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LOVD 3.0 user manual Build 3.0-14

1. Figure 2 4 Watch the progress bar complete while LOVD informs you which part of the database table installation is currently in progress LOVD setup The only setting that cannot be changed at a later time is the install lock which is checked by default Setting the uninstall lock will prevent uninstallation of LOVD by the database administrator The only way to remove this lock is directly through the MySQL database backend For more information on the options of the LOVD system settings see the LOVD system settings section of the manual After filling in the form click Continue If everything was filled in correctly LOVD will register the LOVD system settings Click Next to continue to the last step Almost done 2 Installing LOVD Install process KOD LOVD 3 0 Leiden Open Variation Database so Bulky POOR le se Installation steps pemen peti IIA 0 100 sie ec Configuring LOVD system settings Please complete the form below and press Continue to continue the installation We re almost done Administrator account details General system settings Title of this LOVD installation LovD Leiden Open Variation Database Installing database tables Institute optional Leiden University Medical Center Database URL optional http databases lovd nl shared check Configuring
2. O The following users are currently not a curator for this gene Click on a user to select him her as Curator or Collaborator 1 entry on 1 page Showing entry 1 10 per page Test Manager manager Leiden University Medical Center Netherlands O Manager 10 per page All users below have access to all data public and non public of the IVD gene database If you don t want to give the user access to edit any of the data that is not their own deselect the Allow edit checkbox Please note that users with level Manager or higher cannot be restricted in their right to edit all information in the database Users without edit rights are called Collaborators Users having edit rights are called Curators they receive email notifications of new submission and are shown on the gene s home page by default You can disable that below by deselecting the Shown checkbox next to their name To sort the list of curators for this gene click and drag the 1 icon up or down the list Release the mouse button in the preferred location Name Allow edit Shown f Ivo FA C Fokkema M M x t Curator M x t Collaborator Oo x Enter your password for authorization Save curator list Cancel Figure 5 1 The Authorize curators form with on the top the users who are available to be selected and on the bottom the selected curators and collaborators
3. 3 Go Editing me database oc co si mocu mi maik pies e a EK eS 5 4 Deleting a gene database o a a 5 9 Assigning curators and collaborators moe meea epe ea be ea ews Gene transcripts 61 Which tramectipt s should I pick o oo ee eee ee ee tner tss 6 2 Creating new transcripts es be ee ee cas de TOOT a anseio e ep a Ha a Be Sei ee e a Geen Ow ae Ga Delta treet sat Be Se AA ae oe ae eee a Custom columns FL Custom column categories escusa T a Creating a new custom COMIDA o coo csc be eR RRR ER RE RE a Ta Enabling custom columis o os ce nica ERO EERE eee BE 7 4 Editing custom column settings coccion dass To Changing the order of custom columns s so dos goes 244 ee bee ww RES T6 Disabling custom Connie o oa he ER aa TI Deleng custom OO e cc i oea AAA AE G 7 8 Downloading custom column data to text files 0 o 7 9 Importing custom column data from text files Adding data to LOVD 8 1 Starting a submission by creating an individual 8 2 Continuing an unfinished submission gt lt gt ss so sra sasra trario 8 3 Submitting summary variant data s so sso ccoo eee 11 11 14 16 17 18 20 21 22 23 23 27 27 28 28 31 31 31 32 32 33 33 34 38 39 41 42 44 44 45 Contents 8 4 Adding data to already finished submissions 000 50 9 Downloading amp importing data 52 9 1 The LOV DS taper IE
4. depending on the type of column Please note that if this shared custom column will no longer be active for any parent object and your database already contains a lot of information disabling this column may take some time If this is the case LOVD will display a warning Type in your password in the Enter your password for authorization field for verification of your authorization and submit the form If the Remove column link is not enabled i e you see it but you can t click it the column is an HGVS standard column and it can not be removed To disable the given column for multiple parent objects at the same time start with one of the following steps e From any disease or gene that you have authorization of open the Options menu button and click the View all available phenotype columns or View all available variant columns link depending on which type of column you wish to disable e If you re a manager or higher click the Browse all custom data columns link of the setup menu tab dropdown menu or from the setup area click the Browse all custom data columns already available to enable or disable them or view or edit their settings link listed under Custom data columns This is the list of all custom columns To filter this list for category click the options wheel icon on the top left hand side of the columns listing to open up the menu and select the category you are intereste
5. edit all data in the system Selecting them as curators doesn t grant them additional access rights but does enable the notification emails Also please note that all genes in LOVD should have at least one visible curator To be able to successfully submit the Authorize curators form there needs to be at least one user with the Allow edit and Shown checkboxes checked Sorting curators KONI D LOVD Leiden Open Variation Database rator isovaleryl CoA dehydrogenase IVD Your account Log out Curator Ivo F A C Fokkema acti s rico Y A Sort curators for the IVD gene To sort the list of curators for this gene click and drag the 1 icon up or down the list Release the mouse button in the preferred location If you do not want a user to be shown on the list of curators on the gene homepage and on the top of the screen deselect the checkbox on the right side of his her name Name Shown t Ivo FA C Fokkema M t Curator Save Cancel Build a 10 ty Medical C Figure 5 2 The Sort curators form allowing curators to resort the gene s list of curator names and show or hide curators from the gene homepage and the page headers 29 5 Gene databases Assigning curators and collaborators Required level Curator Since the curator names are shown on the Available from LOVD 3 0 Build 01 gene homepage and on the page headers it is sometimes
6. ID referring to the ID in section Individuals This field cannot be updated during an import mandatory from section Columns If set to 1 this column is mandatory When entering new data this custom column s field must be filled in See also section Creating a new custom column Default value is 0 mapping flags from section Variants On Genome Information about how LOVD handles the mapping of this variant LOVD has an auto matic mapping script that finds transcripts in the range of a genomic variant and can annotate the genomic variant on the transcript using the Mutalyzer web service Whether or not LOVD is allowed to map the variant and how LOVD will handle the mapping is stored in this field This field is a boolean flag column multiple options can be grouped in this field by adding the numbers up Possible values 57 9 Downloading amp importing data The LOVD3 import format ID Name Description 0 No mapping allowed 1 MAPPING _ ALLOW When set the variant can be map ped by the LOVD mapping script 2 MAPPING ALLOW CREATE GENES When set LOVD is allowed to cre ate new genes in the database if needed to annotate the variant 4 MAPPING_IN PROGRESS Not used when importing when set LOVD is currently busy mapping the variant 8 MAPPING NOT RECOGNIZED Not used when importing when set LOVD did not recognize the vari ant and was therefore unable to map the variant 16 MAPPING ERROR Not used when im
7. This field cannot be updated during an import position_c_start_intron from section Variants _On Transcripts The position relative to the start or end whichever is closest of the intron of the first base of the variant The first base of the variant is defined by the HGVS nomenclature rules and may be the same as the last base This field only applies to variants that start in an intron This field cannot be updated during an import position_c_end from section Variants _On_ Transcripts The position relative to the translation start site of the last base of the variant The last base of the variant is defined by the HGVS nomenclature rules and may be the same as the first base This field cannot be updated during an import position_c_end_intron from section Variants _ On Transcripts The position relative to the start or end whichever is closest of the intron of the last base of the variant The last base of the variant is defined by the HGVS nomenclature rules and may be the same as the first base This field only applies to variants that end in an intron This field cannot be updated during an import position_g__mrna_ start from section Transcripts The genomic position relative to the chromosome of where the transcript starts This field cannot be updated during an import position_g mrna_end from section Transcripts The genomic position relative to the chromosome of where the transcript ends This field cannot be
8. To add a screening to an existing individual click on the Indivi duals tab and select an individual for which you are authorized Options Click on the Options menu button to open up the individual Options menu button entry s menu If you do not see the Options menu button you are not logged in or you do not have rights to edit this individual In the opened menu click Add screening to individual to open up the screening data entry form You are now in the submission process described in section Adding a variant screening to the individual The option Back to individual is not available when you submit a screening to an existing individual You can only finish this submission if you also add at least one new variant to this new screening or select at least one previously submitted variant as confirmed by this new screening After finishing the submission LOVD sends an email to the curator s requesting the publication of the submission Adding phenotype information to an individual To add phenotype information to an existing individual click on the Individuals tab and select an individual for which you are Options authorized Click on the Options menu button to open up the Options menu button individual entry s menu If you do not see the Options menu button you are not logged in or you do not have rights to edit this individual In the opened menu click Add
9. type application atom xml href http api rest variants IVD 0000000563 gt lt id gt tag databases lovd n1 1970 01 01 1VD 0000000563 lt id gt lt author gt lt name gt Unknown lt name gt lt author gt lt contributor gt lt name gt Unknown lt name gt lt contributor gt lt published gt 1970 01 01T00 00 00 01 00 lt published gt lt updated gt 1970 01 01T00 00 00 01 00 lt updated gt lt content type text gt symbol IVD id 0000000563 position_mRNA NM_002225 3 c 860 position_genomic chri5 40707154 Variant DNA c 860G amp gt A Variant DBID IVD_000001 Times_reported 1 lt content gt lt entry gt lt feed gt Figure 10 2 Example LOVD API output format The three longest lines have been shortened to fit this page This example output of a search on DB ID returns one variant in the IVD gene and its basic information Source LOVD3 shared installation The variant information shared through the API consists of the official gene symbol of the selected gene symbol the variant s internal ID id the variant s position relative to the transcript in HGVS like format position_mRNA the variant s genomic position position_genomic the DNA field in HGVS format HTML encoded to not break XML parsers Variant DNA the variant s DBID value Variant DBID and the panel size of the individual of the variant entry Times_reported If the variant could not be interpreted by Mutalyzer the position fields will
10. 5 Gene databases Creating a new gene database Human readable reference sequence location To create a human readable reference sequence file you can use our Reference Sequence Parser It retrieves the reference sequence from Mutalyzer and formats it into a human readable format with good annotation of the upstream sequence the exons the introns the downstream sequence the predicted protein sequence and the alternative stop codons Fill in the complete URL of the file including http or https Customizations LOVD allows you to customize the gene homepage by adding citation references headers footers notes and a disclaimer The header and footer will also be shown on the variant listings Citation reference s Using our PubMed custom link you can add links to PubMed articles to cite your database or that you want to point visitors to Include disclaimer If you want a disclaimer added to the gene s LOVD gene homepage select your preferred option here Text for own disclaimer HTML enabled Only in case you selected the Use own disclaimer in the field above you can enter the text here Text in this field will be ignored if you disabled the disclaimer or selected the standard LOVD disclaimer Page header HTML enabled If you want a gene specific header on all public gene specific pages please enter the text here Header aligned to In case you defined a page header here you can select how you wan
11. Available from LOVD 3 0 Build 01 database However if you d like to add more transcripts later please proceed to the gene homepage Click on the Options menu button to open up the gene entry s menu If you do not see the Options menu button you are not logged in or you do not have rights to edit this gene s settings In the opened menu click Add transcript s to gene to open up the gene s edit form Please wait while we contact Mutalyzer to provide a list of available transcripts If you get the error message No more transcripts available that have not been added yet then all transcripts that are available to Mutalyzer have already been added to this gene Select the transcript s you would like to add and click the button Add transcript s to gene After the confirmation you will be forwarded to the gene homepage Beneath the header Active transcripts you can see which transcripts are now active 31 6 Gene transcripts Editing a transcript 6 3 Editing a transcript Because LOVD standardizes the transcript in Required level Curator formation there is very little information that Available from LOVD 3 0 Build 01 is freely editable At this moment you are only allowed to assign or change Ensembl identifyers to the transcript s you use To edit a certain transcript proceed to the gene homepage scroll down to Active transcripts and click the transcript in question Alternat
12. Installing LOVD is a piece of cake However you might require help from your system administrator since there are a few dependencies that need to be taken care of first 2 1 Before you install LOVD is a web based software project Therefore installation requires a correctly set up webserver A suitable server with the necessary software installed is available at virtually all academic institutions and countless commercial hosting providers If you don t want to run LOVD on a server but rather want to have it running on your computer we can recommend the XAMPP package which installs all needed software on your computer regardless of whether it s Linux Windows or Mac Also at the time of this writing we are offering free server space if you need to set up an LOVD See our website for more information In that case you don t need to install anything and you can skip this chapter If you re experienced with web servers and you want to set it up yourself LOVD has been extensively tested with the Apache webserver but any webserver able to run PHP scripts should suffice You ll need PHP 5 3 0 or higher and MySQL 4 1 2 or higher LOVD will force the use of the UTF 8 character set but we recommend setting this as the default value for your software nonetheless Also you ll need to install a properly configured Mail Transfer Agent for sending emails such as registration information LOVD may work with other database platforms bu
13. been filled in and stored correctly the installation is complete Now that you re done installing LOVD click the Continue to Setup area button to be forwarded to the LOVD setup area From there you can perform the most important actions for managers in LOVD such as creating new gene databases or disease information entries registering new user accounts or authorizing curators or manage the custom columns and links The button to create a new gene will be highlighted as a suggestion of your next step 10 3 LOVD Setup To change system wide settings but also to perform actions with system wide effects start at the LOVD setup area The setup area is only available for managers and the database administrator and can be accessed by clicking on the Setup tab in the menu If you do not see a Setup tab you first need to log into the system with a manager or administrator account The LOVD setup shows some statistics on the left of the screen like date of installation number of registered users and variant counts separated by status Furthermore there are two columns of options The left column has options for the system settings authorized users the custom columns custom links full data download and the LOVD system logs The right column has options for genes transcripts diseases individuals and variants Some of the general options from the LOVD setup are also available through the Setup tab s dropdown men
14. can uninstall LOVD provided the uninstall lock has not been set during LOVD installation When the Forward messages to database admin setting in the LOVD system settings is enabled the database administrator will receive copies of submitter registrations and data submissions or edits Manager A manager has access to almost everything the database administrator has access to However the manager is not able to create new managers or to edit existing managers Also a manager cannot uninstall LOVD even if the uninstall lock is not in place A manager can only be created by the administrator and often assists the administrator or takes over the customisation of LOVD for the curators Curator The curator level user is actually a submitter which has been given curatorship of one or more genes Therefore a curator only has access to the gene databases he is appointed to and not to the system wide setup area However also the database administrator or a manager can act as a curator by being appointed to certain genes but in this case there is of course no restriction in access To assign a user to become curator follow the steps explained in section assigning curators and collaborators available for managers and up 17 4 Authorized users Registering a new account Collaborator The collaborator level user is a new type of user introduced in LOVD 3 0 Collaborators are submitters with read access to non public
15. chr15 40697686_40713512 position_match exact Chromosomal range exclusive match only match genes completely within this range http databases lovd nl shared api rest php genes search position chr15 40657686__40762512 amp position_match exclusive Chromosomal range partial match match any gene overlapping the given region http databases lovd nl shared api rest php genes search position chr15 40657686__40762512 amp position_match partial Variants Listing of all variant entries in a certain gene http databases lovd nl shared api rest php variants IVD Searching on the DNA position Coding DNA or genomic position exact match only http databases lovd nl shared api rest php variants IVD search_ position c 157 This does not allow for partial matches so variant c 157 158del is not matched c 157 will match 157 and c 157 158 will match c 157 7 _158 However c 157 does not match c 157 5 Searching on genomic locations can be achieved using g as a prefix http databases lovd nl shared api rest php variants IVD search_position g 40699840 Genomic position only exclusive match only match variants completely within this range http databases lovd nl shared api rest php variants IVD search position g 40710300_407104104zposition_match exclusive Genomic position only partial match match any variant overlapping the given region http databases lovd nl shared api rest php variants IVD search position g 40710300_40710
16. column is now disabled and removed from the data entry forms and the data listings and detailed views If the Disable column link is not enabled i e you see it but you can t click it the column is an HGVS standard column and it can not be removed 7 7 Deleting custom columns Custom columns which are created by users Required level Manager managers or the database administrator can Available from LOVD 3 0 Build 01 also be deleted permanently from the system for instance if they were for testing purposes only or if they are no longer needed First you need to make sure the column is no longer active See section Disabling custom columns on how to inactivate a column First proceed to the column s detailed view access the custom data columns listing through the setup menu tab dropdown menu or setup area find the column you wish to delete and click on its entry Then from its Options menu button select Delete column Type in your password in the Enter your password for authorization field for verification of your authorization and submit the form If the Delete column link is not enabled i e you see it but you can t click it the column is either still active check the Active in LOVD field it s an HGVS standard column check the HGVS required column field or it is created by LOVD itself check the Created by field In any of these cases the column can no
17. contain a question mark The difference between the id field and the Variant DBID field is that the first is the ID of the variant observation whilst the latter is the ID unique for this variant but shared for each observation It is used link back to LOVD from genome browsers for instance When variant observations are grouped together the Times_reported field will contain the sum of the values of all observations together 68 10 The LOVD API Possibilities 10 3 Possibilities A full list of options for this API is included below Please note that although rest php is included in all the URLs simply rest will work also However for LOVD2 installations this does not always work and as such the extension is included Genes Listing of all genes in the database http databases lovd nl shared api rest php genes Searching on the gene symbol full match only http databases lovd nl shared api rest php genes search_symbol IVD Showing only one specific gene entry http databases lovd nl shared api rest php genes IVD Searching on the genomic position Chromosome only http databases lovd nl shared api rest php genes search_ position chr15 Chromosomal location http databases lovd nl shared api rest php genes search_ position chr15 40705600 Chromosomal range exact match only match genes having exactly this range http databases lovd nl shared api rest php genes search position
18. data on a certain given gene Just like curators these users must be appointed to genes by managers or the database administrator See section assigning curators and collaborators for more information Submitter Submitters have no special rights except to submit data to the database which then needs to be checked and published by curators or managers Depending on the LOVD system settings submitters are also able to edit the data they have submitted previously Submitter accounts can also be created edited or deleted by managers or the database administrator although usually this should not be necessary Curators do not require a separate submitter account they can use their curator account to submit new data 4 1 Registering a new account Please note that you do NOT need to register to view the data available in the database You only need an account for submitting new variant data Anyone can create a new submitter account For collaborators curators or managers register ing as a submitter is often the first step their account can then be upgraded by a manager or the database administrator respectively The major difference between registration and direct creation of a new account by a manager or the database administrator is that the registration can be performed by the public and therefore it requires you to be logged out of LOVD The registration form is protected using a reCAPTCHA module which makes sure the form ca
19. databases could exist for the same gene by setting a suffix on the gene symbol there the id field could have a different value than the symbol field Having two fields for the gene symbol is retained in the API to keep the format between LOVD3 and LOVD2 consistent Please note also for consistency with the LOVD2 API that the refseq mrna field can contain only one value whilst in LOVD3 one gene can contain multiple transcripts The LOVD API shows only the first transcript added to the gene 67 10 The LOVD API Format Variants lt xml version 1 0 encoding UTF 8 gt lt feed xmlns http www w3 org 2005 Atom gt lt title gt Results for your query of the IVD gene database lt title gt lt link rel alternate type text html href http databases lovd nl shared gt lt link rel self type application atom xml href http lovd nl shared api rest variants IVD gt lt updated gt 2013 03 11T15 30 41 01 00 lt updated gt lt id gt tag databases lovd nl 2012 05 02 web01 shared REST_api lt id gt lt generator uri http www LOVD n1 version 3 0 09 gt Leiden Open Variation Database lt generator gt lt rights gt Copyright c the curators of this database lt rights gt lt entry xmlns http www w3 org 2005 Atom gt lt title gt IVD c 860G amp gt A lt title gt lt link rel alternate type text html href http search_VariantOnGenome DBID IVD_000001 gt lt link rel self
20. detected using a certain screening Categories indicated with an asterisk are data types with custom columns also see Custom column categories and the exact list of fields in this category depend on the LOVD settings Lines in the import file starting with one hash character are settings The following settings are currently recognized charset Indicates which carset was used when creating the file During import usually the file encoding is detected given the file s contents in which case this setting is ignored max_ errors When this setting is not defined in the import file LOVD stops processing an import file when 50 errors occurs This default value can be modified in the import file with variable max errors Increasing the max errors allows LOVD to process the import file without interruption Decreasing the max errors interrupts the import process earlier Regardless of the value of max errors all errors must be solved before the import is saved to LOVD Warnings however do not interrupt the import process and data can be saved in LOVD even when warnings are displayed Each section header is followed immediately by a line that indicates the names of the fields used in this section When reading a downloaded file this nicely indicates which column represents which data When importing a file being able to change this line allows you to skip certain columns or decide yourself in which order you
21. ece A A 52 9 2 Downloading amp importing data ici a a 61 9 3 Downloading amp importing the complete data 63 9 4 Downloading 4 importing the custom column data 63 9 5 Downloading amp importing own data a e o 64 9 6 Downloading amp importing a gene s data a ee 65 10 The LOVD API 66 10 1 Terms of service and fair use policy o oc socs ee e moeg ee Ree Re ws 66 MS Format ds o kG eee A ER a REM MESER ROMS HES 66 PO Pee ee oo Ee EIA 69 11 Keeping your data secure 71 11 1 Built in sec rity meas res dedicara EE 71 11 2 What you can do to protect your daba 244 6 Fee 5 we Pe eb Re eee es 72 12 Troubleshooting 73 1 Introduction This is the manual for the Leiden Open source Variation Database LOVD version 3 0 LOVD 3 0 is a partial rewrite of LOVD 2 0 which first stable release was completed in 2007 Also LOVD 3 0 has a greatly improved database model and includes lots of new features aimed at making LOVD useful for more research environments LOVD is designed to provide a flexible freely available tool for gene centered collection and display of DNA variations LOVD 3 0 extends this idea to also provide patient centered data storage and storage of NGS data even of variants outside of genes LOVD was developed approaching the LSDB in a Box idea for the easy creation and maintenance of a fully web based gene sequence variation database that is pla
22. in the database or not Please see section Importing data into LOVD on how to import data into LOVD 45 8 Adding data to LOVD All registered users can submit or add data to LOVD A complete submission contains infor mation on an individual disease and phenotype information optional variant screening s and at least one found variant You can add more information to your submission at any later time like new variants phenotype information or a new screening If you are a submitter level user all new data submissions have to be published by a curator before the data is visible to the public When finishing a submission the curator will receive an email notification inviting him to publish the data 8 1 Starting a submission by creating an individual You can submit new data by clicking the Sub Required level Submitter mit tab or by selecting the option Create a Available from LOVD 3 0 Build 01 new data submission from the dropdown menu of the tabs Individuals Screenings or Variants Depending on your authorisation level you have different options for submitting data As an submitter level user your submission always starts directly with creating an individual to whom you can link phenotype or variant screening information If you are registered as a curator or higher choose I want to submit information on individuals to enter individual information As a curator or higher
23. installation Gene databases can also be created automatically for you when you are importing VCF or SeattleSeq annotated files in LOVD However this chapter deals with manually creating gene databases You can create new genes through the LOVD setup area Editing and deleting genes is done through the Genes tab Curators assigned to genes can also edit these after they ve been created but can not delete genes Emptying genes removing all associated variant and patient data and managing its variants is done through the configuration area This chapter describes how to create edit and delete gene databases in LOVD 5 1 Creating a new gene database Creating a new gene database in LOVD is largely Required level Manager automated Click the Create a new gene entry Available from LOVD 3 0 Build 01 option of the Genes tab dropdown menu or the Create a new gene database link in the setup area Fill in the HGNC ID or the gene symbol of the gene you want to create and click Continue LOVD will check if the gene already exists in this LOVD installation and if the gene symbol or HGNC ID is correct For this it contacts the HGNC website If the gene symbol you used has been replaced by a new one or if LOVD can find genes for which the given symbol is an alias LOVD will report back the official symbol s Unfortunately due to some problems on the side of the NCBI we are unable to handle variants on the mitoc
24. is set to the user ID of the user importing the data panelid from section Individuals Optional The internal ID of the individual in the database that represents the group to which this individual or group of individuals belong to 58 9 Downloading amp importing data The LOVD3 import format panel_ size from section Individuals The number of individuals represented by this entry default 1 Only used when multiple individuals for instance from one family are aggregated into one entry in the database position_c_cds_end from section Transcripts The position relative to the translation start site of where the translation ends Is always a positive whole number should always be dividable by three This field cannot be updated during an import position_c_mrna_start from section Transcripts The position relative to the translation start site of where the transcript starts Is always a negative whole number This field cannot be updated during an import position_c_mrna_end from section Transcripts The position relative to the translation start site of where the transcript ends Is always a positive whole number This field cannot be updated during an import position_c_ start from section Variants_On_ Transcripts The position relative to the translation start site of the first base of the variant The first base of the variant is defined by the HGVS nomenclature rules and may be the same as the last base
25. last to modify data that is linked to the gene This field cannot be updated during an import updated_data from section Genes The date data linked to the gene was modified last This field cannot be updated during an import variants_ found from section Screenings If set to 1 this screening is reported to have found variants If set to 0 this screening is reported to not have found variants Please note that other values are not allowed width from section Columns The displayed column width in pixels See also section Creating a new custom column 9 2 Downloading amp importing data Downloading data from LOVD For backup purposes or to move data sets from Required level Submitter one LOVD into another LOVD supports differ f Available from LOVD 3 0 Build 01 ent download options All downloaded file types lack the LOVD system settings registered user accounts and object specific custom column settings 61 9 Downloading amp importing data Downloading amp importing data In order to have a full backup for instance to restore LOVD in case of a hardware failure more information is needed It is therefore recommended not to rely only on this feature for a full backup of LOVD However it works perfectly as a backup for your variant and patient data for instance if you accidentally deleted the wrong entry or the wrong column If you re planning large parallel changes to data entries in LOVD using sprea
26. necessary to sort the curator names in a specific order This can be done on the Authorize curators form see figure 5 1 on page 29 Curators who don t have access to that form use the Sort hide curator names option from the Options dropdown menu on the gene homepage This form greatly resembles the bottom part of the Authorize curators form allowing to sort and show or hide the curator names see figure 5 2 on page 29 To resort the list of curators move your mouse over the drag handle see figure on the left of the curator name and click and Drag sort handle drag the name up or down the list Release the mouse button in the preferred location Don t forget to click the Save button to save the new sort order 30 6 Gene transcripts LOVD3 handles transcripts very differently from LOVD2 In LOVD3 configuring at least one transcript for a certain gene is necessary to be able to add variant data to the gene database Genomic variants can always be added but to record the effect of a variant on a certain gene that gene must have at least one transcript defined As a source for transcript information LOVD relies on Mutalyzer which gathers transcript information from different sources Therefore it is possible that new transcripts recently included in the NCBI database are not yet available in LOVD because either the NCBI hasn t rebuilt its mapping database yet or Mutalyzer didn t pi
27. not be able to work with LOVD until he has changed his password 20 4 Authorized users Editing user accounts Security This section contains more options when creating a new user account for a new user compared with when registering your own account Level Managers only see the option Submitter here The database administrator may also select Manager here Please note that to create a Curator account you need to create a Submitter and then grant this user rights on the necessary genes See section Assigning curators and collaborators for more information For a complete description on all user levels see the subsection User levels Locked Users can be locked which blocks access to LOVD even if they provide the correct username and password This locking happens when too many times an invalid password was given while logging in with this username depending on the LOVD system settings or it can be done manually Other fields This option is only available while creating a new user it s not shown on the submitter regis tration form Send email with account details to user When enabled the user s details will be emailed to the email address es given informing the user immediately about his account details The submitter registration form does not have this checkbox but this feature is always active for submitter registrations 4 3 Editing user accounts Every user in LOVD can edit their
28. not specified LOVD will use the autodetected website name LOVD has been installed on 11 3 LOVD Setup LOVD system settings Database URL This is the URL with which the database can be accessed by the outside world including http or https and is not necessarily the URL you are using right now to access the database It will also be used in emails sent by LOVD This field is mandatory if you select the Include in the global LOVD listing option If you click the check link LOVD will verify or try to predict the value LOVD email address This email address will be used to send emails from LOVD to users LOVD needs this address to prevent problems with spam filters to make sure that emails from LOVD arrive Please note that although strictly speaking this email address does not need to exist we recommend that you use a valid address to make sure that bounces of emails sent from LOVD to submitters or curators are still caught by someone so that they can be handled Forward messages to database admin With this setting enabled LOVD will forward messages to the database administrator about submitter registrations submissions and such Human Build to map to UCSC NCBI This value can only be set during installation and cannot be changed later It defines on which version of the Human Build hg18 Build 36 1 or hg19 GRCh37 genomic variants are described Links to the UCSC and Ensembl genome browser
29. or from the setup area click the Browse all custom data columns already available to enable or disable them or view or edit their settings link listed under Custom data columns This is the list of all custom columns To filter this list for category click the options wheel icon on the top left hand side of the columns listing to open up the menu and select the category you are interested in You can also filter for category by typing part of the name in the Category column filter box and press the Enter key To further filter the list for columns not yet added to the data table fill in a zero 0 in the Active column filter box and press the Enter key From the column overview click the column you wish to enable In the detailed view of the custom column you can review all the column s settings to verify that it suits your needs Click the Options menu button to open up the column s menu and click on Enable column Please note that when your database already contains a lot of information enabling a new non shared column may take some time If this is the case LOVD will display a warning Type in your password in the Enter your password for authorization field for verification of your authorization and submit the form The column is now enabled and visible in the data entry forms and the data listings and detailed views You may want to review or change the order of the custom c
30. that you would like to link to such as other gene variant databases or websites with more information about diagnostics If you want to include more than one link put every link on a new line in this field If you do not want to include a title for this link simply paste the full URL in this field such as http DMD LOVD nl If you do want to include a title use the format Description lt URL gt such as Other LOVDs on this gene lt http DMD LOVD nl gt HGNC ID This information has been filled in for you and can t be changed Entrez Gene Locuslink ID This information has been filled in for you and can t be changed OMIM Gene ID This information has been filled in for you and can t be changed Provide link to HGMD If you wish to include a link from the gene homepage to the gene s page on the HGMD site enable this checkbox Provide link to GeneCards If you wish to include a link from the gene homepage to the gene s page on the GeneCards site enable this checkbox Provide link to GeneTests If you wish to include a link from the gene homepage to the gene s page on the GeneTests site enable this checkbox This gene has a human readable reference sequence Although GenBank files are the official reference sequence they are not very readable for humans If you have a human readable format of your reference sequence online please select the type here Coding DNA or Genomic 25
31. to an LOVD J Available from LOVD 3 0 Build 04 installation This can be done for backup pur poses but also for importing to an other LOVD installation The records downloaded can be both records created during installation of LOVD as well as records created by users To download the custom columns data click the Download all LOVD custom columns link from 63 9 Downloading amp importing data Downloading amp importing own data the setup menu tab dropdown menu or from the setup area click the Download all LOVD custom columns in the LOVD import format link listed under Custom data columns The download begins immediately Depending on your browser it will save the file to a default location on your hard disk or ask you whether to open or to save the file Importing a custom columns data set into LOVD The custom column data set downloaded by a Required level Manager manager can be uploaded to the same or any Available from LOVD 3 0 Build 05 other LOVD Columns which already exists in the database are not imported but skipped instead For this LOVD checks if the column s ID already exists in the database No other fields are compared 9 5 Downloading amp importing own data Downloading own data set from LOVD LOVD allows you to collect a file containing all Required level Submitter information in LOVD that has been submitted Available from LOVD 3 0 Build 01 by you or is currently owne
32. would like to display the columns in the file To clearly separate the line with column names from the data lines the column names are surrounded by two curly braces on each side and Field names can not contain spaces match the field s name in the database exactly and the field names are separated by exactly one tab character from each other The section s data is also in tab delimited format Each field is preferably enclosed by double quotes All existing quotes in the data are escaped by the backslash character so becomes Other special characters are t for a tab character and r n for a linebreak Specific fields explained For each section the import format contains all fields that are stored in the database Some of these fields are not displayed on the normal LOVD data entry forms and therefore may cause confusion Others are displayed but for the user appear as selection lists with human readable 54 9 Downloading amp importing data The LOVD3 import format values whereas in the database only numbers are stored To aid in understanding these fields and their values all fields that may cause confusion are listed here Custom columns are not listed here since every LOVD installation has different columns enabled and custom columns provide explanations about their use by themselves allele from section Variants_On Genome Indicates on which allele the variant is located Does not necessarily imp
33. 1 0 feed with the LOVD information in plain text A more advanced API will be included in LOVD3 later allowing the querying of variants genome wide and getting more detailed information out of LOVD such as patient and phe notype data This API will be configurable so submitters decide for themselves under which data sharing license which type of information will be shared 10 1 Terms of service and fair use policy These terms of service and fair use policy are applicable to all APIs present on the LOVD site and any LOVD installations hosted by the Leiden University Medical Center recognizable by domain names ending by lovd nl lumc nl or liacs nl Other servers hosting LOVDs may also have terms of service in place If in doubt try to contact the party hosting the LOVD installation e Read the API possibilities below carefully and choose the most efficient method to query the API meaning the least amount of requests to get the information you need e Limit your requests to a maximum of 5 per second per server domain name e If the API indicates a certain entry does not exist do not repeat the same request for at least 4 hours unless you have reason to believe the entry may exist now e Not required but appreciated please set a User agent string that identifies you so we can see how the service is being used and we can contact you if necessary 10 2 Format When searching for genes an Atom feed is returned wi
34. 3712 607036 Transcripts Do not remove or alter this header id geneid name id_ncbi id_protein_ncbi 00064 IVD isovaleryl CoA dehydrogenase transcript variant 1 NM_002225 3 NP_002216 2 Diseases Do not remove or alter this header id symbol name id_omim 00006 IVA isovaleric acidemia 243500 Genes_To_Diseases Do not remove or alter this header geneid diseaseid IVD 00006 Individuals Do not remove or alter this header id fowned_by statusid Individual Lab_ID Individual Reference 00000124 00001 9 FB102 PMID Vockley et al 2000 10677295 Individuals_To_Diseases Do not remove or alter this header individualid diseaseid 00000124 00006 Screenings Do not remove or alter this header id individualid owned_by Screening Technique Screening Template 0000000116 00000124 00001 RT PCR SEQ DNA RNA Screenings _To_Genes Do not remove or alter this header screeningid geneid 0000000116 IVD Figure 9 1 Example partial LOVD import format file This example file contains information about the IVD gene its first transcript variant the IVA disease the link between the IVD gene and the IVA disease and an individual linked to the IVA disease and screened for variants in the IVD gene Note the gen
35. 4104zposition_match partial 69 10 The LOVD API Possibilities Searching on the DNA field http databases lovd nl shared api rest php variants IVD search_ Variant DNA c 157C 3ET This does not allow for partial matches but c 157C gt T or c 157C gt T will also match Searching on the DBID field http databases lovd nl shared api rest php variants IVD search_ Variant DBID IVD_ 000001 Showing only one specific variant entry internal ID only http databases lovd nl shared api rest php variants IVD 0000001350 World wide LOVD quering service There is also a world wide LOVD query API that allows you to query a genomic location to find out whether there is a variant reported in any public LOVD installation that has registered at LOVD nl Please contact us directly for more information on that API 70 11 Keeping your data secure LOVD contains several important security measures to protect your data from unauthorized access This page explains IT experts what kind of security measures are implemented in LOVD but it also shows what you as a LOVD user can do to protect your data 11 1 Built in security measures After a public request on a programmer s internet forum a LOVD installation had been sub jected to various attacks and hack attempts Furthermore the source code has been security audited by three different software packages to ensure no security holes were left open Some of the security risks LOV
36. D protects you against are displayed below Safe login procedure If someone tries to break into LOVD by repeatedly trying different passwords brute forcing for a correct username this account will be locked preventing unauthorized access The account can be unlocked by a manager or the database administrator They can also check the LOVD logs which IP address was responsible of the locking of the account which can be used by the server s system administrator to block access to LOVD from this IP address entirely As an additional security measure each user can restrict access to their account from only a certain IP address or a range of IP addresses preventing unauthorized access even with the correct password from unauthorized IP addresses Protection against SQL injection SQL injection is the process of including unwanted SQL database commands into a database through the manipulation of online web forms SQL injection can be used for amongst other things unauthorized modification of database contents or unauthorized access to the adminis trator account Protection against Cross site scripting XSS Cross site scripting is a vulnerability where malicious users can include Javascript code into webpages through entering a script in web forms or including code in variables which are being printed on the web page This can for instance be used to forward a user unnoticed to a different site The protection against XSS is the reas
37. LOND spotin LOVD email address noreply lovd nl settings Forward messages to database admin ov Human Build to map to UCSC NCBI hg19 GRCh37 Gane List database changes in feed for how long Not yet implemented Connection settings optional Some networks have no access to the outside world except through a proxy If this applies to the network this server is installed on please fill in the proxy server information here Proxy server host name 0 Proxy server port number Q Customize LOVD Here you can customize the way LOVD looks We will add new options here later System logo gfx LOVD_logo130x50 jpg Currently only images already uploaded to the LOVD server are allowed here Global LOVD statistics The following settings apply to the kind of information your LOVD install sends to the development team to gather statistics about global LOVD usage Send statistics e Include in the global LOVD listing eM Security settings Using the following settings you can control some security settings of LOVD Lock users after 3rd failed login eN Allow locked users to retrieve a new password Q M Enable submitters to change data e Enable getting counts of hidden entries Not yet implemented Force SSL only access to LOVD 17 Use data versioning of biological data 0 Not yet implemented Disable LOVD uninstall eN Continue Figure 2 5 The system settings form with example data filled in Done When everything has
38. Override setting More information about htaccess files http httpd apache org docs 2 0 howto htaccess html More information about AllowOverride http httpd apache org docs 2 0 mod core html allowoverride If you use a different webserver make sure to configure it to deny access to the config ini php file LOVD will access the file through the filesystem Also the htaccess file sets a couple of PHP options and enables mod_rewrite If you use a different webserver please disable the following PHP options register_globals magic_quotes_gpc mysql trace_mode Also make sure there is MultiViews func tionality which allows a PHP file like setup php to be accessed as setup 2 2 Install process To install LOVD on a remote webserver upload the LOVD directory with all the files to the webserver by for instance FTP If you install LOVD on your own computer you do not need to follow this step Next point your web browser to the directory where you ve uploaded the LOVD files This could for instance be http localhost LOVDv 3 0 or http www your domain org LOVD LOVD will tell you it s not installed yet and include a link to the install directory 2 Installing LOVD Install process KO D LOVD 3 0 Leiden Open Variation Database COU nui bets Ce Leiden Open Variation Database LOVD was not installed yet Please install LOVD first Powered by LOVD v 3 0 Build beta 04 2004 2012 Leide
39. RO 7D Leiden Open Variation Database H GVS HE gt 4 HGVS HUMAN VARIOME HUMAN GENOME cari VARIATION SOCIETY UTE RECOMMENDED SYSTEM LOVD 3 0 user manual Build 3 0 14 Ivo F A C Fokkema Daan Asscheman Leiden University Medical Center Last updated July 31 2015 LOVD has received funding from the European Community s Seventh Framework Programme FP7 2007 2013 under grant agreement no 200754 the GEN2PHEN project This work is licensed under the Creative Commons Attribution ShareAlike 4 0 International License To view a copy of this license visit http creativecommons org licenses by sa 4 0 or send a letter to Creative Commons PO Box 1866 Mountain View CA 94042 USA Contents Contents 1 Introduction 2 Installing LOVD 2 Peeve on stall sk kc oe ewe mirar oe Instal POS laa ia ee Be ke PERSE OYA EERE EER AE RSS LOVD Setup 21 LAPS system Sees o c c pea ios Re ee p e Mee ee ee ES Ja OYM DOS cn ek e nd e EE a e ESR aai e A E a e a e AR a a h oo Doma LOYD e raoe ca hE maoe eee Oe he See bee k BAR Authorized users 4 1 Registering a new account cos 44 464 cs dns Ha eee ee ee Ee ee La Creating new user a0 ce ee Oe Oe ee wee oe A a 43 Editing Weer accounts lt aoe sar ra p we Pee oe Ce ewe aa ws dd Locking users out of the system 24 s sa be eee a wR ee Gene databases 5 1 Creating a new gene database 1 e 5 2 The gene Lomepag lt c c ccc ac ear cnc e
40. VD 3 0 Build 01 this username provided this security setting is enabled see section LOVD system settings but this lock may also be placed onto or re moved from an account manually Locking or unlocking a user account requires you to have a level higher than the user you are trying to lock or unlock Proceed to the user s account details page through the Users tab Open the Options menu and click the Lock user option If the user is already locked there will be an Unlock user option The Lock user and Unlock user menu options are quick ways to deny or allow access to LOVD although it can also be accomplished through the Edit user option Users who are logged in can also be booted out of the system If a user is logged in the option Force user log out is added to the Options menu This will destroy the user s session causing the user to log out Locking the user essentially also causes the user to be logged out of the system the next time the user performs an action although in that case it s not possible for the user to log back in until the account is unlocked 22 5 Gene databases Although in LOVD 3 0 you can enter data into the database without having genes in your installation the genes still embody an important part of LOVD Configuring genes in LOVD allows you to see the effects of variants on transcript level and draws submitters with variant data to your
41. ailure more information is needed The download file lacks the LOVD system settings registered user accounts and object specific custom column settings It is therefore recommended not to rely only on this feature for a full backup of LOVD However it works perfectly as a backup for your variant and patient data for instance if you accidentally deleted the wrong entry or the wrong column To download the full dataset from LOVD click the Download all data link from the Setup tab dropdown menu or from the setup area click the Download all data in LOVD import format link listed under Download amp Import The download begins immediately Depending on your browser it will save the file to a default location on your hard disk or ask you whether to open or to save the file Importing the complete data set into LOVD A complete data set downloaded from the LOVD Required level Manager can be imported into a LOVD This can only be Available from LOVD 3 0 Build 01 done by the manager Not all data can and will be imported and some data needs to be modified to be able to import in LOVD Genes and transcripts can currently not be imported directly See section The LOVD3 import format for details on each section 9 4 Downloading amp importing the custom column data Downloading custom columns data from LOVD Managers can download a data file with only the Required level Manager custom columns which are added
42. alues created_by from sections Columns Genes Transcripts Diseases Individuals Phenotypes Screenings and Variants_On Genome The internal ID of the user that created this data entry If left empty during import the current user performing the import will be selected as the creator of this data entry Creators are allowed to edit the entry and add new data to the entry They are fixed and can not be re assigned at a later time This field cannot be updated during an import created_date from sections Columns Genes Transcripts Diseases Individuals Pheno types Screenings and Variants On Genome The date the entry was created in the format YY YY MM DD HH MM SS This field cannot be updated during an import description_ form from section Columns The column s notes on the data entry form This text is shown on the data entry form 59 9 Downloading amp importing data The LOVD3 import format just below the data field for instance as clarification See also section Creating a new custom column description_legend_ short from section Columns Description on short legend for this custom column See also section Creating a new custom column description_legend_ full from section Columns Description on full legend for this custom column See also section Creating a new custom column diseaseid from sections Phenotypes ID referring to the ID in section Diseases This field cannot be updated duri
43. ations where LOVD is used for next generation sequencing the gene homepage serves more as a summary page of the gene specific data in LOVD Besides showing the basic information known about the gene in question symbol name chromosome band variant statistics etc curators also have quite a few options to customize the gene s homepage If the gene you wish to view is already selected its name is on the top of the page simply click the Genes tab to open the gene s homepage Otherwise move your mouse over the Genes tab and select the View all genes menu option Then locate the gene you wish to edit by searching or browsing through the given genes listing Clicking the entry will direct you to the gene s homepage Once on the gene s homepage the gene will be selected its name will appear on the very top of the page which allows faster navigation to information related to the gene of interest For instance when a gene is selected and you click the Variants tab you are directed to the gene specific variant overview If no gene is selected clicking on the same tab shows all genomic variants in the database If you do not like this behavior simply move your mouse over a tab and select a different option from the dropdown menu 5 3 Editing a gene database Curators appointed to a gene database have the Required level Curator rights to edit its settings Managers and up can Available from LOVD 3 0 Build 01 e
44. ave your custom logo on the top left of every page instead of the default LOVD logo enter the path to the image here relative to the LOVD installation path If left empty it will be set to the default value which is gfx LOVD_ logo130x50 jpg Currently only images already uploaded to the LOVD server are allowed here Global LOVD statistics Your LOVD installation can send some general information on your installation back to us We use this information to see how many LOVDs there are worldwide which versions of LOVD are currently in use how LOVD is being used amount of data to see what type of software is used to run LOVD and to construct the public list of LOVD installs Send statistics When this setting is enabled LOVD will collect general usage statistics and send this to us The following information is sent the number of submitters genes individuals variants and unique variants in your system No specific information is sent just the numbers Include in the global LOVD listing On our website we keep a list of public LOVD installations This list is also feeding our worldwide LSDB list through which submitters can locate databases for a specific gene to submit data to If you enable the Include in the global LOVD listing setting your LOVD installation will send us all the information we need to build these lists the LOVD installation s name the URL the available gene databases the date of last update of the ge
45. ber of variant entries matched without showing them Force SSL only access to LOVD SSL is a secure protocol allowing for encryption of data sent between you and LOVD When you record sensitive individual information in LOVD you should enable this setting as the individual information can otherwise be sniffed off the network If you do not record sensitive information enabling SSL is recommended Use data versioning of biological data Note Not yet implemented Versioning allows you to see all previous versions of a certain data entry individuals variants phenotype information etc and allows you to return the entry to a previous state Please note that this feature requires quite a lot of space in the database Disabling this feature later will not free any space just prevent more space from being used 3 2 System logs System logs were introduced in LOVD 2 0 to al Required level Manager low authorized users to keep track of events in f Available from LOVD 3 0 Build 01 LOVD This can be for security purposes to fol low each other s progress when working together or to track down errors in case something went wrong The logs are initiated when LOVD is installed What is logged by LOVD LOVD logs four types of events authorization events and errors general events general errors and installation and upgrade events In case the event or error was triggered by an authorized user the username of this user is also log
46. ces are used to automatically retrieve gene and transcript information Also new in 3 0 is full Next Generation Sequencing NGS support with the ability to import VCF or SeattleSeq formats For VCF file imports LOVD allows for automatic annotation of the variants Both formats support the automatic creation of genes and transcripts in the system greatly reducing the amount of work required by curators to get LOVD set up for their research data LOVD 3 0 reached beta stage in January 2012 Currently the latest release is 3 0 14 Keep an eye on our news page for the latest information on LOVD 3 0 development Wherever you see he or his written in this manual it should read he or she and his or her respectively Please note that this manual is work in progress Since LOVD 3 0 is still under development and the development is the focus of our efforts many features in LOVD 3 0 are not yet described in this manual Also features described in this manual may become inaccurate or even incorrect in later versions of LOVD 3 0 Please bear with us while we finish this manual 2 Installing LOVD Please note that if you re just going to use an LOVD installation that already exists you do not need to install anything on your computer Any web browser that you already have installed such as Mozilla Firefox Google Chrome or Microsoft Internet Explorer will do This chapter describes how to install a new LOVD
47. ck the Re order all category columns link You now see all custom columns in this category both active and not active On the left of each column s header you see a handle see figure to drag the column up or down To change the order in which the columns are shown move your mouse over the drag handle and click and drag the name up or down the list Release the mouse button where you wish to drop the column Don t forget to click the Save button to save the new sort order t Drag sort handle 41 7 Custom columns Disabling custom columns Changing the object specific order of shared custom columns When a new gene or disease is created the cur Required level Curator rent system wide order of Variant On Transcript Available from LOVD 3 0 Build 01 or Phenotype columns respectively is copied and becomes this object s order of columns Curators and up can change this order for instance when a new column has been enabled since newly enabled columns are very likely to end up as the last column which may not be desired To change the order first you need to proceed to the detailed view of the disease or gene in question For Phenotype columns move your mouse over the Diseases menu tab and click the View all diseases link from the dropdown menu For Variant On Transcript columns move your mouse over the Genes menu tab and click the View all genes link from the dropdown m
48. ck up the new mapping information yet LOVD3 does not restrict you in the number of transcripts you can configure per gene but note that for each transcript added each variant gains more data fields that need to be filled in by the submitter so make sure that the additional transcripts are actually needed 6 1 Which transcript s should I pick In principle we suggest using the predominant transcript especially if only changes in this transcript cause a change in phenotype Otherwise we recommend using the longest transcript i e the transcript resulting in the longest protein Using the predominant transcript makes confirmation of the variant effect on RNA level easier and usually the variant numbering on this transcript will be most familiar with other research groups Using the longest transcript has the advantage of being able to annotate all exonic variants with a predicted effect on protein level As said LOVD3 allows you to use more than one transcript per gene Good examples that justify using multiple transcripts in LOVD is when different transcripts are expressed in different tissues when changes in different transcripts cause different phenotypes or when different research groups focus on different transcripts for example when no transcript is availabile that contains all exons 6 2 Creating new transcripts The simplest way to create a gene transcript Required level Curator in LOVD is to select it when creating a gene
49. config ini php lovd to config ini php and edit it in for example a basic text editor This is absolutely mandatory because you will need to enter the MySQL hostname username password and database name here In case you re using XAMPP the needed values are localhost root empty and test respectively No quotes around the values needed Please note that these are not the recommended settings for production environments but it will help you quickly set up LOVD on your computer Please go through the entire config ini php file to determine if you need to change any of the other settings A htaccess file is put in the root directory of your LOVD installation protecting the config ini php file This will prevent the config file from being accessed by others on Apache HTTP servers if configured properly the most commonly used webserver If you use Apache please check that your version and configuration support this feature Make sure you have the htaccess file into your LOVD directory on Unix and Linux systems it s a hidden file so it can be missed easily For the htaccess file to work you need to have Limit and Options enabled in Apache s AllowOverride setting Also make sure you have MultiViews or mod_rewrite enabled This allows a PHP file like setup php to be accessed as setup The mod_rewrite rules in the htaccess file require FileInfo enabled in Apache s Allow
50. d lovd nl shared api rest genes IVD gt lt id gt tag databases lovd nl 2011 04 05 IVD lt id gt lt author gt lt name gt Gerard Schaafsma lt name gt lt author gt lt contributor gt lt name gt Ivo F A C Fokkema lt name gt lt contributor gt lt published gt 2011 04 05T16 04 49 02 00 lt published gt lt updated gt 2013 03 11T15 30 41 01 00 lt updated gt lt content type text gt id IVD entrez_id 3712 symbol IVD name isovaleryl CoA dehydrogenase chromosome_location 15q14 q15 position_start chri5 40697686 position_end chri5 40713512 refseg_genomic NG_011986 1 refseq_mrna NM_002225 3 refseq_build hgi9 lt content gt lt entry gt lt feed gt Figure 10 1 Example LOVD API output format The two longest lines have been shortened to fit this page This example output of a search on gene symbol returns the IVD gene and its basic information Source LOVD3 shared installation The gene information shared through the API consists of the official gene symbol id symbol the gene s Entrez ID entrez_id the gene s official name name the chromosome band chromosome_ location and exact locations position_start position_end not always available its genomic reference sequence refseq genomic first transcript added refseq_mrna and the code of the reference sequence build that the genomic positions are based on refseq_ build The official gene symbol is mentioned twice because in LOVD2 multiple
51. d an email to the curator s of the gene s affected by the variant s submitted or the manager s for variants described only on genomic level They are thereby requested to publish the newly submitted data You as submitter of the data will receive a copy of this email As long as the data is not yet published the data is invisible for other users You will however be able to see the data previously submitted by you at all times 8 2 Continuing an unfinished submission If for whatever reason a data submission has Required level Submitter not been finished it is stored in the list of un Available from LOVD 3 0 Build 01 finished submissions This also means that the curator s did not get an email with the request to publish the newly submitted data You can continue an unfinished submission at any time adding any missing information and finishing the submission to alert the curator s of the new data To proceed with an unfinished sub mission select Unfinished submissions in the top right corner of the screen You will see an overview of data submissions which are not yet finished Select any submission to proceed The normal submission process will continue where it was left for instructions see the appropriate section in this chapter 8 3 Submitting summary variant data If you are a curator or higher you can choose to Required level Curator submit only summary variant data This means Available from LOVD 3 0 B
52. d by you Proceed to your account details by clicking the Your account link on the top right hand side of the screen Then click the Options button and click Download all my data The download begins immediately Depending on your browser it will save the file to a default location on your hard disk or ask you whether to open or to save the file This file compared to the full data download that LOVD offers to managers and the database administrator lacks the Columns data section The following sections contain data that is not owned by the user in question but merely serve as a reference to allow interpretation of all data Genes and Transcripts the ones where variants were reported in are shown and Diseases the ones linked to submitted Individuals are shown These section are marked with For reference only not part of the selected data set Importing own data set into LOVD The own data set downloaded by a submitter Required level Manager can also be reuploaded into LOVD But as with Available from LOVD 3 0 Build 13 all import files only a manager can import the data file If the diseases in the import file do not exist in LOVD these diseases will be added during the import Downloads in this format do not contain any links between genes and diseases To create this link you will have to add records to the Genes_ To Diseases section or manually create the links See Relation to diseases
53. d in You can also filter for category by typing part of the name in the Category column filter box and press the Enter key 43 7 Custom columns Deleting custom columns To further filter the list for columns currently enabled fill in a one 1 in the Active column filter box and press the Enter key Please note that in this custom column overview the Active field simply states whether or not this column has been added to the data table i e is active for any parent object From the column overview click the column you wish to disable In the detailed view of the custom column open its Options menu button then select Disable column Please note that if this shared custom column will no longer be active for any parent object and your database already contains a lot of information disabling this column may take some time If this is the case LOVD will display a warning From the Remove this column from selection list select the parent objects diseases or genes you wish to remove this column from For help on how to use this type of selection list move your mouse over the blue help icon If the parent object you are looking for is not shown in this list you have no authorization on the object to change its column s settings Finally type in your password in the Enter your password for authorization field for verification of your authorization and submit the form The
54. delete Either manually select the checkboxes next to the entries you want deleted or click the option button on the top left of the log overview and select the Select all entries option after which you can deselect log entries you do not want deleted Then open the option menu again and click the Delete selected entries option Please note that deleting log entries can not be undone X Delete log entry Options menu button 15 3 LOVD Setup Uninstalling LOVD 3 3 Uninstalling LOVD Only the database administrator can uninstall Required level Database administrator LOVD provided the uninstall lock has not been Available from LOVD 3 0 Build 01 set during installation of LOVD The uninstall lock is set within the MySQL database and can only be removed by directly accessing MySQL If you know how to handle MySQL you can also uninstall LOVD through MySQL directly by removing all LOVD tables but this is not recommended To uninstall LOVD and remove all data stored in LOVD click on the Uninstall LOVD link in the setup area This link is only available if the uninstall lock is disabled You will need to fill in the database administrator s password twice to complete the uninstallation process Once you have uninstalled LOVD you have lost all variant and individual informa tion If you wish to store these data elsewhere make sure you download all data first Please note that the LOVD uninstall
55. dit all gene databases in the LOVD installation To edit the gene s settings first proceed to the gene s homepage Click on the Options menu button to open up the gene entry s menu If you do not see the Options menu button you Options are not logged in or you do not have rights to edit this gene s Options menu button settings In the opened menu click Edit gene information to open up the gene s edit form The fields on the form are explained in the section Creating a new gene database After you submit the form LOVD redirects you automatically back to the gene s homepage 27 5 Gene databases Deleting a gene database 5 4 Deleting a gene database Only managers and up can delete gene databases Required level Manager from LOVD To delete the gene database in f Available from LOVD 3 0 Build 01 question first proceed to the gene s homepage Click on the Options menu button to open up the gene entry s menu and select the Delete gene entry option To complete the removal you need to fill in your password and submit the form Removing a gene can not be undone you will need to create the gene database again If in any doubt first make a download of the database so that you can restore your data if needed Please note that deleting a gene removes also its transcripts in the database and therefore all variant annotation on the gene in question but it does not r
56. dsheet software such as OpenOffice org Calc or MS Excel you could use the download files as a starting point In that case read the instructions at Downloading amp importing the complete data before you begin Importing data sets into LOVD For Managers it is possible to import data di Required level Curator rectly into LOVD using the LOVD3 import for Available from LOVD 3 0 Build 01 mat For curators only simulation is available see below starting from LOVD 3 0 14 See section The LOVD3 import format for more details about the file format Files created or modified using spreadsheet software such as OpenOffice org Calc or MS Excel must be saved as a text file The file must be tab delimited otherwise LOVD will produce an error To import a dataset to LOVD click the Import data link from the Setup tab dropdown menu or from the setup area click the Import data using the LOVD import format link listed under Download amp Import Curators can import data from the Configuration area Click the Import data using the LOVD import format link listed under Download amp Import The LOVD import has a simulate option allowing you to check if the import file is correct without importing anything Check the Simulate don t actually import the data checkbox to use this simulation option This option is always enabled for curators and cannot be disabled This allows curators to test t
57. e custom column order For non shared columns changing the system Required level Manager wide custom column order will effectively change f Available from LOVD 3 0 Build 01 the current order in which they are shown in data listings and data entry forms For shared columns changing the system wide order will merely change the default order in which the columns appear when new parent objects diseases genes are created It also influences where a newly enabled column will show up amidst the columns already active for the object it just got added to The order of already enabled shared custom columns will not be affected To change the custom column s system wide order you should start from the list of currently available columns Click the Browse all custom data columns link of the setup menu tab dropdown menu or from the setup area click the Browse all custom data columns already available to enable or disable them or view or edit their settings link listed under Custom data columns This is the list of all custom columns To filter this list for category click the options wheel icon on the top left hand side of the columns listing to open up the menu and select the category you are interested in Now click the options wheel icon again and click the Change order of columns link Alternatively first select one of the columns from the selected category and on the detailed view open the Options menu and cli
58. e for this field one options per line If you want to use abbrevi ations use Abbreviation Long name like DMD Duchenne Muscular Dystrophy In that case the user will see the long name in the selection list but the abbreviation will be stored in the database Also store time date field only Select this to also store time hours minutes seconds in this date field 36 7 Custom columns Creating a new custom column Default value all input fields except text area A default value that will appear in the field when creating a new data entry Click the Finish button to have the data type wizard fill in the MySQL data type and Form type fields for you based on the information you provided Column settings Here you can change some of the column s settings For shared columns see section Custom column categories most of these settings can also be changed per parent object where this column has been added to Include this column for newly configured genes diseases shared columns only When this is selected new genes for VariantOnTranscript columns or diseases for Phenotype columns will have this custom column enabled by default When you leave this off the curators of new genes or diseases will have to enable the column themselves should they want to use it Column display width in pixels For shared columns this value can be changed separately for each parent object this column ha
59. e options to submit more variants or return to the individual Uploading file with genomic variant data If you are a manager or higher you can upload a file with genomic variant data This option is not displayed for users with levels lower than manager For uploading genomic variant data files two formats are supported Variant Call Format VCF version 4 0 or higher and SeattleSeq Annotation files Adding a variant to the individual The option Add a variant to this individual Required level Submitter as displayed in figure 8 1 is only available when Available from LOVD 3 0 Build 01 you already created a screening and you selected Back to the individual after creating a screening When you want to add a variant to the individual using a screening you previously created you have to select the appropriate screening Click the Add a variant to this individual option then click the screening you wish to add another variant to and you will be redirected to the menu where you can submit a new variant See section Adding a variant to a screening 8 Adding data to LOVD Continuing an unfinished submission Finishing the submission The option I want to finish this submission is Required level Submitter enabled for submitters when they completed a Available from LOVD 3 0 Build 01 submission i e an individual screening and at least one variant have been added Finishing a submission will sen
60. eady enabled ones you may want to review or change the object specific order of shared custom columns 7 4 Editing custom column settings Shared columns have some settings mostly related to the display of the column which can be set per parent object a certain disease or gene We will refer to these settings as object specific settings All other settings are system wide and can only be performed by a manager or higher Non shared columns only have system wide settings and can not be configured per disease or gene Editing system wide custom column settings Both shared and non shared columns have sys Required level Manager tem wide settings that can be changed by a man Available from LOVD 3 0 Build 01 ager or higher However the way these columns respond to changes to the system wide settings are not the same For non shared columns each change to the system wide settings will be effective immediately For shared columns only the settings that are not object specific see above are effective immediately All changes to object specific settings however come to serve as new default values for when the custom column in question is activated for new genes or diseases Already enabled shared custom 39 7 Custom columns Editing custom column settings columns will not have their object specific settings reset unless they are explicitly reset to the new default settings described in the paragraph below To edit a cust
61. ed which are not affecting this gene and therefore not shown in this file Importing a gene s data set into LOVD The gene data set downloaded can be uploaded Required level Manager without modifications into the same or any other f Available from LOVD 3 0 Build 01 LOVD installation However the gene and its transcript s must exist in the database in which the file is imported The column section is missing in this download file but apart from that this is the same import file as the complete data set See section Importing the complete data set into LOVD on details about importing a gene s data set 65 10 The LOVD API Just like LOVD2 from version 2 0 22 released October 5th 2009 LOVD3 includes a simple webservice enabling simple queries or listing of variant data not patient data This API only shows very basic information and can therefore not be disabled The LOVD installations that have indicated to be included in the global LOVD listing are included in the overall LOVD querying service which is based on this API Examples of possibilities are searching on a gene symbol getting the list of available genes in the database or on a per gene basis list all variants or search for a certain variant or DNA location Even though LOVD3 is not gene based like LOVD2 was we have decided to keep the same gene centered design of the API to make sure LOVD2 and LOVD3 can be queried alike The output it creates is an Atom
62. eid field in the Transcripts section which links a transcript to a gene and the individualid field in the Screenings section which links a screening to an individual The link between genes and diseases and between screenings and genes are in a separate section because each gene can be linked to multiple diseases and each screening can test for variants in multiple genes Please note that a full LOVD download contains many more sections and more columns This file has been shortened to fit this page This example file is therefore not a valid import file The first line of the file contains the file s header line which indicates the LOVD version number as well as the type of file The LOVD version number is encoded and provided by 52 9 Downloading amp importing data The LOVD3 import format LOVD when creating a download When importing LOVD can decode the version and in case the download format has changed between versions convert the data into the correct format When this line is not included in the file that is imported LOVD cannot process the file and halt The file s data sections are indicated by lines starting with two hash characters followed by the name again two hash characters and a note that the header should not be modified or removed Other lines starting with two hash characters are regarded comments A downloaded file may contain comments like the number of entries for each section The following sectio
63. eir IDs Individuals Individuals and related information like links to the parents of the individual Links between individuals and diseases are described in the Individuals To Diseases section Individuals To Diseases Links individuals to diseases Phenotypes Phenotype information of a certain individual related to a certain disease A phenotype entry is linked to a disease using the diseaseid field A phenotype entry is linked to an individual using the individualid field Screenings Variant screening information with which variants are detected A screening is linked to an individual using the individualid field Links between screenings and genes are described in the Screenings To Genes section Links between screenings and variants are described in the Screenings To _ Variants section 53 9 Downloading amp importing data The LOVD3 import format Screenings To Genes Linking screenings to genes indicating which genes were screened using a certain screen ing Variants On Genome Genomic information of all variants detected Links between variants and screenings are described in the Screenings To Variants section Variants_On Transcripts Possible effects on a transcript caused by a genomic variant A variant on transcript is linked to a variant on genome using the id field Screenings_ To Variants Linking screenings to variants indicating which variants were
64. elatively experienced computer user Dane The installation progress bar at the top of the screen shows how far you are in the installation process The installation steps are shown at the left of the screen Start gt gt 3 0 Build beta 04 rsity Medical Center Figure 2 2 If all requirements are OK you re ready to start installing LOVD Administrator account details Fill in the database administrator data to install LOVD The database administrator will be the first user registered with LOVD and has full access to all of LOVD s functionalities The database administrator is the only user capable of creating manager accounts Managers can only create curator and submitter accounts Most of the form is pretty straight forward but I will highlight one field Allowed IP address list An IP address is an address a computer is known by on the network To help prevent others to try and guess the username password combination you can restrict access to the database administrator account to a number of IP addresses or ranges This also means you need to be very careful with this setting as being too restrictive may lock you out of your account The default unrestricted value is 2 Installing LOVD Install process E 5S VD v 3 0 Build beta 04 KO Dd LOVD 3 0 Leiden Open Variation Database EON YO Bord eta Ot
65. emove the genomic variants from the database To remove these as well you should first empty the gene database which deletes all its variants and also deletes all other connected data such as individuals and phenotypes as long as these are not connected to other genes as well 5 5 Assigning curators and collaborators Managers and up can assign curators and col Required level Manager laborators to gene databases as well as revoke Available from LOVD 3 0 Build 01 curator or collaborator rights Directly after cre ating a new gene database you are forwarded to the page that allows you to make these changes but you can access that page at any time by using the Add remove curators collaborators link in the Options menu on the gene s homepage On the top of the page you see a listing of all available users in the system whichever level they have Users that are already selected as curators or collaborators are shown in the bottom To add a user as a curator or collaborator search for the user in the top user list and click the user entry The user is then moved to the bottom In the bottom table you see two checkboxes for each user Also you can sort the curators by dragging and dropping them in the list see subsection Sorting curators The first checkbox indicates whether or not they are allowed to edit the data in this gene s database Users allowed to edit the data are curators Unchecking this checkbox turns this u
66. enu Then select the parent object you would like to change the order of the custom columns of From the parent object s detailed view open the Options menu and click the Re order enabled phenotype columns or Re order enabled variant columns link Alternatively click the View enabled phenotype columns or View enabled variant columns link from the menu and on the page that follows open the Options menu to click the Change order of columns link You now see the enabled columns for the selected parent ob ject with on the left of each column s header a handle see figure to drag the column up or down To change the order in which the columns are shown move your mouse over the drag handle and click and drag the name up or down the list Release the mouse button where you wish to drop the column Don t forget to click the Save button to save the new sort order t Drag sort handle 7 6 Disabling custom columns Custom columns that you no longer wish to use can in most circumstances be removed by disabling the column Exceptions in this case are HGVS standard columns HGVS standard custom columns are columns that are part of the mandatory minimal data set as defined by the HGVS for Locus Specific DataBases LSDBs This is to preserve the minimal quality of the data within the database and LOVD will not allow you to remove these columns Disabling non shared custom columns is a sys
67. er will not remove the LOVD files itself just the database tables that it has created during install Thus to completely remove LOVD from the system also remove the files from the server 16 4 Authorized users In LOVD 3 0 authorized users are everyone who registered for an account at the LOVD instal lation including the database administrator who created his account during the installation process The authorized users come in five levels the database administrator of which there is only one managers curators collaborators and submitters The different levels of users are described in more detail below Registering for an account is necessary to be able to submit data or to become a gene curator Directly after registering you are allowed to submit individual phenotype and variant data to the database but the data needs to be checked and published by a curator or a manager Curators and managers can submit and publish data in one step User levels Database administrator The database administrator is the first user within LOVD this account is created during the installation of LOVD After installation the database administrator can create other users managers curators and submitters in the system if desired These users can also register themselves after which the database administrator can upgrade them The administrator has full access to all areas and settings of LOVD The administrator is also the only user who
68. for how to create a link between a gene and a disease For more details on each section of the import file see section The LOVD3 import format 64 9 Downloading amp importing data Downloading amp importing a gene s data 9 6 Downloading amp importing a gene s data Downloading a gene s data set from LOVD Curators can download a file containing all infor Required level Curator mation related to a gene they have authorization Available from LOVD 3 0 Build 02 on This can be done for backup purposes but also for importing to an other LOVD installation From the gene homepage click the Op tions button and click Download all this gene s data The download begins immediately Depending on your browser it will save the file to a default location on your hard disk or ask you whether to open or to save the file This file compared to the full data download that LOVD offers to managers and the database administrator lacks the Columns data section All sections are filtered to show only data related to the gene in question The following sections are perhaps not obvious Diseases the ones related to the gene in question as well as the ones linked to the individuals in this file are shown Phenotypes the ones linked to the individuals in this file are shown and Screenings the ones which found variants in the gene is question are shown The individuals in this file may have more variants report
69. ged Authorization events and errors Auth This list stores all successful and unsuccessful login attempts and password reset attempts In all cases the IP address from where the login or password reset attempts have been made is also logged For successful and unsuccessful login attempts the given username and the length of the given password is stored so you can easily uncover brute force attempts where in general the attacker will try many random passwords If a user can t log in because of the IP restriction on the account the current IP restriction is also stored in the log entry Please note that it is recommended to have LOVD lock user accounts after three failed login attempts See subsection Security settings for more information General events Event General events are logged to show a user s activity to allow collaborating users to track each other s activities or to check what happened to a certain data entry over time 14 3 LOVD Setup System logs General errors Error Whenever an unrecoverable error occurs LOVD logs the error and stops processing Also some non fatal errors are logged such as when only part of the requested action could be completed In principle during any database event an error can occur This is then logged under the name of the event so any of the event names used in the general event log can also be found in the error log Installation and upgrade events Ins
70. he Enter key From the column overview click the column you wish to disable Click the Options menu button to open up the column s menu and click on Disable column and remove values Please note that when your database already contains a lot of information disabling a non shared column may take some time If this is the case LOVD will display a warning Type in your password in the Enter your password for authorization field for verification of your authorization and submit the form The column is now disabled and removed from the data entry forms and the data listings and detailed views If the Disable column and remove values link is not enabled i e you see it but you can t click it the column is an HGVS standard column and it can not be removed Disabling shared custom columns Shared custom columns can be disabled for one Required level Curator parent object only or from multiple parent ob Available from LOVD 3 0 Build 01 jects at the same time To disable the given column for one parent object only proceed to the detailed view of this parent object disease or gene Then open the Options menu button and click the View enabled phenotype columns or View enabled variant columns link depending on the type of column you wish to disable Click the column then from its Options menu button select Remove column from this disease or Remove column from this gene
71. he basic fields with which the user identifies himself Name Please enter your name in the way you want to be referenced to usually in the format lt First name gt lt Last name gt Institute The institute for which you work Deparment If your institute consists of department please enter the department for which you work Postal address Please provide the full postal address of your institute Email address es one per line Your account can hold multiple email addresses which will all receive notifications sent by LOVD This is useful if you re sharing an account with a colleague or when you would like to also get emails on a different account You can enter as many email addresses as you like one email address per line no spaces quotes or other special characters allowed Telephone Optionally provide your phone number where you can be reached Username LOVD requires the username to be 4 to 20 characters long and starting with a letter followed by letters numbers dots underscores and dashes only Password LOVD requires the password to be at least 4 characters long containing at least one number or special character Please choose your password wisely don t use the same password as your username and better not use words that are in a dictionary Password confirm To make sure you din t make a typo while entering your password please repeat it so we can check if the two fields are equal Referencing
72. he individual Figure 8 2 After adding a screening you can add a variant to this screening Back to the individual will leave this screening unfinished and will return you to the choice to add phenotype information or another screening Adding a variant to a screening After adding a screening you can add a variant Required level Submitter to this screening It is possible to add more than Available from LOVD 3 0 Build 01 one variant to a screening A submission can only be finished when at least one variant has been added to the submission Confirming variants using a screening When different variant screenings have been applied to the individual for instance to confirm a variant found using a different method the screenings can be stored separately in the database Multiple screenings can be linked to the same variant or have their own sets of variants The option to confirm variants using a screening is only available when at least two screenings are added to the individual and variants have already been submitted After choosing this option you are shown a list of variants already linked to other screenings of the individual but not to 47 8 Adding data to LOVD Starting a submission by creating an individual Create a new variant entry Do you want to confirm already submitted variants with this screening Yes want to confirm variants found using this screening What kind of variant would
73. he internal ID of the individual in the database that is the father of this individual form_ type from section Columns The custom column s form type definition When importing new custom columns we recommend you use the Data type wizard available when creating a new custom column and to use the form type definition generated by the wizard See also section Creating a new custom column head_ column from section Columns The custom column s header shown above the column in data views See also section Creating a new custom column 56 9 Downloading amp importing data The LOVD3 import format hgvs from section Columns If set to 1 this column is HGVS recommended These columns can not be removed This setting can not be set when importing columns Default value is 0 id_entrez from section Genes This field cannot be updated during an import id_hgnc from section Genes This field cannot be updated during an import id_mutalyzer from section Transcripts This field cannot be updated during an import id_ncbi from section Transcripts This field cannot be updated during an import id_omim from section Genes This field cannot be updated during an import id_protein_ncbi from section Transcripts This field cannot be updated during an import imprinting from section Genes Whether or not a gene is imprinted either maternal or paternal individualid from sections Screenings and Phenotypes
74. heir import files but it still requires a manager or up to actually import the file On the import form in the Import options section you ll find the Import mode The two options available are Update existing data see section Update existing data via import and Add only treat all data as new see section Insert new data via import Insert new data via import The option add only on the import page will Required level Curator insert all data in the import file as new also f Available from LOVD 3 0 Build 01 if the identifiers used are already present in the database See section The LOVD3 import format for more details about the file format Update existing data via import For Managers and higher it is possible to update Required level Curator certain data via an import curators can run a Available from LOVD 3 0 Build 14 simulate There are some restrictions on what you can modify and what not In general when you can modify certain data via the LOVD data entry forms you can modify them via the update import as well Furthermore to prevent unintended edits you can currently only modify one field per line You cannot modify the created_ by created_date edited_ by edited_ date fields from sec tions Columns Genes Transcripts Diseases Individuals Phenotypes Screenings and Vari ants On Genome These fields are set by LOVD and changes in these fields are ignored See
75. hondrial genome at this time NCBI does not handle the MT genes by their official names and doesn t allow for automatic retrieval of reference sequences for the MT genes When the NCBI has fixed this problem we will implement support for MT genes LOVD will show a progress bar while it contacts several webservices to retrieve gene infor mation reference sequence information and available transcript information Usually retrieving this information takes about 1 3 seconds but this depends on the internet connection between the server and the internet and the current load on the webservices which are contacted When LOVD has retrieved all the information you are forwarded to the data entry form where you can review the retrieved information and complete this gene s settings 23 5 Gene databases Creating a new gene database General information This part describes the bare essentials of the gene information Therefore most of the infor mation in this section has been filled in for you and some values are fixed to ensure the data is correct Full gene name This information has been filled in for you and can t be changed Official gene symbol This information has been filled in for you and can t be changed Chromosome This information has been filled in for you and can t be changed Chromosomal band The chromosomal band on which the gene lies is retrieved from the HGNC You may modify it if you wish Im
76. ings All other fields on this form are explained in the section Creating a new custom column Editing object specific shared custom column settings The object specific settings editable per gene or Required level Curator disease are also see section Creating a new Available from LOVD 3 0 Build 01 custom column e Description on short legend Description on full legend Notes on form List of possible options for selection list type columns Column display width in pixels Mandatory field Show contents to public Show field on submission form To change these settings first you need to proceed to the detailed view of the disease or gene in question For Phenotype columns move your mouse over the Diseases menu tab and click the View all diseases link from the dropdown menu For Variant On Transcript columns move your mouse over the Genes menu tab and click the View all genes link from the dropdown menu Then select the parent object you would like to change the object specific settings for From the parent object s detailed view open the Options menu and click the View enabled phenotype columns or View enabled variant columns link From the list of enabled columns click the one you wish to edit the settings for Open up the Options menu and then click Edit settings for this disease only for Phenotype columns or Edit settings for this gene only for Variant On T
77. ion form we implemented a reCAPTCHA module In the provided text field type the two words you see in the image This will proof that you are a human and not a computer After completing the form press the Register button LOVD sends you a confirmation of your registered information through email If the Forward messages to database admin setting in the LOVD system settings is enabled the database administrator also receives a copy of your data 4 2 Creating new user accounts Besides the public registration form managers Required level Manager can also create new users This offers the ad Available from LOVD 3 0 Build 01 vantage that the new user s level can be set to the required level in the same step and the manager does not need to log out first You can create a new user by clicking on the Create a new user account option from the Users tab dropdown menu or the Create a new authorized user or submitter link in the setup area The process is largely equal to the submitter registration process except that there is no reCAPTCHA test but instead you must enter your password for authorization and the form has some additional fields explained below User details This section contains one additional field compared to the registration page Must change password at next logon If you want to force the user to pick a new password after logging in for the first time select this checkbox The user will
78. ively click the Transcripts tab from anywhere in LOVD If you already had a gene database selected you now see the transcripts active in this gene and you can click one to view its details If you did not have a gene database selected you now see all transcripts in the database Use the filtering boxes to find the transcript you are looking for and click it to view its details Click on the Options menu button to open up the transcript entry s menu If you do not see the Options menu button you are not logged in or you do not have rights to edit this transcript s settings In the opened menu click Edit transcript information to open up the transcript s edit form General information This part contains IDs to other sources to aid in data exchange Transcript Ensembl ID If this transcript is also known in Ensembl enter its Ensembl ENST ID here Protein Ensembl ID If this transcript s protein product is also known in Ensembl enter its Ensembl ENSP ID here Protein Uniprot ID If this transcript s protein product has an Uniprot ID enter it here 6 4 Deleting a transcript Deleting a transcript removes all information re Required level Curator lated to the transcript in question from all vari Available from LOVD 3 0 Build 01 ants in the database Just like when deleting a gene this does not remove the genomic variants from the database From the transcript s de tailed view click on the Opti
79. led Y T 0 100 Introduction Administrator account details Please fill in the Administrator s account details and press Continue to continue the installation Administrator account Js User details Name Ivo F A C Fokkema Installing database tables Institute Leiden University Medical Center Department optional Human Genetics Configuring LOVD system Postal address Einthovenweg 20 settings 2333 ZC Leiden Done Email address es one per line LFA C Fokkema LUMC nl Telephone optional Username ifokkema Password Password confirm Referencing the lab Country Netherlands City 0 Leiden Reference optional 0 Security Allowed IP address list Q Your current IP address 127 0 0 1 Please be extremely careful using this setting Using this setting too strictly can deny the user access to LOVD even if the correct credentials have been provided Set to to allow all IP addresses use to specify a range and use to separate addresses or ranges Continue ed by LOVD v 3 0 Build beta 04 y al Ce len University Medical Cente Figure 2 3 The database administrator registration form with example data filled in The database administrator is the absolute owner of the LOVD installation Not only is he the only one that can uninstall LOVD from the database using the unin staller he will also be able to create edit or delete all user accounts i
80. ly inheritance This field cannot be updated during an import ID Name Description 0 Unknown Heterozygous parents not screened or de novo and al lele couldn t be confirmed 1 Parent 1 Heterozygous parents not screened but useful in com bination with Parent 2 to indicate cis or trans com pound heterozygosity 2 Parent 2 Heterozygous parents not screened but useful in com bination with Parent 1 to indicate cis or trans com pound heterozygosity 3 Both homozygous Variant is present on both alleles 10 Paternal inferred Variant is on paternal allele not confirmed in father but inferred from other information 11 Paternal confirmed Variant is on paternal allele confirmed in father 20 Maternal inferred Variant is on maternal allele not confirmed in mother but inferred from other information 21 Maternal confirmed Variant is on maternal allele confirmed in mother If left empty during import the default value is 0 chromosome from sections Genes and Variants On Genome The chromosome related to this entry gene or variant When importing do not fill chr here as prefix just the chromosome number or letter This field cannot be updated during an import chrom_ band from section Genes The chomosome band like q15 col_ order from section Columns The order in which the columns of this column s category are shown Low values are shown before higher v
81. mation You will need to enable the column after defining it so it actually gets added to the data entry form and show up in the data tables To create a new custom column click on the Create new custom data column option from the Setup tab dropdown menu or the Create new custom data column link in the setup area Firstly you will need to choose which type of column you would like to create For more information on the different column types see the previous section Please note that you can never change the type of a column once it has been chosen Select the type of column you would like to create by clicking its description You are then forwarded to the entry form specific for this type of custom column Column name and descriptions Here the description of the new column is defined its displayed name and the explanation of its contents to the users Column ID Choose a simple unique name for your column consisting of only letters numbers and underscores Subcategories must be divided by a slash such as Geographic_ origin Country Blood_ pressure Systolic Protocol Date_ updated Frequency dbSNP or Protein Codon Column heading This will appear above the column in data tables and on the legend In principle this is free text but try to keep it short because a long name will increase the width of the column Description on short legend HTML enabled For shared columns this
82. n only be used by humans and not by spam bots To register a new submitter account click Required level None public the Register as submitter link on the top right Available from LOVD 3 0 Build 01 corner of the screen next to the Log in link First you are asked to provide an ORCID ID if you have one ORCID provides a persistent digital identifier that distinguishes you from every other researcher and through integration in key research workflows such as manuscript and grant submission supports automated linkages between you and your professional activities ensuring that your work is recognized If you don t have an ORCID ID yet you can get one created by using the register link also given on the page If you don t want to register at ORCID at this time click the I don t have an ORCID ID button to continue to the registration page If you do have an ORCID ID fill it in and click the Continue button Your ORCID ID will be verified and the associated data is shown on the screen If this data is correct click Yes this is correct to continue to the registration page As much information as possibly will be pre filled for you If the information shown is not correct click No this is not correct so you can try and enter a correct ORCID ID or register without using one 18 4 Authorized users Registering a new account User details This part of the registration form contains t
83. n University Medical Center Figure 2 1 When pointing your browser to the LOVD location it will tell you it s not installed yet Click the link to start the install process LOVD will first check a few requirements Both the PHP and MySQL versions will be checked to make sure your LOVD will function properly on your webserver environment Also some settings of the web server PHP and MySQL will be checked Finally LOVD will check if your config file has been hidden If all looks well LOVD will tell you all requirements are OK and you re ready to start installing LOVD Installing LOVD consists of only 4 simple steps and will take only a couple of minutes or less LOYD LOVD 3 0 Leiden Open Variation Database FA aera 0 100 Introduction Welcome to the LOVD v 3 0 beta 04 installer System check for requirements all OK Administrator account details Y PHP 5 3 5 5 1 0 required Y PHP function mb_detect_encoding Y PHP function xml_parser_create Inataling datebese tables Y MySQL 5 1 62 4 1 2 required Y MySQL InnoDB support enabled required Y MultiViews mod_rewrite or equivalent enabled required Configuring LOVD system tti e The installation of LOVD consists of 4 simple steps This installer will create the LOVD tables in the MySQL database create the Administrator account and will help you configure LOVD Installation and initial configuration of LOVD should be simple for a r
84. n on the variant s found in general or on the genomic level such as restriction site change DNA change on genomic level or reference describing the variant Variant On Transcript Information on the variant s found specific for the transcript level such as predicted effect on protein level DNA change on mRNA level or exon number Of these five different categories two are shared they can be turned on or off by curators for specific diseases or genes their so called parent objects Some of these columns settings can also be changed per parent object they are enabled in The two shared custom column types are Phenotype configurable per disease and Variant On Transcript configurable per gene The other three categories are system wide meaning they are either always on enabled or always off disabled These column are referred to as non shared columns and can only be enabled disabled and managed by Manager level users or the Database administrator The three non shared custom column types are Individual Screening and Variant On Genome 33 7 Custom columns Creating a new custom column 7 2 Creating a new custom column By creating a new custom column you can de Required level Manager fine what kind of information you want to store Available from LOVD 3 0 Build 01 in the database Please note that defining this type of information does not automatically make LOVD store this infor
85. n the system and depending on the settings receive submission and registration notifications After completing the database administrator account details click the Continue button at the bottom LOVD will apply a simple username and password quality check If LOVD tells you that the provided details are OK click the Next button Installing database tables The next step is to create and fill all necessary LOVD database tables LOVD will do this automatically and you can watch the progress bar complete while the tables are created the country list filled the database administrator account created the custom columns preconfig ured the standard columns enabled and the custom links generated This may take a while on non optimal conditions so please be patient When everything is done a Next button appears click it to continue Configuring LOVD system settings The final form in the installation process is completing the initial configuration of the LOVD system settings These settings can be changed after installation at any time through the 2 Installing LOVD Install process KO D LOVD 3 0 Leiden Open Variation Database Installatio Installation steps EE 100 Introduction Installing LOVD 82 Administrator account details Creating LOVD account amp LOVD database administrator account Installing database tables Configuring LOVD system settings Done
86. ne databases the disease abbreviations and names of the diseases related to these genes and finally the names institutes and email addresses of the curators of these gene databases If you change this setting please allow one day for the setting to take effect Security settings In this section you can control some security settings of LOVD Lock users after 3rd failed login With this setting enabled submitters curators and managers will be locked out of the system after they have provided the wrong password three times A manager or in the case of a locked manager the database administrator needs to unlock the user s account once it s locked This does not affect the database administrator account Allow locked users to retrieve a new password If a submitter curator or manager has lost his password enabling this I forgot my password feature allows them to receive a unlocking code in their email with which they can unlock their account and choose a new password Enable submitters to change data This setting allows submitters to make changes to data previously submitted by them or assigned to them 13 3 LOVD Setup System logs Enable getting counts of hidden entries Note Not yet implemented Enabling this feature allows the public to find the number of entries in the database including hidden entries matching one or more search terms on a specified set of columns This feature will only mention the num
87. ng an import effectid from sections Variants_On_ Genome and Variants On Transcripts The variant s affect on a protein s function The first digit indicates the reported variant s effect The second digit indicates the variant s effect as concluded by the curator The possible values of each digit ID Name Description 1 Does not affect function strong proof 3 Probably does not affect function strong evidence 5 Effect unknown 7 Probably affects function strong evidence 9 Affects function strong proof A score of 97 means a variant is reported to effect the function of the protein having strong proof but the curator thinks more proof is needed still accepting there is strong evidence for the variant s effect All options are ID Name ID Name ID Name ID Name ID Name 11 SL ar 51 7i 27 91 B A a 0 53 7 a 12 93 7 15 35 2 7 55 75 2 95 7 17 0 ms 17 57 7 47 TM a r a 19 39 2 2 59 79 2 99 In the Variants On Transcripts section this field indicates the effect of the variant on this specific transcript In the Variants_On Genome section this field indicates the overall effect of the variant on the function of any gene it influences basically the maximum score of all of the variant s effectid values If left empty during import the default value will be 55 fatherid from section Individuals Optional T
88. ng in this field LOVD will add a question mark icon next to the field on the data entry form When the user moves his mouse over the question mark icon the text entered here is shown Since the text is shown as a highlight it does not disrupt the structure of the data entry form so feel free to type lengthy texts 35 7 Custom columns Creating a new custom column Notes on form all field types HTML enabled For shared columns this value can be changed separately for each parent object this column has been added to If you think the data field needs clarification for all users add such clarification here The text given here will be shown directly underneath the data entry field Therefore keep it short since long texts will make the data entry form very long Width on form characters all input fields and text area The input field width on the form in number of characters Height on form lines text area and multiple selection list The height of your field on the data entry form in lines For multiple selection lists this implies the number of options visible at the same time Maximum input length characters text and integer input field types The maximum number of characters allowed the be filled in If a user tries to enter more characters in your field an error is issued For the integer input type this implies the maximum value that can be filled in Number of digits before the decimal point decimal field o
89. nly The maximum number of digits allowed before the decimal point This practically limits the maximum value of the field Number of digits following the decimal point decimal field only The maximum number of digits allowed at the right of the decimal point This limits the maximum precision of values in the field Regular expression pattern text input only For advanced users only You can enter a full regular expression pattern PHP s Perl compatible regular expression syntax including delimiters and possible modifiers Using this you can force a certain format for the input Make sure it s valid otherwise you risk getting all this column s data input rejected Allow only positive values integer and decimal fields Select this to allow only positive numbers to be entered Provide select option drop down list only This will add an option named select to the list of options that will be selected by default and will be regarded as an empty value If this option is not set the first option of the list will be the default selected option Provide select all link multiple selection list only This will add a link next to the selection list that allows the user to instantly select all available options List of possible options both list types For shared columns this value can be changed separately for each parent object this col umn has been added to Enter the options availabl
90. nomic reference sequence NG NC or LRG accession number Only the references that are available to LOVD are shown Whether there is an LRG available is determined by contacting the EBI Checking for an available NG reference sequence is done at the NCBI The NC reference sequence is always available and depends on the chromosome on which the gene lies 24 5 Gene databases Creating a new gene database Transcript reference sequence s LOVD retrieves a list of available transcripts from Mutalyzer Mutalyzer currently only supports NCBI reference sequences Please select which transcript you want to use to name the variants in this gene If there are more transcripts usually you would pick the transcript that encodes for the longest protein or the transcript that is expressed in the tissue you focus your research on If you want to add more transcripts later or change which transcript s you want to use for this gene database see the chapter Gene transcripts Links to information sources Here you can add links to other resources that will be displayed on the gene s LOVD gene homepage such as Entrez Gene OMIM HGMD or GeneTests but you can also add links to any website you want Homepage URL If you have a separate homepage about this gene you can specify the URL here For the format use the complete URL including http or https External links Here you can provide links to other resources on the internet
91. ns are currently recognized Columns Custom columns and their system wide settings In a full data download this section contains records created during installation of LOVD as well as records created by users During import columns in the import file that already exist in the database are skipped In that case a warning is displayed but the import will continue Genes Genes including external IDs Can currently not yet be imported When importing genes can be listed in the file but they should already be present in the database If not present they should be created manually before importing the file Links between genes and diseases are described in the Genes To Diseases section Transcripts Transcript variants including external IDs Can currently not yet be imported When importing transcripts can be listed in the file but they should already be present in the database If not present they should be created manually before importing the file A transcript entry is linked to a gene using the geneid field Diseases General disease information Diseases should have a unique name and OMIM ID During import diseases in the import file that already exist in the database based on name or OMIM ID are skipped In that case a warning is displayed but the import will continue Links between diseases and genes are described in the Genes_ To Diseases section Genes_ To Diseases Links genes and diseases by referring to th
92. o be a more flexible and more powerful successor of the popular 1 1 0 version and soon it received the interest of LOVD users eager to try out the all new version With more features being added and bugs fixed rapidly LOVD 2 0 reached beta stage in April 2007 after which more and more users started to upgrade their 1 1 0 databases to 2 0 Finally in October 2007 LOVD 2 0 reached the stable stage after which LOVD 2 0 was continuously improved with monthly releases for two years after which the releases became less frequent LOVD 2 0 is described in the second LOVD paper By 2009 it had became clear that although LOVD 2 0 was a great step forward there were still key improvements to be made Since the complexity of necessary changes had become to great to gradually upgrade LOVD 2 0 systems to include these options it was again decided to start from scratch writing LOVD 3 0 This allowed us to redesign the complete data model in full freedom although it should still be possible for existing LOVD 2 0 databases to have all data transferred to LOVD 3 0 LOVD 3 0 adds even more flexibility allowing users to focus exclusively on sequence vari ants whilst also allowing an exclusive focus on individuals and clinical data and anything in 1 Introduction between It will be possible for different submitters to work together cooperatively on the same data Searching through the data is improved extensively and webservices of many different sour
93. olumn Then click the gene for which you want add a variant to proceed to the variant entry form You can check the help icon 48 8 Adding data to LOVD Starting a submission by creating an individual next to the form fields to see details about the fields and suggestions on how to use the fields Complete the form and when ready click the Create variant entry button If successful you are redirected to the options to submit more variants or return to the individual Please find the gene for which you wish to submit this variant below using the search fields if needed Click on the gene to proceed to the variant entry form 2 entries on 1 page Showing entries 1 2 10 per page v Gene ASIC4 BCS1L ASIC4 acid sensing proton gated ion channel family member 4 2 BCSiL BC1 ubiquinol cytochrome c reductase synthesis like 2 o g o o yl 10 per page v Figure 8 5 Click the gene for which you want to submit a variant Adding a variant only described on genomic level You can create a variant which is only described on genomic level The data entry form is similar to the form for adding a variant within a gene but lacks the transcript specific fields Check the help icons next to the form fields to see details about the fields and suggestions on how to use the fields Complete the form and when ready click the Create variant entry button If successful you are redirected to th
94. olumns now Enabling shared custom columns The shared custom column types are Phenotype Required level Curator and Variant On Transcript Before enabling Available from LOVD 3 0 Build 01 more shared columns you might first want to check out the default order in which they will appear To change the default order for shared custom columns see subsection Changing the system wide custom column order To enable a shared custom column you should start from the list of currently available columns You can get there in two ways 38 7 Custom columns Editing custom column settings e From any disease or gene that you have authorization of open the Options menu button and click the View all available phenotype columns or View all available variant columns link depending on which type of column you wish to enable e If you re a manager or higher click the Browse all custom data columns link of the setup menu tab dropdown menu or from the setup area click the Browse all custom data columns already available to enable or disable them or view or edit their settings link listed under Custom data columns This is the list of all custom columns To filter this list for category click the options wheel icon on the top left hand side of the columns listing to open up the menu and select the category you are interested in You can also filter for category by typing part of the name in the Categ
95. om column s system wide settings you should start from the list of currently available columns Click the Browse all custom data columns link of the setup menu tab dropdown menu or from the setup area click the Browse all custom data columns already available to enable or disable them or view or edit their settings link listed under Custom data columns This is the list of all custom columns To filter this list for category click the options wheel icon on the top left hand side of the columns listing to open up the menu and select the category you are interested in You can also filter for category by typing part of the name in the Category column filter box and press the Enter key Now click the column which settings you wish to edit Click the Options menu button to open up the column s menu and click on Edit custom data column settings The form to edit the system wide settings is equal to the form used to create a new custom column with two exceptions The Column ID field is not present here since you can not change a column s ID once you created it Also for shared columns at the bottom of the form a checkbox is present labeled Apply changes to all genes diseases where this column is active Checking this checkbox effectively resets all enabled instances of the column and applies all changes you make on this form to them overwriting possible modifications of object specific sett
96. on most forms in LOVD do not allow HTML content Password protected data manipulation forms To prevent manipulation of your variant or patient data when your computer is used by someone else while you are logged into LOVD all data manipulation forms are password protected Before the form can be submitted and processed your password is required to confirm the changes This also protects you against Cross site request forgery CSRF attacks 71 11 Keeping your data secure What you can do to protect your data 11 2 What you can do to protect your data A chain is only as strong as the weakest link Even with all the effort we have put into making LOVD as safe as possible some weak links may still exists Read this section to learn about how to protect your data in LOVD further 1 Choose your password carefully and protect it Even though LOVD does include a pass word quality check please take care in choosing a password that can not be guessed by others and you don t use for other systems as well Also don t write it down on a sticky note stuck near your computer In case you re the system administrator who installed LOVD make sure the MySQL password is also chose securely Don t leave your computer unattended while logged in This will give anyone who uses your computer in your absence access to the data stored in LOVD Also don t leave your computer unattended if you re not logged in but had your browser remembe
97. ons menu button to open up the transcript s menu and select the Delete transcript entry option On the next page confirm by typing your password in the input box and submit the form to complete the removal 32 7 Custom columns To make sure LOVD can be used by a great variety of users who all focus on storing different data LOVD allows great flexibility in the form of custom columns data fields that can be personalized by the curators or even completely newly defined All standard LOVD columns can be edited and removed except for the HGVS recommended columns which can only be edited but not removed Besides this default set of selected columns which are added by default LOVD also comes with a set of columns that have not been added to the data tables yet but can be added with a click of a button Additional columns can be created to suit your every need 7 1 Custom column categories In LOVD3 custom columns come in five different categories Individual Information on the individual not related to disease not changing over time such as date of birth geographic or ethnic origin Phenotype Information on the phenotype related to disease possibly changing over time such as blood pressure body length or date seen by specialist Screening Information on the detection of new variants such as detection technique laboratory conditions or type of sample taken from the individual Variant On Genome Informatio
98. ory column filter box and press the Enter key Please note that in this custom column overview the Active field simply states whether or not this column has been added to the data table i e is active for any parent object From the column overview click the column you wish to enable In the detailed view of the custom column you can review all the column s settings to verify that it suits your needs Click the Options menu button to open up the column s menu and click on Enable column Please note that if this shared custom column was not active yet and your database already contains a lot of information enabling this column may take some time If this is the case LOVD will display a warning From the Add this column to selection list select the parent objects diseases or genes you wish to enable this column for For help on how to use this type of selection list move your mouse over the blue help icon If the parent object you are looking for is not shown in this list you have no authorization on the object to change its column s settings or the column is already active for the object Finally type in your password in the Enter your password for authorization field for verification of your authorization and submit the form The column is now enabled and visible in the data entry forms and the data listings and detailed views To make sure the column ended up in the right order between the alr
99. own account Required level Submitter Editing other user s accounts requires you to Available from LOVD 3 0 Build 01 have a level higher than the user you are try ing to edit Managers can edit submitter accounts including collaborators and curators The database administrator can also edit manager accounts To edit your own account click the Your account link on the top right hand side of the screen which leads directly to your account overview Then click the Options button and click Update your registration To edit someone else s account click the Users tab Locate the user you wish to edit by searching or browsing through the given user listing Clicking the entry will direct you to the user s account details If you have permission to edit this account you ll see an Options button Click it and click Edit user The fields on the form are explained in the section Registering a new account Please note that the New password fields are optional when editing an existing user account You only fill them in when you want to change the password After you submit the form LOVD redirects you automatically back to the user s account details 21 4 Authorized users Locking users out of the system 4 4 Locking users out of the system A user is automatically locked if a wrong pass Required level Manager word is used three times while logging in with Available from LO
100. phenotype information to individual to open up the phenotype data entry form or in the case this individual has been diagnosed with multiple diseases to select which disease you wish to add phenotype data for If you do not see the Add phenotype information to individual option then the individual does not have any diseases linked yet In that case edit the individual and select at least one disease from the list After you submitted the phenotype data LOVD sends an email to the curator s and redirects you to the phenotype data overview 51 9 Downloading amp importing data 9 1 The LOVD3 import format The LOVD3 import format is based on the LOVD2 tab delimited import format but all data is split into separate sections preventing data duplication Examples of sections are Genes Transcripts and Diseases Each section has its own set of fields Sections refer to each other using IDs For instance the Transcripts section has a geneid field that refers to an entry in the Genes section with the same value in its d field This way transcripts are connected to genes LOVD version 3000 010 Full data download To import do not remove or alter this header charset UTF 8 max_errors 50 Genes Do not remove or alter this header id name chromosome chrom_band id_hgnc id_entrez id_omim IVD isovaleryl CoA dehydrogenase 15 q14 q15 6186
101. porting when set LOVD has encountered an error while mapping 32 MAPPING DONE Not used when importing when set LOVD is done mapping the vari ant regardless of whether the vari ant actually got mapped For instance a value of 11 means for this variant mapping has been enabled 1 LOVD is allowed to create new genes while mapping the variant 2 but LOVD does not recognize the variant and therefore can not map it 8 1 2 8 11 If left empty during import the default value will be 0 motherid from section Individuals Optional The internal ID of the individual in the database that is the mother of this individual mysql_type from section Columns The custom column s MySQL data type When importing new custom columns we recommend you use the Data type wizard available when creating a new custom column and to use the MySQL data type generated by the wizard See also section Creating a new custom column note_index from section Genes Notes that should appear on the gene home page note_listing from section Genes Notes that should appear on gene specific data listings owned_ by from section Individuals Phenotypes Screenings and Variants_On_ Genome Optional The internal ID of the user that owns this data entry Owners are allowed to edit the entry and add new data to the entry Owners are not fixed and can be re assigned When no value is provided during import this value
102. printing If known please fill in if this gene is imprinted maternal or paternal or not Date of creation Note This field can only be filled in when creating a gene database and can never be edited afterwards The database s date of creation is mentioned on the gene homepage Today s date will automatically be stored if you leave this field empty but in case you already had a gene database but you re moving it to this LOVD installation you may want to fill in a different date Relation to diseases This gene has been linked to these diseases By linking the gene to disease s LOVD can help predicting next steps in data submission and the link to the disease information will be shown on the gene homepage If a disease you need is not present in this list you can click the configure more diseases link below the selection list to create a new disease now Afterwards reload the gene form so you can select the new disease Alternatively create the disease after the gene has been created Reference sequences Collecting variants requires a proper reference sequence Without a genomic and a transcript reference sequence the variants in this LOVD database cannot be interpreted properly or mapped to the genome When properly configured LOVD will add links to the Ensembl NCBI and UCSC genome browsers from the gene homepage generating a nice visual overview of the variants in the database Genomic reference sequence Select the ge
103. r custom column is now created and you can choose to enable the column if you wish Also you might want to check the column order since newly created custom columns are appended to be the last column 37 7 Custom columns Enabling custom columns 7 3 Enabling custom columns Directly after creating a new custom column or at any later time you can enable a custom column It must already exist in the database otherwise you first need to create it Non shared custom columns Individual Screening and Variant On Genome categories are enabled system wide which requires manager access Shared custom columns Phenotype and Variant On Transcript categories can be enabled by parent object disease or gene respectively and require curator access Enabling non shared custom columns The non shared system wide custom column Required level Manager types are Individual Screening and Variant On J Available from LOVD 3 0 Build 01 Genome To enable a non shared custom col umn you should start from the list of currently available columns You can get there in two ways e Depending on which type of column you wish to enable click the Enable more custom columns link in the Individuals or Screenings menu tabs dropdown menu or the Enable more genomic custom columns link from the Variants menu tab dropdown menu e Click the Browse all custom data columns link of the setup menu tab dropdown menu
104. r your password for you Once you re done using LOVD log out Be careful where you leave your backup files Making backups of your data in LOVD is a smart thing to do Errors made by both machine hardware error or man accidentally deleting data can be solved easily if you have proper backups However these backups do contain all your sensitive patient and variant data in a non encrypted way Be careful where you store your backup files Don t store them on network drives accessible by more people than the ones who you would allow to access LOVD itself Use SSL Ask your systems administrator to enable SSL https on the server your LOVD is installed on and enable the Use SSL only to access LOVD option in the LOVD system settings This encrypts any data exchange between you and LOVD such as your password and sensitive patient information Don t allow access to your LOVD files or the database to other users on the server If there are other users on the server you have LOVD hosted on make sure they cannot access the LOVD directory or get access to the same database LOVD stores its information in 72 12 Troubleshooting In case you run into any kind of problem or when you have a question we recommend you first check in the manual to see if perhaps the answer can be found there A newer version of the manual may be available online on the LOVD website If that doesn t resolve your problem or answer your question plea
105. ranscript columns For explaination of the available fields please see the section Creating a new custom column After submitting the form the changes are effective immediately but applied to the chosen parent object only 40 7 Custom columns Changing the order of custom columns 7 5 Changing the order of custom columns Custom columns are shown in a predefined but adaptable order This order determines how custom columns are shown in the data tables in the download files and on data entry forms It is therefore important that the columns are sorted in a sensible order Just like the custom column settings shared columns can have an object specific order different from the default order Similarly the order of non shared columns is system wide and needs to be configured by a manager or up Please note that columns from different categories can not be mixed Some data listings show overviews of different types of data joined together such as variants on genomic level joined with the variant s effect on transcript level In this case the columns representing genomic data such as chromosome DNA description on genomic level and the allele field can not be mixed with columns representing data related to the change on the transcript such as exon number DNA description on the transcript level or the effect on protein level Only the order in which each category s columns are shown can be changed Changing the system wid
106. rt select_ options from section Columns When the custom column is a selection field the selection options are listed here See also section Creating a new custom column for the format Please remember that linebreaks in the LOVD import format are displayed as r n standard from section Columns If set to 1 this column is enabled by default When importing this is only useful for shared custom columns When set the column will then be enabled by default for a new disease or gene depending on the column category See also section Creating a new custom column Default value is 0 statusid from section Individuals Phenotypes and Variants On Genome Optional This numeric status ID defines if the data is public or not ID Name Description 1 In progress Not used when importing data entry is in the process of being submitted 2 Pending Not used when importing data entry has been submitted await ing approval of curator 4 Non public Data entry is not public hidden from view for non authorized users 7 Marked Data entry is public but marked shows up as red for authorized users 9 Public Data entry is public Data with status In progress or Pending respectively value 1 and 2 can not be imported Instead there are 3 options 1 If the import file originates from a different LOVD installation then curate the data there and download the file again 2 Change the statusid value to a
107. s and the NCBI sequence viewer also depend on this setting From LOVD 3 0 beta 07 the hg18 setting is no longer available for new LOVD instal lations although it will remain to be supported When hg20 will come out LOVD will start supporting multiple genome builds per installation List database changes in feed for how long Note Not yet implemented LOVD includes a newsfeed that allows users to get a list of changes recently made in the database Select here how many months back you want changes to appear on this list Set to Not available to disable the newsfeed Connection settings optional Some networks have no access to the outside world except through a so called proxy server more info on WikiPedia If this applies to the network this server is installed on please fill in the proxy server information here Proxy server host name The host name of the proxy server such as www cache institution edu Proxy server port number The port number of the proxy server such as 3128 Proxy server username In case the proxy server requires authentication please enter the required username here Proxy server password In case the proxy server requires authentication please enter the required password here 12 3 LOVD Setup LOVD system settings Customize LOVD Here you can customize the way LOVD looks Right now there is only one option included we will add more later System logo If you wish to h
108. s been added to Here you can define how wide the column should be in data listings This is measured in pixels Since the width depends on the screen s resolution a hint is provided how wide the currently selected width is on the current screen Mandatory field For shared columns this value can be changed separately for each parent object this column has been added to With this option selected users can t leave this column empty Show contents to public For shared columns this value can be changed separately for each parent object this column has been added to This controls whether or not users with no specific authorization on the data entry can see the contents of this column Show field on submission form For shared columns this value can be changed separately for each parent object this column has been added to If you don t want submitters to fill in this column but reserve the use for curators disable this checkbox Please note that unsetting this will not hide the contents of the column from the public it merely stops them from entering data in it Link settings Here you can select which custom links will be active in this custom column Active custom links Select any number of custom links or leave all unselected if you do not wish to use custom links in this field Note that the use of custom links only makes sense for fields that accept text input Enter your password at the bottom of the form and submit it You
109. s been diagnosed with one or more J Available from LOVD 3 0 Build 01 diseases or when this individual is marked as healthy control it is possible to add extra phenotype details to this individual Select I want to add phenotype information to this individual figure 8 1 fill all required fields and click Create phenotype information entry The option I want to add phenotype information to this individual is disabled when no relation to diseases has been selected during the creation of this individual If you wish to add phenotype information while this option is disabled you have to edit the individual see section Adding phenotype information to an individual on how to proceed Adding a variant screening to the individual By selecting I want to add a variant screen Required level Submitter ing to this individual you can add a screen Available from LOVD 3 0 Build 01 ing to the individual For Detection template Technique s used and Genes screened more than one item can be selected Complete the form and when ready click Create screening information entry When the entry is suc cessful a message is displayed for several seconds Successfully created the screening entry Hereafter you are redirected to a menu where you can choose how to proceed Submission of screening 0000000008 What would you like to do want to add a variant to this screening Back to t
110. se follow the following steps Check the Frequently Asked Questions on our website to see if that provides you any answers If not check the LOVD forum to see if that helps you If not please submit your question to the LOVD3 support forum If you re sure the problem you are having is an LOVD bug please use our bug tracking system to report your issue Only in case you don t want to publicly put your problem or question on the forum or bug tracking system you can contact us also directly through the website 73
111. ser in a collaborator for this gene he can still see all public and unpublic data in this gene database but he can t edit it like curators can If the user is to be a curator he will receive notifications of variant data submissions and submission updates Collaborators do not receive such emails The second checkbox indicates whether or not the user s name and email address is shown on the gene homepage and on the top of every page while this gene is selected Curators can be hidden from the gene homepage and the page headers by unchecking this checkbox Collaborators are always hidden it is therefore not possible to change the second checkbox while the first checkbox is unchecked To remove an user as a curator or collaborator click the red cross at the far right side of the table You can only assign or remove curators if your user level is higher than that of the user you wish to assign remove Please note that managers and the database administrator can never be made collaborators since disallowing them to edit data contradicts their user level They will always be allowed to 28 5 Gene databases Assigning curators and collaborators KO AD 3 LOVD Leiden Open Variation Database LOVD v 3 0 Build beta 10 Current LOVD status Welcome Ivo F A C Fokkema ariation Database isovaleryl CoA dehydrogenase IVD Your account Log out Curator Ivo F A C Fokkema enn de de e A Y Authorize curators for the IVD gene
112. t be removed 7 8 Downloading custom column data to text files LOVD supports exporting the custom data col Required level Manager umns including the columns system wide set f Available from LOVD 3 0 Build 04 tings to the LOVD import format This file can then be used as a backup or to share the custom columns specifications with other LOVD3 installations by re importing the file into LOVD from LOVD 3 0 05 Please note that from LOVD 3 0 05 the custom column data is also included in the full LOVD download available from the setup area 44 7 Custom columns Importing custom column data from text files To download all custom column specifications click the Download all LOVD custom columns link in the setup menu tab dropdow menu or from the setup area click the Down load all LOVD custom columns in the LOVD import format link listed under Custom data columns We do not recommend you to edit this file For more information on the format please see section The LOVD3 import format 7 9 Importing custom column data from text files Custom columns downloaded in the LOVD im Required level Manager port format can be reimported into LOVD Available from LOVD 3 0 Build 05 LOVD will only import the custom columns from the file which are not already in the system LOVD does not compare the column s settings in the file versus what is in the database LOVD just checks if the column IDs are present
113. t it aligned left center or right Page footer HTML enabled If you want a gene specific footer on all public gene specific pages please enter the text here Footer aligned to In case you defined a page footer here you can select how you want it aligned left center or right Notes for the LOVD gene homepage HTML enabled Text entered here will appear in the General Information box on the gene s homepage In general curators put additional information about the database here such as how the data in the database was collected grants supporting this work or news Notes for the variant listings HTML enabled Text entered here will appear below the gene s variant listings 26 5 Gene databases The gene homepage Security settings Using the following settings you can control some security settings of LOVD Allow public to download variant entries This controls whether or not the public can also make downloads of your gene s variants Allow my public variant and individual data to be indexed by WikiProfessional Note Not yet implemented If you ll allow the WikiProfessional concept web to index your variant and individual data enable this checkbox 5 2 The gene homepage LOVD automatically generates a gene homepage Required level None public for every gene created within LOVD The gene Available from LOVD 3 0 Build 01 homepage is the entry point for visitors of a locus specific database In install
114. t we are not developing for other database backends You are welcome to try other database backends and report the results to us but we can t provide any support for it For more information see the FAQ about software needed Before installing LOVD be sure you have the required credentials for connecting to the MySQL database You need a hostname username password and a database name to be able to install LOVD If you are installing LOVD on a remote server be sure to have the FTP username and password to be able to copy the necessary files to the server Download amp Extract To download LOVD go to the LOVD website and click on the Download tab You can download LOVD in two formats GZIPped TARball and ZIP archive The first format is common for Unix and Linux systems while the ZIP archive is popular on the Windows platform Usually you will be able to open both formats Download the file of your choice and save it to your hard drive Now extract the file using GZIP TAR or ZIP to the desired location On a server common directories may be var www on Unix or Linux servers or C htdocs on a Windows server When using XAMPP 2 Installing LOVD Install process the directory is C xampp htdocs for Windows opt lampp htdocs for Linux or Applica tions XAMPP htdocs for Mac To be sure consult the documentation of the webserver soft ware you are using Pre install Setup You will need to rename the standard config file
115. tall LOVD creates a log entry on completion of the LOVD installation procedure Also after each upgrade LOVD will add an entry stating from which version to which version it has been upgraded and how many database queries have been used for the upgrade Also errors during an LOVD upgrade might they occur will be logged here Viewing and searching through the logs To browse the system logs click the View system logs option of the Setup tab dropdown menu or the View search and delete system logs link in the setup area The system log overview is fully searchable and sortable allowing you to find log entries quickly The Log column shows the type of log every Auth Event Error or Install The Date column shows the date the log entry was created The User column shows if available which user caused the log entry to be created The Event column lists the type of event that occurred Finally the Entry column provides more information about the event that has occurred For login attempts it will contain the IP address of the user attempting to log in For most event types it will include the ID of the entry that was created edited or deleted Removing log entries To remove a single log entry click on the red cross in the 6th column To remove multiple log entries at once first apply as many search terms on the log entries as needed to restrict the view to the entries you want to
116. teger input field A standard input field visually similar to the text numeric input field but allowing only whole numbers to be filled in Decimal input field A standard input field visually similar to the text numeric input field but allowing only numbers with a configurable number of decimals Large multi row textual input field A large text field with multiple rows allowing large amounts of text to be filled in Drop down list one option selected A drop down list with a set of options of which the user must choose one value Selection list multiple options selected A selection list where the user can select one or more options or ranges Date input field A standard input field visually similar to the text numeric input field but allowing only dates year month day optionally also storing time hours minutes seconds The input format is YYYY MM DD or YYYY MM DD HH MM SS On off checkbox A simple checkbox allowing only a yes no answer Select the wanted data entry type and click Next The next page shows you some additional options that depend on the type of field you ve chosen Column name on form all field types The name the column will have on the data entry form This is usually the same as the Column heading field Help text all field types If you think the data field needs clarification for users especially those who don t know this field well add such clarification here By filli
117. tem wide change which requires manager access Disabling shared custom columns can be done per parent object and requires curator access Disabling non shared custom columns To disable a non shared custom column you Required level Manager should start from the list of currently active Available from LOVD 3 0 Build 01 columns You can get there in two ways e Depending on which type of column you wish to disable click the View active custom columns link in the Individuals or Screenings menu tabs dropdown menu or the View active genomic custom columns link from the Variants menu tab dropdown menu e Click the Browse all custom data columns link of the setup menu tab dropdown menu or from the setup area click the Browse all custom data columns already available to enable or disable them or view or edit their settings link listed under Custom data 42 7 Custom columns Disabling custom columns columns This is the list of all custom columns To filter this list for category click the options wheel icon on the top left hand side of the columns listing to open up the menu and select the category you are interested in You can also filter for category by typing part of the name in the Category column filter box and press the Enter key To further filter the list for columns currently enabled fill in a one 1 in the Active column filter box and press t
118. tform inde pendent and uses PHP and MySQL open source software only The design of the database follows the recommendations of the Human Genome Variation Society HGVS and focuses on the collection and display of DNA sequence variations but it has fully implemented methods for storing complete clinical data as well The open LOVD setup also facilitates functional extensions with scripts written by the community The development of then nameless LOVD started in late 2002 while it was first officially released in January 2004 Before that LOVD was only in use by the Leiden Muscular Dystrophy pages as a not so modular system with lots of characteristics specific for that website only With the official release of LOVD in 2004 the system had become much more dynamic and customizing LOVD was made easy mostly by editing text files In 2004 LOVD became available under the open source license GPL and with the 1 1 0 release most of the text files had been replaced by online forms so customizations can be performed through the web interface Early in 2005 the first LOVD article was published and in 2005 the development of LOVD was more targeted at improving the ease of use of the system In 2006 the development of LOVD 2 0 started after the decision was made to rewrite all of LOVD from scratch to be able to include a long list of upgrade suggestions that were hard to implement in LOVD 1 1 0 Aimed at modularity and data redundancy LOVD 2 0 was meant t
119. th zero or more entries When requesting a specific entry just the Atom entry is returned The Atom format is described in detail on Wikipedia The content of the Atom entries is in plain text with headers and values separated by a colon Other formats as a payload of the Atom entries are not available The new LOVD3 API release date unavailable will probably support multiple formats such as VarioML and JSON most likely not wrapped in Atom feeds since this API serves a different purpose 66 10 The LOVD API Format Genes lt xml version 1 0 encoding UTF 8 gt lt feed xmlns http www w3 org 2005 Atom gt lt title gt Results for your query of the database lt title gt lt link rel alternate type text html href http databases lovd nl shared gt lt link rel self type application atomtxml href http databases lovd nl shared api rest genes gt lt updated gt 2014 01 14T12 20 24 01 00 lt updated gt lt id gt tag databases lovd nl 2012 05 02 web01 shared REST_api lt id gt lt generator uri http www LOVD nl version 3 0 09 gt Leiden Open Variation Database lt generator gt lt rights gt Copyright c the curators of this database lt rights gt lt entry xmlns http www w3 org 2005 Atom gt lt title gt IVD lt title gt lt link rel alternate type text html href http databases lovd nl shared genes IVD gt lt link rel self type application atom xml href http
120. the lab This part describes the reference that LOVD makes to your institute Country Please select the country from the given list City Even though you entered the city also in the address field above please enter it here as well It s used for sorting purposes when creating a list of the institutes registered to the installation Reference Your submissions will contain a reference to you in the format Country City by default You may change this to your preferred reference here 19 4 Authorized users Creating new user accounts Security To prevent unauthorized use of your account we implemented a security feature that you can configure here Allowed IP address list Note Please be extremely careful using this setting Using this setting too strictly can deny you access to LOVD even if the correct credentials have been provided An IP address is an address a computer is known by on the network To help prevent others to try and guess your username password combination you can restrict access to your account to a number of IP addresses or ranges For instance to make sure your account can only be used when accessed from your institute or from your home Set to to allow all IP addresses use to specify a range like 192 168 0 1 20 and use to separate addresses or ranges like 192 168 0 1 192 168 1 34 Registration authentication To prevent automatic submission of the registrat
121. the section Specific fields explained to check which fields you are not allowed to update 62 9 Downloading amp importing data Downloading amp importing the complete data The IDs in the import file are used to identify the records in the LOVD database Therefore you cannot modify the ID fields in your import file To make sure your IDs in the LOVD database correspond with the IDs in your import file and to prevent unintended edits it is recommended to make a new download complete data set custom columns own data set or a gene s data set depending on what you would like to update before you start preparing your changes On the import form select the Update existing data option for the Import mode field if you wish to modify data in your LOVD database You can use the simulate option to check your file for errors first 9 3 Downloading amp importing the complete data Downloading the complete data set from LOVD LOVD supports a full download that contains Required level Manager most currently not all data stored in LOVD Available from LOVD 3 0 Build 01 The data sections included in the download file are Columns Genes Transcripts Diseases Genes_ To _ Diseases Individuals Individ uals To Diseases Phenotypes Screenings Screenings To Genes Variants On Genome Variants On Transcripts and Screenings To Variants In order to have a full backup for instance to restore LOVD in case of a hardware f
122. u allowing you to quickly navigate to other setup options without having to go through the setup main page The other options shown in the setup area are available through their own tab s dropdown menus In this chapter we will describe changing the LOVD system settings how to check search and clean up the LOVD system logs and how to uninstall LOVD The other actions available from the LOVD setup are described in their respective chapters see the table of contents 3 1 LOVD system settings The LOVD system settings allow you to adapt Required level Manager your LOVD installation to your preferences For Available from LOVD 3 0 Build 01 instance by changing the installation s displayed name or email address general settings proxy server settings connection settings settings on statistics or the security settings To view or edit the LOVD system settings click on the Setup tab then on View and change LOVD System settings or move your mouse over the Setup tab and click the LOVD system settings menu option from the dropdown list General system settings Title of this LOVD installation This title will be shown on the top of every page above the menu tabs The default value is LOVD Leiden Open Variation Database Institute The institute which runs this database is displayed in the public area and in emails sent by LOVD It s commonly set to a laboratory name or a website name If it s
123. uild 01 that no individual phenotype or screening data is submitted only variant data Although you can submit summary variant data it is highly discouraged because individual and phenotype data make the variant data much more valuable An example of a valid reason to submit summary variant data is for storing variant frequency data of large populations 8 4 Adding data to already finished submissions It is still possible for the submitter to add data Required level Submitter to an individual or a screening when a submitter Available from LOVD 3 0 Build 01 finished the submission regardless of whether the curator published the data or not Adding a variant to a screening To add a variant to an existing screening click on the Screen ings tab and select a screening for which you are authorized Options Click on the Options menu button to open up the screening Options menu button entry s menu If you do not see the Options menu button you are not logged in or you do not have rights to edit this screening In the opened menu click 50 8 Adding data to LOVD Adding data to already finished submissions Add variant to screening From here you can follow the steps described in the section Adding a variant to a screening After you submitted the variant data LOVD sends an email to the curator s and redirects you to the variant overview Adding screening to individual
124. updated during an import position_g_ start from section Variants On Genome The genomic position relative to the chromosome of the first base of the variant The first base of the variant is defined by the HGVS nomenclature rules and may be the same as the last base This field cannot be updated during an import position_g end from section Variants_ On Genome The genomic position relative to the chromosome of the last base of the variant The 59 9 Downloading amp importing data The LOVD3 import format last base of the variant is defined by the HGVS nomenclature rules and may be the same as the first base This field cannot be updated during an import preg_pattern from section Columns For text field custom columns regular expression checks can be performed See also section Creating a new custom column public_view from section Columns If set to 1 this column s contents are visible to the public only for public entries See also section Creating a new custom column public_add from section Columns If set to 1 submitters can fill in this field Otherwise only curators and higher level users can enter data in this field refseq_ genomic from section Genes The genomic reference sequence this field cannot be updated during an import refseq_UD from section Genes This is an internal ID for the genomic reference sequence generated by Mutalyzer This field cannot be updated during an impo
125. valid value being 4 or higher 60 9 Downloading amp importing data Downloading amp importing data 3 Exclude this record for import by either removing it from the import file or hiding the record by putting a in the beginning of the line If you do this make sure that all related data from other sections are excluded as well or LOVD will return errors when trying to resolve references in the file When no value is provided during import this value is set to 9 Public symbol from section Diseases The disease s abbreviation preferably the most commonly used one transcriptid from section Variants_On Transcripts ID referring to the ID in section Transcripts This field cannot be updated during an import type from section Variants On Genome The type of variant on DNA level as defined by the Mutalyzer web service All possible values are ID Name Description compound Compound variant Not normally in use multiple variants grouped to gether del Deletion One or more DNA bases have been deleted delins Deletion Insertion One or more DNA bases have been deleted while others have been inserted when not a substitution dup Duplication Duplication of one or more DNA bases ins Insertion Insertion of one or more DNA bases when not a duplication subst Substitution One DNA base has been replaced by another updated_ by from section Genes The internal ID of the user who was the
126. value can be changed separately for each parent object this column has been added to Describe the meaning of the column in short This will appear when a user moves his mouse over the column header in the data tables Description on full legend HTML enabled For shared columns this value can be changed separately for each parent object this column has been added to Describe the meaning of the column You can be very elaborate here This text will be shown on the full legend of the data table Data and form settings Here you define what the column looks like on the data entry form and what kind of data it will store There are two ways to define the data type of your custom column The recommended way is to use the data type wizard which will fill in the MySQL and the form type values Only if you really know what you re doing you can edit the MySQL data type and the form type directly Its formats are out of the scope of this manual and therefore not explained here 34 7 Custom columns Creating a new custom column Using the data type wizard To start the data type wizard click the Start data type wizard button The wizard will open in a new window Firstly you need to select what type of data entry field you want to create for your custom column In the Basic form style field choose from one of these options Text numeric input field A standard input field allowing textual or numerical free text input In
127. you can also choose to submit only summary variant data although we do not recommend this Please see section Submitting summary variant data for details In the data entry form for data on the individual most fields are optional in a standard LOVD installation You can check the help icon next to the form fields to see details about the fields and suggestions on how to use the fields After completing the form click Create individual information entry When successful a message is displayed several seconds Suc cessfully created the individual information entry Hereafter you are redirected to the menu as displayed in figure 8 1 where you can choose how to proceed Submission of individual 400000026 What would you like to do want to add phenotype information to this individual want to add a variant screening to this individual want to add a variant to this individual I want to finish this submission Figure 8 1 After completing the data entry form you can choose to add phenotype information if a disease or healty control has been selected or a variant screening to this individual A submission can only be finished after at least one screening with a variant is filled in 46 8 Adding data to LOVD Starting a submission by creating an individual Adding phenotype information to the individual When you created an individual and this in Required level Submitter dividual ha
128. you like to submit A variant that is located within a gene A variant that was only described on genomic level want to upload a file with genomic variant data Figure 8 3 Creating a new variant entry Note Only managers and up have the option I want to upload a file with genomic variant data available the currently selected screening Click the checkmarks left of the variants that you would like to mark as confirmed and click Save variant list Confirm variant entries with screening 0000000013 The variant entries below are all variants found in this individual not yet confirmed by added to this screening 1 entry on 1 page Showing entry 1 10 per page Legend Effect Allele o Reference DBD Frequency Owner Status Fs Unknown g 220379188C gt T ASIC4_000002 daan asscheman Public 10per page vj Legend Enter your password for authorization Save variant list Cancel Figure 8 4 Select a variant to confirm Shown are the variants already linked to other screenings of the individual but not to the currently selected screening Adding a variant located within a gene After choosing this option you are shown a list of genes If certain genes have been selected while creating the screening these are pre selected You can remove or edit the pre selection by removing or editing the configured filter in the Symbol c

LOVD 3.0 user manual Build 3.0-14

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