILOH Algorithm Jucameticomsupporechnicalitegspenina SNP CHLOH Algorithm t algorithm whitapaperp t SNP CNLOH uses the BRL goin which to BRLMM P with some diferent Ses the esting FLIP asocia ih SNPS or more nor SUP 60 CN GC waviness ape Implemented into APT and sinos GTC 30 1 he summary ol he arm correction i or ach sample markers are ddd 25 dierent bins based on equal spaced of Ine average GC count GC content i e upsueamdounetrakn 2506 or parier meter toa Wh esch o 25 e markers are baned on thelr ENISNP marker enzyme Tagen Nap Sty Nap Sy ues 5 sui per major bin as here is na CN probes in Siy oniy tor a o 25 125 Fo autosomal markara ineach be e Meslan ratio of esch bini adjusted 1o zero and tique anges OR are equaled across dl e bs tt Genet Corsi User ana Than te log ratios o all markers nein X and Y markers in mat bin re adjusted using ad
65. generate an optonai Segment Summary Report segments summary e Segment dats Tor all of I CNCHP Has analyzed in a nari The Segment Simma Report page 245 can be viewed in a spreadsheet program Generate Custom Reports Using Custom Regions File optional You can ao use Custom Regions to generate Custom Regions reports tor each number The liom Ragone datnes regione ot the genome treat The Regions Reger slows ardor regens o genome needing er the segment repart manual ese regione needing ew data in ba GTC Browser A sample template Custom Input Regione fe Custom Regins template en nul regens bed locata the Lexar tie See Custom Region file Format page 20 to more information he Custom Regione reports Include formation on segments wh ruber changes in the dined customi aegra Te report induces tt Gehe Core Ue ana custom region name overlap of the region wh he segment and vice versa genomie locaton et markers in he segment ovetap wim anonn CHS Thecus Regions Report Nos can be Inthe Copy Number Segment Report table ot GTC 30 1 You can aso generate an opens Custom Reglons Summary Reporte custom regions summary onctenting ho custom regions dats la analyzed run The Custom Regions Summary Report page 243 be viewed spreadsheet program MPORTANT
66. hence homozygous detect such Copy Neural LOM hel cl eror rate af 02 mare propriate Alpha and Beta The LOH depends on 2 concept Alpha FLOM present Pi ihe chance alo call t Given LOH sty present what are odds hat not found given the het cal eror rate This referred to Type or referred to a Alpha in slate Decreasing sipna decreases the oss gorien i falsely against LOM increases he ods wally Ind COR Beta i normal Heteanygot present hs i tne chance of mietakey caling N LOH Given usual or expected rate of heterozygosity iva region wnat are odds of sl nding LOH This is Type I error or power and i t as Bea mates Decreasing decreases ie oads earth wl say fod LOH but increases Pa odds wi al to f LOR when Tha Minimum Markers parameter sets the minimum number of SNPs to used in evaluating LOH The agri e unter f SNPs needed to sal and bela For be sube and beta detaule is unter s wei exces fhe deal 10 mater rinm but you 1o change bea parameters ten e Markers parameter can be wed a n Separation is assuming conquis regen in the genome has LOH In gaps in he genome such as across a centromere LOH be caused separately The pial dietance between SNPs on
67. ho same il CNCHP wah a MAPD vale greater 03 shoud nal be used Tor rar ana Afer Genctyping Cane Uter Manual Changing Algorithm Configurations for SNP 6 0 Analysis attymeti recommends that you perform NumberiLOH analysis with regional GC correction configuration Note You cannot edit a configuration fe hat was crested In GTC 21 ar earlier You ean only edit configuration fles that were created in GTC 30 GTC 20 1 GTC 30 Zor GTC 40 To open the Configurations dialog box 1 Fem e Eat menu select Copy Number Contiguratons New Configuration The Select Probe Array Type dialog box opens ed Figure 10 14 Select Probe Array Type box 2 Select GenomelideSNP from he let and Select Te Select Conlguran Template dilog box opens tt Genet Canace User Har Pire 1015 Select Contgraton Template wih or without regional GC correction Select a contiguration tps win regona GC comen and cick OK Toe Oplon og box opens 4 Or select a configuration regional GC correction and cick OK The Oplon dialog box opens Cony Number LOH Configuration Options Template Genome WidesNP Figure 1010 Basie Optone S Entar vos tor configuration Options parameters are deserted in frei Genetyping Console User Mart Base Opens tor SNP 6 Ante Opens ter SNP 60 fee Save me charges tthe configuration To sa
68. rectory Enter name ter the Export Foe Rogan ese Pee pv nade sn Discs p ee cca ten pure 14 Export Options dialog box 3 Choose Genotype Export and Select options and then ciek OK tt Genotyping Cora User Hart The data eor to one or more tex es depending upon opens selected Note An export hat generates NoCromosome indicate trad SNPs at are no longer annotated Tle 74 Tab Delimited Export Options Genotype Expert Options Description Only esport cat codes hasen fiz apie ale cal ondes AA or Oniy spont onan aran base ca rmt neant araras baee ca AT Esp tlh cal antowan cala Dese tue option i th alee cit codes Scie oal mita Select Description Fy SAP Li Sepa or ach oor Generate 28 tex fes ne ec error ee ies au caus to nee onec ap ae singe op and ake ha o e value tor aach cat ne po aceto riorem NCO nf an arena veu tivum Shs ar sre meron iro moris cemere ard croce rahe Eu SC Te ash ate ped ei ia SP ten ured terga gm Ris ten npr are ang enone singe ih pn nen i Sore pure tine ema i megan atone
69. sample andre abu mast shared b boh members of a samples enzyme se Tho Sampie va Reference stiute be helpful entered bui not reque Toperorm unpaired copy number L OH analysis 1 Open he Workspace and select tne Data Set with me data or anal 2 Select he Intensty Data set tom te Data ree From e Workspace menu select Intensity Data gt Pertarm Copy NumberLOH Analysis or Intensity Data set select Perorm Copy NumberiLOH Analysis a popup ek the Perform Copy Analysis ution in he taba Copy Number Analysts Options dalog box apens mm canyon tra Anpi Lovet Henge meum CED Figure Copy Number Anise Option dialog box Select Un Paired Sample Analysis or Sengle 5 Select he anaiyais ype CN LOH or bo ty Canale User ana Copy Number Anais Options dialog box opens Same Tye Un pom pm Veg res nce oi Caneel select Member JUD pe Connon prm mi Sokat LOM Eas am Sd Bk ers Figure Copy Number LOH Anais Options log box unpaired asi Review ans cotgraton parameter and select rew arai See Changing Algor Configurations fr Human Mapping 100KI500K page 79 lor moreinfrmation on reato a hex nales contu Change he folowing deste Output Foot Pam locaton of he Results Group tie
70. sate othe ll va he my Wi copy rer seh alla wth ria trat Magat Logo p ve how deer Logd ate peter roe ones en The ea Dor bere the SNP rese te died in the List tor Pe tecon aray e it st digi Pa Sa Lt fers Genotyping Core Uter Marat Data Section For Chi ohchp LOH es Tho resin dala fies conan he daa em Description ca Gere or he morte arg Gera cal or he pared france are pared lyon ct ta given SNP lance un ea sae on Lover toad NP LON sn coer a arg Listes hat a SNP in lere ang Selecting Results Groups You may sea higtikghted in tne Avaliable ties Figure 5 Mghighe in te unable Fest You wil not be able to select highlighted and move hem to he Sampie oReletence Files tets choose a CHP Vom group il ocurra parte CEL has baen genotyped n more hana inge bach ore same CHP presen in mare Pun on lesus group tyr Genagrirg Corsi User ana Hes Fire o tiple Genotype Reste groups CP Summary Paired Anais 2007102911915 Mapping EET UNE WIES Ich c umen o WIES Mes mh era mua aze mee lene nas cp
71. selecied he Coor and Shape down ists TRE SNP pic cod 10 rent shapes Han arl han 10 Shape Tho remaining Velie re put iria a Bin caled Oe Al vduos n he Ober bin have he cane or or shape When ne atre value date or number the software divides tha ange of data 10 equal bins ad asigra a ctor or shape o each 10 ba ha data redes one of mir 1 poate o one value a partei and alor vduos n nomo bi The SNP user graph shows he SNP summary Information The def display the same as the SNP Sire Table To toggle through SNPs To change the graph axes te Set Sate sont nn raph a Alara ge ap ana Sete 2 in me dialog tox ha spears enter values orte x and yas minimum maaan To automaticaly scale he axes choose Auto Sesle X Axis and Aula Sesle Y options sets th graph wid to incluse sample symbol Figure 732 Sesle dialog Inthe graphics porton o te indo you con me current image la the or seve the curent image bad ong tyr Genagrirg Corsi User ana sio export tendering for all he SNPs in tas window See Save AI SNP Graphs 1o PDF Save All SNP Cluster Graphs to PDF File You can save he cluster graph visualizations for al SNPs in a SNP List to single PDF or 1 Rightaiek on a Genotype Results group in he vee and slat Show SNP Cluster Grap
72. tine ram one SNP data set in the Heat Map viewer t E Not Loading data into the Heat Map may take long time especial with large results seta You can Use the Quick Lond feature o save loaded and rolond t more quic ace Using he Quick Load Feature page 27 ty Corsi User Har To open the Map and iod it wlth data 1 on he CHILOH batch you weh to view and select View Results in Heat Map or From he Hagae loci Copy Number OR Rests gt View sun Het Map o Caos we tap ton E n main mre than bach of CN results is avaiable a dalog opens Figure 132 Stet Copy Number LOH ent group 2 Select me Results Sel you want and cix OK A tst of e in te ath set opena ty Corsi User ana rod 5 prd rd p ga por pure 123 ACH Mes Select Nes you wish to ond or ck Select AI 4 aok CNVCHP associated wiin each selected CNCHP of CNVCHP ties avaliable data Nl star bom CNCHP mateng CNVCHP Nes mio Ie Hat Hag Msome ofthe CNCHP do not have matching wi just load CNCHP fos tor these samples f Some ol CNCHP are associated wih more han one CHVCHP than you gt e logue wand M mutile CHVCHP are associated wh e selected CNCHP he CNICNV Fla Association dialog rapere tt Corsi Ue Hart po cue NADE
73. to ent he contratan adn d Cx The Heat Map menu appears in e GTC main mena bar Changing the 1og2 Ratio Range You can change the range of 1092 rato values displayed on e selected heat map palene Changing the ratio range must be done betore loading in Hest viewer To change the log Ratio range 1 Open he Heat Map viewer without kading data dick me 2 Entar te rato values in the Range bores in the toa Using the Quick Load Feature Loading Map may tak a long me especially wi large ent sets The Quek Load teature of he Heat Map you to save loaded data you ean reload t mare quil CI NOTE You wil not be able to add any more feature onee you toad in a quic load change a CNV map or to use qulek load To save a set in a Quick Load after losing data 1 xax me alk Loe soe El The Save Quick Load dialog box opens tr Gehe Coracle Ue Hart Figur 34 Save Quick Lond dialog box 2 Select a location and enter a name for the To reload a Quick Lond 1 ok me ulek Lond ave tuton TE The Select ick Load fle dlalog box opens tt Corsi Ue Hart rae u Figure 137 Select Gulek Lond dialog box 2 Select s previously crested Quick Load o ciek Open The loaded irt te more quicky IE Note You cannot ad
74. tt Canale er Han Enzyme Fragment Copy Number variston E LC LCS e eet be DESDE om ha seh west Vh laren may fom hee acid th een by geroni a tray gne mapa Marco SLN te Sean nea e rr ronem markers SNP probe lange The Any ri Shs tr oe wn recti agnam sigh be gra tr ipee wel sii Cer eas ry hen a o Coy urbe Variation Ragion CN prabe bye Dota Gano pt eiie Carme Wc Hamas Aro Tiga Sony pe tind tr own Sones ane ry Ame Gener Cane Uter Marat M he ae pnt bom hul an Porton an usus rese ana ang te Amen greg roy AG pe E Sample sime el Frequeney extras SNP prebe Doses me majar and rinor af tne alee tom Yon Han nd CP ses uan De Mee etry ar Spies Inde Mirer Aele ola SNP SNP probe sets oriy Thana Mi a SN SNP prabe GMI wc boo sed under s horrea ete vent Ts toss ane fo arare RID METUIT Mies Genotyping Cane Uter Marat Appendix E Gender Calling in GTC 40 can generate gandar eats tom mersiya gt Genatyping Analysis C Segment Raport or SNP 60 oniy Copy number aras or
75. tyr Genet Coa User ana E sin erect Tel Step 3 Open two cluster graphs one of the cases and one ol the controls both using the same SNP List T Tovlew the SNP Custer Graphs or the Cases on he Cases Genotyping Ress custom bach and aedi Show SNP Cluster a EE Sma army E sn E Tapena E cemse on outa as Remove Geta emits Genotyping Console wll lo compute he SNP statisti tor s new group You wi be promoted ora mene bi Me o save tho es d Yeti mesi hres Cx noma OF ah e Mm g Next select he new SNP List 10 Genotyping Conse cate he SNP summary statistics and collect he data draw SNP rah of e Case Repeat stepa 1 3 or tne Contes Fer BRL he csteng in e contrast dimension where contrast defead as Conde User Mart Fer deta ofthe wansfermaton applied othe contras soe me BRLMM P whte paper For Aste performed in a o dimensional A versus space See wiae paper t mote elle For the GT clustering performed n Log at versus strength space Log rato nd strengi se dened as Lag ato ogjA Hoo 8 loas Apop B 4 Display the two cluster graphs side by side tor easy inspection ol the SNP cluster
76. 4 Save in he Save Segment Summary Report Fle dialog box Using a Custom Regions Fie You can use Custom Regions fe to look for copy number gain and toss in select regions of e genome Custom Regions detned in tab bod oat Thi infomation results Hom ring te whole genome Copy Number Segment dala generated by lhe Segment Reporte Too took at ony daa regne dug esame run farne same Custom Input Regione fe Custom Regions template nul regens bed located in the Leran tie tt Gehe Corsi User Hart pL utem edre ieee mj E Dee Dunt Regana Sunny qet Catenin Sunray eel eroe m Figure 11 17 Opens or custam reins He and cresting a Custom Reglons Summary report Create Custom Regions Summary report you to generate summary segment report wth intormaton on CN charge segments rset regne ral he CNCHP you are analyzing Tis i delimited contains e Merion custom regions summary To select a custom regions and generate custom regions report 1 Selec he Process segments with custom regione chechan 2 Chek e Browse buton Te Open Custom Input Regions dog box opena D SS Figure 1 18 Open Custom input Regionale Select the Custom input Regions bed Clck Open tt Gearing Cosi User Hart Custom Region File Format he Segment Reporting so generaton Cust
77. C You can uae GTC 4 0 ang an cater version of GTC on erent corpus however you need o separately mantan io sets of ibrary and annotation es on he To dolis 1 Create a new GTC 40 teary fle on your computer 2 Download or copy new GTC Alban and anolaton ee to is der See Obtaining Library amp Annotation Fles page 34 tor mare information Sette asy path for GTC te new brary foldet Sae Seng Lary Path page 31 Note GTC 40 workspaces cannot be opened in earlier versions of GTC Workapaces crested in ater versions of GTC can be opened n GTC 49 but then cannot be used in ear versions of GTC I Note Custom analysis contigurations for GTC 3 wil be updated to work with GTC 40 Once they have been updated hey not work with aider versions of GTC Starting Genotyping Console 1 Double choke Genotyping Console shortcut on me desktop Amat tom te Windows Start Menu suc Programs Ayer gt Genotyping Console Tre Genolyin Conse opens wi he User Profe window aye 2 Select or crests a User Profe ee User Prol Cle OK in the prompt Figure 23 ype Conc A sret sostet tomos seba tray tosta Cac Fire 21 Prompt to seine brary path OK and select or a Iran for Miei Gehe Cora Uer Hart Saket apah hue he Ganache brary Cx Com gure 22 Slt or cr
78. C Browser See he GTC Browser User Manual or more Genotyping Console displays workspace nfomalon in the om ot e The ems win the Data Sets section fine are ordered y ical user se ur blow Dat sets siart a colapsed nodes nhe voe Dock dala ot t expand tne node and show ihe Wee double Yee ama tho fesl ten he rt ick nen wit automata For example you docto ck ne Al merely e QC Talla wil open showing i tete I em i iieri ras eta va fis Dine ge 1m gure 15 GTC dito ree Tha Status window displays al status and gor progress information p S12 bsid pr lt m Fire 26 Situs window To diable view go to the Window menu and select Hide Status Messages Window tyr Cosi User Manusi Fire 27 Enabing disabling the Sats window display Status Bar The Salus bar at the bottom oe GTC window displays infomation on the path trary le and te user moe arem Fire 28 Statue bar shows rar path and current se profile File Types amp Data Organization in GTC oy use ne capables of GT you ead to understand te tle types and data organization used in GTC GTC uses fiaa QC a speres ty Cora User Hart Notez QC fies ge are longer avaliable tor AGCC CEL fles QC 4 in GTC 49 The OC information sate
79. C te string uses the ul precision o red matics The precision in tables is less an P Cluster Graph amp SNP Table The te ol ih graph indicates displayed SNP allowed by Genotyping Results bach rame and SNP name in panties The defaut viem shows samples cored by the genotype cal To change the calor or Shape assigned oan ste make rom he or Shape dp down isis For example n Figure 729 he clusler graph displaya genotype by color dates gender using shapes ema T sample missing a value fore atte selected from Color rop down a but has a value for me tribu seated hon the Shape drop down lat he graph a gray shape a missing values forthe sibus sci e Color and Shape drop down ts He graph displaye a gray spade The state var you sme of the fies do not have matching sample fles ARR B rd EE ene LL Figur 131 Mash sample Res prompt Mime Coa User ana Yes The graph gray spade AV or sarees atiuos selected tom the ote ce Shape dris doen iste Na The cluster graph a ot rested iato he CHP les do nol have matching sample ties lor example hes generated by GCOS no waning appear and cae graph generated The Stas wow shows te sing sample io No user libus avatabie ta ise aos carer D or des omn f canbe
80. CHP Summary abi veras he nme 2 To sort X ass by category e p Sounds select te catagory Pom he drop down menu or hok on e graph ad set Se Category 3 Toran atonal results on e graph and elect Se Val or use me Yat dros 4 Toast ne ania scale roh esc on th graph and select Set Seale or select he Set Seale shortcut Meis Gesch Coracle Ue Hart Fire Ure Graph The ine dala can be copied to te Chose saved as an image i ng omar or saved as e Qd os bi torar Mime Corsi User ana Chapter9 Copy Number amp LOH Analysis for Human Mapping 100K 500K Arrays can be used to perform he analyses or Haran Mapping 1006 arraya copy Number CN Loss of Heterozygosity LOH Copy Number Segment Costo Region Copy Number Segment Reporting Copy analy tor Genome Wide Hunan SNP 6 0 data described on page 189 Feature canman to Hunan Mapping 1000600 ras and Genome Wise Human SNP Arrays 60 stays cle runing te Segment Rezring Toa are descbed Chaplet 11 Common Funct for Copy Nambari pope 27 important CN and LOH analyses for Human Mapping 100K and 500K platforms ln GTC 4 0 are algorithmically e same as in CNATA 01 sofware and for more detalla users shoul refer to he Whi Paper Copy Number and Losa ai Heterozygosity Estimation Algorith
81. GTC 2 1 tar performing e inital tee you can proceed wih the oret analyses Genotyping Analysis Workflow Genotyping ana provides SNP cal tor the towing aa ypes Human taping 100K Ars MappingS0k Xba240 and MappngsOK araye Human Mapping 500K Arrays Mapping 250K Nep MappingastK Sy arare Geneme Wie Human SNP Atay 80 Akon Genome Wie Human Array genotyping analysis 1 Select a group or set of intensity data les CEL in a data set 2 Peon genotyping analysis on te group of tles De nial genotyping analysis QC data in the CHP Sum Resulta table Cal Rate and other mates thet are displayed ables graphs View me SNP rests he SNP Summary Res table that provides the information and ather Hary Weinberg pue Minor Atele Frequency Cal AA AB SNP Lists can be generated by ering on any of hese values Miet Gehe Core Uwer Mant Note You need a SNP ist to genotype result daa 5 The SNP raph can be spayed based on SNP List and group of CHP fles Genotypes can exported in tn denied lx a SNPs ora suae based SNP Lal See alas page 5 or moro tartan Number LOH Workflow for 100KI500K Arrays Toperom a CHLOH analysis lr 10005000 arraya you must have bul he CEL inel dala es and the gelang GHP Tor me arraya you wen o anao To perform s CHLOH Analysis tar 100K S00K
82. Graph or ising Esport Gee Import Custom SNP Lists lunes be ignore by th sofware A SNP List can bo generated aae the Warton eamele Renal ol Spec Gane Liss To import SNP List 1 Righel on SNP Lista in he Te select Import SNP Lt gure 12 SMP List menu The Open dig box appear i Gehe Cora er Hart us m i Dm Deane ws TSV neris Figure 721 Open log box 2 Morale 1o he locaton of he SNP List and select osek open Te input Vale dialog box opens Em mz Figure 722 Enter SNP Lit name 4 Enter a name o ne SNP List and cick OK The SNP List wit be dopage in he data bee tt Corsi User ana m Figure 12 Imported SUP Liat Azalyng per SN or helps eme he of probat SNPs However no Marina scheme is petet Even win singent iting a small proparton of par SNP may Moreover poly taming SNPs se fen Pe ones most katy ta parom dieron cases and conve The lato ontcandy associated SNPs oim lor auch probate SNPs Tha SNP fer process greaty me occurence of hese But given mei landen to end pi he lat of SNP i ly at some il Before arg oth SNP subsoquent Phases of analysts paci of S
83. Human SNP GOAT Aviom Genome Mie eps ees enis 1 hems Eo omne i Er Bre Fire 213 Overview of GTC works fr diferent aray types Initial Setup Poon hese intal steps trat analyses 30 Create workspace and dala set for the data soe Crate New Workspace amp Add Data page 43 2 Importers dala CEL and SarmglalArray Data the dala set see Add Data page 48 Perform inant QC lo determine basie data see Quy or Genotyping Ansys page 6 Mets Gehe Cora Uer Hart Tre testy gusty conto check Can be performed on a selected set of CEL les ral CEL Nes can be automaticaly portot CEL to he data set natal group CEL ties irio Al Bounds Out of Bounds groupa based on QC resto Natcnalcusom CEL Hes can also ba made The resuting 0 Cal Rates and oer metres played tatis and apra od can be Removing poor CEL les tom sel can prove De quai ate of he CEL Note GTC looks for existing information in the CEL first then OC qo avaiable GTC lon and does not execute the QC algorithm he information not available y OC and store the Information n the CEL ts an AGCC CEL or in the acte iiis GCOS CEL However ti requried perform intensity QC again far SNP 60 ires with information generated n GTC 20 due toa algorithm update since
84. MAD between tod obo mane rd pre ments ey te moll nantes an proba meneses the rl Test se eet te gpa oh Tena A es t SPS cn e pr rate ery Tre araga probe net retard Xenon poner GN eam on Cen pre ch ra gender mean Cen probe ch ra gender rao computed Gender Contrast Qc Random Contrast ac piap p Contrast ac spy Overiap oc ca nate ca Rate pty One ac cat nate niom sina conan AT axiom pra convas AT tt Coracle User Han penbe nent ann rer ane aay en nse ENP Aem ey n arid ts je E Gor Cal CE PAL Tr DEM EO errs OC ter 10K rendan anal SNPs SNP BO amiy Grim OC or QC 20K SNPs on Na gras SNP cl eren OC tar QC 20K SNP on Sy SNP Don rst OC ter QC 20K SNPs on beth an Nsp amd Siy ren Computed OC Cal Rat D apc or SP std aniy on agre ONES SNE Computed OG Cal Ra ia D or SHP eto t Computed OC Cal Rat D or SNP std aniy on Sizes sopra Se St dcn arguing ol eect GC prebe tnt netur naan AT cha Asm on ea conii rte nen ite A chanel non Lar Dacian ter background n he chamat
85. Meis umber stata ge e 5 Mein mm Fire 1112 Select Fitore To set resholds ter vaes tor he fer parameters Minimum number ot markers per segment namber of SNP ang CNV probe sts almi ne present to report ne segment Minimum genomie size ol a segment xpb Minimum size of a segment in klobase pairs Include segments tnat overtap with known CNV regions by CNV regions trom the CNV map are the known or user defined regions genome as having numer variants CN or number n ne general popu ori some nane Tus dea conce fam e Toronto DOV dabas or as use defined nd an be as Variants Inthe Browser wack cao genome vans or comes lom ober resources n e of nove regiona wi copy tia posi o exclude segments Pat overlap Inese uter vant The ol segments obe s based on he Att Core User Haru tae te marters makara hal overlap runde c SNP and CN n he 1t me percentage ol marters in a copy changed segment wich wah known CNV regions ate Toro DGV databace rue ded CNV regios exceeds th percentage Hen Segment Reporting Tool nol repo tat segment gir tn tear OW abus oS Fire 11 13 Overlap Fiter sting To set the threshold Ear valu
86. NPs e clustering space sony recommended Val Inspection cay Key casen Ganotyang Canale has an apn 1o SNP cust Ine cluster graph user selected colors and shapes can be assigned o alluseratrbues ray pata melon ides instrument tente of avaiable Far i graph in Figure T2 dpi orla color and dierent shapes la dicat gone most have sample ARR in order to display user stiributes by color or shape If re not availabe example CHP in GCOS then any piae laic instrument format or scanner avaiable the CHF e can be ing color or shape tyr Corsi User ana _ 4263484 00000508 19034 SNP LS 5 reae Li d H i i mese asm seus HY Cure s 1 x ee rams 1 i om sex onn soma e seam me Gees mo as was seem le Po Same Figur 7 24 SNP cuter graph Inti ware ane genotypes ae played by cole and gender is by shape To generate SNP cluster graphs 1 Gantyping Results bae and select Show SNP Custer Gras on the shortcut menu tt Genet Cora User Har p aser Dense 5 Eu EE ES sense 1 ey teni RO Bom suman Tie po Fiir 125 Genotype Results men
87. NumberiLOH File Format for Human Mapping 100K 500K Array Data The copy namtar and LOH dala are in separate tes or Human Mapping 100KISDOK Hender Section The resulting CNA enehp and CN ah dala es contain he folowing i the header formation stout array SNPs pote type brary Agathe parameters and command ine hat was execute egal advanced parameters Nat were used f Man eg paired copy number Sample Name Releence lls used Dats Section For Copy Number Files Tho reslin dala contain he folowing data L Note Those values that are labeled paired analysis only require that the Generate Ali Specie Number check box s elected in he Advanced Analysis options tem Description tt Genet Cosi User Hans logia Negtogiopvaiue NegLogtopvaiuottar aon Laga rato value o st contiguous SNPs in te gien MA copy nutre Teen Nur inated Log rato value or he aloe wth tower sat rer pec Mactan Lag rato value alal the SNPs n he gren A sate sente lal wae copy urs of the alla wth the verliert pee ht SOR cid NTS ert pier pareil en nated Log2 ate or he lle wih he higher sa ay pec Medo Lag ao value lh SNPs n he given HAL
88. OH analys lou Generale Number Segment pars he CN dala in the Hest Map viewer Export dala to oer sonare Noles on Selecting Files tor Creating Reterence Model Files fmt recommends using minimum of 44 samples when creating a Reference Model Fle A minimum of Ne ls requ orn t aate For Chromosome X samples ference Amet recommends using atleast 15 temae samples Then cresting a Model Fle of v X cromosoma For Chromosome Y male sagas the relerence Amb recommends using st east 15 male sangle a Reference Fle or of recommends sing mixed gender samples when creating Raterence Model Fle for analysis Analysis with a Previously Created Reference Model Fi important artis recommenda at you rai wth regional OC important Attymetrix recommends that you run Copy Number LOH analysis with batch sample mode and regional QC correction using chips run at the same lab using the same reagent its o reduce eneral vartaniiny and to correct OC waviness See Appendix J page 313 or more deals on hard Gisk space requirements ntis anas you compare he slated sample CEL flos 1o a previously created Reference tle einer 270 one supple Amati or a reference you have created uang he CNLOM Reference Model Fie Creaton Analyst procese deserted above I is
89. Posti Processing Thes abso SN onan Ses an Mei E Venise Omane Hata Fant E ox eg sa oz E Bei Cem oo a m S E 4 E rr uo Meceninoew Mi Besim Gee nen ae JEn Fire 6 Option DB wt vanced Options shown Copy Number Parameters HMM Parameters adjust tr Gehe Cora Ue Hart Decay Temm Pine 2 az o2 Fire 37 parametere CN State Prior Value HMM s apple far smoothing and segmenting he CN Gata The priors and decay leng ar two user unable partes The HUM hs 5 poss states Simeo CN ato homozygous delalan Stale 1 CN at 1 heterozygous deletion Sime2 Not normal CN at 3 single copy gain Nota The delau tor sach state la 0 2 indicating that each SNP nas equal prior probability ot ben in any one ot the 5 slates Generaly speaking anauia not bo adjusted unesa tie lon ta he bu fe data Comprised ct nomi zy in his cae e prr corresponding Sta 1 can be changed om 0210 orner prer sas ousted accor to C ote e prior values entered only il estimates The tis parameter based on Standard Deviation Standard deviation of me parameters
90. S See F Cotas for SNP 6 0 Date page 512 and Append Best Praciees SNP 8 0 Analysis Workow page 314 o mare deas DISH Dian ac DOC he recommended QC meli for he Aulam Gereme Huan Array in Genotyping Console defaut vest s greater han cua 10 0 B2 oe each operates by measuta nal of sles in a genre that are ow notio vary ena dul 1o Because mons now lah eaters I s kon eseh wi ln chanel im he say shoud nta signal and whieh shout te backround DOC i a measure of he edet whieh ha ston of Signal value separate Hom background vale wih O indicating no separation ang 1 parlec aparaton tt Cosi User ana a usatu sige sample of performance an unde crcmstances t correlates wel wth ipaa perfomance One xtepton a cas of manga sameie coraig of iret inda together ean sili have a good DOC ace ree e gal anon polymer locana rema e ame in a mie Suc samples can general dented by having abnorma low cl ales how hey may shave good DAC vues Call Rate The OC anas provides an estimate of tha overall qual tor a sample based on a QC lor shonn inthe iube belon Tris analys provides a quick preview of data qual pea performing a Suing ases ray Number ol SNPs used lor 0 aC Algorithm ara Magn 100K Ara yam ote Mert ase Wai Mapping sok sio
91. SNP 0 on e order S380 This parameter controis how many base pairs must separate 2 makers before ha agam Saris een As foul seting 1 eal each chmaszme a a region No Call Threshold n any one sample not al SNPs are crested equa Some give high quali nfomalon about e genotype they ail dad omera vow quy Inducing tw ually SNP oresse the het cal ata over improvement In e aor accuracy by including these exta SNPs Tne qual o e SNP cals Captures by e Contdence os deead genotyping ana ha No Cat vested excludes SNPs wah a greater C ntdence valve an parametar vue Minimum Physical Size Threshold fers Genotyping Core Uter Marat Th parameter sets minor size for LOH blocks to be as LOH Pa descrbod ater sima reins ot Copy Neus LOH are very common arise from portons of paired Chromosomes tat can ba Wace tough diferent ies of descent pack Wo sgl ancestor and so ese regos re ante and hance homozygous Thus some Copy Neural LOH regen are associated win haplotype As ron siza creatas he odds we see Neural 1o haplotype block The Hapa phase study shows rough 70 o common haplotype humans are about 100 bases rhe neessing tv Is crean yel mae Copy LOH ang Tomate cis at ps enpense carere LOH ee tang am a ete Smoothing Signal Graph Output
92. SNP 50 arraya provides formation about cats tar te X chromosomes and about cate based on ata toe qr cr ende aM Tho processes used tor gender cating dii depensng upon array being analyzed Step in the worktow being Gender Calls in Intensity See Conta QC page 89 for intommaten on the algo used for he nal OC step GC anys tor genotyping uses sigorlthrn to make SNP calls QC purposes It uses the following processes or making e gender cal dug s Contrast OC he recommended QC meli for he SNP amp in Genotyping Console 30 1 Te dota s han or equal o 0 4 o each sample When adating Pis mates vests value or hanging SNP 62 OC setings to another metie such as QC Cal Rate adding additonal matic 1o esed agin e conigzaton selong diis vor at te estas aro dierent ian doll mete at captures abilty Of an experiment to resolve SNP signals into lee genotype Vet 0 00 randam SNP SNPs See opera Conta OC Tor NP ity Dal ge Gender Calls in Intensity QC and Genotyping Analysis Tabie D 1 summarizes he methods used for gender calla dung lately QC and genolyping andi array Type Gander Ca Ago Reference poi tyr Geen Cosi user Han aay Type Gander Call dil rte Genotyping Gender Call Process cn probe chrxY ratio gender In GTC me ge
93. Segment Raport con produce folowing pes of report tles Segment Report i n segments or each copy number segment Summary Report on segments toncatenang ina dala tor al fies run at a ene Custom Regions has been selected Ie report generates Custom Regiona Raport fle custom regions tor each number Custom Regions Summary Raport cvm egone concatensiing ae data ra tles run ata me CN segment custom region fes are automaticaly saved wth CNCHP tles in same CN resul tokter surmay cum regen surnay fos ean be saved manualy Segment Report File The Segment Report ties contain on the copy segments detected in a gen CNCHP tt Cosi User ana Seaven Raport es can n he GTC Browse n e Kayo and as on ack In Segment Data Hes tor Human Mapping 10K S00K anas have he CN n segments extension Segment Data ties tor he Genome Wide Huan SNP 6 0 have he CNS extension Fire 1121 Segment Reports To View the Segment Report rom Genotyping Console 1 Genotyping Console data ree select Copy Number OH Resulte group for ich you have Besos generis Segment Reports ang e Segment Reporing Too To do e Right on a Resul group and chanse Show Copy Number Segment Aye Genotyping User Mart
94. Ta windows oigo win a who background ead an orange neon te To cose a tantes vino use me ns ap atte ta Figure 217 Cose a tabbed window In me Window layout each open tahle or graph can be ss Expanded toe maximum size in a cascade Wed hortzontaly or tied vericaly To select the Cascade Tile Horizontally or Tile Vertically layout From Window Menu select Layout gt spay option Casi User Manual Chapter3 User Profiles A user pie stores a users preferences tor custom anal senings tab and graph viewing options and ather aopieaben setings Securty by ptas ot provided By he apio i sipiy means f sog pleat The flowing sections in tis chapter rede a User Profi page 27 Delete a User Profle page 28 Create Select a User Profile Auer pot has agen parameters reat Ireshol s and oiher polcatn parameters selected by user Seda ra providet by a aplican To creste a new User roll 1 Start Genotyping Console by doble ts shortcut on me Desktop or From he Windows Start Manu select Programa gt Amel Genotyping Console Genotyping Console opens wih tho User Poe dialog box spayed tt Gearing Coracle Ue Hart Figure Genotyping Console main window and Ure Pro dlalog 2 Type in a name or your prie and cick OK The stare w
95. The Custam View alog box opens tyr Canace User ana Ene E0 E ont ons E E Fena occa ret etel pres E Deme p Figure 8 2 Custom View dialog box 2 Select he columns to be displayed To re order the columna lk on a conn narra and use the Up and Down butane 3 Che Save and enter a name for tiis vew Use me drop down menu ta spay tis custom view REIS vus aa an Fire view edita previous generated custom view he Edi View sharteu F and select me View to edit ty Genet Cora User ana To electa range ot rows To select multiple rows tht aren t adjacent options are avaabl for comas an cel as wel Te copy a selection to the Clipboard 2 on he Copy to Clipboard shortcut 8 on te or Fight tk and selec me same command CI Copy to Clipboard may tal much data is copled lor example copying the entire SNP you Save Tale To Fei you wish to ante Tabie To save ali of the data la the open table to le 1 Select te Save Table to Fle shortcut Dom he tab or Fight sk and select to same command 2 Enter a name tor he tie and select Sve Al dlaglayad tala wil be wetten to o text le To Find dala in the table Sect te Find shortcut and enter te value la searen on nd of Ihe document la each wi resa Tre search he tp
96. Uer Mant Chapter 1 Introduction The Genotyping Console sonware GTC provides an easy way to genotype cala for of CEL Genotyping Console generates Number Lose Copy Number Segranta data and copy varaton data depending on array ye eee Tate 11 Table 1 1 Genotyping Console analyses for array types Maren Mapping VK Arai Mem uen yer ve Mappingsox Waren Mapping SK Ara Mapping 2504p ye Maing 2504 ipe E Geneve men NP yee 5 prec p Genotyping Console displaye meles and aanoaten infra m standard tabular Torm to evaluate the data ually for a gwen Scatter ha gaps and heat ap ve gue jou ower to quc dont ot you data set Numer dala and vauatzaton expr fate make share i and users GTC Browser enaties you to survey your Number and Los of Heterozygosity data Genatyping Console not secondary anas package However I does create CHP fies and tab dented tex ette fr secondary anale package aval ton companies in a Amet Geraci Compa Progam Te lowing sections in bis chapter About Tis Manual page 2 support page 3 Aye Gero Corde User Mart About This Manual This manual presents intonation about Genotyping Consol ln he f
97. a or each array ype wil be displayed in s owm table Each abe wil have Ine appropriate array type appended o t ase baten name You may choose a create a custom group that contains all CHP e la J Hole The BALI algorithm require at least wo observations ol each genotype to create prior so Sis the absolute minimum number of samples required to run this algorithm However runing i his small number advised Performance has been seen o peak when running 50 ar so Samples Depending on sample quality fewer can yield acceptable results E Mote For and Blrdseed v1 there la no minimum required number of CEL tles You ean ether on a single CEL le although perormance may be poor Running Bidseed v2 requires a minimum of wo samples although performance be poor Iis recommended tnt each BRLMILP Bidseed v1 or Birdesed v2 clustering run constat of at least amp 4 samples See IE Note Running Axlom requires a minimum of 20 distinct samples with eter zero female samples rat last 10 stint female samples See Appendix or more deat h Note Birdseed v2 uses the EM algorithm to derive max likelihood f o 2 dimensional Gaussian mixture model in Avs B space A key dileence between Birdseed v1 and Birdsee v2 is thal vi ses apechie madeit or priors any a niil coni from which pe EM is ret iti conditions lor EM are incorporated into the is
98. ae ECCLES sus sz 3 E 4 Mme Op SENE AT Nope le ma IL EL VOU EJ ONE Yi RO bela ende EZ 4 amv A mde rmpbeiche ena ma TV usse Og OUR ve ende Ez 1 Gp SENE VW rele mm x Fire 17 CHP Summary tle For more intormaton see CHP Summary Tate CHP Summary Table Tne CHE Summary Table contains the balch genotyping resuts see Tabie 7 5 E For Human mapping tere used for dierent enzyme sets wil be displayed in separate ables Each table wil hav Soproprate array ype appended 10 Ws base batch name Separate fesse are displayed in the Genotype Results Figure 78 Genotype ret or Human Mapping 300K sys with paired enzyme sete See Features page 148 for moreinematan on customizing te tate view Table 14 CHP Summary table computed gender Computed gender or sane chart aray ps Araria Gender Calina pae Meis Gating Coracle Ue a raw tena sew Ame Gener Cane Uter Marat cated AB ie he tasty Percentage of SNPs caled AA or BB cot reap dace te csr arf th ced ge ome mong ih aw Poe nnn Sen ition he re Ppa enon vege cle animales Sand itn te ade rage he seo fence sen he og alele at verge ota median alte evan
99. arrays 1 Need CEL and genotyping for the araya 2 Peta Copy Number andor LOH analysis in GTC producing Copy Number Data Fies Se Copy Number amp LOH Analysis tor Human Mapping 0KSQ0K Araya page 153 Run the Segment Reporting on he CN fles to generats Segment Data Fas Segment summary fle Custom Regin Data fes Custom Regio Summary Fle See Using the Segment Teal amp Custom Regions page 227 4 Review dala in be GTC Browse using Whole Genome View Segment Report able 5 Export dta tor heer analis MumberiLOH Workflow for SNP 6 0 Arrays To pertorm Copy NumberLOH analysis on SNP 6 data 1 Need intenaty tes CEL or he araya 2 Palam Copy Number andlor LOH analyst in GTC o generate Copy dala flea See Copy Numer amp LOH Analyse fr Genome Hunan SNP 8 Arraya page 18 3 Run the Segment Reporting Tol on he CNCHP ies to generate Corsi User ar Segment Data tes Segment Summary tie Cust Ragion Data ties Custom Region Summary tis See Using me Segment Reporting Tol amp Custom Regions page 227 Segment Report table 5 Mew the log2ratio values in he Heat Map Viewer Export the dala tor turer analysis Copy Number Variation Analysis Copy Number Variation CNV analysis the Genome Wide Human SNP Array 62 oniy For CNY analysis he Canary oct makes CN se cale 0 1 2 3 4 lor regione wih known var
100. ates We have not extensive tested me ree of mod ing is vital estimate o how wel he HM proe Not The prior values entered are only ini estimates The HMM optimizes parameter based on the dat The mean the expected ig ratio of cach CN state Forexamole reference s lid or each marker hen e expected io rato for CN 2 8 0 A Comosome X Naton experiment was perormed aig samples have dien anter o chromosomes parang e range c he HM Te ciem 2 a ar dieran numbers of X wer used i se he mee Tor each siate except CN O wich changes fom CNAT 4 Standard Deviation Standard deviation s oe parameters hat affect he probabit wih wich undertying CN state le ite ia produce the observed tate Special etes unde varance or in each CN Ste Standard deviaton of ecchundalng ste can bo adus Te delta the SNP 0 lite han observed SD s each alate b whan asd dug malen he SO id nt he eau of e HMM Note mat 1004 500K Copy Number Parameter Settings gage 183 are not necessariy applicable tor parameters in SNPS Te tats 0 fr al tes or SNP GO analyses tyr Genotyping Corsi User Har Parameters Transition Decay This parameler controls the expected correlation between adacent markers The copy number state of any given markar i partly sependen n Delf marters and s based a distanc
101. ation with regional GC correction wili nad NAZG or higher version ol annolaton fles Configuration without regional GC correction wil need HELAN or higher Copy Number and LOH analyses ar done dug the same anys run and data are kept in same Meis Gesch Cora Ue Mant Reference Model File Creation and Analysis Batch Sample Mode imponan Afters recommends that you perform Copy NumberiLOH analyse with regional GC correction configuration importan Atynetr recommends that you run Copy Number LOH analysis with batch sample mode and regional GC correction using chips run at the ame lab using the same reagent its to reduce General variability and tocoreet GC waviness See Apendi 4 page 319 or more deals on hard sk space requirements reales a Reference Model Fle REF using CEL les for he selected samples Then each TEL wert no ma Reference oder Fo agar ia odd ie samples Numer and data are generated Nole a he genotype cs on e fom the BLM pe reused or pre LOH analysis Tha Reference Fe ed entension To creste a Reterence Model Fle tor SNP 6 0 analysis and perform CNILOH 1 Open he Workspace and select Data Sel wth data tor ani 3 Fem te Workspace menu select Intensity Data gt Create NumberiOH Reference Model File and Analysis or on
102. ations to display tut pat names of he dala ties tt Genet Corsi User ana CP Feli Dd Deinen Ay ler Danfiet PITE n n 5 8 Missing erri Data Fer Data Se 1 ano nent Cie T D Ta ERTAYU Heung 188 tme ENET CDP ERN T Dt e tee Figure 7 Workspace He acabons payed Create a Data Set automaticaly performed part of creating a new Workspace To crente a new data set in a workspace 1 Ciek he Create Data Set shortcut on me main or Right click Data Sela node in me rse sat Create Data Set eral e Workspace ar selec Data Seta gt Greate Data Set Miei Gehe Coracle Ue Hart mem A Fire Creste New Data Set lg box 2 Inthe window hat appears enter a name and select he array type for new Dala Set and elek Mote Data Sets can only conn les which belong to the same array type For example a CenomeWideSNP 5 Data Set cannot contain data om the GenomeWiosShP array you wish to have daa arrays In one Workspace you need to create t least one Data St fr each array type Ac yo a dataset e soare yau to data to hi See Ada Dale Add Data automaticaly performed as part ol creata new data set 1 Toads ARRAL CEL CHP slo an
103. ay 6O ned atom Genome Wise Haman TY The flowing sections Nw Anais Contgurations Genetyping Analysis page vw Genotyping Results page 95 Export Gena Results page 131 New Analysis Configurations Cert genotyping ago setings coa be changed to math experimental conditons Tha section describes o Nodiyog he Parameters ty Corsi User ana Parameters for Human Mapping 100K S00K Arraya Genome Mide Human SNP Array 060 amp Genome Wide Human ScoreContidence Threshold The maximum va cf confine for wich a wil make a genotype al Cats wi confidence scores ess han the aro cat For axa the resto a 0 1 hen any SNP wth confdence lt 0 38 cale any SNP wih contdenee gt 0 15 not caled te Treshold icon e ada is awh are hernia c vi Parameters tor Human Mapping 00K SQUK Arrays only In addllon tothe parameters above he parameters can be set for 100K S00K array dala Prior Size How many probe sets to use tor determining pror DM DM confidence used or seeding clusters Moditying the Parameters To modiy the det gorithm setings 1 Select he New Genotyping Configuration sort Kon re moe tatur or From he at menu select Genotyping Configurations gt New Configuration Tre Select Probe Array Type ilo box opens Miei Gesch Coracle Ue a
104. be epee In bat cases the check compares SNPs hal are boh spia and reference fles and have ala SPs base f share eae ee nd SNPs do net hae sre Important The delilen o allele A and B cll codes tor Axlom Genome Wide Human Arrays le leven other arraya For Axiom arraya SNPs are mapped to the forward stand ot he current genome hg For other amays SNPs can be on ihe forward strand or revers strand ol the Genome meane that a particular SNP thats present in both Axiom and ather arrays have cal codes for the same base cal For example he same GG base eal be AA in SNP 60 Table 77 Example GIC SNP on the Genome Wide Human SNP Array 4 Axiom Genome Wide Human Aray XK Gerome Human SNP Jai Genome Mie Human Aray uem ao 0 Important When performing CHP vs Text Concordance Check between Axiom Genome Wide ne genome he tea in Axlom AB cae AB alsin Table Possible genotypes tor an example GC SNP encre ise Human SNP Array Aion Genome Mae Human ray ji Core Ur nemen ad cc ec 5 3 a relerence concordance check 1 Open he Workspace and select Data Set wilh data Tor ana 2 Select Genotype R
105. c Natio ooa emo n ueri vro pu a erae arie venio WAYS tm era ELITS Ibm ne sss NAZI n oc gun gr NAT moe woar cope er tt Corsi Ue Hart perm E emi Select Fies dialog bor You need o select he Resuli set with CHP fle you wish to use Coracle User ana To select the Results set for a le EE Select ne CEL fie rame and cic Select Results Group ton The Select Results Group dig box opens TETER prs 20 Select Rests Group dialog 2 Select he group wih the you wish to use and ck The i ne Avalabie Fist displaya e CHP name T va ue Fire selected Resta Group You can now select he and movet the Sampie Fes List or Reference Files it Using Shared Attributes to Group Sample Aes e array ties LARR XML ean be sed rop samples for dierent arai yos dierent enzyme set arraya arising Hom esame locat sourcerstate tyr Corsi User ana The Enzyme Set shared aute FUNCTIONALLY couples the enzyme set types tom the single sampe and interleaving he data nthe esu sgl noto ndr single octo ie Thus he Enzyme Set Aute funcional
106. com then to Support Technical Tutorial GCOS 2 Select ie dala ype CEL GOC andar CHP t to created Data Sat and check ak any atra sep mat ahold alao ecur scias dala or au C tena tana select an antre directory cic the Select Dietary radio buon Then tok OK Miei Gesch Coracle Ue at E Sark hea ont Hey etc OCI Soha Decoy C uh Sense CH seca rte LO Rond ls NCH SEGMENT E gato Marb air Rondte Falter UD tape te pee Yet Aie ise cee aad hr LIC Figure 10 Add Data dialog box Note You must have access to the folder in which the CEL relocated for GTC to be able to ete OC intonation yau oniy have read aces you mt frst copy te data solder Where you dala to alto DataSet Desorption Sect Doct radio buen At a ena alee rc ne data set Sample AR Grating Conca wit od user anni spl fe oh Dal hare tes an be sar AGE ARA poses tomar DAN and OC Fane asad Ganalyping Conc wit ad user anced ery CEL and aad 2651 Ganesya Cela Qo is GOC e Du Sat om period mule Carne Rar pe tide Coracle Uer Mant CUSTOM REGIONS Results er ENVCHE ato Sample Fin at and OC Fie ters Fes ect Come oa CH
107. d To reduce same Vari irese 1141 CNV agn are subst Mered 1o ensure at each region mapped o more an one amari probe set rodoced by ration enzymes io re an one fragment produces GURA consent in ho Il sta o apa samples Independent pocessad separate dta tt Corsi Ue Hart Appendix J Hard Disk Requirements appendix proves example hard disk requirements for 450 CEL fes dierent types of sad rale The fer reque lor anas and the esl o s required t save daa Table J 1 Hard D requirements for 480 CEL emp fede andrea tolder on derent hard oum Table 1 2 Hard D tor 480 CEL temp oder and resta folder on ha hard Teese e ty Coracle User ana Pesut Folder Lr Appendix K Troubleshooting p De tee ARR GOC er CHP carnet be meer ander me tro CEL Hes dee sole he Myra tating alerg ire TT Rd porci es atid o wae ma rot at Core hat e as war ert by Mme ome sd hne Pdl esed utro elg y tse we Se eed ne el ee cr may por fr gl Te capy iza Wows teatre rssh corn wc ie anced Wows To ti tum coy Sar lone caro an e
108. d a dala set wim more an on copy number eau batch e olo notice ask outa choose CN rest bale ty Genagrirg Cosi User ana Fire 113 Select Group dialog box Select e group you wish to analyze and cick OK The Select Fles dialog box opens tt Coracle User Han Fire 114 ties dialog box 4 copy number dala you ish to analyze an ek OK Tre Segment Reporting Tol Fitts dog box opens Aye Genotyping User Mart gure 113 Segment Reporting Tool dialog box 5 Options you weh 1o use see below The optone desorbed in Selecting CNV Map page 235 Selecting Fite page 236 noe segments at veri wth known CNV ragione by pape 238 a Sutta othe Segment Report Fle page 237 Creata Segment Summary Report Fie pape 237 Using a Custom Regione Fe page 23 Create Custam Region Summary Report page 240 Myers Gere Cane Ure Mart OK inthe Segment Roporing Too Filer dalog box Toe Progress bar dispose progres ofthe Segment Reporting Tool L Note An error message appears you do not have 24 annot db for Human Mapping 100K or SOK ays or te correct version of annot db lor SNP 66 Rinna Sennen Roots Tool Fire 1 6 Progress bar The nates appears te Custom Regions fie la nat in he correct format Fire 1 7 Noe of incorect nen he Segment report ished a notice appear
109. d addtional calagotes to ier on select e Add buton 4 Using arrows select 1e Threshold Name e g Minor lel Frequency S Choose he operator gt has The hss option is used when he category ting Mares text based Resccatd Gene in apie ic nara Comparison Value e 99 YES et Select OK To remove Ner orteria select Remove bution Toe esting SNP Liet wi be automaticaly played and added to e SNP List inthe Tee ty Gehe Coracle User Har Fiir 718 Custom SNP table and Bist in vee For ore ination displaying daa in SNP Lists see Tati and Graph Festes page 146 SNP Lt canbe exported renamed or removed by on e SNP List and selecting he spore EEG Baer Fire 718 SNP tat mens ew a SNP Lis select me Show SNP Let apn To review the Nier efter ora SNP List select the Show tyr Genotyping Cosi User ana E When the ther criteria are unknown e an imported SNP Li Wil only Indict te SNP count the Show Information option E Note SNP lista are crested based on a batch and the fiers apply to the origina bach on whieh they are based For example tering by cali rate bath A il contain SNPs that pass this threshold hie SNP ftis used with dierent batch SNPs in e may now demonstrate eal rates below the Ate raga SN Lst you ean apply any SNP Lst o generale SAP Cr
110. d data or use quick losd ure in an opened quick lod te Changing the CNV Map Yau can change a CNV map when you have ade flea to heat ap you have both CNCHP and CNVCHP ies onde changing CNV map 1 ash out al tha fs because CNVCHP Me are CAV map spasite onc you tanga your CNV map you longer be 1o se CNV cala sad cal conces en can choose NV reglon or browse nhe heat af because we dn support Sitom map Tr GNV analysa a une Overview of the Heat Map Display The Heat Map viewer displays value Data tom CNCHP tes copy anb or ach SNP or CN probe se on tha rosca a a dor value ina aal acl lt Genemi poston of the SNP and CN probe ses and CNV regiona tor hat chromosome Copy Number cal for the CNV regina Kom he CNYCHP f vaa in the status bar by mouse over e heat map nen test opened viewer pays data fr Chromosome 1 tt Cora User ana ae INNUIT RINT TRS age TIUS GR Fire 34 Pans ol the Hest Mop The Hoa hos te folowing components Tool bar sae belo WV Mop page 270 Error Reference source not found pags Error Bookmark not defined page 282 Suns Bar page 282 Navigate to regions of interest dierent aes medan intensty valves or CNV ca Export atat ot tne sorted or unsorted fles with fle path and te name Export mages show
111. d nthe GEL Data amp ac Files Some data Nes are generated by oter and used by GTC is ania dala fies eel GTC generates oer dala fies the analysis of the tty fies Genotype Data tes chp Copy Number Data Nies Lene LOH Data ties Copy Number OH Data fies tor SNP anal Copy Number Segment Data n sognent Copy Number Segment Summary summary custom Regions Report custom egre Custom Regions Summary Report regons sumar Copy unter Variation Data is evel for SNP 60 analysis GTC generates OC informato to help you evaluate your dala QC wormaton for assessing for batch genotyping andlor Copy NumBerLOH analysis dala Copy Number OH anas Report fies tor viewing data and racord keeping You secas te data in hese fles ough GTC Support fles Tho support is are necessary ous all of me of GTC rye et in tles tor genotyping copy unter OHCN Segment and number vin Relerence Model tis for SNP 50 single sample Copy Nonber OH analysis SNP tete bom provided by Aflymet and generated by user ty Genet Corsi User Hart Data Organization in Genotyping Console The dala used in GTC is organized by Wenspace User Pots alow you to keep your alormation about lott parameters abi and graph viewing olore ard oner setings Workspaces woonace contains dala sets dala
112. da maker lowing ton he genome MAPD a per chip estimate Standard Deviation SD he log2 ratlos are norma ra constant SO hen MAPDIO 98 egual SD However using MAPD robust against high Voi in 1092 raios ced by avions such as cancer sabi ratos in a chip arises from tuo distint sources intensie variably in he staring material cocta preparation he chip the scanner Apparet varity induced by the fact mat he reference have systematic lor ha chip Regardless of the source of tne variably increased varity decreases quay of CN cala Very high MAPD ia a alize Varbity o genera pe reduced by using reference generaled iom chipa una he sing he same reagent is sin genotyping here can be subeant bach elects or labo systematic elects I a reference is generated fom c run In anther la sch eyemate diirence te apparent arabi Afmet has Shoered hat ung 1e sped Afymati reference wih ch a n flere abs vit Male MAPD by found Soke bua tector of 2 a poaae Ifa chip with MAPD generated trom me reference greater han 0 35 hon we recommend against Using hal eni in an analysis When using Reference Meda made up ot NOT generated in he same tab us the same reagent CNCHP fos wih a MAPD value greater Inan 0 35 shouid be uted Tor futher snae When using Reference Fie made up ol ares that WERE generated in te same lab using
113. dialog box Aller a Data Set ls created he sofware automaticaly prompt you to add dala to la data aet See At Data page a o more E Sarl C Soins Hey etc OCI E euh esse enis in EHP C Batty Dony Munte LOB Ron ls END LOOK SEGMENT E tatg Marta air Rondte Falter UD Dos eae poe per Yet ae etcetera hr Figure 5 Aa Data dialog bor There Io waya to open wonapaoe in Windows Explorer doble clck workspace ge workspace This wa open the workspace In a new station of Genotyping Console You can also open an exiting workspace in Genotyping Console workspace is currently open open a workspace in Genotyping Conse select Workspace use the CTRL O or cick ne Open Workspace te main Browse to the locaton of me workspace and select Open Miet Gesch Cora Ue at pP ramen pese puasane Sach jb P 0 eels 5 5 Fire S Workspace dilog box The Workspace dalog box opens and plays the descrplon and data set interrato Tha Vey fle locations contam all data tie upon opening the Workspace I any fies are missing or nave ben deleted you bo prompted t ether update pal or gnere th maeng is Se Missed Data page 60 tor more norman lek Show Loc
114. dialog box appears CNEL Rec hatne ol teeta n Borer Tha ae port Trestad Nene T Comparison Value C Figure 11 40 Copy Number OC Thresholds dialog bor 2 Select te array ype lobe madd trom te dropdown Entar te mete in esta Name lat in the table The metrics isted in he Intensity C Tatie AI Calumma Vin 4 Select he comparison operator lees nan or equal to s greater hon p rete tan or eusi to p ot ua io t 5 Enter me Comparison value for e To debite a tetas tem ciek Remove tt Cora User Hart Note The defaut threshold tor Genome Wide Human SNP 6 9 is based MAPD while tor Human Mapping 500K arrays i 1s based on OR The Human Mapping 100K array do iat tenho When Die value or ding CNDP Bes h nek bo mad hbo These Treshold Name Comparison voe Fe rachat diet ia dea Lx gure 1141 Vals have been changed rom deoa Note You can restore the Default threshold values by clicking Default Ifyou wish to add another mee Select Add 7 Type the exact name of ia metriin the Thal Name fed select a comparison and enter a value Fer ation metnes to be applet noy muat existi e Intensity QC Tale A Comes Copy Nanter QC Summary Table or 100KIs00K page 178 Copy Number QC Summary Tabie tar the Genome Wide Human SNP 80 page 207
115. dr ne relaonahip between ARR CEL and GHP Hes remaing he dependence on the names a vaek Gehe Cora Ue Note The sample atributes contained in the XML ties crested by the Data Transfer Too cannot be aed within Genotyping Console edits are needed please ed he information n GCOS or GTYPE Prior 1o using the Data Tranater Tool To edit an ARR 1 From Do Fle menu select Open Edi Sample File The Open dialog box opens 2 Browse to the directory hal contains he ARR be eed Select and select Open Tre tbe tor om a Figure 20 Mte Editor 4 Select he atte to edl o edl the gender Toa Enter New Atul Value dialog box opens ty Gente Corsi User Hans 5 Type he value of he atrbul in the Enter New Atribute Value windo cick OK tbe a date then select the correct rom the calendar a select select the correct value trom e pil down menu Figure 52 New atte vn Gencypng Console wi prompt you to save te changes El ote Only one ARR e can be edited at a time To batch edit ARR Mote ARR tes are updated by the attribute editor N the ARR is in a directory that is monitored by AGCC then changes made In Genotyping Console wil aiso be retlected in AGCC Missing Data When opening workspace Genotyping Console software wl entm ala me locaton tor sles in me workspace se wel
116. e fe name You can soet by tna values for e SNP and CN proe sets diaplayed in tha heat map iin the afe o window an unser to go agin order You can so by the CNV cala trom tles in the bat map i your window has CNV region n and goto tne nna order some CNCHP Hes do not have CNVCHP data hese es wi be displayed at the olor of he Hat Map sher on CNV Cal values You can expr alist af he CNCHP and CNVCHP path an names in their order beoe ans aer soning You cn select afferent color palettes for the splay blow or change Ratio range page 274 To select trent color palettes tor the display Color Palettes button in the viewer toolbar and select a palette coke mo m p Fire 1213 Heat ap color options To display the attributes and other data It avaliable Map in the fle row you are nested in on cpg sae CNCHP and CAMP pa ans Ne nanes vaio and angle tt Corsi User Hart Fire 12 14 Sample data Histogram The histogram indios te frequencies of probe sets with certain int values alt peru When you navigate o certa repo the histogram automaticaly adus and dapi Sets win Wat pacte region De requences ot probe Yu can display me atoning inomaton in te Sab bar by puting Me mouse over SNP or CN probe set postion
117. e between by dn is markers can eer have re es oa dependence on each Toreduce me infiuence f neighboring markers decrease is value rain faster For examgle you set the decay ta 1 MD and a given marker CN Siate th probe tati fon he fehl tein State is much ower compared he case where deca 100M Toineroase me nfuence of neighing markers increase Bis value vano some Number Parameters Post AM Processing Parameters Pet Rossa Paar hein Nob Tobin Ji Fire 1029 Pot processing parameters casonaty a marker CN probe on the SNP 6 0 pros abe tor unknown reasons The come be ar glason fate CN aeren ram ulehenging fang markers boh CN and SNP auroundng ha mater Seting is parameter o 1 changes e CN detemalon such marre yee wih Do abor markers surrounding 1 For example mere is a single marker mat is called CN State 1 by the but he surrounding markers are aed ON State 2 en i Singleton SNP wil hanged CN Stale 1 10 CN Stale 2 Senin is parameter to 0 leaves the ongina CN State vae unchanged For ha SNP tote marear of ranking markers oniy be or 1 On the parameter tor SNP Ouer Adjustment an i sat in base pars LOH Parameters 5 Tu ea 35 m Marone Meta et Lon omn Ps Tei me
118. e downloaded software package This he program and release notes Rees ne release notes and instalan before proceeding in he instalation Doubleclick GenalyoingConacleSetup exor GenotyplngConotaSelup32 exe lo install he sofware ne exe names aren cepen n heber Sd or ela S oou drectons provided by me tale Note The setup process installs the required Microsoft componer framework and Java components and Visus runtime rares Updates amp General Information Newintoraton about Genotyping Console wli b made avallatie to customers Brough a Update Button on Dera ata eig Cosi re opten Uns Kati No nias o Updates Omne When update Inlormaian is avatable cick on the green Updates Ava buton on he main oo bar ant Web bowser wil be launches indicating what maton avait TIS When here are updates available the flowing bution be dieplayed onthe main too ba Cig on Wetten web browser shoving ne crei Poemata messages D jets to computer i Genctyping Console be unable to determine bote are any updates aval and Updates tution ideae We fine aus tyr Genagrirg Coa User Hart rs ore Notes for Users of Earlier Versions of Genotyping Console GTC 40 snd earlier versions of GTC cannot be run on the same computar The GTC 4 0 bay and annotation Mies ace nat compatte wit sate veriora of GT
119. e for Axiom Data default view testy QC Table coni be QC res See Tabie Features for more infomation on te abe By he columna are displayed Giessen oa ton chau dida presto n p Son Soon GC SUR whee al basata a altos probes nis somata Gt probe erates meson of AT probe entes Aon ara ts AT RGR T hus ial conta AT EOT tyr Cosi User Han E gna GE ORs Anca Sn EN anit Omnia tete The tigation nucleotide th nucleotide are detected The GC chanel the optica channel In which signal tom ligated or C nucleotides are detected The AT probes are those control probes that correspond non polymorphic genomie posltons for which the expected ligation nucleotide A or T The GC probes control probes tat correspond lo nor polymorpi genome positions fr which the Sipected igation nucleotide is or C Intensity QC Table for SNP 6 0 Data default view The wing columns can be payed for SNP data flr rung OC in Ganatping Console Column tiame Description Contrast 0 Random Contrast OC tor 10K nam anal SNPs SNP 0 en Contrast ac ep ores QC for OC 20K SN on ep gmat SNP 0 Sania WepSly Cain tra ANK NP on Siy agnen NP 8 p Corea OC for 20K SNP on Siy
120. e i ale postues and creat in power Suc SNPs can caused by systematic or sporadic tnat occur dua sample cir Prior 1 analysis tis prudent 1o apply some SNP Miring cte to remove SNPs tnat are not performing esi he data t in question The sujet ot SNP Irs essc bent prre are eng developed Se Remove SNPs wit a signticanty low per SNP cal rate tyr Coa User ana Remove SNPs sniianty out of HW in cases ando cont Remove SNPs wth oret cal rates in cases and contis Remove SNPs wit Hendelan erc Slides on mulil dats seta have shown tel SNPs with wer per SNP ca ale tend have higher error Tate and eror an e experiment Most importan ug ey ay consta very smal acto fh tol pot o SNPs t a eos happen tly by stats y aro to show up apparent associations To creste a SNP lat for tering SNPs 1 gencypng bac resus and select Create SNP List EE p p pur rerenga net Cbron Ded p nds Ga Fir 7 16 Cres a SNP lat The SNP Firs Threshold window box opens ty Genagrirg Cosi User Har Ene ASHP Lit meto ete 1 poet diete te SNE Le Clk ie SA iste m tret Figur 717 SMP Fler Thresholds 2 Entar a name tor SNP List The resting SNPs are stored in e SNP Liat Adame desired te crt To ad
121. e o De dri e CHCHP Nes cut Cn he box and ariar Note This tolder is the location where the diferent Data Results les are kept To view report es access the folder through Windows Explore Entar Fie Suh tor he CNCHP optional ads a sut tote CNCHP fles to help you rack er Clck in e box entar a ae i in Copy OH ea Opn fr Fle Creaton and Nido The Select ios dialog box opens tyr Corsi User Har Figure 102 Select Files tor cresting Reference Select Nes in he Avatable Fles ist A minimum of tve fles is required to run anal e a Reference File It is recommended that you select 44 or more samples hough the software wil accept as lew as 3 obtaining good data on the X and Y J amp J Note I ll other parameters and les are the same reference model es generated wth or without legionai GC correction are exact the same You do not have t regenerate relerence mode fe wie wiin diferent setings nthe regional GC correction option cick the Ada bution o s4 data to me Sample or Reference ist ck the Remove buon E to remove aata tom a nst 14 chek Ox Ate generating me Copy CNS enc Nes you can Meets Geste Coracle Uer Use the new Relevance Made to perform CNIL
122. e set summary ora gen cp an calling ence m lag base 2 median value c ha probe set over al ips To moon i en computed om Ie abate RLE fra he pote Sata ora gen CEL te e rosdan ct he hae al oe flere between iced sample median en state The median of a the calibrated put into CN state space log ratos for he ty Genet Cosi User Har samplecnom tequency The requency homozygous cals all SNP cals of SNP homozygous cals fore sample semplehebtequency The frequency heterozygous cala all SNP cals o SNP heterozygous ca fore sample waviness Tho residual standard deviation SD ater correcting adjacent probe set to roba set SO based on autosomal og ratos The weed is a measure fino sana vanabat i anger range chrom Minsiqna foreach chromosome LogaRalo tor a given chromosome and sample Chrom eSignal one Maur LoqaReto or a hen canon and sanle Fie Date Date was created MAPD and Copy Number QC on the Genome Wide Human SNP Array 6 0 MAPD is defined as the Median of te Absolute values of al Pise Diferenees between ratios for a given hp Gach i defined as in tems gencm distanse wh SNP markers CN markert big equal any o makere bat ae he genomie coordinates are a par Except tthe Beginning and ine and of a cnromosome every marker belongs te 2 pairs 1 adjacent a marter preceding it A
123. edng Upon the ot array bang analyzed Seo or more datae eg Anor To liate QC on CEL tles akeno n he workspace select eier an tenet group rm he tre eleet rowa rom an open QC labe fen an Perm GC erkan Gy Mat nn ses p tt Corsi Ue Hart n pr p some ee a fn ace E bs si When e QC i completed me results wil automatically be dlaplayed QC Tho Results automaticaly be parsed into 3 groupe Al n Bounds and Out ot Bounds AW group contin rests for al fies in the Data both new added and existing Bounds group contains te results or fies which pass he QC Teens Bounds group cons the rss o a ans io which do nat meet the Threat the In an Out ot Bounds grouping is based upon OC Cal Rale To modiy edit he QC page 207 Bounds samples wli be in he tatie Aye Genotyping Mart prane Rmi 7 tens SUPR Tee ma tera a mame ac 3 momma a ewe Fst me ee A Swine saxon ca e ice Or mk rar Se re STELLAR a as araa amara e
124. eng dal you cen nghi elek he data set In he vee Couto sa X tenens Figure 9 Deta et menu Ifyou preter you can add dala to s data set by Ceng on he Data statut lon the main waar Selecting WarkspaceData Data Using me CTRLA shortcut Mets Contin Cora Ue Mant Gencypeg Console wa detect which dat sat mat you want to ad data 1o based highlighted vee tam i sofware canna determine daa sel al you want to add data to you be pond 1o selecta data sel CI Note Only es CEL or CHP generated by Aftymetrx software or GeneChip compatible software partners can be imported ito Genotyping Console Any supported data fies that Seded ae o ese sr may cus al or anal Conde J Mote Attymetrix recommends using data les in format as there is only limited support lor GCOS For example editing o XML sample la not supported CHP es that are generates by Genotype Console and hen imparted nto another workspace wi nat include sample bute intormaton CHP tes were generated rom GCOS formal CEL es Affymetrix ecommenda using the Data Transfer Toa OTT v1 1 1 provided with GCOS Fiat Fle Iranster ol option to creste a copy ofthe XML and CEL He for use by Genotyping Console For more Information go vo Mp woraymeteb com suppor downloads manual daa anser ool user quide ptor
125. enzyme set arraya neede to be assigned at least one shared atribute unique to We CNLOM anas ot nih wi part In he ear above Patent Siate atu ha atribute used to parem ue fers Gener Cane Uter anusi FLUE a p a winana MVNA Y 3 ASLAN Deme YORE ORF 3 NANDA 1 od Nome WST T s Sess SCE THRUST Dime e swank De Dess 1 NAIA swan T Dress Deme M Demum TUNER 18 NALAN E Y MLNA E Nod ems M Y AUS Y Figure Sample table wh trt Sampie v Reterence Shared Attribute Helpful but never required tor analysis atribute pare is when performing pared CN analysis you to he SempioReerenoe di Tor esl selon and provides basic check 1o make sre you Raven exe em up To tes up tor using Sample Reference atiributes 1 Pte Seng aa ers eel and Genotyping Lahe Nes or boh anay pes ine sane dat 2 necessary tor Sample ve Reference in he Sampie tes should be done during ital sample registration but you can ad and ecit using GCOS orAGCC Iar on
126. es Ten each CEL hat weni inta maxing Model analyzed Reference Modele From comparison te samples Copy and LOH dala are generated The geraype cal made one yy Me SRLM Ps are used Tor ine analya Tre analysis provides Gender Calls Female or CNLOH Anais wih a Previously Crested Reference Fle Single Sampie Mode page 200 In this analysis you compare selected samele CEL ties to previousy created Reference Modal te inar supai Ayme or a Reference Model ts you heve usn COH Reference Model Fle Creation and Ansys process above i Ie Sing sample eran here sre no CHP Mes genere and he anaes done win he polyp cal ade on Ba yy the Reference doa Tre analysis provides Gender Calls Female or Note Smali numerics ferences may occur between dierent runs even with he same Inputs due an interaction between rounding Irom double a single precision and tne way the application handles memory management Note CNLOH analysis can be run with configuration with regional GC correction or with Configuration without regionai GC correction in both bach sample mode and single sample mode IE Note Previous GTC 3 0 configuration tles wil automatically be updated by GTC 42 and run as wth scare veni congue rive Note Configur
127. es he reference valo reach probe seis ood by ng median of summaries prebe Sak signals samples in For each SNP probe set summary signal calcuatad atr lenis by using probe logi analy eror LIER with no aplana foreach of he SRP aoo probe sis and suming ba eso bah ailes F0 CN poe sra e a nomlzedinenayony For chromosome X 1e referenca value i formed using oniy sois deta fresh Genotyping Cane Uter Marat rotto have a single X and assumes he majorly of such samples are dii For chromosome Y he reference Value is Torme using he samples determined nave Y present Note Forming a relerence where a large traction of tne samples have one or more chromosomal aneuploidies in common wit give you weird result tor he atlected chromosomes In me proces of calculating signat various noratzaton steps are made so at sigral trom each sample be compared wah asch oiner nese homatoaton stepa we ol he sme the comparason ag single sample votos new songs hese For ifomaton about the algoritm parameters ee Changing Algorithm Canis lor SNP 60 Analysis page 210 Forifamaton about alor description see A Aporia page 292 Copy Number QC Summary Table for the Genome Wide Human SNP Array 6 0 Use he GTC Browser age 249 to view Number LOH and CN Se
128. es tor the Overlap Tibe percent value la sel 1o 25 segments wih up t 25 of their markers overlapping nown CNV regions Wil be reported as part o the Segment Report Segments wan more han 25 hk makers CNV regions wil excluded Fo he Repor 100 means thet all ot the segments wil be reported p to the Segment Report Fie A sux can be added to keep he output es ram ovre results ol an earie analysis The wa be das ta Raport les nd Custom Region Report Nes Sufixes arena adde I Sunimar reports Tan Rel Figur 1114 Add segment report le sutt Todd a sut Entar a tor the segment report tie in the Segen Raport Fle Sut texton Creste Segment Summary Report File epson alaws you to generate summary segment report win information on change regions in alte Net Nes you are analyz Thi ta dele conte na extension cn segments summary Mets Gehe Corale Uer Hart E Cen Samen t Soames Sunray mooti rere ILJ Figure 11 15 Segment Summary report tle option Te creste segment summary report Me 1 Select me Creste segment report summary checkbox The Save Segment Summary Report Fle dialog box opens 3 EE meme Fire 1118 Save Segment Summary Report Fle dialog box 5 Sets lemon r me Segment Sumyar ee and eter a amet e e Segnen Repot Fl are not ulomalcaly sided t Summary es
129. esults fle set From e Workspace menu select Genotype Results gt Run CHP vs TXT Concordance Check or the Ress fle st and select Run CHP v TXT Concordance Check rom the pop mena Myou have not previously selected a Results ie set he Select Genotype Results Groups dag box opens Hes Fire 137 Selaci Genotype Results Group ialog box 4 Select a results group ror he Ist and cick OK ra Corsi User Harun Mote You wil be abe to select arrays rom only one enzyme set at a time when pertorming a CHP va Tex Concordance Check Tre Select fe alog box opens Tune ro pron pros oer prom ERLE NE nw Figure 7 28 Select Resse dialog box 4 Select he fes tor concordance check and elk The Select Reterence Fle opens tyr Canace User ana noma 2 pe Figure 129 Selec Reterence Fle dg box S Browse to he locaton wih bo reeronce you wish to use and toto See Reference Fle Fora page 126 fr more intonation ciek Open The Save dog box opens tt Genet Canale User Hart Sen omwemmmem E 010 E p fo Wire rcm proa Figure 140 Save A dialog box T Browse to te location where you want to save the pot and enter a name far h report Mhe reference does not have the correct formal the folow
130. ete brary tolder GTC 4 automatica assigne a temp fier tor you You can change Me locaton cf me temp folder ln Options dog box alek ie Options button 09 tt Corsi User Hart Spec he deel me the Ray ed er ae oe dere e vakapon ened Ye lr ooh Scythe diclo whe the tampon He ae E ug CeCe Figure 23 Options dialog box The Afynetix Power Too sotare uses te lora ties tolder during calculations The temporary tes must reside o local ard drive not Users mst have wi access oe temporary fies Sca Apoena 319 or on local hard dive space tt Corsi User Hart Parts of the Console Fire 24 Genotyping Console wilh workspace IE See the GTC Browser User Manual for information about viewing the Copy Number Loss ot Heterozygosity and Copy Number Segment data in graphical ormat The GTC components are described in more detai below The manu bar and tocar provide quick accesa to the GTC lnc Display area Som of te data generated by GTC can be wed in tables and graphs in the ply area including niens QC dala an graphs Genotyping Data abies Copy Norbert oss of Heterozygosity OC daa Haat Map Tor Copy Number and Copy Number Variation data tyr Cora Ue ana note The Copy Number Loss ot Heterozygosity and Copy Number Segment data generated by GTC Is dployed in he GI
131. experiment to resolve SNP signals io ee genotype ists uses siale self 10000 fandom chosen SNP 60 SNPs measuring e dierence botocen pois o Contost Fig 217 producea by nomazygote genotype and may share wi he pesk ond taes the sabe i the pot quy e homozygote peaks te Yom the neterazygste and e diference values approach zero Coast QC vues compute or Contrast produced by sat of 20K randomly chosen SNP on agmen sd sat sat of 20K ransom chosen SNP on Sy agents oniy These are calla Contrast Ge ran and Contrast QC St V e absolute diference Between Mese ho vates enar an Mo his evidence tnat that a sample may hae warte properly wih one enzyme et bu ol wah e te ii e vue eae o zaro V refs e rdum These Cras aues are wi wih tha haer Cal Raes and concordance an cae re subsequnly made wih seed versions 1 or 2 The comsiaton between Brdseed accuracy and Brdood Cal Rate i slao very hgh Ae a Siva guara neun of any euler samples rat poss ough the Contrast QC goo dea samples at are notae cure in ems f iat Cal Rate When using Breed v lusting later batches sample he peomance ago The improvements in ideea 2 you 1o chastar by pate wih the samo as use lager balenes f sampes tt
132. fewer ae saan ins pera SCL NAIDE wawara Woo 3 miam ona 1 wasesane Keen eer WENT To Nias Suan t i D e T azman o TO T asp ahh ess E LE 3 _ C Fire 24 Tabie ot Hes and Whe you sort by enzyme sel with these attributes you gel hs tt Corsi User Hart ae he See rc AIDE IG E RUNS me Nae EL E NEL MA Figure 5 sorted by Enzyme St Ate Esch sample deeased sue s he value Disease he Sampie wi trom normal sus gen the value Normal a os bora acia Enae MIENE Figure 8 25 Sorted by Enzyme Set an Sample Reeence alow you to pair up the s bo by Enzyme set and by sangleeorenco p as shown in Figure 927 tt Cosi User ana See Fee Tone Fei Ein mmus em o gete ut ET Seda um RED SEE 3 pO eee po Run
133. gments data ln a genome context Use ha Heal Mao ewer page 289 o view Huber long wh Copy Number dat The Copy Number QC Summary Table dlaplays QC information about he number and LOH antes The Copy Number QC Summary Table uses al he table optona as described in Table Features Te open the OC Summary table on the Copy Numeri Result set af interested and select Show Copy Number OC Summary Table or Rig e mena lt Copy Number OH Results gt Show Copy Number QC Summary The C Summary table opens tyr Corsi User ana Figure 10 13 Copy Humbert OH OC Report for Genome Wide Human SN 6 9 array A Columna Viem The Copy Number OH QC Report provides me folowing inbrraten t SNP daa Fie Fie name Bounds inaro ot OC bounds See Seting QC Thresholds page 257 tor more information Gender Gender tor MedianAulosomeMedian Ostine by taking me median of the medians of the og rates ot all aiosomes men ths tom each a cng X and Y Tris comecion asumas the of ie autonomes represent normal SEGNA ni conectan fern ia Sp cp ae n p Melan absolute pairwise See MAPD and Number QC on a Genome Wide Human SNP 50 below for mote Li range average or ai probeset re mean The mean absolute relatio og expression RLE hs ma generated by takin me prob
134. gonucieotil Array Data Based on Vance and Bias 2003 Jan 22 182 5 4 8 Bul A izany M stand and T P Speed Background Corecion tyr Gehe Corsi User Hart he SNP 60 assay uses boh and enzymes to cut he orignal DNA into fragments Each enzyme has Jot t ses adapters Fragment peolcampitieaton has been depending on e parca pal of adapters used eut out Suen speclic elec are cal vay sera bin a of samples run ogee but between sample sat suc eec occasional qule fret The robe lev Type araz used o enaure te agement eects are al aes For any ange Copy Anais n he Naaluaton Probes Background configuration parameters tho b sl same for analys hes parametar ware tet generaton o Reference Made ie used in e anal There is a secondary optional normatzatlon done tr log rate are termed elg ratos median of a metian og aloo usamos adjustment can be sc o omes with autosomen when probe evel normalization be amp fecied by an auch ae high CN gain in Chromosome X Nol et ha aduement robe eve background Soon Ths cn recommended samples ae most ol he rat Copy Number Parameters HIM Parameters with regional
135. he data lor anal 2 Select he Genotype Results fle set optional 3 rem the Workspace menu select Genotype Results gt Run CHP va CHP Concordance Check or on the Genotype Results le set and Run va CHP Concordance Check tom te Popup The Select tles dalog bor opens tyr Corsi User Hart rr Figure 7 48 Selec Rent dialog box cick me bution to me or reference it the Remove buton remove aata trom a lat Note The firat fle in the Sample Files list ls compared to the first e in the Reference Files second in both liate are compared to each ather and on Cote You can pair Mies trom ferent enzyme sets tor Human Mapping 100K 300K array Sowa you to compare te signature SNPs Tor arrays Wih dierent enzyme sts tyr Gente Canace User ana Figure 4 Fles pared tor concortanc check S hen you have selected he fies for te concordance check elk OK Save As diog box opena Aye Genotyping User Mart Fire 747 Save Aa dialog box 8 Browse to tne location where you want to save the pot enter name for the report ie relerence e ia corect he Progress bar appears Fire 748 Progrese bar When abs he Concordance Report appears tt Corsi User ana We orca ne pu
136. he new rag 2 Rick and select Selected Rows to Result Group ty Cora User Hart ZEEE 01 setae Tor 7 apse oe ear gure 712 Ad Socio Rows to sits Group The Selecta nen or esting data group dialog box appears ge 13 Selec neo exiting dala group ar a nare or select an existing dta group and select OK The naw group wil be in here Custom groups are ca by uhite EET UA DERE en Fire 714 Custom Group in ee Custom tray groups can be renamed or deleted by he group and selecting Rename Genotype Results Group or Remove Genotype Results Group ty Cora User Har B Sachets 1853 uen p East SP Srey Te Espot Verani KE hears Cerone K Fence tens aino Figur 718 Removing or renaming custom group Mote Removing custom Genotyping Results Group does not remove the d remove Genotype Resa dat sse Removing Data rom a Data Set page 50 rom the Data Set To notet a custom Genotype Results group is selected tor displaying SNP summary results or SNP loser graphe he irat tme the SNP summary labe or SNP cluster graph ts generated Genotyping Console wit prompt you to seve the summary statisties Create a SNP List For many appcstne peromig SNPs can ead to increas
137. her references Maren Mapping 00 Array gt Dram Model DU man Mapping EC Aray 1 Drama Model OU aor Gere ie Huron SNP 72 Dyan Model OM rt i QC COC is ne py QC metne y SEES DA lg arab nd Dev OC 000 loved oy tein cal rate Mir Gore Wie rn Ary To visustae hos genotypes OC group and select Show Signature Genotypes Mine Genagrirg Cosi User Hart Paes ETIN Dacos d pone kiray bas on E poem elenco arbe vaasan e Figure t t Show Signature Genotypes able wll open showing the genotype calis tar me Signature SNPs Fire 1 Signature SNPs default te folowing columns are displayed tt Genet Corsi User Har AFFXSNP set ID or signature SNP Preclatons tor ese siae SNPs can be obtained eir om NetA or by frst importing SNP lat erlang te ttd Probe Sat 0 For more tomato on dspayg data in he Signature Genotypes Tale Tati ans Graph Features page 144 ty Corsi er ana Chapter7 Genotyping Analysis Genotyping Console enel CEL tom he ling types of araya gt Human Magpingt ook Array Sets Human Mapping 500K Aray Sets Genome ide Human SNP Aray 50 Genome Huan SNP Anay 60 appeton supports e folowing analy zum n Genome Wiee Maman ENP Array S0 Genome Wide Human SNP Arr
138. holds stria on maln or selecti 2 Inthe Tivestlds window iat appears selact e array type 1o be modd tt Corsi Ue Hart Fur ety OC Select e metle te comparison operato than lt lese han or equal to greater man gt greater anor equal egual to or not equal to 1 and he vali Jue tor esch array type I Miei Gesch Coracle Ue at CEL ien 4 di abe a ae Teh ae Threshold Nome Comparison vole sp vH Chus Figure 2 Fog in OC Thresholds dog box Ifyou wish to change to using anotar etc you wi ed ta select text in the Testo Name fled and et uaa ae eive Ss nw mec is Fr metres ep epe he QC Tabie Coens Mt you wish to another select Ada You wl need la type exact name of ie metie in he Name teid For sonal etes to be pote they must ent n e tant OC Tatie Al Cains Ve Contrast ac i the recommended meli fr ne Genome ide SNP 60 in Genotyping Console The stu la greater hn crus 10 0 4 Tor aach When adjusting Pa QC mete shai value changing SNP 6 0 QC setings to anamer such as Ca Ral adding merica t a Tag he ste dal box wi nao esl we een Dan te Contrast OC is meti that castires abit of an experiment to rescve SNP dnas ino ee Musee 1 000 random SNP 6 0 SNP
139. hs Once you nave selected an appropriate SNP Lit the SNP Cluster Graph window ul 2 on he Save Cluster Graphs to POF shortcut Hon me graph toolbar Pe 3 SNP eno roooncos 484344 SNP USEN ane 2 be PH D 229 SE H a E 1 i Figure 7 2 Save to PDF buton in graph foobar Inthe dialog box hat appears select a octo o save hla fle and enter a name for the 4 Enter a tite for the PDF tle This wil be deployed at the top ot page in ho POF document pm Figure 134 POF Flo name IE Note The PDF has 55 character int The data or he PDF le wl be coacta and wet and contain 8 graphs per page Mime Cosi User ana Aye Genotyping User Mart Fire 136 SNP cluster graphe PDF frei Gere Conc Une Mart Concordance Checks The concordance checks enable you to compare ha SNP cals in diterent Nes You ean perform CHP va TXT Concordance Check below Compares SNP cats in a CHP wih SNP cats in a preva create tant In Wa eck ou can compare mulie CHP Res he same You can use esc uh S Ra e Wet nee rt yoro CHP va CHP Concordance Check age 127 Compares the SNP in one CHP Neto he SNP Cals in tater CHP This s dene pare bei you can perform check an mute pare of en me same Tne ouput ba hti same opt We tcn
140. i prompt you to create me prole M eranste taane m rtt pure 32 Conemation box Mar sting up user the stare simer prompt you select ibrary path Command Coreoie not slated on e workstation or mo rar odor has not already been specited during ror session or a workspace 10 open See Seting ne Library Pah on page 31 cr Crete New Workspace and Osta on page To select an existing Profile Use e drop down menu en the User Profle window tt Genet Corsi er Hart an etra es ona rane Figur User dialog box lk Note You can select diferent rote without terminating the program but the Workspace must be To change proies 1 From De Edi menu select Change User Profle The User roe dialog box appears 2 Enter a new pole nam or seca previously generated rote rom e drop down box ese above User Profile The tat ot prevousiy created potas feud athe drop down mena on he Profle formation window Te remove protes no longer needed 1 From he Edit menu select Delete User Profle The Delete Protes dialog box opens Miei Gesch Coracle Ue at Fire 34 Delete auser prote 2 Select te User Pri to be deleted and select OK The selected User Profle and al parameter tles sasociated wih e ih be removed To ac a new Ust Pohl see a Uae Prot page 27 tt Genet Corsi User ana
141. iants CNV or number pymerpieme CNP The region win copy number variants can conan one of more CUN probe sets To pertorm CNV analyse 1 Start wih intensty data CEL 2 Pafom the Copy Number analysis See Number Var on Andy page 280 ew he he Heat Mao viewer in number esu See Hest Viewer page 289 Working with Commands in Genotyping Console Commands in Genotyping Consol can be accessed tom on ree lame Rent dick on tatie rows on graphe or tom the graph toolbar The vee tems serve dual cione organizing ha dala an results well guiding you through te Tha ie menus are sense which means hal serne commands wi hadden you ve selected the Tamsin he or tbi waich e command apples Aara Gere Cane User Manasi Es bed Figure 214 Data re bor mena p mm Cony tasterom posute Figure 3 Seeing operations trom the Workspace menu Window Layout Options Genotyping Console windows can be arranged ether as tabbed windows or muliple windows To secta layout ptm choose Tabbed Windows or Mtl Windows tom the Wino Layout tt Corsi er ana Fire Window layout options Inte tabbed window layout each open table or rap the ente avatable space and sting between Seve wins can be accomplished by acing he lab at e ip othe window
142. iation Results trom the popup Myou have one bath fer of CNVCHP fes they ar Monica elected Myou have not selected bath resulte data set he Select Copy Number esuts group dalag box opens Figure 12 Select esu Set dialog box Select a results group lor export and ick The Select Fles tor Export dlalog box apens tt Genet Corsi User ana Fire 29 Select o Export dilog bor 4 Select Copy Number Variation Results ies or spot or cick Select AN cok The input Value dialog box opens gure 1210 put Value dialog box 5 Ener a ufc or he ouput as sed cick OK aa tI are created tor each CNVCHP fle Each le has header wth information seu CNV analysis inherited Hom the CNVCHP fles and tour pu Regen Signal cu Aye Genotyping User Mart fei Genotyping Cane User Manusi Chapter 13 Heat Map Viewer The Hent depos Copy Number CN testy values ratios om proe sets in he CNCHP tes Copy manier stala cats tor the copy number variations CNV in corresponding tles aval E Note You can view CN data with or without matching data t you change the default CNV map ter data la loaded in tne Heat Map viewer lite associated CNVCNP wi be removed CNVCHP fle are You must have data to load CHVCHP dala alone you te Compare me CNV cl CNVCHP fias vang om tan
143. il aiso appear lor nemiy created custom Results groupa tyr Canace er Har sen nomernsswes mos Qe E pd 2 De Decne VT po I Fire 710 SNP statics tt Corsi Ue Hart Fire T11 SMP table H Note You can see additional annotations by to Al Columns View L Mote For readability metrics are not displayed fl precision and tables saved to e contain the Same precision as displayed in Genotyping Console However SNP ling la performed using the Ral precision stored inthe binary SNP summary The SNP Summary Table contains he SNP level results and metis Tabie 76 L Mote For Human Mapping 100K S00K the SNP Summary data tor the diferent array types wili be displayed in labes wih dierent names See the Genotyping Anal section page B3 or more on pertorming geting See Tale Features 146 or more mation co cutn the able Conn Hender Desorption pr ne Ate ne er he zet ot protez ure parte Single Nise omer SNP LLL BE pm Percentage for hiz Se bh tyr Cosi User Hart Percentage cA cal fore SNP e ih Percentage c for ie SNE sa tegere for li aid p Ah Cal s eB alle tequeney iz Puts alle eget i ho n PAPO ET a cd fe pm Per en cate
144. ing error message appears ena honat nother he Wht be lath rama a athe manda Fire 741 Error message ii message ciek OK 1o cance he operation and then the problem Ses Reference Fle Format page 125 x more intonation te reference ia corect he Progress bar appears tt Genet Corsi User Hart Patino eorex hv Figure 7 42 Progress bar When the analysis ls Iniahed me Reference Concordance Report table pase Taher 1 ms em gure 743 Ralerence Concordance Report table You can open concordance report om te menu vee Te Reference Concordance report contains e information Fle Saree Reference Reference tle name SNPs Called Number ot SNPs common t bh sample and relerence wih genotype cala d concordant SNP Number of ested SNPs that hav he same genotype cal Concordance Percentage of called SNPs that have he same genotype cal Copy selected data in the table to he Reference File Format tt Cosi User ana Figure 744 relerence tle eterno fle can be crested by esting genctyping resulta age 131 IE Mote The column headers must be capitalized as shown Toperorm a CHP vs CHP concordance check 1 Open he Workspace and select he Data Se wih t
145. ion emptis Copy Number LOH Configuration Options Template Generne 6 E No Regional GC NT uana Places Nec Fe Denn and LH Arabs f Fire 10 24 Basie Options no regional GC correction chosen The Basie Optons alow you to change Contguraton Contiguaton Type You can reste acontguation fer the folowing ot ana CMLOH Anais tr Gehe Core Uer Hart Relerenco Model Fle Creation and Andi Cete aps ratte ny Rete Model Fle Creaton CNLOH Analyst olo Confidence Score Threshold auc she nace us cran cal Cale win oan cs reso signed ano cal Probe leve Normalization tor Reference Model File Creation Quante normalization is recommenged er number analysis ot associaton and cylogenetcs sangles ante romain e mest seprapate fr samples where ost at e chromosomes rli n contrast many cancer samples contain sicat abnormalities tat impact much fhe genome Pretore median normalization a ecomanded important For any single sample Copy NumberLOH Analysis run he Probe eve Normalization and Background Correction parameters most be and wil be set te same ore Analysis ese parameters ware sel during the generation o te Reterence Model used In he Anaya Advanced Options for SNP 6 0 Analysis Advanced Opti
146. ions and enter score thesia value 4 Save te changes the congeaton as new contiguraton Cic Save Sve default Ck Default Detautt is clicked a new window wi haw up wit two options one win reglonal GC conecten on minout regana GC comoctn By chosing on of he two opns the Siri tar wi gera conecten ar detain crgo riu ind caeci tyr Canace User ana TT 58 pure 10 18 Select Configuration dialog bor Toedita configuration that was created in GTC 30 cc Copy Number Configurations gt Open Configuration The Open dialog box appears ty Corsi er ana EE Er BTCS 11 GC cum 1020 Open bos 0 Note Configuration fles that were created in GTC 3 0 wil be displayed in the Open dialog box for election You can edit these les directly see below for more information 5 0 coniuraion fie are opened in GTC 20 these es wil be tested as coniuratione without regionai E you are editing s contiguration crested in GTC 30 you need to update the Score Threshold tom 00518 1 0 ae recommended new setting 2 Select the configuration and dick Open The Basle dialog box opens win No Regional GC Correction adde tyr Corsi User ana C
147. ites te erent Number OH works or Huanan Mapping 100KIS00K arrays Poe Copy Number ana LOH Analysis elo Unpated Copy Number and LOH Analysis page 162 Copy Number OH Fle Forat or Human Mapping 100KISODK Array Data page 167 Selecting Results Groups page 180 Using Shared Atte o Group pape 172 Copy Number dala fies tor Human Mapping 100K 5O0K arrays have the extension CNA Loss of Me or Human Mapping 100KISOOK have extension CNA och Paired Copy Number and Analysis Ped CN Analysis i used to compare two samples tom the same 1o loo kc number in derent pes of tesues Normal Ture To perform Paired CNLOH analysis Genotyping batch analysis must be perormed on the dala to be analyzed test Enzyme Set atibus are required to have ben assigned to th arrays to malci sets originating wi he Same sample For ampla you vae e Patient sti tha Enzyme Se dani Isi also be rapuit another sample ambu teid oss to help group arrays into ether Reference category For example You could uae Disease Slate atribuatan Sample or The Copy Number and LOH flea resting from combined Enzyme Set data wit be named using te Enzyme Set tribut e sk Outou Nes can be en a suf Tor ars intormaton about using shared to pair les by enzyme set group see Using Shared Alrbues t
148. justment based on me atsomal markers on alti Finaly ne loe al the adjusted ratos We X and Yaromsomes y factor at males ne of a adjusted ratos equal 1o OR of i anginal og ratos SNP Canary Algorithm The Canary Acta is a clustering developed by the Broad Insitute use 1o provide number Ste call ra pre determined set of genomic ens wth copy number variation CNV regione Tha copy habe siate cal reportat by an lager af copy umber Each cai wil a contdence 0 and f retecing evel ol confidence hal he calli correct The CNV region polymorphic in ihe sense that hel copy number is apc variatie reiaton o he genome sea wole The terme copy number variation CNV nd copy number bomorpm CNP are each used to descrie ha same of number arbi of gere regions Inputs tote Canary 1 Aregin fle containing region names and sets of SNP CN probe sets for esch reglon 2 A pfr fle containing clustering information eal derived from extemal raining data 3 containing a lato names of probe sets used for ormaling te data 4 Aselot CEL fles one for each sample to be genotyped A GOF i nad by he soar ruin Canary i order eee probe esee recorded n he Output consists of a set of CHP ties one for each CEL tle wih the sufix CNVCHP Each contains tegian names menalles cals a
149. le Forward Strand SNP_A 2001752 Dems Reverse Stand Translation allele amp s c tr Gehe Coracle Uer Mant Appendix C Advanced Workflows Appendia describes flowing Advanced Workflows Analyzing Genotyping Results of Specie Gene Lists pape 296 Mew SNP Custer Graphs of Cases versus Samples page 299 Analyzing Genotyping Results of Specific Gene Lists Figure B 1 Workflow to analyze spei gene tels shows the basie steps on how to get SNP information for a Spete set ot genes and ane ose SNPs in Genotyping Consi Fire 8 1 to analyze gene te Step 15A lat of ger eg kinases The iat ot genes must be contained In a text fle where each gene ID is on a separate Ine generated Perhaps the gene list contains a set ol biologically relevant genes Step 2 Using perform a batch query to identity SNPs which are mapped the location ot the Specled genes inthe lat Login 1o NAT webste tpn fet conanasinder aft 2 Select Genotyping Baten Query Select te array search option gene lat tle and view tt Gente Canace User ana amp kon searen N t wl deny SNPs which mapped he spacited genes 5 Cack on me Export buton Select he TSV aport option tt Corsi User Hart bera X ie spes de netsut
150. lgorthm Contgutator cr SNP 0 Anas pape 20 CN tles om GTC 30 30 1 and 302 are amatesy updated when GTC 40 launches or whe user poll or ian e leary changed Conuraon les om GTC 20 or 2 not on tyr Corsi User ana e pe REY eruca ort se DI Ua eerte pe porc pd MEE M T bot he sri te e CHAT M Figure 103 CN contigurtin update SNP 6 CEL fies are needed or ana by RUP you do nol have o have genotyping CHP ote GTC 40 does not perform copy number LOH SNP 50 pes Copy number region analysis on data trom tyr Cora User ana recommends that you perorm Copy NumberLOH analysis wth al les stored locali For more details on hard disk spate requirements Appendix J page 319 9 attymeti recommends that you perform Copy NumberiLOH analysis with regional GC correction configuration Tha basie workflow for Copy NurberiLOH anal for SNP 8 0 aay involves 1 Performing Copy Numen OH analysts on a of CEL ties page 192 There are two options or thi ana Releence Fle Creston and Batch Sampie Mode 193 Analysis wih a Previously Created Reference Model Fi Single Sample ede page 200 2 Performing the Number Segment analysis on he CN dela ties page 227 Note Segment Re
151. m 2 RAN ASEM mos o 980 eA Figure 7 48 Rlerence Concordance Reportable You can siso open the concordance report rom ne wee The Relerence Concordance report lable contains folowing Fle Sarge CHP le name Reference Reference CHP rame SNPs Called Numer of SNPs commen to bon sample and reference es wth genotype cats Concordani SNP a Number of cad SNPs that have he same pencype call Concordance Percentage of calles SNPs that have some genotype cal Copy secte ln the table to te clipboard Exporting Genotype Results You can expert gereype resul in he folowing ways Export genotypes o a tet lle Export each CHP fe toa separa text fle page 135 Export AL to One Fle page 135 Export he Combined Rests of an Array Set page 137 Export Genotype Res tor PLINK page 141 Export genotypes to TXT format Genotyping Resits con be exported it abit text Ne 1 a Gantype Resulta group an select Export Genotype Results on he shortest menu In he dl tox at appear select the eal por and cic OR sect rest ows in the CHP Summary tate Figure 75 gh cic and loose Export Genotype Result on ho nao tt Genotyping Cora User Hart Mine Gehe Corsi Un 1 Fire 151 CHP Summary table shorts mana 2 in me dialog nat spears he Browse tuton o select th output
152. ms for he Genechip Human Wapping Array Sats hia set of analyses relered fon Genotyping Console as CNe in aput tle names El tote does not pertorm copy number LOH or Copy number region analysis on data tram Genome ide humin SNP 20 b Axlom Genome Wde Human anaya recommends that you perform NumberiLOH analysis wih all stored locally The basic warktow Copy Nanberi OH analysis voles 1 Performing Copy Nerberk OH analys on a selection of CEL or CHP tles Thare are o options forth 1 Copy Number and LOH Analysis page 155 Copy Number and LOH Anas page 162 2 Peforming We Copy Number Segment analysis on te CN data fies page 227 I note Segment Reporting Analysis can be performed on Human Mapping 100000 data and on Genome Wide Human SNP array 60 data Viewing C data in tatie tornat page 178 Viewing e data in the GTC Browser page 249 Meis Coracle Ue Mant S Exporting data nt formats hal can be used by secondary anas oae page 251 You can eo Change he setings pape 257 Change the algotthen parameter 00K 500K anal page 178 Introduction to 400K S00K Analysis Anay design Array Design non apg Ino arrays to prove fut coverage of he genome OK or 250K Human taping 100K combination o and Hind 240 belon Mappings youzan Mappingso Hazan Funan Mapping 500K
153. n Ug e unin row keys yt Geen Canace User ana Viewing CNV Regions The CNV regions the faded CNV map are displayed in the Chromosome Map To look eta speci region Selec the region tem b Region Ist nthe viewer toolbar Fire 12 10 Regione dropdown tst The soci region is displayed in he Heat Map as deae Fir Selected Ragion displayet You can serali trough regions by cing in ha Region drop down using the ty Cora User ana Upon row oy region nthe CNV Map o he markers and to oor fo hat region IRL OE HA ry AA og ege CAE CH gure 1220 Highlighted region and markers Zooming in on an Area You can zoom in on a seston ofthe Heat Map by selecting the area he hest nap at tne start and release at he end o tne area you wish to on tt Corsi User Hart Figure 1121 Selecting e map region to zoom inom The region displayed in he heat map and me CNY tt Corsi Ue Hart Figure 122 agite elon can auo ume he buttona viewer br and the he Mest ap mano arg ve nite ent E Meen Nove ght isi E Double cick on a reglon in me CNV Map to Highlight he markers and to zoom t that regn Sorting Data in the Heat Map Yo can sor he displayed SNP valvas by Median Log2 rao values or al and CN probe sets displayed as curent view in Het Map ty Gente Cosi
154. n by any one segment in he ragion sa measured by tengin Segments as lage or leor an Reg wl a value ol 10 Percentage of overiap ot e Segment by he Region as measured by Seg Ragione sa ringer Pan Segments wit heve Number markers viti the region Whether Copy number change is a decrease or increase trom the specto norma va Size ot ine segment of Copy Number change as measure in klobese pos Sunt segmant ot Copy change as mesure n tt Length of segment aded by umber of markers encompassed by tat segment of mars inthe segment which ovetap me boundaries o The Chromosome cyoband within whieh Copy Number change segment egna The Chromosome s cyoband wihin whieh a Copy Number change Segment ens The base pal poston on the Chromosome at which frat macer in qa om top ar pam o he boton oe The base poston onthe Chromosome at which east marker in ng pament beans ong fom ep of pe pam 1o he boton o He Ame Genotyping Cane Uter Marat Region star The base par postion on me Chromosome a which me Custom Bepon mara gong ver ap he pam oe botera o e Region end The base poston on he Chromosome at which me Custom Pe anas gana fom atom ne amet Custom Regions Summary Report Thesummary report be displayed i te Browser can be viewed in a spreadsheet program You will be rectos io a name cation Tor
155. n me REIS EM E L3 RE 28 fui m E fresh Gener Cane Uter Mant Wer reps Vase prise p peer NM Eon Er Figur 29 LOH Parameters Advanced Options page Analysis te opima tho spei LOH experiment by changing aget parameters Table 9 esas set of econmendd parameter slings soe common experimenta conan Relevance Set Tranaiton Decay b 220 omit 10 tt Corsi Ue Hart Chapter 10 Copy Number amp LOH Analysis for Genome Wide Human SNP 6 0 Arrays GTC 40 can be usea to prom he along analyses or he Genome Wide Human SNP Array 0 Copy Number CN toss ot Heterozygosiy LOH analyses are permed on he CN data generated during anas Copy Number Segment Custom Region Copy Segment Reporting 15 Note copy Number Variation CNV analysis is pertormed in a separate step trom analysis The CNV data can be viewed in the Het Map withthe CN daa See Chapter 12 Copy Number Variation Analysis page 200 tor more 40 proves an updated defaut CN confguralon to accommodate updates in CN analysis For ihe Seti y Peri Nero opten e Met Ace e etu confusion You manualy change me Marke tevel Normalzaton opion by eng Sigua te more delaia soe Chang A
156. n on me Cleonoson at which frst marin ENS aanert beane ang apnea oe toon d the qain af o End Linear Poston base pai postion onthe Cleonosona at which the last marter in ESS amet beane ang rom pde parm tton of the aarm ot me dooce Start Marker Name of e frst SNP or CN marker ot a Copy Number change signent tyr Cora User Hart End Name of me last SNP or CN marker ofa Number change Segment Annotation Information tom tne Toronto Database of Genome Variants about the CNV varianta heh overlap Copy Number change segment or Genome Varats om abe database I Pea custom map Segment Summary Report The segmant summary report has every n segmant into from ne whole batch va segment report only has en no orgaala tom one NCHP fio ad ne hetda concatenated to ride iion alte CHER Tis summary report cani be displayed in tne Browser can be viewed in a sprendsheet program Yu wit be directed to spect a nome acto or he Segment Summary Report le belare the on SRT stings and CNCHP fies analyzed in he hender Copy Number Segment imation same as in Segment Raport Aye Genotyping Console User Hana Custom Regions Report Tne Custom Regiona Report lea contain infomatan on me copy number segments detected in te custom designated nd Cuntar Region Tora uen Each
157. nd condoncos Mies Genotyping Cane Uter anusi Appendix B Forward Strand Translation The conventon n e genomie research eid has become o map stele gerotypes to he toward strand ot De genome The used 1o select the relerence sand ta daa Af yet allie fr Mapping 100K OOK SNP sand SNP 6 0 based an alphanateat sorts me Narking sequence or SNPs Thay may on tor ward sano reverse of e curent geram However na ratore between Amet alles and cl e genome provided in e pui NetAT areca fen For Atom Genome tho Henan al Alma ales have been mapped ona arand ol ihe unt genome defines and based on folowing convento For AT or CO SNPs SNP ales are AT or TG ne aloes codec re ahabetcl order on hal stand alle aee B i G or stele Als A alie B ART Foro AT and nonc SNPs sale Aia A or T allt B i Far Aom ales stas A alle Bia aaron Tabie B 1 1 Ati le cal codes defined by Nets convention Asim Genome de man vay oni For example s4607103 SNP 2091752 on Genome Wie SNP 6 0 s nonAT and nan CG SNP aed nth reverse sand at poston 64888544 Cvomosome 3 ul 38 1 GTC Bis io provide foward arand bas cal Tabie B 2 2 Example stand translation or NP A 2041782 Genome We SNP 60 PS Annotation Fi
158. nder cating gor used to populate Computed Gender clin the testy OC Table Sta ine CHP Summary for SNP 60 and arrays caked probe cho ato gender manod tom Power Tals Tha erode six eso gender memod is more caus what desing wih lower quay samples Optimal genotyping of sex chromosome SNPs rues use of Ine yee hago or iid arii models are ued tr X and Y chromosome SNPs when the gender cal maie wo odes wed for X cromosoma SNPs wren the gender ais Tama A No made tor Y Chromosome SNPs when the gender cal Tonal The en probe method deemines gender based on ato em probe gender ralio ol the average probe iens ol nanpoiymorpie probes n the Y chromosome cob Sho rao Gender mean to he average probe ent o hongelymomhic probes on X chrome robo ato gander mean Me probe aro raw and untransformed fr hes calcata and py number proces wil peeaoautosona regions PAR region OF he X and Y cleomosomae ate Far SNP 6 saya tha alo an 0 48 the gender cal and treater han 071 gender mie Ie fato sbetweon ese Pa gone alle unknown For Am Genome Wide Human arrays f ato lcs tan 0 54 e gender cat ema anti greater an 10 gender Sali mae V e ao e between Pese vales ia gender call unknown Ayre Genotyping Cane Uter Marat Figur D 1 The SNP
159. nge he tataning options nate Contguraton Output Root Path Enter sut CNLOH output es Note You cannot change the annotation Nies in thi Meis Geste Coracle Uer at 5 Selec dierent Analysis Conizaton without regna GC correction or any other custom confguraton fies oral Boolyisconlzatons sre sets ol parameters used in the analysis See Changing Aor Contigurstans or SNP B Any sage 210 F mare information on creating new anale Note For a tew parameters you cannot select dierent parameters than those used in the generation Tt the reference te used for the analysis fervere Um pou p To add a new Coniguation pese and act umber organo How te Eat mer Ei Senden ie UTERIS m pem See LOM Es ane Ero Dupe suwarek lama Figure 103 Copy Number LOH Options configurations cop domm ist ferent contguraton trom e dropdown ist G Select a Reference Fle for he anal Seka ote ene hens cle he Set Rare Moda Fle A browse buton in me Open dialog tox na appears selec reference fom te tat and ciek Open tyr Gein Corsi User Har Sec Fanen Meane one matte Mensa Fire 10 10 Open dig box E Note I you choose the GenomeWideSNP S hapmap70 6111 aS rel as reference model e you re required o have NAZE 1 version of annotation He
160. ngle SNP in a 1 Mo reglon mat is cated CN State 3 by the but al surrounding ns caled EN State 2 hen by checking he Re dus utes checkbox INS singleton SNP wi be Sherard on GN Sie TON Sate pei Nee ad See roug states of me singleton SNP are two diferent states computes a weight medan to etme wich atate assig o he SNP Note Weighting of ine median is determined by the distance to the flanking SNPS tor SNP Cuir Ausiment This parameter too parame the distance tatis applied ta determine ithe Tanking SNPs he readustment of sion SNP The default vaus s 1000 the singleton SNP amp in he centar of ia reglon parameters highly correlated with the Gaussian smoothing used heavily smoothed or example IN the readjustment should be turned ot the readjustment enabled tthe etait eshala distance 1 may not have any The readjustment parameter shuld be dela or detection of mio aberat Miei Gesch Cora Ue Hanu Suggested Cytogenetics Settings for Human Mapping 100 50 Arrays You may who save tne HMM Parameters setings when performing cyiopenetie nas Suggested values Copy Number Parameter Settings Analysis con be opes to the spei copy number expetment by changing he algo parameters The abe bow set o recomended pramete setings for sare common expermenalconstions 2 pem rem pe deno
161. not ound a waring message mil appear and at import actiona wil pe aborted See bran end Annotation Fez on page itor intormation on downloading and setting up the library path You can import batch genotype rosis CHP Miei Gehe Coracle Ue Hart Genotype anas rests CHP Copy NumberLoss ot Helarazygosty andy esu ties CNCHP and LOHCHP Copy Number Vataton CNV analysis esl tles CNVCHD When you impor these you wil be asked to select the folder containing the CHP Do 1s and select OK You d nat have the oplan of seeing CHP les foler E umor Paetos PET Dionem EE imis saa Cz Fire 13 For Folder dialog box enclyping Console scan the sal CHP tles in the selected tider renard al he Wes bong same batch analysis operon and ay belang 10 ihe array used by Data Set you wat bashed to proue a name or ha adad esu Group ibe CPs bean mule bath parton Console as mile Groupa You wi be asked provide a nare or pc pum EXIT Fire S14 Enter name deat he Genotype Results Copy NumbeLOH Results and Number Variation Reste Group names are based onthe olde you lle rename Results Group name you Wil need tuse the Windows fles system to rename the actual older ou wish them t continue to Rave the same name Actual Tolder names for sll res
162. notyping Conde User Manusi Appendix Copy Number Variation Analysis ls peomed using he Canary agri which was developed by the Broad lle tor ha purpose raking copy number ste cal or genie rer wa mer vato Those genome repena can be caled regions wh copy amber raten ENV regno o reor ih menter These CNV rogans observed be more vata regard 1o copy anter ano The spaced Conary was developed rese CNY ys method assume copy Neer o 2 W be a predominant con state sample didus Ths frequency seston nol elabi in ne CNV regions and can Copy Number Variation Analysis and robust response we two tera aiu o smal scs Win each CNV region sdeced rond alite sommer c mar rao esu n sting ih rue siate he wi a cet number slate as el as cure er and eaa was pror wed by Canary n GTC 40 he sets of probe set mapped to CNV regione are red reglon and pror cluster stored plor Al mart probe the reglon NCBI bul 3 1 af ne human genoma The CNV regions wi hel Expanding 8 peiora are recordad in the CNV Te The CNV map is required Tof ENV Tesut abe tor ne heal map viewer 40 uses set al 1141 CNV regions derived tom ose nia by he Broa
163. nt Raport View CNLOHICN Segment data in the GTC Browser View he CN data in he Hest Map viewer Export data to ater sonare The fe tornat is described elc tt Corsi Ue ana NumberiLOH Data File Format for Genome Wide Human SNP Array 6 0 Data For Gann Wide Human SNP Array 60 analysis the Copy Number and LOH data are kapt in te same Header Section The header selon contains he folowing boston Imormelion about the Software and Algoritem version used to generate the data Asay ype Genome version and tray intonation Alti parametere Data Section tor CN fles Tha dala secton contains the folowing intormaton meian vates n edere i IN respect copy number siate smoothsignal Smosthed ratos or smoolhed ratios calibrated to Copy Number and 0084 depending on plans ton Loss of Heteranygosy 1 LOM and Detention Logz rato vae Adjusting Normalization and Background Parameter tor Reference Model File and Sample Fes The Copy Number algorithms oo comparing sgnal ter each marter in esc sample agains a reference formed om 8 group or sample The underlying astro mal for each marker the reference slate in un wi be 2 exoept lr he Y chromosome tne reference sata and hence devon fom ihe can be seen by teo ato of each marre iral compared 10 reference For aubsom
164. ntensity QC Files Genctyping Consol allows tor custom grouping of test OC Fies To make a custom group of intensity QC Files 1 Select he rous tom an open nly QC table to be added to the new group Meis Gehe Coracle Uer Hart 2 Rink and select Data to Group D TED POLT i nace Figur Selected Data to Group Figure Sect data group The new group i be cisplayed in the ree groups are indicated by wha icons Fev buen Daa gure Custom daa group in tn Custom Intensity groupe can be re named by th group and selecting Rename tens Data Custom intensty groups can be deleted by oo he group and selecting Remove Data tyr Genagrirg User ana custom Intensity Data Group does not remove data trom the Data Set sly Qc see Remove Data rom a Dala Set page 30 Graphing QC Results In to the tabular pay of the mats ha QC reste can be displaye in a Ine graph The graphical play sein oer samples apen line graph onthe Line Graph short 2 on te iens QC Tabie Intensity QC test AN sorted by File M wv ry gure 6 10 Graph of so the by a meti example Sounds select he mete tom ina X is drop down mena The let of valle matres based on columns
165. o oeste moved or missing Mes the search option is chosen you must rows missed e tyr Corsi User ana aea Cus ea 3 B Boaz N m Bocca ees am 5 Fern Farc 5 even am Boxen nac occur Bocca evoca ovorum Ford S mrn EN matme a memi I tote le ere option Genotyping Console wl adh pci o he Workspace You ibe prompted to locate cach missing To Sharing Data mte users he same orgarizslion vant to share me ame workapace Kor iret comptes you may acea place Workspace fle in a sed iar However ny ne ser can ave n workspace fe apen ata Ao note processing daa vang some aie libe slic tasler dala es sn he sara compute asthe Genotyping Coral Tne Zip Wodapsceleaure in GTC gathers al of he Nes in a selected workspace s wel as he workspace fie isa engle package ie The package can en be used lese move he enire workspace Wom one leat arce Tre Zip tastare vi mady e data fe locations nhe wortpace when pacing Note Files not part ofthe workspace such as Segment Summary Summary repos are nt packaged ss line ped wor Zip that were created in earter versions o GTC However GTC 4 0 ean and unzip Workspaces crested within GTC 4 0 wih a zip size gt 4 GB
166. oelelerence atlas cick OK You cannot perform paie analysis upon array seta using boh enzymes at he same me niese tey have matching enzyme st artes usque to ta etn the eo sengles or Paired CNLOH analysis using arrays tthe aarde can be sare beeen ot sot and one ungue s each e ne Rlrence Fe la Pared CNILOH analys using enzyme sls Nlep SIy sel to instances an enzyme set tute selec ena sei Srp Tatan unue Yaseen toning ung pared selecting an enzyme st Ca Tre Copy Number and es wl be named using the Enzyme Sot bul tor he arraya progress windows open as the raya proce Aer generating he Copy Number ae LOH tes you can Generate a Segment Report Miet Gehe Coracle Uer Hart View he CNLOHCN Segment data in the GTC Browser Export dala 1o oer sofware gata tle omat s desorbed Copy NumberLOH Format or Human Mapping 10K SOOK Array Data page 167 Unpsired Copy Number and LOH Analyst CN use to compare sample fles to set of reference ties Peeing bate genatyen stalls regard on the data CEL gt CHP tes betore running pared Copy Number OH Winen using a single enzyme array type S0K 250K in an unpaired Copy NunbariLOM analysis an Enzyme Set Sue When using Enzyme Sets 10068000 sels you do need to have me Enzyme Set atribute avalable tor Each
167. of the probe narmalzaton Select ane of the allowing to aplana n the Nomao group tox I Norraatin group tox Quante nomazaon sketch based on perfect match PM probes across the CEL Tes Quante s te dell et Ine he medan o CL tis nein ea A PM an Copy Number Parameters pr TE Aine Cy nt p Fire Copy Number Parameters Generate Allele Specie Copy Number For pared analysis ale epecf analys can be performed on e SNPs lich are heterozygous inthe pared norat Tis can be dated ay unchecking Generate Alle Space Number bar Genomic Smoothing The genome rooting option he user spect he genomic seating eng in megabases lo be Used The genome smoothing al apated Gauss Te dala bandh vues 100 KD Nb Wat resule n a window size o 400 Kb Th detaui ophmzad tr Human Mapping analyses For man Mapping 100K analyse ae 0 5 Na Genomic oat can be disabled by ape a dicm of O bp See Copy Number Parametar page 18 or reconvended CN parametar comparable to or tess han the size a th micro et hal la being studied yu are looking or large chromosomal deletions you may choose io ise age Mb smoothing bandwidth Advanced Options Advanced Options button to display the options mr Geste Coracle Laer Hart
168. old Arow appears in the table wih drop down rt posable to ter on any ot me exported comas Chromosome and Polon tt Corsi User Hart gt onc tatoo abo sach olan Noe vendi hoa slds Column Noms m Figure 1130 Selecting Select he comparison operator tess than tess nan or equal io 9 rater han p greater than or equal 2 emaite te mot equat io Tonma Nene Thes h gure 1137 Selecting a comparison type Ener avabe for e threshold parameter Repeal he above steps 1o mer on aitaren parameters 1 chek OK ty Genet Corsi User Hart Tre Progress bar dila e progress ol he export The export process creates a text fe using a name based on the names wit a tension The ria place nthe same deta usc or he Number OH Rasul group Setting QC Thresholds set is dalog box wit be ag a he Copy OH OC le Ces hd et d eder dba naked Br Tol edet ire yt Tiesto Name Comparison volue ma ox Figure 11 39 Copy Number Thresholds log box eer tis Du meri at ar econ values You can modi OE Destra tt Genet Cora User Hart To modi the OC threshold options 1 on Copy Number QC Thresholds butan EE on main oar or From he Ea menu select Copy Number QC Thresholds The Copy Number Taal
169. oler Reese Fe Dust Omer Premi p one see ra ID os Gee 7777177779 r7 Figure 1021 Basic Options dialog box Select he configuration options and entra acre een 4 Save me changes tthe configuration To seve as new contiguraton ick Save as Save as Cick 1 me is chosen a new dialogue appears wih two options one wih GC correction and wot regionai coron By choosing one at he wo optione te deat lof wi Gc conecto dla or ioa eral GC Canecon wil ve restored tt Corsi Ue Hart Fue 1022 Select Contgraton Template dialog box To transter parameters trom a contiguration created in GTC 21 1 From me Windows Explore ind the configuration fle and open it using xt edl software 2 virte dono pate old contours le 3 Make a new configuration Ne in GTC 3 using te old configuration pararaters a few parameters are new o The parameter are described i Basic Oplons Advanced Optone Basic Options for SNP 6 0 Analysis Ths basie pon ae hen e alg bax test apens when tha regional GC tores angit tt Genet Corsi User ana Tanne Regional GE Cone EE Fetes Hea Fla Cister ari NH Figure 1023 Bai pios regiona GC correction empate chosen Thetescopton ae deplayea uten he dalog bot feel opena when no regen GC conect
170. olowing chaplers and appendices rper Caer 2 Won th Genotyping Censos ages pane Mow 1 Iran contre Gareth Concent up user ap Ur Pres ge 27 reper Ly Aoi Flee age at pM or Grae amp Data Set page 42 pr apr cay Conor Get iyi get Aris pag mE v2 or Atom OTT abr hap Tate amp Graph Fone page 148 Wak we ite Genting Canale Capir Copy Mare LON Anat or SEG Arrapa ge 183 Peto py nna LOH ano reper 10 Copy Nameer amp LOH Ari er rau Par rantur and LOH rali or NP d pe Vote Ae inge 27 reper 12 Vataton Als hap 1st Map Viewer page 209 Arpanet page 282 no D anal aata analy hat are eritis frei Genetyping Console User Manusi egere C Inca Wet page 208 aa po at ae Georg pera neato Often age aot E Calg in Gong Crete page SD rocasses ured gender or aterert array D Apareix F Conran OC br SNP Dia page 312 aeneon anta mane Conr OC rta e Aparain G Ba Practices SNP BA Alp aga prr a nen spen ias Copy ter Varo my Agri non Reena pae eee a rene CEL es tam doren ee pena Treating page 320 oer
171. om Regione Report custom Custom Regent we any regant oto genome dened by corshates ened mo nt le abetted bed farmat ves edu The Custom Regions Report trat resus iom processing Segment tor Custom Regions conan copy number and oes segment CNV ova intormaton about jst P dead eons You can use Custom Regions ta lock tor copy number and loss in select eon ot me genome Custom Regane od a it wih Galumna Tor custom region start positon custom region stop positon custom region name The header ines marked wih me are ignored mmn reson an Figure 11 19 Custom apt Regions File Custom Regions tampa cn ipu regions bed can s custom region fr SRT heat map viewer load into ether browsers such as USCS genome browser Create Custom Region Summary Report To create custom regions summary report te 1 Select ihe Create custom reglon summary report heit Miet Gehe Cora Uer Hart The Save Custom Regions Report Fle dialog box opens Figure 11 20 Save Custom Regions Summary Report Fle box Selecta location orte Custom Regions Summary Repon fle enter a name tor he Segment Repot are not autora sed Srna fs 4 Ck Save inne Save Custom Regions Summary Report Fl dog box Segment Report Too Results Files The
172. ons to daria me folowing opone lt Model Fle Creaton Advanced Opens Copy Number Parameters HRM Parameters win regional GC correction Copy Number Parameters HMM Parameters wit reponat GC correction Copy Number Parameters Post HMM Processing Parameters Smooting Signal Graph Output ty Corsi er ana Cony Number 10 Configuration Options Template Genome Tendais GC eios de Freres Hee Dd OU O Beteree Fe Denon el Nri eran Gene Theos 0 Figure 1025 Basie Options Reference Model Fle Creation Advanced Options Fels Heh Cnr Matos erosion Feliz 9 dee E Figure 10 26 Probe and mara level background core parametere Probe lve Normaization Quante Nonalzaton makes e entre tion of torn e diferent chip the same The empta orta ai tne signal om sio the hou simlar The ac la sorted and raked rom the wet 1a he highest wah each ran represent a quante The average intensiy of Sach quantis collated cree ane aya Then for saen amy n ot tba inen n a gn nio wah pe cute aerate ron nea e ow ave ee raton al ol ha araya a el a0 hal hey have ba ana cn iene Ama Fora mere detaleddecussin of nomatzaton ease reter to A Comparison of Methods for High O
173. ony or higher venir GenamaldeSI _ canary v1 nermalenien or hgher higher verso ercreliseSh tran vi ge cn says conan or higher venera Hos Germa Waa Haman Aray GW Murai se GN gene tray raport GU Ha Aion GU Hu SNP iren Hte Gencpirg Core User Mart pe GU Ha SNP a geile buon lon Arte select Fle gt Download 2 in me dialog box appears enter you NetA account Inlormation and ciek OK you do not have a NAAT acount cick Register Now which launches www mec con Foie Instone asl up an account Sa Figure Selecting annotation Hes o downoad Select te Aray set annotation tes to dowd and li The downland progre ty Cora User ana pe mus 0 S jJ Doeiorira errare Pigs 48 progres Mote Pease be patient The download may take severa minutes or more depending onthe Connection speed toss es large Aer Genotyping Consle dowd selected annot tom NAA optimas te Te o Ths may lake several minutes We recommend hal out cancel a opeaten V canes paran can manualy opta anotar ale File gt Optimize Annotation Files on he ren Es Manually Copy amp Optimize Annotation Files 1t me workstaton wit Genotyping Console does have an conaecon and cannot do
174. ort Copy NumberiLOH Resulta tiom tha pop dp man The Select tles tor export dialog box opens 1131 Select tles tor export dialog box Select ie ies lo expert rm the stand ick OK IE hote You can click Select Alto select ali les nthe it The Select Columns to Expo box opens tyr Gent Canace User aa bonorem Fon per p gure 1132 tor export SNP ty Corsi er ana Select the c rea ce Beta TRI Figure 14 39 Select columns tor CNLOH export Copy Manes OH Di Forma for Wie Haan SNP Aray 2 Dia paga 208 L Mote not al of these columns may be avaliable depending upon whether or not you are exporting CN dts LOH data or both 4 Select the dila to export and cick OK IE Note You can cilek Select Al to select all data types In the list Pn inpia dlalog bo opens enabling you to enter a sf to be apleg the defaut name so at Brev expr ras wot be oven 5 Enter a suf and select OK ty Gente Canace User ana Erle sirta lix re culo tera ard ER Figure 1134 input Value dialog box Tre Export Options dialog box opena ha Threshold Fiir 11 35 Export Thresholds dialog bor export options dialog box aos you to Nier te expor output using dierent parameters Todd a thresh
175. ote abe tyr Genagrirg Candle User ana Fire dno bot Doe The Find funcion does not wildcards To sort the table Select a column header select he Sort Ascending dor Sort Descending shortcuts In me Intensity QC and CHP Summary tables a Ine graph can be payed To invoke the ine graph on the Show Line Graph short See te Graph Festes section tor more Imation to these operans certain Tables have addon testues fite nes OC tatie eter on row abet or hom e Table Venu De oi mer ru PE 7 Bande Figure menu Custom Grove of esl OC Fes page 78 Quai Conto or Genotyping Analysis Genotyping Analysis page Mme Cosi User ana fette CHP Suny ttie om er nghi iking on the or tom e Tabie en e loin dota pe CEES Figure 8 7 CHP Summary Table menu See Cat Groups o Genotyping Ress age 101 and pring Ress page 131 Graph Features Genatyping Consola supports ine graphs and SNP Cluster graphs Line Graphs Le graphe can be generated fom QC results or Genotyping Results Line graphs initiated trom eere Inert OC table he CHP Surenary labe To invoke the ine graph 1 Cek on he Line Graph shortcut LS trom eter of hese tables graph display ether QC Call Rate 1 invoked rom the Intensity QC tatie or the CHP Cal Rate iaa Yom a
176. ou change the view he sofware remembers your oceani open 1a the selected aw he nex nee opened me sls have then wi be Gai at he tar Hf he able o select AL tt Genet Cosi User Har Figure 12 4 payed in table For enc chromosome he lane Fle Name Name of th copy number variation CHP Cal and Consdonce Score tor each defined CNV Regien by CNV Region ID Te CNV Ragion De are pena by genome postion Cell Copy number state estimated by me Canary iari Conlidence Score Probat ol Canary copy number state cali ven a posite Canay calls To dicla resus tor diferent civomosome select he chromosome number rom the Chromosome stin he tanie teli can scl trough chromosomes by cling in Ie Chromosome dropdown ist Using me mouse unesl f Using te union arrow keya ter table are desorbed in Table Features page 145 can view CNV cal in Heat Map viewer pape 26 tt Coracle User Hart Exporting CNV Data You can export CNV Ress alain ree ferent ways Copy select dala in the table to the cipoard paste t into a fhe Epon he Tabie as text wi data for all CNVCHP fies ard he curenty selected chromosome Exporting trom the Table To save selected dala to the clipboard 1 Select he celt you want to export in the bie 2 hen he table and select Copy Slaton to Clipboard
177. owser manual lor IE Nale Copy Number and Copy Number Variation data or SNP 6 0 is also displayed in the Hest Map Viewer together wit copy number data In order to view Copy Number Variation data in he Heat Map ever you muat have number daia that originates om sme CEL es See Cre enl Viewer on page 289107 more information SNP alow you to manage makers at interest You can generate SNP custom SNP ints Basic Workflows in Genotyping Console You can use GTC 4 0 win the folowing bes ct arrays Human Mapping 100K arrays Mappings araya Mapping sok array Human Mapping 500K Mapping 250 Np araya Mappngasok ars Meis Cora Ue Horat 23 shows te types of analyses avalatie used o pertorm the analyses fr the rent aray No every peo nalis avail lor pe 23 Analyses setae Genotyping Console 40 eroi ENV Anais pm You need o have teary fes on your computer to perform these analyses tor the dierent aray pes Tne intial setup needs tbe whenever you want to od data ee page 20 Genotyping Analysis page 21 Copy NumberLOH Work tor 100KIS00K pape 22 Copy Number OH Worktow fr SNP 6 pape 22 Copy Number Variation age 23 tt Corsi Ue Hart numum oman Mapping Genome Human GenomeWide
178. porting Analysis can be performed on 100K 00K ds Running the Segment Reporting on he SNP 60 CN dala page 227 For SNP 6 0 data he Segment Report also provides gender cal nude reports far samples win como or ambiguous gendera 4 wing QC data in tate tornat page 207 5 Viewing he CNLOH dala in the GTC Browser pape 249 Viewing ha Copy Number and Copy Number Vataton CNV data in a Heat Map Viewer page 269 Cote CNV analysis e pertormed in separate trom CNLOM analysis The CNV daa can be esed In Heat Map wi the CN daa See Chapter 12 Copy Number Variation Analysis page 280 T Exporting data into formats that can be used by secondary anas suae page 251 Change ne QC trestia settings page 257 Change he algrten parameters or SNP 60 analysis page 210 Mote Smali numerical ferences may occur between dierent runs even with he same Inputs due an interaction between rounding ram double a igi precision and the way he application hand memory management tr Gehe Coracle User Hart Copy Number LOH Analysis for SNP 6 0 Arrays oe Affymetrix recommends that you perlorm Copy NumberiLOH analysis with all files stored The NOH wa bh ano CNS rh and trese int bah copy mbar and Tha types analysis can be CNLOH Reference Fla Creaton and Ans Batch Sample Made below anal at crestes Reference Model using CEL tie tor he selected sampl
179. r I Note This tolder a the location where the diferent Data Results fes are kept You can access the alder rough Windows Explore t view report es Output Fle Sut aded to output fle names aok The Select Fie dialog box opens tr Gesch Core Ue Mant ecu Figure 811 Selaci for unpaired analysis 140 Select Enzyme Se shared attribute tom ihe Enzyme Set Shared Atribule dropdown ta saved abo RS xn ea a The hea sorted by Enzyme Set Abu tt Genet Canale User Hart Fl rre NU e AS BUE D pora E op m E un Don FE 5 FOE p p Dp m R Fire 312 Fes sorted by Enzyme Set 11 Select he Sengle v Relerence tul ion the op down it ol ri Samples Fio vos Fono Fl _ sorted by o sampirelerenes Miet Gehe Cora Uer Hart Hm 1 Cn ES EON X 4 uelit hata SP Summe eae por qu pa po RESCUE p mom D Pim Mana mds Nma Remi tems mds Nama amd Nama Nmd Ed me Nami ama Mami SpE RFT bde Mam Dind Natoma Mi Hemden Nmd Macs TLS wi md Fire Sorted by Enzyme Sat and
180. re expected t have Copy Number Siats 2 ore X Gente Cora User ana he oral meles ore expected to have Copy Number Saee te and tor Fist ne orti checka mat he Copy Number OC MAPD less than 0810 ensure data is ot sicnt quay Next he mean number or e nn geeudoaulosomal porton of the X chromosome and Y chromosome are used gender e mean copy number Tor he X chromosome between 0 810 13 fd ihe mean copy number er Va between 2 1o 12 hen a Tal assigned ithe mean copy number ar X and Y rom 019 0 4 hen a nde assigned Finaly neher of Ine above cases are to Mhen Unknown eenqnes Samples Unknown by e satiare ange a f hoy were CN Ste X2 and fei Genotyping Cone User Mart Appendix F Contrast QC for SNP 6 0 Intensity Data Contest OC is te per sample Quality Coni tst meter SNP ny data CEL ls When al steps of are WOKING as expeced me Contras QC i italy reser man 04 As an added la Tor polentally dta sts cook tat o proprion of samples rt al Celo t 0 4 are ies a and e verge of he samples mat p s e 4 estre greater an or equal 1 7 Ihe proportion Taling below O4 le greater han he average o he pasting a at or below 17 hen sample and process Sod to close earned for positio The Contrast QC a metic Wat captures abi oan
181. rom HW where posable and aperte T Genotyping Post Associaton Study Ana Visuaty analyze al canditate SNPs Copy Number Reference Model Fi Creaton Sel of samples used to creste Relerence Model Fle should contain a meinem ot 44 wilh a least elena ergs 9 Copy Number CNCHP Qualty Check Track CNCHP cally using Raprocess samples wh MAPDs greater tan 03 whan using an reference teres Model Fle made om ate cwm samples or reser an 235 when using etal ternos Relevance generated dere such ashe supped Z tHapMap Rete tt Genet User Hart IEHAPDs ae consistent Nigh whan using an external reference recae MAPOS wih an irai Ihe MAPOS A ro sical hen te igh MAPD 8 an aac etoduced by a between curent sampler and We samples thal made up e reference rather Ian aliene fei Genotyping Cone User Mart Appendix H Best Practices Axiom Analysis Workflow 3o Study Design Where poste rendomizaten of cases and controls acres sample plates usualy a good idea In studies ining s usualy good to ensure ta al veo members of a tso are on he sample 2 Sample Quality Chede samples wih Den OC lt 02 Genotyping preminary eund Custer Samples wi Axiom hte 96 wl pat ot Esch cluster should conan miran o 20 dst samples weh eer samples or atleast o
182. rt Genotype Results tor PLINK Geteype rests can be enporta format ats compat with PLINK sofware To export tes tor PLN ihe genotype CHP rst Nes must have aiches sale aute Hes ARR created wih 1e Pedigree template value a e Ayer ACCC software and e conesponding oat Yor each sample the ARI es were i or are missing data lor some athe samples me ARR as Sng elore you data using e option Fight clk a Genotype Results group and sect Export Genotype Results fr PLINK onthe sort menu Fae TOT Select Workspace gt Genotype Resulte gt Export Genotype Results lor PLINK on the manu bar tt Gehe Corsi User Hart Select rests ows he CHP Surana lable Right click the selection nd choose Export Genotype Rest or PLINK on me sort mend Faure 182 28 nnsa 28 nasi poo Gti nc EI funr f Reis orsi ede es DEM Fire 161 CHP Summary table select resus export tor PLINK Aye Genotyping User Mart pos a aS A gure 7 62 Select genotype results to por or PLINK 2 In the dialog box hat appears select the reste 1o export and cick 3 Inthe next dialog box ick the Browse bunion select he output drectory Enter a name tor he Exon Foner tt Corsi Ue Hart matan RI 1 Date Figure 7 62 PLINK export options
183. rts on regions tat are defined Custom Regio opina tyr Corsi Uc Hart Ate endo cse procesos Segment Repor cn segment or ach copy rumbo generaled Segment Surnnary Report fa conesenses The segmenta Tom each Segment Repor can sio be pom the Custom Region option is used Custom Regions Report is created fr each CNCHP analysed Custom Regine Sunenry Report ha concsterates e segments fom each Regus can also be genta Detect CN Segments that meet ini requirements This process detects al the copy number change segments nthe CNCHE tles that meet he ni ring manete tor Mian sumer of marters per Segment Mima genomic size ot a Segment Fiter Out segments that overlap wit known CNV regions optional The SRT can filer out Segments that overlap wilh koum CNV regions by a user defined percentage of markers inthe segment Ito titer value la slo 25 all Segments tat know Regine by mor than 25 are not cluded in ie report Segmenta Wat by 25 of leas are in the epos he SRT produces a Segment Report le segments or each copy number le hat is analyzed The Segment Reportes contin information ca he Copy number segments detected gen CNCHP The Segment Raport tes can be viewed Ine Copy Number Segment Report able of GTC 40 See Segment Report pape 241 lor more information The SRT can siso
184. s of results or dlsplay Segment Data ties segments Copy Number Data los neh LOH Data herp Note Not al te le types may be available depending upon he pe ot array used Select te fies you wien to view or ciek Select AIL 4 aok GTC bowser apens and splays data long wih the ties See he GTC Browser User Manu for more intonation C Mote To compare results trom diferent analyse runs use t Me open tunctionaty with te Browser to open the Export Copy NumberiLOH data Tho ber data be exported as ab d mited tax tie that can be inio ther Sars ty Gente Cora User ana E Notez You can export data in dillerent formats in the GTC Browser se the GTC Browser manust Tor more information Annotation tes annot are required to include dbSNP RS ID in the export option for CNCHP Mes generated in ealet versions ot GTC For Human Mapping 100K or 8006 data the export Wil require naz version of the annotation annot db For Genome Wide SNP Array 50 atte export wil require nas o a9 version of annotation iles Cannot depending onthe nv taton version thal was used to generated CNCMP Toenport 1 Select he dala set iat you wish to export in the te 2 From the Workspace select NumbeiLOH Results gt Expert Copy NumberiLOH Results or Rightaiek on he Copy Number OH dala set and select Exp
185. space requirement 23 Vetted 32 bit operating systems amp recommended requirements tor GTC soltware cem MID Lu etna ey Oge uve mem erem uu ieee wa e E me 22 Veiled 64 bit operating systems amp recommended requirements tor GTC Sotware it Operating System p Memory Svatale Olek We Browser P XP operating 000 10968 H0 amet pone Deemer Pack 20 Macedon 2001 Seve 808 pere praes The flowing sections in tis chapter station page 6 Updates amp Genera page 6 Note fr Users of Ear Versions of Genotyping Console page 7 Genotyping Console page 7 Pans ol he Console page 10 tye Corsi User ana Fie Types Data Organization in GTC page 12 To use Genotyping Consi you must 1 nelal the GTC solare page 6 2 Create s user protte page 27 Download or copy e necessary trary and annotation tles page 31 4 Sat up a workspace and data setts page 43 Installation Instructions 3 Dowload me sofware tom Aymet com olo e Genatyang Conele ink You wi need 1o downoad ie 32 nse depending on ya Sang iy Gown he SE po E 2
186. sy values rom dividual probe sets itin irons tom CNCHP os Survey large quantties of genomic data to detect novo CNV regions The Heat Map viewer displaye ONV regions les the dett CNV map wth BED format wil automaticaly fale Genome postions of he current viewing window oghato value data tom CNCHP ties inst value tor each SNP or CN as calor value representing converte og ratos in a heat map predefined aca Summary nde ok he of probe sets wit cet In me status bar hows Sample names CNCHP fle name and CNVCHP name aviae SNP or CN prate set 1D lag rao of a SNP or CN prabe set of Wah asdltonal CNV region 1D copy number cat orte reglon confidence score tar the copy umber call erm CNVCHP tes f aval you mause over a CNV region contains CRY ty Genagrirg Corsi User ana gure 33 Hent map ln GTC Opening the Heat Map Tope he Heat ap veer without loading das me Hest ap ton E man abet gee lsg Ralo Range er loading deta ote 274 The recomended renge IE Note You can view CH data wih or without matching CNV data If you change the detsult map aner data is loaded in the Heat Map viewer sll the associated CHVCNP tes wil be removed CNVGHP es are map specilte You must have CNCHP dat available to load CNVCHP data E Noe You can CHCHPICHVCHP one
187. t um Figure 71 Select Probe Array Type dog box 2 Select array pe hom the at and ciek Select For he Genome wide Human SNP amp array you wi be asked to choose whether 1o edt the configuration or Birdane v1 or Bedseed v2 Select the algorithm to configure Figure 2 Sect deed version Not tor al array he appropriate Analysis Configuration dialog box opens Tre deat parameters avatable tor eding wl be payed tt Coracle User ana Parameter Nome Voli Lx Figure 73 Analysis Contguration dilog box Forifomation about te parametara and setings tor fierent array yes see Parameter Derston page 84 abe Eter a ne va eal you wah charg and Yu wi be asked to provide name for new genotyping ante configurar Human Mapping MoK S20 dist parametere RL Agri Det sening Agito ett Sting Table 13 Genome Wide Human SNP Array dla parameters tr Contig Cora Ue Mant eie v2 isto dtl he two ngo The debt ignium parameters tor Breed v1 and Bread v2 14 fiori Genome Wide Human Array Axiom GT Algor Seting Perform Genotyping Analysis Associaton are designes to ently SNPs wih sube alele tequency dierences between dierent populations Genotyping evar erences in sul collecten and processing and populate d
188. t he image ol the viewer the Export he image ol he viewer to a PNG te To print out the Heat Map viewer From he Fle Menu select Print The Print dalog box opens 2 Select he printer other options and click OK In the Print lg bx Toesport the image to the clipboard in the heat map and select image to clipboard Pom he popup menu or From he Heat Map menu select Copy mage o clipboard Paint You can paste he image lo a graphics using star sch From he Heal Map menu selact Save image to Toexport the hest map image A Save As dialog box opens 2 Ener a name and locaton tor te PNG ie and ciek Save Aye Genotyping Cane User Manual The PNG He ia eroatea Viewing Regions in Other Sites You con view the region selected tn the Display area at ane of the publie stes Torona DOV To view the selected region From te Heat Map menu select External Links gt desired link The era tnk wli pay the view using the genomic postions in Heat Map viewer Figure 1327 Display n he UCSC Genome Browser Aye Genotyping Career Mart Appendix A Algorithms Tha desis of used by GTC 4 and her ical perfomance are described in various white ps Genotyping 100K S00K algorithm peu ates corsupportecicalantepaperabin_wiepsper SNP 5 0 arrays BRLMNEP algorithm hp eu corvauppart
189. t view page 75 menally GC Table for Hunan Mapping 100666000 amp SNP 50 Data defaut view page 76 ty Genagrirg Core User ana For mare information on displaying Tabie see Tabie and Graph Fetes page 148 Mete For taster performance Atymetrix recommends perlorming OC analysis with al focal the QC Result at any ime on an Group and select Show QC Table or chk on an tens rop n B Fire 6 Displaying the Intensity OC Tai for SNP The Intensity OC table contains tha QC res Ifthe step is shipped ome alo the testy tles eve OC results he tes maig or rot updated wih Conzas QC values tom tne CEL Ve Yo meaty fes inte daa sel have been he metis urinal nat pest inerat GC C Noe The Contrast QC metric default metric tor the GenomeMide Human SNP Array 6 0 a not present in GOC fea generated In GTC 22 software SNP Array amp 0 data generated n GTC 20 wil need Te re QCed io generate me Contrast data See the Quai Contra section er more nturmaton n running te step OC Cal Rat data wil sis be regenerated during tha step and avaliable in ine AN Columna View or by making custom view See Table Features tor more information on Customizing tv lable view Choosing All Columns View displays al datacolumas Intensity QC Tabl
190. tacicalantesapersnnpwhzpacer p SNP 6 0 Birdsced vi and Birdseed v2 genotyping algorithms Genatyping Console 4 0 atows users to choose between genotyping SNP 6 array wth he v1 nd the v2 alt Breed v2 usea E t derive manum o a dimensional Gaussian model iA v B pace A key between Beises v1 and Bidoeed v2 is hal v uses SNP apeciie models or priors only as an ld contin rom when the a ee o wander an tare Occasions dows tthe istas For V2 the SNP ape priors are used no oniy as ntl conn er EM bre corporatd inio the Iciood as Bayesian priore This constans a extent to whch te EM NE can wander of Correct labeling SNP chats whose centers nave relatie to he prre probem ort fees Versions However gen the corsa on te EM ead v 1 riore ly nan Budaeed eir tab clusters or set genotypes lo No Br sed v2 usually more robust han Bedseed in te tace of poor expefments and increases accuracy smal decrease In cal rate in Dese cases In high cua datasets tie perfomance ference between v v2 le seen wow qul datasets rg morts concordance are seen wih v2 Brassed v2 clustering by plata evento clustering al samples unike Sted v1 where clustering by Bate etesues False Dicovery Rale Because of ia ase of V2 allons cualag by cat Al samples at onee wich evet best laboratory woo
191. te GTC 40 workspaces cannot be opened in earlier version of GTC Workspaces trom eter Versions o GTC can be opened n GTC 40 but then cannot be opened again in earlier versions ot Se Greate a Now Workspace amp Add Data nen wipe Geta propi out ala new Data Sel ard 2 Te creste new workspace and add dala 3 Ater soplaton and selecingzeatng a user grofe he Workspace log box wi open TOG Affymetrix Form Gane Fire Workspace dilog box 2 Selec Creste New Workspace radio buon and select OK Enter a name and locaton tor te new Workspace and select Save Miei Gesch Coracle Ue at seek Dumm Qs B em pud Doe decree Mee Saeaenpe if Figure 2 Save As dialog box CI Note Only one workspace can be opened at a time 4 Next enter a description of he Workspace by png in he Desciplon window oplona Select Emend Cosas Deaton Wels Dese T Cx Fire 3 Workspace dercrpon dialog bor 5 Aer Workspace software wil automaticaly prompt you t create Data Set Entera ame an select me array for he new Dala Sat aloe you Cici ia OK bution See Greats Dala Set tyr Genagrirg Corsi User Hart Wow Data Set Fire Creste New Data Set
192. teencas are mong the many tgs contrite loe potes o lee gates Eforts should be made 1o Ine of account lor or experiential erences example rendomzabo of cases and cantus to genotyping an ee cera ay pese om ng cues conis ee Attymetrix recommends that you pertorm genotyping and GC analyss with tles stored locally For more details on he hard disk apace requirement to genotyping see Appendix J page 319 To initiate genotyping analysis on a CEL iners group e In Bounds or Custom Group and select Perform Genotyping tt Corsi Ue Hart gure 74 Genotyping The Perform Genotyping dog box opens Selec Conus ETT M Figur 75 Genotyping dialog box Genome Wie SNP 510 2 Select he Anaya Cooturaton Al available analysis contigurations are avalable on the drop down manu To modiy he dea stings New Aral Contquratns page B3 Selecta locaton orte analysis output by eher select a tolder or manualy enter 1e Iul pall t a feider tt Genet Coa User ana The Base Bach Name s generated automaticaly This name is assigned to a crested stomatal ne pier herent Fran mda andis uva ia e Vou can ose L For Human Mapping 100 00K array seta he algorithm la run on each array type separately Threlore he Mes are grouped in batch rests and the CHP Summary dat
193. that affect probabit wih wich he undertying CN state le rid 1o produce he observe Spealealy reti the undeyog varanca or n each CN Te tanda dean of each unda ste canbe Ae hub he lower Genome Sincomag value a sandara deviation shouid be used fr each CN state Ta basicaly Ihat wih increased noise o smoothing o varians of ha CN sales shoud be increased Te delala DOT or state 2 0 09 tor al other states 0 1 3 4 See Copy Number Parameter page 187 for suggested changes tone parameter tyr Coa User Hart Transition Decay parameter conis he expected corelation between afacent SNPs The copy number state of any gen P s oral dependent on holo ls SAPs a are woghied based on me distance betwen thn i pem erg SNP can ew i re a pede on eh To reduce uence of neighboring SNPs decrease hia vention taster For example ou set tne decay 1 1 Mb and gen SNP ia CN State 1 he probably Inat the Ranking he bein Sate Tu owe compre ole ze were Union Sn To me tence of neighbofag SNP increase ths value anon sioner Post Hla Processing Impe pod Fire 28 tiers Beagust cules This parameler enables adjusting the CN slate ot singleton SNPs in a diferent slate i comparison to saos at me anning SNPs For example bere s si
194. the GCOS database fo an independent folder in order to retain al sample attributes detailed Instructions can be found a 7 The test ime Genotyping Console downloade or uses the SQUIe anolan tie anette be Tics proces may te several minutes or more based on conaecn sped and compar Obtaining Library amp Annotation Fil Gencypag Consola 40 aware requires new and updated bran and anotan es GTC 40 uses SOLE arta es nat She ry ar SOL volto ic ean be donde Ron Myra There several ways lo oblaln brary an ties Mine Genotyping Cora User ana Computer Wh intemmet Access Computers Without teret ayes Bowens Lary Fler page Lay Fie page ersten e Darina hartaien 38 Marly Copy amp Opts Jer fam mitin GTC ek ha star Downloading the GTC 4 0 Analysis Files Zip Package The package GTC 40 Analysis contine ibrar an aanclalien ties for Avon Gane Wie Human Array con douricaded Wom the Ayia wenste 1 Goto Atymetix web and downlod the zip package GTC 40 Analyse Fl 2 Unzip hie fle and hen copy he Me fom tne GTC 40 Anaya Files older to Genotyping Console ary toe Download Library Files 1 in Genotyping Console cick ho Dowload Library Fies bution select Fl Download leary Pies on menubar 2 In the dialog box hat appears enter your flet acco
195. the nna Data set an select Create Copy Number Reference Model File and Petiorm Analysis om te pop up men or ek the Create Copy Number OH Analyse button TF n te toos and select Creste Copy Number LOH Felerence Fle and Perform Analysis Yom ie mana The Copy Number OH Ansys Optone tor Reteence Madel Fle Crean and anal alg box opens Miet Gehe Cora Uer Hart pu Coane p Te edd a new pese and select umber cnn Howe Et mer Sava Fala Mate Foe I Senden ie S 1 1 perm Priest Read LJ See LOH Es ane tirk mdi Fire 102 Copy Number Options dialog box 4 he Advanced buon to review analysis contgurstion parametere Yo can aso change me tolong Analysts Output Root Path Ener auto be added to CNILOH Bach Name Erter sut tor CNLOH output as Select a arent Analyse Coniguaton witout regional GC conection or ay other ust contguration ies Boalyieconlgzatens sre sets of parameters used in the analysis See Changing Abarth Confguratons for SNE GO Anais 210 on ced a new analya coniun tt Canace User Hart fervere m Coane p nd pem ddp Coni plene ad aceto Nuber prope te Et mer I Eee JI perm Cim Fes aD
196. typing is CHP number CNCHP LOH LOHCHP andlar copy number segment number Sim region fes iar rapona Copy number vation CNVCHP workspace eres etn ol na dal tert copy ft tes themselves one user workspace open at one me I other usera need have access othe same dala ies ean copy of a Workspace Inat ja ol in use or crest new and add e same Zate esto me naw workspace Semen genotyping ol esame setet CEL WIN wonqace The lowing sections is iis chapter elude Create a New Workspace age 45 Open Workspace page 45 Create a DataSet page 47 o Ada Data age 48 Sample Aries Tabie page 55 Remove Data tem a Data Set page 56 itt Sample Atrbulos poga 58 sing Data page 69 Shar Dats page 63 E tote GCOS users must use 1 using the Flat File option to vana Genotyping Console rom the GCOS database to an independent oder rules More detailed Instructions can be found at way metri com Support Technical Tutorial GCOS IC Amet recommends that you do not use long names for the CEL and CHP tles since these long names can cause dispay problems n ihe Hent Map Viewer The status bar in tne Neat Map Viewer mil orbe to display ali tne information the CNCHP and CNYCHP names derived dom the CEL e names are too iong Miei Gehe Cora Uer Manat o
197. ults groups in Data Sets in a Workspace can be Mime Genagrirg Cosi User ana found by the command Crist and clicking the Show Locations button or rom the menu WonteplcesProperiese Show Information and the Show Locations bution Ar you cick OK the CHP es are added 1o Data Set Sample Attributes Table The Sampie Atributes Tale contains tom he Se Table Features page MS forore itormaton on custonzng ie tale vew e comas daplayed vary on wneler is data wes generated by ACC generated by GCOS or converted GCOS toAGCC Torat wel tempat was applied To open the Sample Attributes table lt he Sagie Atben icon in e vee Atemataly tom the Workspace Menu select Sampie Attributes gt Show Sample attributes The Sample table displaya the ARI tle Information or e tles in he Workspace Tre sorte SSE BEE Maran enam 8 Figure 5 18 tutes table Sy defaut a alae columns ote peed e Sangle Aut Ala Sale Aute tb tt Cosi user ana Aso see Edt Sample page 58 Removing Data from a Data Set In Genotyping Console dala be removed by ehe removing he eire Data Set or by remaing sata of Mes ofa particuiar typa o dala on CEL taney fes or CHP
198. unload the tes manualy coo Da aces foe tota rat our Error Reference source not ound hows annotation thal Genotypng Console requires to process an ne annotation fee ace pad ote ray fee hey must be oped 1o prive appicalon performance 1 Copy he required annotation fos annot to he Kray older seo Reference source not found 2 Select Fle gt Optimize Annotation Files on the menu br in me diio box hal appears select Hes t optimize and cick OK Fiecotmizaon take several minutes or more depending on your FE poe you do ot manusiy Minize he annotation fles GTC automaticly optimizes the the tr Gehe Coracle Ue Hart Four Opis annotation tles 42 Current annotation Hes ure by Genotyping Consi GeneChip ray Annotation Fie p Mapp a amet 0 Note To export Human Mapping 100K300K analysis results or 1o turther process samples in segment reporting ton SAT annotation Hes annot db required For Genome Wide Human SNP 60 export analysts resus 10 further process samples In SAT Miei Gesch Corale Uer Hart Chapter5 Workspaces amp Data Sets get started using Genotyping Console you wi create workspace an ad datasets consisting o he folowing types o tes or mais an examination ARL iners fies CEL Geno
199. unt imation and OK you have NAAT acount cick Register Now which launches mic con Folow the itor lo aat up accaunt tt Corsi User Hart Figure 45 Soci rary 1o download Select me ary et to dowload and cick OK Tre dowmload progress a p Deer Viene reir ee air aea een eim reu apes tp mi Pe 48 Dunia progress Note The download may take severa minutes or more depending on connection speed as the rar Hes large Pease be patient Ite workstation wih Genotyping Console does have an Interet connection and caanal dounload he Iran manually tne necesas fes 10 he ira eider Tabie 4 1 hows th ray tes Dal Garang Console eques to process an anay ty Cora User Hart ually Copy Library Files 1 Copy e requre les to the tray oder E Do not creste subdirectories within the bar e tolder Genotyping Console does not look at Tale 43 Library Hes required by Genotyping Console tyres GeneChip Array Library Pies Margit Hee hg carie p rentre 0K ry Napata cora tr apna Sy cit apn Syene Syl comiter Mares Syon Gena Wie Human SNE 50 Aray it Cora Genomes Human SNP 6D Array GanomabeSHP et Canaries 6 Ful specus encres rere tran zegion or ghar veniare t
200. ve as now coniguration Cick Save as Seve as ll Ck Default 1 me Default ie chosen new dialogue appears wih two opona one wih regional GC correction and regionai coran chaosng one at he eo optione te dea configu or wi Gt conecto or deal conowatan or ioa erai wi be 8 Figure 10 17 Select Contiguraton Template dialog box E Note GTC cannot edit a configuration that was crested in GTC 21 or earlier You can only edit contiguratian fles that were created in GTC 3 0 GTC 30 1 GTC 30 2 or GTC 45 Teelt a configuration 1 was created In GTC 301 GTC 3020r GTC 42 1 From De Ed select Copy Number Conligurtions gt Open Configuration The Open dislag box opens tyr Cora User ana iium SIC sone epo Scot eni are BC Tt bch ser oen cen 10 18 Open ig box The Open dialog box shows configuration tles that were crested in GTC 3 0 GTC 30 1 GTC S02 or GTC a2 You can ed hese Ted direc sce below lor more Information Note Configuration tes that were crested in GTC 21 or ater wil be displayed in the Open dialog Boro help you avod ovenwriting them You cannot edt these drei see below for mare Information 2 Select he configuration and dick Open The Base Options dig box opens Select he cenfgurton opt
201. y open wortapaces 2 Cickthe Optone El toolbar shortcut Arata Fle gt Options on the renu bar The Optons dalog box appears ty Genagrirg Cora User ana Spec he deel me the Ray ord annotation er ae oe yauma dere uakapszete red Ye lir ooh Scythe diclo whe Hoe E ug CEDE Figure 42 Options dialog box Directories ab Ener path o the new decoy or cick he Browse bution The Browse For Folder dialog box opens tt Corsi User Hart lect apel hre be Gantt biry ler ore xam EES pro Fire 43 Browsing tor bar tier c Note You can select any location lor the bar fles tolder I the Ayelet GeneChip 4 Bronse o Do odor hh contains me Rbraty es or crest falder tar your any Hes Make sure a brary ues or use Genotyping Console copie a vs older or are downoad o a lider braun N t ung GTC downoad uncon om the Fl meno 5 inthe Browse to Folder dialog box Cick OK inthe Options dialog bor select brary path la splayed in he bottom le comer of he applcation window Figure 4 4 tyr Gente Canace User ana Te tk Wm Wim p p oun gure Genotyping Console main window ply hera path Note GCOS users must use the Data Transfer Tool OTT using the Fat File option to transfer thes analyzed by Genotyping Console software rom
202. you reete you my rat your cwn prora Weite rectis ema Ben seat verona spared valor ae Ameis eiii caen B Step 3 Open Genotyping Console and import the SNP List generated by Neth SNP List 9 Select Import SNP tist 70 Mateo locaton ofthe TSV fle generated by Nei an Select Open 11 Provide a name for the SNP List o be deployed in Genotyping Conse and Select The SNP List wit be splayed in he data Siep Ater the SNP List is imported in Genotyping Console SNP List can be used tor many diferent Vien he SNP List page 106 Exporting genotypes ter SNP in te ist page 131 Vet he SNP Cluster Graph far SNPs in e page 108 Att Genet Corsi User Har View SNP Cluster Graphs of Case versus Control Samples per SNP tars hls remove majorty o probemati SNP However o scheme la pereat Even singen a amal proportion ar por SNPs wil roman Moreover poly SN wil onen ba e ones most kl o peor dient betean cases and corto The lato tian associated SNPs oten amiced tor such problema SNPs Tha SNP fite process greaty reduced the occurrence f hes false potes But ven their tendency 1o end Upon e sof associated SNPs V ay hal some Before carrying oth SNPs subsequent phases of analya visus spacio o he Ss te lusien space a son recommended Visual peton yen probata aces

Genotyping Console 4.0 User Manual

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