SCAIView 1.0 - SCAIView Version 1.4.2
Contents
1. Node Attribute Browser Edge Attribute Browser Network Attribute Browser Perturbation Analysis Welcome to Cytoscape 2 6 0 Right click drag to ZOOM Middle click drag to PAN Step 12 The target co citation network for Parkinson s disease is ready for further analysis in the Cytoscape environment amp Cytoscape Desktop New Session Fle Edt View Select Layout Plugins Help SBE QQQQ 9 BR hB Network visMapper Edtor Fiters P J Network i RY A Va i ba NIN rA A Bes ANY AS ARR d WS SS SN j i W 4 y fi SCAIView user manual Human version 32 QUERY 3 What SNPs single nucleotide polymorphisms are targeted by drugs in the Epilepsy disease Report their distribution on the human karyogram and the list of drugs that target them SOLUTION Step 1 Press Reset botton to start a new search Step 2 Type in the query field epilepsy Step 3 Select Epilepsy in the MeSH classification tree under MeSH Disease gt gt Nervous system Diseases gt gt Central Nervous System Disease gt gt Brain Diseases gt gt Epilepsy Step 4 From the Entity tree select the followings orderly a Human Genes Proteins to consider those abstracts that contain the name of genes carrying the SNP b Drug Names to consider those About documents which contain drug aK sg ma A O Subcorpus Statistics O Serer Statistics2. epilepsy names related to epilepsy pa _ Human Genes Proteins Chromosomal Location The following entities relating to epilepsy were found in 27 documents Pete u a N l d S N P t t 1 f L STS Marker Select Columns Expor Table Expo gt Export Entities Export kleogram Expor BIANA c Normalize to retrieve a list o Fl nonionnatzsasae Normalized SNP 26 entities found displaying 1 to 25 First Prev 1 2 Next Last 25 Entities per Page Y Normalized CRF SNP i Ref SNPs relevant to epilepsy ET aa Selo my gl MIGO Cata Doc Don IWPAC like Eo PP Links PA oO Reference O G rstos7si0 Wi s osne cve2co d 109248 es 40 Be TIEN Corpora C Epigenetics Step 5 Press search This should result in mic e LR iterator a tabl e CO ntal n l n g 26 entiti es i ines comes and Mycose Virus Diseases 7 Parasitic Diseases _ Musculoskeletal Diseases Step 6 From the Select Columns menu DS Sordos 3 la Respiratory Tract Diseases add the cytoband and HUGO columns The rigs wes iaa 11 Autoimmune Diseases of the i a DB Autonomic Nervous System former lists the chromosomal locations of Elem EN aii y 1 t ten Elrs17908s3 Mi S 02374 cypaca S 109248 Ba 2 the SNPs and the latter lists the name of genes corresponding to the SNPs Step 7 Now click on the IdeogramBrowser icon D Help Documents O rs130m83 MS 04473 k
3. AZ Fraunhofer SCAI SCAIView 1 0 Human Version SCAIVIEW The Knowledge Discovery Framework User Manual Edited by Dr Christoph Friedrich Erfan Younesi Last Update May 2010 Disclaimer This system is provided by the Fraunhofer SCAI as is without warranty of any kind We may modify or halt this system at any time without prior notification We do not warrant or assume any legal liability or responsibility for the accuracy completeness or usefulness of any information apparatus product or process disclosed This system is built on the Medline database leased from the National Library of Medicine NLM Title and MeSH Headings are adopted from MEDLINE PubMed a database of the U S National Library of Medicine We cannot assume any liability for the content of external pages Solely the operators of those linked pages are responsible for their content We make every reasonable effort to ensure that the content of this Web site is kept up to date and that it is accurate and complete Nevertheless the possibility of errors cannot be entirely ruled out We do not give any warranty in respect of the timeliness accuracy or completeness of material published on this Web site and disclaim all llability for material or non material loss or damage incurred by third parties arising from the use of content obtained from the Web site Registered trademarks and proprietary names and copyrighted text and images ar
4. Gene Ontology lists the GO ontology annotations for the corresponding gene protein entity and each annotation is hyperlinked to the AmiGO definitions The column Last Publication Date contains the most recent last publication date that have been found for the documents containing the entity of interest Reordering on this column gives you a ranking on the entities The column Link outs provides several links to external databases e g SwissProt NCBI HGenetInfoDB etc SCAIView user manual Human version 19 e Export Table By clicking this icon the full results of query search including all the entities found in the literature and their relevant information shown in the result table can be exported to the text file CSV format It is possible to export the results for each entity type selected in the subtree e g gene protein Drug Names etc if applicable Export PMIDs E This functionality allows the user to export the list of all the extracted entities e g gene names along with their corresponding PubMed identifier and thus provides a means for tracing back the reference from which the entity has been extracted Export results to clipboard This option allows users to export selected entities from the Entity View to the clipboard Desired entity names should be check marked first in the Select column then a click on the clipboard icon opens a small window containing the selected entities This fun
5. 8 Griffiths Jones S HK Saini S van Dongen AJ Enright miRBase tools for microRNA genomics NAR 2008 36 Database Issue D154 D158 SCAIView user manual Human version 12 Relations Relations describe the general associations found between the entity of question and other nearby entities in the text For example if we are searching for the genes proteins related to the query term breast AND cancer which additionally have a certain positive or negative association to a disease or drug we can determine the type of association in Relations subtree In this case the found expression may look like this Forkhead box A1 expression in breast cancer is associated with luminal subtype or the F311 polymorphism in AURKA is not associated with a modified risk of breast cancer in BRCA1 and BRCA2 carriers These associations can be further specified for finding positive negative associations between the entity in question and a gene or a SNP specifically Controversial associations are those associations which are found to be contradictory in the scientific literature neurlST Ontology The entities of the Entity Class neurlST Ontology are found by an approximate string search with ProMiner while the dictionary is generated from the particular in text mining part of the neurlST Ontology and normalized to those IDs Link out is provided to the Ontology Browser with definitions at UKFLR username password needed via Th
6. 9 Back to the Entity View move the magnifier symbol from the Normalized SNPs to Drug Names without clicking on them Step 10 Press search A A F SE 2 Help a F Saboomuys Siabistics dl Serer Statistics Step 11 Under HUGO column a list of fertens SNP carrier genes which are targeted by The following entities relating to epilepsy were founi Human Genes Proteins fi en Chromosomal Location FF LA those drugs IS found if exists Click on the S75 Marker Select Colums Export Table Export PD Export Entities D non Normalized SMP Normalized SNP 22 entities found displaying 1 to 10 FirstPrev 1 2 S Next La DrugBank icon to see the properties of er B n A roy A E Drug Names TECI Entropy E the drug in an overlaid page ia OMIM Reference L Elcamphane di 2 1 4918 Corpora LARS2 6 de 5 ret LOMT1 Step 12 Click on the first drug name Frisenstos curt Human miRNA O El lLeucine Ml Z 1 2860 Scar Camphane in the Entity table to be sHserss Senes Lars f Ll Mouse Genes econ l directed to the Documents View O ee ee E 1 MeSH Disease Os Bacterial Infections and Mycose SE E Virus Diseases a Step 13 To find out which SNPs are i 2 nee wos28 4 EA epplasms aos Bp e E E L Arginine d l 12860 WOS24 targeted by this drug tick the Normalized a m on Se SNP in the highlight bar Now you are able
7. Cols Export Table Export PHI Export Entes D Entity Export deogan Export BIAN 22 About Export PP 1 243 entities found displaying 1 to 10 FirstPrev 1 2 3 4 5 6 7 8 MextLast 10 Entities per Page z Relativ Doc SEIFS EOI lee Cons xt Count O ars ll 42187 48632 2884 O gcom WE 04193 4518 203 0 CO moe dig 02579 3406 181 Y O erca Ws omea sear 178 8 CO Elkras Mg o1999 5611 161 O Elercas Ws ois 3123 117 8 O acous ds 01393 5982 1m8 0 2 Export the results to co citation network Call Mb OMIM amp OMIM OMIM ON E OMIM OMIM OMIM ON El EOMME y Fall EOMME OMIME zia M5 OMIM i OMIM ES OMIMEB ON Fag OMIM amp OMIM OMIM E ON Ea EOMME y Click on the Export PPI button to export co citation network in sentence level The export file is in tab delimited text format In export file column 1 and 3 are interactors while column 2 describes the type of interaction usually pp or protein protein interaction 4 and 6 columns represent the Entrez gene identifiers of the proteins in columns 1 and 2 respectively Column 7 is the frequency of co citations interaction Notepad GSPTL 35361 Cap COK4 1021 ql CPP IL4 fli Cpe Cap ES FOO pp Cap MYC 898 CPPI pp COKNZC 129025 pp pp GADD4 5A 7157 pp pp MMPLS 4878 pp CPP FNL TE Cpe pp PIKSCG 891 pp pp TFCPR2 7157 pp Cap POU5F1 6657 pp 1014 3565 2152 46509 1031 1647 422 2339 329 r z 35460 MRRer
8. Green Human Genes f Proteins Step 3 Select Human Genes Proteins entity class r a HINT The position of small magnifier symbol determines which entity must be a oa non Mormalized SMF returned as result Normalized SNP Step 4 Press search D Select Columns E L Aneurysm Linker Degree Step 5 Click on the Select Columns button and from the menu select KEGG C odds Ratio Pathway then press OK Document Count Full Corpus Document Count C Entity Count d Cl Synonyms Step 6 In the results table click on the Filter icon ES in front of the U structure image l l C cytoband annotation with Alzheimer s disease 05010 B e a InterPro domain L SciMago Score Step 7 Press search again O ate code L Drug Target L Entrez Gene Identifier Step 8 Now you should be able to see your results in the Entity View as a list ri KEGG Pathway of 27 genes proteins which are all annotated to the Alzheimer s disease C Reactome Pathway LJ Gene Ontology pathway in the KEGG database alongside with other pathways and ranked C Last Publication Date according to their relevance to the Alzheimer s disease see the next page Link Outs SCAIView user manual Human version 29 27 entities found displaying 1 to 10 FirstPrev 1 2 S MextLa t 10 Entities per Page Ref Doc Count KEGG Pathway Doc Count Relativa Select Entropy Entity ma BYR TIT app Ll Alzheim
9. Hospital Beijing 10004 er a O statistics MiGsetect iD with comment 159934839 R503 R Variants with a relatively high frequency Ih the gene have previously been identified in cases of childhood absence epilepsy CAE in the Chinese Han population most of which are located in exons 6 to 12 In present study we attempted to further investigate whether the 1H gene is associated with Exons 6 to 12 of gene were sequenced in samples of 100 rios recruited consecutively and 191 normal human controls Single nucleotide polymorphisms SNPs were studied in both single locus and haplotype analyses in 218 trios of which 118 trios were selected from our previous research Case control comparisons and the transmission disequilibrium test TDT both supported a coding SNP cSNP R6O3R in exon 9 as being close related to The carriers of the G allele of had a 3 fold higher risk of CAE than non carriers Moreover another cSNP rs8044363 was predicted to be connected directly with in a Bayesian network In addition two haplotypes consisting of five CSNPs in the region of were statistically associated with CAE Our research provides new evidence to further support the hypothesis that may be an important susceptibility gene for CAE in the Chinese Han population MeSH Asian Continental Ancestry Group genetics Bayes Theorem Calcium Channels T Type genetics Case Control Studies Child Child Preschool China Epilepsy Absence genetics Ethnic Groups genetics Exons Female Gen
10. RESULTS The frequency of the risk conferring C allele did not differ significantly between CAE patients f C 0 190 and controls f C 0 183 P 0 376 one tailed Similarly no evidence for an allelic association was found for 373 patients with idiopathic absence epilepsy 303 JME patients and the entire IGE sample P gt 0 77 two tailed CONCLUSION Our study failed to replicate an association of the common GABRB3 exon 1a promoter SNP rs4906902 with Moreover the present results do not provide evidence that the common functional C variant confers a substantial epileptogenic effect to a broad spectrum of IGE syndromes in the German population MeSH Alleles Epilepsy Absence genetics Epilepsy Generalized genetics Exons Gene Frequency Genotype Humans Mutation Polymorphism Genetic Protein Subunits Receptors GABA A genetics Title and MeSH Headings from MEDLINE PubMed a database of the U S National Library of Medicine amp PubMed Step 16 Press Reset e to begin a new search
11. and life science researchers Most of the current knowledge exists as unstructured text publications text fields in databases and SCAIView provides users with full text and biomedical concept searches which are supported by large biomedical terminologies and outstanding text mining technologies Using machine learning and dictionary based Named Entity Recognition NER SCAlView extracts information of genes drugs SNPs and other Life Science entities from MEDLINE abstracts SCAlView uses a multi threaded Lucene to allow semantic and ontological search on this data Documents are retrieved via free text queries chosen by the user and a span of biomedical entities such as genes proteins SNPs drugs etc can be selected from the terminologies and ontologies Complex queries can be asked such as what drugs are mentioned in the context of Alzheimers disease or what genes are co mentioned with Diabetes and are on the insulin signalling pathway 1 1 Development SCAIView has been developed and maintained by the bioinformatics team of the Fraunhofer Institute for Algorithms and Scientific Computing SCAI The selected biomedical entities are found by an approximate search algorithm implemented in the Fraunhofer Gesellschaft information extraction tool ProMiner which additionally disambiguates synonyms of entities to unique identifiers in public available databases Visit www scai fraunhofer de scaiview html L 1 for more information lt
12. column Odds Ratio ranks the results according to their likelihood of occurrence alternative to relative entropy The column Document Count lists the number of documents in the corpus of the search query containing the entity This corpus is called hit list Click on the numbers or red circles results in the export of all PubMed identifiers which refer to a specific entity The column Full Corpus Document Count lists the number of overall documents in the MEDLINE containing the entity The column Entity Count includes the number of corresponding entity found in the MEDLINE abstracts The column Synonyms lists all synonym names aliases of the corresponding entity gene protein or drugs or disease The column Structure Image shows a thumbnail of the chemical structures for retrieved drug names source DrugBank and clicking on the thumbnail downloads the chemical structure in SDF format NOTE This option only applies to the drug named entities The column Cytoband includes the chromosomal location of the corresponding gene entity in human genome The column InterPro family not only exhibits the family class to which the protein or protein product of the gene belongs but also provides a direct link out to the InterPro database The column InterPro domain not only lists the name and identifiers of the domains present in the protein in question but also provides a di
13. in Man References are found by a regular expression search for the IDs of the OMIM database performed by ProMiner Link outs are provided to at NCBI Reference corpora Under this class 7 subclasses are embedded which contain collections of structured literature texts from specific resources publications dealing with the topics related to the Alzheimer s Parkinson s and Schizophrenia as well as general full text publications from PubMed Central database The subclass Full text makes it possible to analyze those abstracts that are exclusively found in PubMed Central repository with access to the corresponding full texts By selecting the Fulltexts ftp subclass it will be possible to access and download the full text Wishart D S Knox C Guo A C Shrivastava S Hassanali M Stothard P Chang Z amp Woolsey J DrugBank a comprehensive resource for in silico drug discovery and exploration Nucleic Acids Res Department of Computing Science University of Alberta Edmonton AB Canada T6G 2E8 david wishart ualberta ca 2006 34 D668 D672 Klinger R Kol rik C Fluck J Hofmann Apitius M amp Friedrich C M Detection of IUPAC and IUPAC like chemical names Bioinformatics 2008 24 1268 1276 SCAIView user manual Human version 11 articles from the PubMed FTP service The option of Systematic Review enables the user to see the results of text analysis on the abstracts of systematic reviews fro
14. must be noted that the development phase of this system has been partially funded by neurist project in the framework of the European integrated project 1 2 License SCAIView Human Version is free for academic use commercial users and those users who wish to access the API for large queries must contact Dr Christoph M Friedrich via friedrich scai fraunhofer de The content of our database might be accessed for copying purposes but we do not allow bulk downloads SCAIVlew Human version also includes a number of other open source libraries which are detailed in the User Manual Acknowledgements below SCAIView user manual Human version 2 2 Quick Start Step 1 In the grey search field type your query The query could be a disease name a biological process the title of a journal the name of an author or the PubMed identification number of an article A number of predefined query terms are provided in the dropdown menu Step 2 Select from the entity tree what you are looking for in your query results genes proteins SNPs Chromosomal locations GO annotations MiRNAs etc Click on the entity class of interest in the tree only once and make sure that your selection turns into green with the magnifier in front of it Leave the confidence level on the default the level 5 returns the most stringent results NOTE Clicking any entity class twice turns it to the red colour meaning that this class is excluded from the searc
15. 0 0373 154 46 2009 Sa OMIM GO Process F lt O Emam W s 6 0 0348 1784 71 0 200 a OMIM q 1 422 entities found displaying 1 to 10 First Prev 1 2 3 4 5 6 7 O Next Last 10 Entities per Page Y Select Confidence 1020 30 lt b NM SCAIView user manual Human version Statistics To obtain detailed information on the conducted query you can expand two statistics tables at the top of the entity view By ticking the Server Statistics you obtain information on the performance of SCAIVIEW system during information retrieval for your query whereas Subcorpus Statistics provides a quick overview of all entities found in the subcorpus of your query see below By clicking on each entity class an overview table appears containing information on the individual named entities and their corresponding relative entropy document count and link outs if any The content of these tables can be exported to CSV Excel and XML file formats 1 Credits i Help E ad SWC OMS Statistic s LI Sener Statistic The following entities relating to breast cal Be 5 Select Columns Export Table Export PICS via the links provided at the bottom of each table HOC WSs Stet sie s Server Statistics Chromosomal Drug Protein Gene STS OMIM aneurisT Locations Hames 1 800 entities found Entity Mammary Carcinomas Human Meoplasms Metastases Undifferentiated Carcinomas Cancers Ovary Lymphatic
16. 04867 04610 05010 55651 0005515 04330 05010 4035 0004872 C 5010 3028 0003857 CO0062 00071 00260 00281 51107 0005515 04330 05010 713 0005576 C04610 05010 05322 8883 0003824 C 5010 2597 0003824 200010 05010 05040 05050 840 0005515 04210 05010 05050 712 0005576 04610 05010 05322 4023 0004465 00561 03320 05010 7124 0000060 04010 04060 04210 04350 21q21 3 19q13 2 14924 3 17q21 1 11923 2 q2 1q31 q42 4q21 04360 04510 0 3q13 3 10q23 q25 1 q22 q23 05010 05012 0 4q34 11p15 04640 04940 0 2q14 3q25 1 q2 21q22 3 12p13 3 p1 19q13 12 12q13 q14 00310 00380 01 p11 2 X 1p36 13 q3 1p36 12 16422 12p13 10425 1p36 12 Gp22 04620 04640 0 6p21 3 Step 10 Press Reset botton e on the left top of the page to start a new search SCAIView user manual Human version 30 QUERY 2 Find all those proteins that are known drug targets for the Parkinson s disease in the KEGG Parkinson s disease pathway and reconstruct a co citation network out of them SO LUTION parkinson Step 1 Type in the query field parkinson sa STS Marker non Normalized SNP Normalized SNP Normalized CRF SNP Step 2 Include all possible synonyms of Parkinson s oO OS disease by selecting the corresponding entity type in the FOO orate MeSH classification tree under MeSH Disease gt gt Nervous sue System Diseases gt gt Central Nervous System Disease g
17. 6 H5047755 H5046122 H5048821 H5053077 H5055706 H5044679 H5054795 H5053068 H5047735 H5053072 3 4825 74665 0 748 45439 0 485 11825 0 2 3044 0 1913 4530 0 1571 5616 0 0863 12264 0 0603 10601 0 0209 2954 0 0281 1049 0 0256 51455 0 0208 724 0 019 193509 0 0167 16763 0 015 697 0 0141 9945 0 0134 356 0 0063 1447 0 0049 409 0 0036 47 0 0016 75 0 0014 111 0 0009 14540 0 0006 1859 0 0002 88 0 0008 33234 0 0021 369872 Ready 58718 14945 8919 1687 3623 102069 102069 102069 102069 102069 102069 102069 102069 102069 102069 102069 102069 102069 102069 102069 102069 102069 102069 102069 102069 102069 102069 102069 102069 102069 102069 102069 19213 11520 3034 1475 1093 14186 3603 2019 857 704 756 505 300 168 146 427 93 612 190 70 19740 19740 19740 19740 19740 19740 19740 19740 19740 19740 19740 19740 19740 19740 19740 19740 19740 19740 19740 19740 19740 19740 19740 19740 19740 19740 19740 351 0004867 C 5010 348 0000302 C 5010 5663 0000139 004310 04330 05010 4137 0000226 04010 05010 23621 0004194 C 5010 5664 0000139 04330 05010 6622 0001956 205010 05012 2932 0000166 04012 04110 04310 04340 3416 0004231 C 5010 23385 0005515 04330 05010 636 0005515 04010 04115 04210 04650 322 0001540 C 5010 3553 0000187 04010 04060 04210 04620 4311 0004245 04614 04640 05010 25625 0004194 C 5010 2 00
18. Metastasis Cribriform Carcinomas PROSTATIC NECGPL Breast Invasive Ductal Carcinoma Heoplasm Invasiveness 1 500 entities found Export options CSW Excel XML Marker Reference Relative Entropy 3 5064 2 4013 0 6351 0 4607 0 2922 0 2183 0 2058 0 1935 0 1935 0 1561 Normalized E non Hormalized SHP Doc Count 45699 31353 aa 6015 3015 2050 2657 2527 2526 2450 SHP Links SCAIView user manual Human version 16 3 4 1 1 Entity Tab Components Select Columns In the Entity table the following columns are shown by default Entity Relative Entropy Reference Documents Count Documents Count and Link outs However the results table can be expanded by adding more columns to include additional information such as links to KEGG or Reactome pathways as well as Gene Ontology Cytoband synonym information SciMago score InterPro family and domain information ATC Anatomical Therapeutical Chemical Classification code and HUGO standard gene naming Moreover it is possible to indicate whether a protein has been already targeted by any drug and to visualize and download the structural images of the drugs These options can be added to the result table in the form of columns by ticking them in the drop down menu Information on these columns are detailed as follow 3 4 1 2 Entity Table Columns The column Entity displays the official entity name If you click on the entity name the Result Com
19. Nomenclature for the description of human sequence variations Hum Genet 2001 109 121 124 Roman Klinger Laura Furlong Christoph M Friedrich Heinz Theodor Mevissen Juliane Fluck Ferran Sanz amp Martin Hofmann Apitius Identifying Gene Specific Variants in Biomedical Text Journal of Bioinformatics and Computational Biology 2007 5 1277 1296 Bonis J Ll Furlong F Sanz OSIRIS a tool for retrieving literature about sequence variants Bioinformatics 22 2667 2569 2006 SCAIView user manual Human version 10 Normalized CRF SNP The entities of this class are the SNP mentionings in the text that are found by CRF Conditional random Field algorithm CRF is a machine learning method which is best suited for sequential data Drug Names The entities of the Entity Class Drug Names are found by an approximate string search performed by ProMiner while the dictionary is generated of the synonyms found in the Drugbank database version 2 and normalized to those IDs Drugbank provides information to more than 4000 different drugs and link out is provided via D DrugBank IUPAC like The entities of this class consist of the names of chemical entities which follow the standard naming rules based on IUPAC nomenclature These entities are extracted from text using a new machine learning approach based on conditional random fields OMIM Reference The entities of the Entity Class OMIM Online Mendelian Inheritance
20. R1 the top ranking protein in the list First we press the D filter icon in front of the ESR1 gene and this entity is inserted into the filtering field automatically Then we select the entity class Drug Names from the tree and repeat the search The result is a list of drug names which are reported to target ESR1 protein A useful feature of filtering option is ontological search i e in the Entity View several entities of pathways or GO identifiers can be copied into the filter field through clicking the filter icons in front of each entity and a new query can be made using these filters for example a query for the keyword breast cancer and searching for the Human Genes Proteins would result in the list of KEGG pathways annotated to each gene protein you must have already added the KEGG pathway column from the Select Columns menu now clicking on the filter icon in front of one pathway of interest e g Erbb signalling pathway will insert the identifier of that pathway e g 04012 KEGG into the filter field pressing the search button again brings up all the genes annotated to this pathway The identifier s can be also inserted manually in the filter filed in the form of identifier entity_type Currently this filtering option can be applied to the following domains GO identifiers REACTOME and KEGG pathways ENTREZGENE identifiers SWISSPROT identifiers HUGO gene names and CHROMOSOME identifiers It is also possible to ap
21. RRSJPRRRREA 3 Import network into Cytoscape using File gt import gt import Network from table in the form of Tab delimited Select Column 1 as Source Interaction column 2 as Interaction Type column 3 as Target Interaction and additional columns as edge attributes Then click import button SCAIView user manual Human version 23 A Y f ER ER LD hizi 4 EA tr ants pam Data Sources Input File file psf Home Documents Downloads interaction txt Select File s E Interaction Definition Source Interaction interaction Type Target Interaction Column 1 vw gt Column 2 v 9 Column3 v AO Columns in BLUE will be loaded as EDGE ATTRIBUTES Advanced Show Text File Import Options Preview Text File Left Click Enable Disable Column Right Click Edit Column li a al ee interaction txt Y Column 1 Y Column 2 Y Column 3 Y Column 4 Column 5 Y Column 6 Y Column 7 IL9R pp GSPT1 3581 pp 2935 E __ CDK6 pp cDK4 _ 1021 pp 1019 i _TP53_ pp IL4 7157 pp 3565 1 THBS1 PP F3 7057 pp 2152 1 _CCNE1 pp MYC _ 898 _ pp 4609 1 ZNF280A pp CDKN2C 129025 pp 1031 e _TP53 pp GADD45A 7157 pp 1647 _ Y NPPA inn MMP13 ARTA inn 423992 1 gt Import Cancel 4 Visualize the co citation network using Cytoscape eac
22. T Ontology GO Component 30 Function 30 Process Show this Entity Class in the Entity View In the Document view mouse over on entities shows the Click once on the name of an item in the tree to include it into the search a little plus Click once again to exclude it a little minus is shown and y gt SCAIView user manual Human version 14 3 4 Result Component lt displays the results according to the searches and can be navigated via tabs You find an Entity View an Analysis View and a Documents View In the Entity View named entities of interest are summarized under the column Entity and are directly linked to their corresponding abstracts By rolling mouse over each named entity under Entity column the full name of the entity e g full gene name as well as its identifier will be shown Shifting to the analysis tab takes the user to the Analysis View where the collective information about the type and number of all other entities that co occurred with the entity of interest in the text can be found 3 4 1 Entity View The Entity View displays a table with the aggregated list of entities found in the documents ranked by a certain column Clicking on a column Header of the table will re order the table depending on the selected column entries You may have to click twice to switch the order You can navigate between pages elther by clicking Next Last or switching directly to a specific result page by cl
23. a Promkan onlo Liu Pimpicha Patmasirivvat Subhas Chakrabarty Date 2009 12 15 Journal International journal of cancer Journal iiemeli nal du cancer SciMago 0 831 Affiliation Department of Microbiala g illinois University School of Medicine and SimmonsCooper Cancer Institute Springfield IL 62794 9677 USA O Statistid i Hen BRCA1 are not fully understood We used a shRNA approach to probe the function of in human breast cancer cells Knocking down expression by shRNA in the wild type B human ounces MCF 7 and MDA MB 231 cells resulted in an increase in cell proliferation anchorage independent growth cell migration invasion and a loss of p21 Wat1 and p27Kip1 expression In knocked down oaks the expression of survivin was significantly up fegulated with a concurrent decrease in cellular sensitivity to paclitaxel Ye also found that cells harboring endogenous mutant or defective MDA MB 436 and HCC1937 were highly proliferative and Expressed a relatively low level of p214Waf1 and p27Kip1 by comparison to wild type BRCA cells Cells harboring mutated also EXpressed a high level of survivin and were relatively resistant to paclitaxel by comparison to wild type cells Increase resistance to paclitaxel was due to an increase in the expression pi survivin in both tre BREA knocked down and mutant BRCA1 cells because knocking down survivin expression by siRNA restored sensitivity to paclitaxel We conclude that dow n modulates the malignant behavior o
24. ast cancer containing the entity ESR1 found in 9490 documents Entity Name Count Entity Name Count Entity Name Count Entity Name Count Entity Name Count Entity Name Count Entity Name Count Tamoxifen 59 TLRS 12 Risk Factor 10 No Common Name MF_K303R 7 154818 2 Neoplasms 227 positive association 66 Testosterone 16 PML 8 Confidence Interval 8 No Common Name MF_S100P 4 151799991 1 Metastases 31 negative association 4 Raloxifene 7 SHBG 7 Odds Ratio 7 Exportoptions CSV Excel XML RS2208532 4 Cancers Ovary 10 Export options CSV Excel Formaldehyde 5 AKT1 7 Magnetic Resonance Imaging 6 No Common Name RS4860 1 Breast Invasive Ductal Carcinoma 4 XML Mupirocin 4 TGFA 4 Case Control Study 6 15722208 1 Hormone Dependent Neoplasms 4 Trastuzumab 4 CYP2D6 4 Logistic Regression Analysis 6 Export options CSV Excel XML PROSTATIC NEOPL 3 Carboplatin 4 RELA 3 Experimental Study 5 Neutropenia 2 Melatonin 3 BCL2 3 Outcome 3 ALZHEIMER DIS 2 Everolimus 3 No Common Name HS070323 a Positron Emission Tomography 3 Leukemia 2 Cholesterol 3 TIMP3 2 Prediction of Qutcome 2 CARDIOVASC DIS 2 Choline 3 FOXA 1 2 Relative Risk 2 Thrombopenias 2 Estriol 2 SLO24A4 1 Regression Analysis 2 Cancer Laryngeal 2 Dactinomycin 2 KLK3 1 Prospective Study 2 Germinoblastic Sarcoma 1 Valproic Acid 2 CXCR4 1 Risk 4 Fatigue 1 Vitamin E 2 MIR206 1 Epidemiologic Study 4 Processes Pathologic 4 Fulvestrant 1 MAPT 1 Pregnancy 1 Indigestion 1 L Arginine 1 NCOR2 1 Case Report 1 Cancer o
25. bles users to input the file directly into Cytoscape software for visualization as well as topological analysis of the co citation network In Cytoscape the entities are translated into nodes and their co occurrence frequencies into the attribute of edges Co citation protein interaction network is defined as a protein protein interaction network where two proteins are connected if they are co cited in one abstract or in the same sentence with one interaction keyword in the text User is able to query for co citation network of one gene protein or many at abstract level or sentence level We use TP53 as an example 1 Use TP53 as the keyword to query SCAIView Select Human Genes Proteins in the Entity tree and tick the Sentence box to narrow down the co citations to the sentence level SCAIView user manual Human version SCAIVIEW _ A ADE TPIS ke JAA i DEDA 00 lLie eele 4 lt gt Human Genes Proteins Chromosomal Location STS Marker non Normalized SMF Normalized SMP Normalized CRF SNP Drug Mames UIP C like OMIM Reterence Corpora Epigenetics Human mira Arabidopsis Genes Mouse Genes Interaction Verbs MeSH Disease Relations neur sT Ontology i Show statistics about the corpus D Help ll CI Suboorews Statistics E Sener Statistics The following entities relating to TPSF were found in 2900 documents D amp Select
26. ctionality allows users to copy the selections or to save them as a text file and use them as direct input for other applications such as GO ontology analysis by BINGO a plugin of Cytoscape software mee Export SNP results A e This functionality is most useful for the visualization of literature extracted SNPs in the human karyogram Note that you need to select Genes Proteins in combination with Chromosomal Location in order to get a meaningful output first select the Chromosomal Location then select the SNP Normalized and press search The output is exported to a text file by clicking on the above icon For visualization of SNP markers on the human karyogram you must install the software Ideogram Browser freely available for download at www informatik uni ulm de ni staff HKestler ideo The text output file can be loaded into IdeogramBrowser from the Files gt Load Markers Depending on the type of SNPs gain vs loss the imported markers are visualized beside chromosome locations of relevant genes Clicking on the Mueller A Holzmann K Kestler HA Visualization of genomic aberrations using Affymetrix SNP arrays Bioinformatics 23 4 496 497 2007 SCAIView user manual Human version 20 imported marker line beside each chromosome provides more information regarding the SNP numbers and contents in the Info tab For example if we search for the SNPs related to Intracranial AND aneurysm and export the data usi
27. e not generally indicated as such on our Web pages But the absence of such indications in no way implies that these names images or text belong to the public domain in the context of trademark or copyright law System Requirements e Firefox Browser gt 2 0 x x Safari or Internet Explorer gt 6 0 Google Chrome and Opera e 1 GB of RAM and a hardware generation gt 2005 e Username Password required and can be obtained by E mail from friedrich scali fraunhofer de Table of Contents INTRODUCTION cortada 1 1 1 Develop meN tiiir a a 1 1 2 LICENS O uriin ao a a en ede ercasedieee 1 2 QUICK SEAR Triana 2 3 DETAILEDEXPLANA TO Nous 3 3 1 Search COMPONediiiisinia a 3 Sokal BUKOM DESCHOU OM nanana E E S 3 L AAA o ii A 3 3 2 Search Examples and Explanations on queries ooccoccconcconcconoconaccoanconnnnns 4 3 3 Entity Tree COMPONENT iraniana aoaaa a aE 7 3371 EN GlASS Sa a a e ce a 7 3 3 1 1 O Gene aoe tee ee ate eto 8 SON oe Rta eer NT Pe mE OO CDE Seo E to aoe Norte Pe ate Ne ONE 13 3 3 1 2 Button Descrip lo o O oe dira 13 3 4 Result COMPONEN osn aia 14 dal ENUY VOW rl E O bl 14 3 4 1 1 Entity Tab COMPONENTS on a 16 3 4 1 2 Entity Table COMAS coi estes 16 O42 IDOCUIMGEIIE Ia a detache 25 Osa oy PANGIVSIS MIO Wilde 27 3 5 Application Scenarios cinc ai ia 28 SCAIView user manual Human version 1 1 Introduction SCAlView is an advanced semantic search engine that addresses questions of interest to general biomedical
28. e entity tree component is not fully expanded a plus sign shows that a subtree is present Clicking on the plus expands the subtree and allows choosing from sub components 3 3 1 Entity Classes The tree component allows choosing several different entity classes of interest singly or in combination Note When switching between different entity classes over the tree make sure that youve deselected the previous selection except that you intend to perform your query over multiple entity classes simultaneously to get more focused results Genes Proteins Human Genes Proteins Chromosomal Location STS Marker non Normalized SMP Normalized SNP Normalized CRF SNP Drug Names IUIPAC like OMIM Reference Corpora Epigenetics Human miRNA Arabidopsis Genes Mouse Genes Interaction Verbs MeSH Disease Relations f QneurnlST Ontology GO Component G Function GO Process The entities of the Class Genes Proteins are found by ProMiner software through an approximate string search and using the dictionary that is generated of synonyms found in the databases EntrezGene and Swissprot and normalized to those IDs There are four separate Gene Protein classes in the tree for four organisms cattle genes pig genes mouse genes proteins and human genes proteins Link outs of this Entity class are provided to the following external databases EntrezGene at NCBI that provides informat
29. e ontology comprises of further sub trees of aneurysm disease terminology which can be used to narrow down the search in the corpus The ontology covers aneurysm specific clinical terms such as diagnostics therapy and risk factors GO Component This class represents the biological cell compartments that are defined by Gene Ontology and contains further subclassifications for detailed search GO Function This class contains subclassifications of Gene Ontology for gene biological function and can be used for supporting the query for finding information attributed to the gene at functional level GO Process This class covers the subclassifications of those terms in Gene Ontology that describe the biological processes for each gene SCAIView user manual Human version Confidence levels By choosing levels of confidence ranging from 1 to 5 it is possible to adjust the level of accuracy in the results corresponding level of confidence as well 3 3 1 1 Tree View The tree view provides several different selection types 3 3 1 2 Button Description Expand Collapse Tree Viewing Click again to disregard it AKO RR Q breast cancer a Human Genes Proteins Chromosomal Location STS Marker non Mormalized SMP Normalized SMF Mormalized CRF SNP Drug Mames IUPAC like OMIM Reference Corpora Epigenetics Human miRIA Arabidopsis Genes Mouse Genes Interaction Verbs MeSH Disease Relations cneurlS
30. enno 1922923 2 0 HVE TIEN O rsze933381 Ml g 04473 kona 12p1332 20 HVB p TIEN Cl rst128503 W S 04201 ABCBI S 792118 30 EW p TIEN O Birstosss42 MIS 02813 apes 702118 30 Bev TIE O rs949626 Mi sg 0 2387 10 CEE Cl Elrsoaass3a W Z 02387 CACNAIHS 16p1338 1 Bre TIEN O rseoga3e3 WS 02387 CACNAIH S 16p13 3 BrE TIEN FL lle Neoplasms Cl rs23og995 W Ss 02387 Kenas 8q2sS 1 EA gt TIEN O Sirses20367 Mi g 0 2387 cLen2 3927 9288 1 Beep TEN O rstsois4s WS 02387 keno28 200133 1 Bea gp TIEN O rs3751664 MIS 0 2387 cacnatHS 16p133 1 BrE gt TIEM O Glrs2298771 WS 02387 soma ld 292438 1 EA TIEN O 8lrs72157s MS 02387 smana 1792338 1 EY gt TIEN O rsasosgo2 lil s 0 2387 1 CHEN O About save the SNP cytoband markers in a text file This file can be E Sees sitios O sever simi he following entities fitered by 1 TARGET relating to parkinson were found in 9539 documents loaded into the IdeogramBrowser software environment and B Es a e E Select Columnas Export Table Export PMIDS Export Entities Export kleogram Expo ot BIANA Export PP SNP cytobands can be visualized over the human karyogramM La eme tou spaying to 10gFrsterev4 2 9 4 5 6 7 ame SCAIView user manual Human version 33 Step 8 Open the IdeogramBrowser environment and under File gt Load Markers import the text file You are able now to see the location of SNP makers on the human karyogram Step
31. er s disease 05010 4 19213 gagaro dl 3 4525 11520 0 7460 Alzheimer s disease 0501 os Went signaling pathway 04310 2 Notch signaling pathway 04330 us Alzheimer s disease 05010 2 MAPK signaling pathway 0401 oie Alzheimer s disease 05010 4 Epse Li s Emart Ll 2 paces UN s Alzheimer s disease 05010 Notch signaling pathway 043302 Alzheimer s disease 050104 Alzheimer s disease 0501 os E el OMIM Parkinson s disease 05012 4 l ErbB signaling pathway 0401 as Cell cycle 04110 8 Vint signaling pathway 04310 2 Hedgehog signaling pathway 043402 Axon guidance D4360 8 Focal adhesion 4510 B cell receptor signaling pathway 04662 2 gipsen W g Gisnea W s 0 0605 3114 gesk W s ES OMIM Insulin signaling pathway 0491 os Step 9 Click on the Export Table button e and save the results in a text file This file can be imported into an Excel sheet to create your own knowledge base e Common Name B C D E F G H J K L M N e P Q R Common Name internal Identifier Relative Entropy Reference Entity Cou Query EntiReference Doc Count Query Doc Entrez Gei GO Identifi KEGG Ident ATC Code Protein Do Protein Fa Cytoband Chromosome APP APOE PSEN1 MAPT BACE1 HSD17B10 APHIA C1QB NAE1 GAPDH CASP C104 LPL TNF HS046797 HS046744 HS050764 H8047872 HS044167 HS050785 H5052659 H5045935 H5046598 H5043986 H5054652 H5046303 H5046858 H5048015 H5044556 H5042956 H503875
32. etic Predisposition to Disease Haplotypes Humans Linkage Disequilibrium Male Models Genetic Polymorphism Single Nucleotide Title and MeSH Headings from MEDLINE PubMed a database of the U S National Library of Medicine ky PubMed 2 Lack of evidence of an allelic association of a functional GABRB3 exon 1a promoter polymorphism with idiopathic generalized epilepsy M PubMed 17215107 Auth ana Cobilanschi Armin Heils Hiltrud Muhle Ulrich Stephani Yvonne Weber Holger Lerche Thomas Sander Date 2007 04 Journal Epilepsy research SciMago 0 251 Affiliation Max Delbr gksis mead R ssle Street 10 13125 Berlin Germany PURPOSE Mutation screening and kage Cleecumpriuim mapping of the gene encoding the GABA A beta 3 subunit GABRB3 identified a common genetic variant in the exon 1a promoter region C allele of rs4908902 which displayed a reduced transcriptional activity and showed a strong allelic association with childhood absence epilepsy The present population based association study tested whether the C allele of rs4906902 confers susceptibility to CAE or other common syndromes of idiopathic generalized epilepsy IGE in a German sample METHODS Seven hundred and eighty unrelated German IGE patients 250 123 juvenile absence epilepsy 303 juvenile myoclonic epilepsy JME 104 epilepsy with generalized tonic clonic seizures on awakening and 559 healthy population controls were genotyped for the single nucleotide polymorphism oe rs4908902
33. f Uterus 1 L Lysine 1 CAS 1 Randomized Controlled Clinical Trial q Preneoplastic Condition 1 Sirolimus 1 FXYD3 1 Correlation Coefficient 1 Fractures Bone 1 Doxorubicin 1 BMI1 1 Cross Sectional Study 1 Nausea 1 Chlorpromazine 1 NFE2 4 Expor options CSV Excel XML Neoplasm Invasiveness 1 Cyclophosphamide 1 CDSA 1 Strokes Acute 1 Fluoxetine 1 CSN2 1 Premature Menopause 1 Gonadorelin 1 FOS 1 INFLAMM 1 Paroxetine 1 PALB2 1 Cancers Heart 1 Export options CSV Excel XML Export options CSV Excel XML Export options CSV Excel XML SCAIView user manual Human version 28 3 5 Application Scenarios QUERY 1 Find all the genes that are mentioned in the literature to be associated with the Alzheimer s disease annotate them with the pathways they re involved in and keep only those genes which are annotated in the KEGG database to the Alzheimer s disease pathway SOLUTION AKO Ep Y Step 1 Type in the grey search field alzheimer alzheimer Y Step 2 Restrict your search to the instances synonyms of the OS ain ero L ementia Complex Alzheimer s disease in the MeSH disease classification tree under Se Se lennont L Primary Progressive Aphasia Creutzfeldt Jakob Syndrome MeSH Disease gt gt Nervous System Diseases gt gt Central Nervous System Disease gt gt Brain Diseases gt gt Dementia gt gt Alzheimer s Disease HINT For a correct selection the entity class name must turn into
34. f p t cancer cells the expression of p21 Waf1 p27Kip1 and inhibits the expression of survivin Moreover loss of expression or function leads to an increase in survivin expression and a reduction in chemosensitivity to per vary MeSH No Medical Subject Headings MeSH assigned Title and MeSH Headings from MEDLINE yPubMed a database of the U S National Library of Medicine ky PubMed 2 Characteristics of health information gatherers disseminators and blockers within families at risk of hereditary cance health communication interventions N PubMed 19833996 Authors Laura M Koehly June A Peters Regina Kenen Lindsey M Hoskins Anne L Ersig Natalia R Kuhn Jennifer T Loud Mark H Greene Date 2009 12 Journal American journal of public health SciMago 0 311 Affiliation Social and Behavioral Research Branch National Human Genome Research Institute National Institutes of Health Department of Health and Human Services Building 31 Room B1837D 31 Center Drive MSC 2073 Bethesda implications for family OBJECTIVES Given the impo emination of accurate family history to assess disease risk we characterized the gatherers disseminators and blockers of health information within families at high genetic risk of cancer METHODS A total of 5466 personal network members of 183 female participants of the Breast Imaging Study from 124 families with known mutations in the genes with high risk of breast ovarian and other types of cancer
35. font size e A Increase the font size Reset the Search E A e E Filter the Results e Show the Information Screen Start the Search gt y Select from predefined queries 3 1 2 Search Field In the grey search field located below the icons you can either enter a string e g a disease name or select from predefined queries by clicking the blue down arrow button right to the search field SCAIView user manual Human version 4 3 2 Search Examples and Explanations on queries In the search field you have the possibility to use certain keywords to make your search more specific lt works like any other search engine but knowing the special features allows you to be more effective with your queries and allows the proper interpretation of the results 1 The boolean function AND is automatically considered between multiple keywords except that the user indicates otherwise 2 Performing null query empty search field on any entity class results in retrieval of entire entities for that class from PubMed abstracts 3 It is also possible to define a subcorpus from PubMed database by invoking the E utilities or programming utilities from inside SCAlView For instance if you want to analyze the abstracts that you have retrieved in PubMed database you can type EUTILS your query term in the search field and obtain the entity analysis results on this set of abstracts We explain the search possibilities by the foll
36. g to parkinson were found in 9539 documents co citation extraction to the sentence level by ticking the LA Ian Sentence checkbox in front of the Export PPI botton Select Columns Export Table Export PMIDs Export Entities Export kleogram Expor BIANA Export PPI 524 entities found displaying 1 to 10 First Prev 1 2 3 4 5 6 7 S NextLast 10 Entities per Page Y SCAIView user manual Human version 31 Step 10 Click on the Export PPI button to export the co citation network as a text file which can be imported directly into the Cytoscape environment Step 11 Import the file into the Cytoscape environment Go to Layout gt Cytoscape Layouts and click Spring Embedded amp Cytoscape Desktop New Session SRR oael l 1 8 Control Panel l i O Network vizMapper Editor Fiters P amp Import Network and Edge Attributes from Table A KJ Import Network from Table Data Sources Input File file psF Home Desktop interaction txt Interaction Definition Source Interaction Interaction Type Target Interaction Column 1 gt EETTEMIN lt gt coma gt Q columns in BLUE will be loaded as EDGE ATTRIBUTES Advanced O Show Text File Import Options Preview Text File Left Click Enable Disable Column Right Click Edit Column interaction txt Y Column 1 Y Column 2 Y Column 3 X Column 4 X Column 5 X Column 6 Y Column 7 ATF4 pp
37. h Step 3 Press search button Q The page is redirected to the Entity tab where the results are listed and ranked according to the relative entropy score By default 10 entities per page are shown and the user can navigate between the pages but it is also possible to see more entities per page by selecting through the dropdown menu to the right side of the page navigation Step 4 Click on one of the entities of your interest from the result list You will be directed to the Document tab where all PubMed abstracts that contain this entity and are relevant to the query are shown To see the frequencies of all entities over all found abstracts return to the Entity tab and click on the analysis icon You will be directed to the Analysis tab where an overview of the entities and their occurrence frequencies in the abstracts is given Step 5 In the Document tab you are able to highlight your entities of interest in the text by selecting the colour coded sections at the top of the page PMIDs or comments can be exported to a text file Step 6 To start a new search click Further selection and filtering of results are possible by using search component as described below SCAIView user manual Human version 3 3 Detailed Explanation 3 1 Search Component On the top left side of the user interface the Search Component is located with several buttons and a search field SCAIVIEW An KO 3 1 1 Button Description o A Decrease the
38. h node represents a protein which is connected to another protein via an edge The co occurrence frequencies can be shown as edge labels SCAIView user manual Human version 24 a a A Filtering option The system provides users with two filtering functionalities the strict entity filtering indicated by E and the cross entity document filtering indicated by D 1 E filtration Despite exclusive types of filter this is an inclusive filter meaning that it limits the context of the search to the terms which are provided by the user For example if you re going to extract co citations of genes involved in for example breast cancer you can limit your search to those genes or proteins and find those genes that are co cited with one or several of these specific genes You can do this either by entering the list of your specific genes proteins into the filtering field in a space separated format e g list of genes from microarray data or by adding the genes from the result list directly by pressing the E icon in front of each gene protein 2 D filtration this option enables the user to filter the retrieved documents for other types of entities which are mentioned together with the current entity For example we have queried the system with the keyword breast cancer and searched for genes proteins involved in this disease Now we would like to know which drugs have been developed for targeting ES
39. icking on the page number Using the dropdown menu In front of the page navigator it is possible to determine the desired number of entities to be shown on the page SCAIVIEW y submit Search iz E j D Help E Entit E About KOARH O i breast cancer a O Subcorpus Statistics O Server Statistics The following entities relating to breast cancer were found in 6286 documents Human Genes Proteins Chromosomal Location Y 4 STS Marker y non Normalized SNP Select Columns Expor Table Export PMMIDs Export Entities Export ideogram Export BIANA Expor PP Normalized SNP Normalized CRF SNP 1 422 entities found displaying 1 to 10 First Prevy 1 2 3 4 5 6 7 O Next Last 10 Entities per Page Y Drug Names Ref gt Relative Doc Date P IUPAC like e ss Entropy a t Count Reported Enka _ OMIM Reference TEA o Corpora O ama i s e 01604 4765 288 2009 prae ro Epigenetics O 8lascoz li amp 0 0648 1553 111 8 2010 PAHE TIOS ee O vecra li s e 0 0641 30544 261 O 2010 ED Ts 5 5 i Arabidopsis Genes A cain a o j i Mouse Genes O arance dll s 6 0 0592 448 81 2009 5 Ta Interaction Verbs O akara li s e 0 0590 87 z0 PERL es MeSH Disease i d r E es O Gram ll 0 0512 2579 104 0 2009 PAB TINTOS neurlST Ontology O encsra iii s 6 0 0510 16139 178 Y 2010 a gt OMIM GO Component O ace Hg Y 0 0376 1231 69 200 BD IS 1 DIOS O E8lscom2a2 dl e p
40. increase in cell proliferation anchorage independent growth cell migration invasion and a loss of p214Waf1 and p27Kip1 expression In knocked down cells the expression of survivin was significantly up with a concurrent decrease in cellular sensitivity to paclitaxel We also found that cells harboring endogenous mutant or defective BRCAI MDA MB 436 and HCC1937 were highly proliferative and a relatively low level of p21 WWaf1 and p27Kip1 by comparison to wild type BRCA1 cells Cells tah mutated also Expressed a high level of is a multifunctional tumor suppressive protein Many functional aspects of expression by shRNA in the wild type human survivin and were relatively resistant to paclitaxel by comparison to wild type cells Increase resistance to paclitaxel was due to an increase in the expression of survivin in both the knocked down and mutant BRCA1 cells because knocking down survivin expression by siRNA restored sensitivity to paclitaxel We conclude that down modulates the malignant behavior of the expression of p21 Vat1 p27Kip1 and inhibits cells the expression of survivin Moreover loss of expression or function leads to an increase in survivin expression and a reduction in chemosensitivity to paclitaxel MeSH No Medical Subject Headings MeSH assigned Title and MeSH Headings from MEDLINE yPubMed a database of the U S National Library of Medicine ky PubMed A direct link to the free full text versio
41. ing this option it is possible to construct information enriched protein protein interaction networks around a set of seed protein gene entities by selecting those entities under the Select column then clicking on the above icon will generate an interaction file in the XGMML format which can be directly imported into Cytoscape environment for network visualization The advantage of this format is that it can include additional information about the biological relationships of the network elements By clicking on the above icon the user can select 10 http sbi imim es web BIANA php SCAIView user manual Human version 21 which type of data should be included in the file The following data types can be included in the network file Entrez gene identifier KEGG and Reactome pathway GO annotations dbSNP PFAM and PDB This information is embedded into the XGMML file by BIANA automatically and can be visualized in Cytoscape environment under the Data Panel by selecting the attributes Export co citation results This option allows users to download the co citations of each entity type e g gene proteins or drug names in the literature The frequency of co occurrences found for the entities as well as other informative attributes including the corresponding Entrez gene identifier is shown in separate columns This option mainly aims at exporting the results of protein protein co citations in a tab delimited text format which ena
42. ining words starting with the prefix chromosome like chromosomes chromosomal etc See the Note Wildcard Find all documents containing words that have only one character after su like sub sun sum etc Author This finds all documents where Hofmann occurs as a co author Journal search Finds all documents where the Journal name contains Stroke PubMed E Utilities Using this command directly typed into the search field enables the user to pull the relevant selected abstracts directly from PubMed database into the SCAlView environment for entity recognition analysis Note Caution should be taken in using asterisk wildcard option Using asterisk wildcard symbol at the end of query keyword enforces the system to apply the stemming functionality for finding terms that have endings other than the usual form For example querying the system for Alzheimer on the MeSH disease returns more than 65000 documents but using the asterisk wildcard as Alzheimer returns only 24 documents containing rare variations of the term Alzheimer such as Alzheimerization Alzheimer apoE4 Alzheimerism etc SCAIView user manual Human version 3 3 Entity Tree Component The entity tree component is used for the selection of the different Entity Classes that are of interest to the user It includes all classes that are indexed from Medline by our entity recognition tools lf th
43. ion on genes e PEN HGenetinfoDB developed at IMIM that provides information on SNP of genes Ly o GeneCards is a searchable integrated database of human genes that provides concise genomic proteomic transcriptomic genetic and functional information on all known and predicted human genes SCAIView user manual Human version 8 e LAS The Online Mendelian Inheritance in Man at NCBI is a database that catalogues all the known diseases with a genetic component and links them to the relevant genes in the human genome and provides references for further research Pp suwissprol swissProt UniProt that provides information on proteins A gene might produce several proteins e g splicing variants so you may find several instantiations of this icon for a single entry Note For some entities there may exist several entries in the same database for example a gene or protein may have several entries in the OMIM database Mouse over or click on the linkout icons presents a list of identifier numbers for these entries and another click on each identifier number redirects you to that entry page in the OMIM database O aer H s e 0 3628 12365 620 2m0 PHAM mT Ta g 0 2729 6043 4070 Y 2010 N Ta O Serca Wis f a I OT E Fr Y 0 2708 412086 4728 Y 2010 IN 1Si2l5 C arer Wt amp p28 137800 E the ae 01672 3201 2419 2m0 N Ts Peer 7 Elercas Wi s amp Ho Te 211980 Chromosomal Location The entitie
44. k When multiple entities selected the latest one is bordered You re also able to select all entity classes at once deselect all at once or toggle the abstracts by clicking the corresponding buttons above the colourful entity types In the text body you see your selected entity in yellow which is highlighted differently other than the rest of entities The colours in the document view are a dimmed version of the colours you find in the legend In this way overlapping entities are resolved as overlapping colours they are in general darker By clicking the checkmark buttons you are able to highlight one of several or all the entities found in the abstracts thus you can focus on a certain entity class or several in combination When you are focused on one entity class documents that do not contain elements of this entity class will be greyed out lighter grey If you move the pointer over a tagged entity in the text a tool tip appears that gives you the possibility to link out to the specific database providing you additional information on this entity e g EntrezGene Please note that the tool tip becomes active only for your latest selection of entity type SCAIView user manual Human version 26 Below the title left to the PubMed ID of each abstract you find a PubMed Icon that directs users to the abstract of the document at PubMed in an external viewer providing in some cases access to the full text of the document Among the docume
45. lication date between the year 1980 and the year 2100 the 2100 is a replacement for up to the newest This is quite useful to avoid false positive hits like the Gene AIR which is often found in the old Medline entries prior to 1975 the titles are fully capitalized MeSH search Similar to the previous query this search query avoids false positive matches It does this by restricting the search only to the documents that have been assigned to the MeSH Medical Subject Headings category of genetics in addition to the term anaemia Please note that the human MeSH annotators at NCBI are slower than the publications This means that it takes up to 2 years to fully categorize the publications in the meantime you will not find them with these restrictions Groupings Find all documents that contain either the word proinflammatory or the word inflammation and which also contain either the word human or the word mouse Note that without the parenthesis this query would be interpreted in an entirely different manner The operators AND OR have to be in capital letters SCAIView user manual Human version 6 breast cancer 5 chromosome su AUTHORS Hofmann JOURNAL Stroke EUTILS alzheimer Spanned Search Find all documents containing the word breast within 5 words of cancer in any of the text fields The 5 may be replaced with any integer Wildcard Find all documents conta
46. m PubMed Epigenetics Under this entity class subclasses of histone modification are assigned Using this option it is possible to detect histone modifications in biomedical literature with Conditional Random Fields Human miRNA This entity class enables the user to find microRNA named entities in the text with the possibility of access to the miRBase database through linkouts from both the Entity view page as well as the annotated text Arabidopsis Genes Selecting this entity class highlights the gene names specific to the plant model organism Arabidopsis thaliana in the abstract texts Mouse Genes Proteins This entity class contains a collection of gene and protein names specific to the model organism Mus musculus and once selected the relevant gene names and corresponding synonyms are identified in the abstract texts Interaction Verbs This option highlights the type of interactions mentioned in the text These are interaction verbs which are mentioned in a biologically meaningful context in the text MeSH Disease This Entity Class contains all the Disease names that exist as Medical Subject Headings MeSH Inclusion of this option in the search allows the coverage of all disease aliases related to the query keywords Kol fik C R Klinger and M Hofmann Apitius Identification of Histone Modifications in Biomedical Text for Supporting Epigenomic Research BMC Bioinformatics 10 S28 January 2009
47. ng the above option it can be used as input in Ideogram Browser to visualize the coordinations of corresponding SNP s on the human chromosomes File View Options Help Chr 2 Chr 3 Chr 4 Chr 5 Chr 6 Chr 7 Chr 8 Chr 9 Chr 10 Chr 11 Chr 12 E E E A I j 3 i lt l E I B m i y f H m y i i F E i l A i l E l a e z E i s 5 I l 1 i l E s a of l f i H l i E 7 i I 5 5i 0 00M 0 00M 0 00M 0 00M 0 00M 0 00M 0 00M 0 00M 0 00M 0 00M 0 00M 250 00M 250 00M 250 00M 250 00M 250 00M 250 00M 250 00M 250 00M 250 00M 250 00M 250 00M 250 00M Chr 14 Chr 15 Chr 16 Chr 17 Chr 18 Chr 19 Chr 20 Chr 21 Chr 22 Chr X Chr gt bd a E E ns H ra El El 5 E El p J 5 2 2 I i j B m Fl D Loss S Loss jin PM Gain Amp el Header _ Condensed Mode v Show Lines number of SNPs 38 Value CNState v Info Value From Base To Base Length Lower bound Upper bound RHCE RHD amplification 25561326 25619949 58 6 KB _ pS Intersecting Genes _ Diff Mode pre filtering v Min length OA Gene Name From Base To Base 2 Group limit 3H TMEMS0A 25537398 25561439 _ Consensus Mode RHCE 25561327 25619950 OK 388606 SDHDP7 25597789 25599078 _ Us
48. ns of the documents in PubMed Central PMC has been provided when they are available 24 Gor idestimkage_and haplotype association studies map intracranial aneurysm to chromosome 7q11 PubMed N PubMedCentra 11536080 Authors H Onda H Kasuya T Yoneyama K Takakura T Hori J Takeda T Nakajima Inoue Date 2001 10 Journal American journal of human genetics A reporting feature which has been implemented besides the Statistics option allows to export the PubMed ID of the selected abstracts as well as any comments by the user to a text file It is also possible to copy amp paste the sentences of interest from the abstract into the comment field After the selection is made and or comments are filled the abstract ID and comments can be exported to a txt file by pressing the Export to File button Please note that paging the document view does not affect the selections made in the previous pages SCAIView user manual Human version 27 Result for breast cancer NE page totals to 3958 and took 50 ms Export use CTRL C Add All Identifiers from Page Clear List Toggle Abstracts I 2010 02 03 14 25 Search breast cancer chrom NER run Human Genes Proteins genes entity BRCA1 vie nal Locations e 19551867 BACAI modulates malignant ceil behavior 19833996 This study deals with family risk informationt survivin and chemosensitivity in human b er cells N Bee 19551867 Authors Moltir
49. nt s information such as authors date and journal s name the SciMago index of the journal has been provided wherever available SciMago is a type of impact factor based on the page rank algorithm introduced by an independent Spanish university Moreover a Statistics option has been also provided in order to give an overall overview of the entities co mentionings in the same abstract APC Abstracts Select All Select All Entity Classes Classes ee All PA Classes Desea AEniy Cases NA g M Drug Names X i uPac El il on at Human miRNA i BRCA1 Modulates malignant cell behavior the expression of survivin and chemosensitivity in human breast cancer cells Wy Pu 19551867 Authors Moltira Promkan Guangming Liu Pimpicha Patmasiriweat Subhas Chakrabarty Date 2009 12 15 Journal International journal of cancer Journal international du cancer SciMago 0 831 Affiliation Department of Microbiology Immunology and Cell Biology Southern Illinois University School of Medicine and SimmonsCooper Cancer Institute Springfield IL 62794 9677 USA Statistics L Select iD with comment Drug Hames Protein Gene MesHDisease MERAB Mouse Pacitaxei 5 BRCAT 12 Mammary Carcinomas Humen 4 BRE A Srca 12 COKNMIA 6 SA A eres 7 CDKMB 3 E fl corra 6 UE regulating 1 BRCA1 are not fully understood We used a shRNA approach to probe the function of BRCA1 in human breast cancer cells Knocking down MCF and MDA MB 231 cells resulted in an
50. owing examples Search query Description Occurrence Find all documents containing the word inflammation in any of the main text fields title abstract PMID or MeSH It will find all occurrences of Inflammation versions of the word inflammation even if they contain capital letters case insensitive Document Identifier Find the documents with the PMID 19551867 OR 19833996 Medline Identifiers PMID 19551867 or 19833996 Conjunction Find all documents containing both the word inflammation and the word stroke in any of the main text fields title abstract or MeSH The two inflammation AND stroke A words may be in different fields The operator AND has to be in capital letters Disjunction formal this form of query finds all p documents containing the word proinflammatory or proinflammatory OR antiinflammatory o antiinflammatory The Operator OR has to be in capital letters SCAIView user manual Human version 9 h moglobin production carcinoma AND DATE 1980 TO 2100 anaemia AND MESH genetics proinflammatory OR inflammation AND human OR mouse Wildcard Find all documents containing the word oroduction in any of the search fields and the word hemoglobin or haemoglobin or hxxxxmoglobin The asterisk is used as a possible replacement for any subtext Date Range Find all documents containing the word carcinoma in any text field which have a pub
51. p to see the corresponding SNPs highlighted 19994839 Feosr frequency in P p gene have toc wth B identified in cases of childhood absence epilepsy CAE i in the Ching hether th iated with E 6 to 12 of di f10 In the abstract text Ps ara dued in both a babloives mayest in 210 trios of iio ward cae ona i RGO3R in exon 9 as being close related to CAE The carriers of the G allele of had i i in a Bayesian network In addition two ha a inthe consisting of five CSNPs in the region of may be an important susceptibility gene for in the Chinese Han population Step 14 Type or copy paste the name of these SNPs from each abstract into the Select ID with comment filed which lies under the title of each abstract Then tick the checkbox Step 15 Click on the Export icon on top of the page to export your comments along with their corresponding PubMed identifiers to a text file SCAIView user manual Human version 34 O Help El Documents Semy Many nl About Result for epilepsy NER run DrugBank for entity Camphane Page 0 with 50 documents per page tatals to 4 and took 24 ms 1 Common polymorphisms in the CACNA1H gene associated with childhood absence epilepsy in Chinese Han population N PubMed 17156077 Authors J Liang Y Zhang Y Chen J Wang H Pan H Wu K Xu X Liu Y Jiang Y Shen X Wu Date 2007 05 Journal Annals of human genetics Affiliation Department of Pediatrics Peking University First
52. ply this SCAIView user manual Human version 25 functionality to list the following information in the Entity view only proteins which are targeted by drugs 1 TARGET only drugs which are known as biological molecules 1 DRUGBIO only SNPs which are genotyped by specific array types 1WAFFY100K 1 AFFY500K 1 AFFYSNP6 1 ILLUMINA650Y 1 ILLUMINA610QUAD 1 ILLUMINAHUMAN1M Please note that these results are Boolean i e whether a protein is drug target or not or whether a drug is biological molecule or not etc In contrary to its application to the non Boolean domains which provides a list of entities e g proteins that share a certain annotation e g protein domain this filtering for Boolean results provides a list of all entities e g proteins which have positive Boolean result e g all are drug targets without any inference about association between the entities If inference of association between entities is desired e g proteins that are targets of the same drug then the same query should be repeated on the entity of interest e g Drug Names only 3 4 2 Document View Document view displays all the documents containing the selected entity from the Entity view and the corresponding search query By default these documents are ranked by date the newest at the top On top of the Documents tab you can select the different entity classes that should be highlighted When you select an entity type it is bordered in blac
53. ponent switches to the Document View and all documents shown include the entity and the corresponding search query You can come back to the entity view by selecting the Tab Entity at the top Note In front of each entity name there are two icons the analysis icon El which directs the user to the statistics page and the filter icon bf that enables the user to copy the selected entities in the Entity view to the filter field so that a secondary search can be performed but restricted to the entities copied in the filter field The column Relative Entropy displays the relevance of the entity for a given search query This measure defines the distance of the entity in the corpus of the search string specific relative to the complete Medline completely unspecific The range of values of relative entropy spans from 1 to 1 The closer this values to 1 the more relevant the entity to the query The value should be used for comparison purposes only The approach chosen in the current version uses document frequencies to calculate the ranking meaning once a document contains the entity in question regardless of how many times it appears the document is counted once SCAIView user manual Human version 17 The column Aneurysm Linker Degree lists the number of the interacting protein partners in the context of intracranial aneurysm protein interaction network for more details refer to the neurlST project website The
54. rect link out to the InterPro databse SCAIView user manual Human version 18 The column SciMago Score lists the SciMago index of the journal where the abstract has been published This index is similar to impact factor indexing which has been introduced by an independent Spanish university The column ATC Code is only valid for Drug Names selection and stands for Anatomical Therapeutic Chemical Classification System This column describes and links the drug name entities to their corresponding classes in the ATC system The column Drug target determines whether the protein or product of the gene in question is already recognized as a target for specific drugs in the DrugBank database The column Entrez Gene Identifier can be added to the Entity table from the drop down menu on top left lt shows the gene identifier for each corresponding gene entity The column HUGO lists the unique gene symbols for each gene protein entity assigned by Human Genome Organization nomenclature committee The column KEGG Pathway describes the molecular pathway s in which the corresponding entity is involved There is also a link out to the representation of the pathway in the KEGG database The column Reactome Pathway describes the biological pathway s in which the corresponding entity is found The link out redirects the user to the original information in the Reactome database The column
55. s of the Entity Class Chromosomal Location are found by a regular expression searching for Cytoband information done with ProMiner This information is frequently used in Linkage Analysis and a search gives an overview on the involvement of genetic information on Chromosomes in relation to a query STS Marker The entities of the Entity Class STS Markers are found by a regular expression search of the Identifiers executed by ProMiner STS Markers are not only used in Linkage Analysis but also used to relate sequential information to clearly defined positions on the sequence Later versions will include link outs to the UniSTS database at NCBI L non Normalized SNP The entities of the Entity Class non normalized SNP are found by MutationFinder system They consist of mutation mentions from text or Variation mentions compliant with the Mutation Nomenclature found by the regular Expression facility of ProMiner Caporaso JG Baumgartner WA Jr Randolph DA Cohen KB Hunter L Mutation Finder A high performance system for extracting point mutation mentions from text Bioinformatics 23 14 1862 1865 2007 SCAIView user manual Human version 9 Normalized SNP The entities of the Entity Class Normalized SNPs are found through a search performed by OSIRIS while the dictionary is generated from the synonyms found in the EntrezSNP database and normalized to those IDs Direct mentions of dbSNP identifiers are fo
56. t gt a Movement Disorders gt gt Parkinsonian Disorders gt gt PE l Parkinson Disease q EEN Q Digestive System Diseases Stomatognathic Diseases Respiratory Tract Diseases Otorhinolaryngologic Diseases L 6 Nervous System Diseases Step 3 Select Human Genes Proteins from entity tree 0 Autoimmune Diseases of the Nervous System ee E Step 4 Press search Step 5 Click on the Select Columns button and from the L_ Entrez Gene Identifier menu select the KEGG Pathway and Drug Target options LI Huso then press OK KEGG Pathway i i i i i gt ma fa d Help Documents Step 6 Click Filtering icon in front of the first target with AVES Oo D sran did i ntities filtered by 1 TARGET relating to par Yes under the Drug Target column LOTARSET dei e E Select Columns Export Table Export PIDs Export Entities Export 624 entities found displaying 1 to 10 First Prey 1 2 3 4 5 6 7 8 Ne Relative Drug Step 7 Press search again P aa Seen Entity Entropy Target 7 Human Genes Proteins 3 Chromosomal Location g snca di s 1 2271 Ves 8 Alzheimer s diseas STS Marker Parkinson s diseas Step 8 A list of genes proteins which are known drug targets is shown 624 entities found Help Documents J S About Step 9 Now for getting a co citation network we restrict the O Subcorpus Statistics O Server Statistics he following entities filtered by 1 TARGET relatin
57. und by the regular expression feature of ProMiner with inclusion and exclusion criteria Link outs of this entity class are provided to EntrezGene at NCBI provides information on genes e ZPCONP HGenetinfoDB developed at IMIM provides information on SNP of genes y o o GeneCards provides concise genomic proteomic transcriptomic genetic and functional information on all known and predicted human genes e L LAUJ dbSNP at NCBI provides information on genetic Variations HapMap describes the common genetic variants in human genome Note A search under the Entity Class Normalized SNP will highlight SNP co mentionings in the Document View Hovering your mouse over the highlighted SNP leads to a link out menu pop up containing a header line about the corresponding dbSNP code type of mutation chromosomal location gene name and the array platform Affymetrix or Illumina or both as well as links to the Entrez gene database HGenetInfoDB database GeneCards database dbSNP and HapMap databases Further information on the array platforms can be obtained by following the link outs In some cases it can be seen that a SNP occurs within the sequences of two genes simultaneously Such information is included in the header line describing the name of both genes as well as additional link outs for both genes to their corresponding entries in Entrez gene SNP and GeneCard databases den Dunnen J T amp Antonarakis S E
58. were identified by using the Colored Eco Genetic Relationship Map CEGRM Hierarchical nonlinear models were fitted to characterize information gatherers disseminators and blockers RESULTS Gatherers of information were more often female P 001 parents P lt 001 and emotional support providers P lt 001 Disseminators were more likely female first and second degree relatives both P lt 001 family members in the older or same generation as the participant P 001 those with a cancer history P 001 and providers of emotional P 001 or tangible support P lt 001 Blockers tended to be spouses or partners P 001 and male first degree relatives P 001 CONCLUSIONS Our results provide insight into which family members may within a family based intervention effectively gather family risk information disseminate information and encourage discussions regarding shared family risk MeSH No Medical Subject Headings MeSH assigned 3 4 3 Analysis View Analysis View provides a statistical overview of the all entities co mentioned with the entity of interest in the relevant abstracts By clicking on the analysis icon in front of each entity in the Entity view the user is directed to the Analysis view page where a statistical overview of co mentioned genes GO terms etc is shown in separate tables The statistics of each table can be exported to file with three different formats CSv Excel and XML Analysis schema for bre
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