LOVD 3.0 user manual Build 3.0-beta-11
Contents
1. 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 Installing database tables 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 iia 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 relatively experienced computer user Done 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 Powered by 2004 2012 Leiden Univ LOVD v 3 0 Build beta 04 University 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 straight2. 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 browsers 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 her
3. 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 12 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 number 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 l
4. 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 17 4 Authorized users Registering a new account User details This part of the registration form contains the 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 Tele
5. 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 not be able to work with LOVD until he has changed his password 19 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
6. 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 gen eral options from the LOVD setup are also available through the Setup tab s dropdown menu 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 T
7. 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 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 in 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 whil
8. 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 mitochondrial 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 22 5 Gene databases Creating a new gene database General information This part describes the bare essentials of the gene information Therefore most of
9. 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 24 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 ignore
10. 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 re CAPTCHA module which makes sure the form can 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
11. 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 Imprinting 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 Alterna
12. to allow collaborating users to track each other s activities or to check what happened to a certain data entry over time 13 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 Install 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 whi
13. 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 21 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 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 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
14. 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 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 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 Opti
15. 1017 Leiden Open Variation Database LOVD 3 0 user manual Build 3 0 beta 11 Ivo F A C Fokkema Leiden University Medical Center Last updated 2012 11 19 LOVD has received funding from the European Community s Seventh Framework Programme FP7 2007 2013 under grant agreement no 200754 the GEN2PHEN project Contents Contents 1 Introduction 2 Installing LOVD 21 Bere YOR Mal coo eRe eS OR Glee pop pian IE a 22 Install process ce ras AAA A LOVD Setup S1 LOVD system setlis caso AAA A K Oke E a wee amp eH Se Unmetaline LOUVO o sa ee te ee ee ee we ee SS a Authorized users AT Registering a new ACOU E cosida drid EO EGE ESR AEE He 4 2 Creating new user ACCOUM S lt lt lt rara ra AA Aa Wie Weer AOOOUI S sia a AAA A a 4 4 Locking users out of the system e e ee Gene databases 5 1 Creating a new gene database o 5 2 The gene homepage coco ocres ee ERS ee ee ES 5 3 Editing a gene database o ce be ee eee resis a 54 Deleting a gene database gt sa o 6b eb coca coa dooa to dioa ee 5 5 Assigning curators and co llaborators 4 4 64 bea ae eae Ea sda 10 10 13 15 16 17 19 20 21 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
16. 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 registration form we implemented a re CAPTCHA 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 f 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
17. Leiden University Medical Center Database URL optional http databases lovd nl shared check 0 0 e Title of this LOVD installation LOVD email address noreply lovd nl M Configuring LOVD system settings Forward messages to database admin Human Build to map to UCSC NCBI hg19 GRCh37 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 0 Customize LOVD Here you can customize the way LOVD looks We will add new options here later System logo Ol 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 es Include in the global LOVD listing eN 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 Y Enable submitters to change data es Enable getting counts of hidden entries Not ye
18. OVD 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 KO D LOVD 3 0 Leiden Open Variation Database LODO Bult beta os LOVD was not installed yet Please install LOVD first Powered by LOVD v 3 0 Build beta 04 2004 2012 Leiden 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 2 Installing LOVD Install process Installing LOVD consists of only 4 simple steps and will take only a couple of minutes or less LO iD LOVD 3 0 Leiden Open Variation Database EOD Bebe pete Ot 0 100 Introduction Welcome to the LOVD v 3 0 beta 04 installer
19. able 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 installations 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 behavi
20. an 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 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 n1 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
21. ch 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 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 14 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
22. d 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 want 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 25 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 en
23. e 2 Installing LOVD Install process K0 Dd LOVD 3 0 Leiden Open Variation Database LODO Bord pele Ot le 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 pitana 2333 ZC Leiden Done Email address es one per line LF A C Fokkema LUMC nl Telephone optional Username ifokkema Password AS Password confirm AS Referencing the lab Country Netherlands gt City 0 Leiden Reference optional O 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 3 0 Build b Figure 2 3 The database administrator registration form with example data filled in on non optimal conditions so please be patient When everything is done a Next button appea
24. e 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 11 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 have 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 nu
25. eedom 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 between It will be possible for different submitters to work together cooperatively on the same 1 Introduction data Searching through the data is improved extensively and webservices of many different sources 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 beta 11 Keep an eye on our news page for the latest information on LOVD 3 0 development Where ever 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 most features in LOVD 3 0 are not yet described in t
26. erefore 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 16 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 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
27. he 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 user 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 edi
28. his 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 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 LOVD has been extensively tested with the Apache webserver but any webserver able to run PHP scripts should suffice You ll need PHP 5 1 0 or higher and MySQL 4 1 2 or higher LOVD may work with other database platforms but 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 A suitable server with the necessary software installed is available at virtually all academic institutions and countless commercial hosting providers Before install
29. iles had been replaced by online forms so customizations can be per formed 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 to 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 con tinuously 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 fr
30. ing 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 com mon 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 To be sure consult the documentation of the webserver software you are using Pre install Setup You will need to rename the standard config file 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 database name username and password here Please go through the entire config ini php file to determine if you need to change any of the other settings 2 Installing LOVD Install process Q A htaccess file is put in the root directory of you
31. 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 T 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 uninstaller 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 15 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
32. mber 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 gene 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
33. 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 platform independent 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 collec tion 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 f
34. o create the gene database again 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 remove the genomic variants from the database 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 KO AD 3 LOVD Leiden Open Variation Database LOVD v 3 0 Build beta 10 Current LOVD status Welcome Ivo F A C Fokkema Leiden Open Variation Database isovaleryl CoA dehydrogenase IVD Your account Log out Curator Ivo F A C Fokkema ico de de Authorize curators for the IVD gene 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 Name Username Institute Country Curated DBs Test Manager manager Leiden University Medical Center Netherlands O Manager 10 per page All users below have access to all da
35. o 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 not specified LOVD will use the autodetected website name LOVD has been installed on 10 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
36. ogs 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 logged 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
37. ons 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 20 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 LOVD 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
38. or 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 edit 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 26 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 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 t Removing a gene can not be undone you will need t
39. page and on the page headers it is f Available from LOVD 3 0 Build 01 sometimes 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 27 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 28 5 Gene databases Assigning curators and collaborators bottom part of the Authorize curators form allowing to sort and show or hide the curator names see figure 5 2 on page 28 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 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 t Drag sort handle 29
40. phone 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 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 18 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
41. r 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 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 L
42. rs click it to continue OVD LOVD 3 0 Leiden Open Variation Database oe aaa Installation steps Introduction Installing LOVD Installation progress 0 100 82 Administrator account details Creating LOVD account amp LOVD database administrator account Installing database tables Configuring LOVD system settings Figure 2 4 Watch the progress bar complete while LOVD informs you which part of the database table installation is currently in progress 2 Installing LOVD Install process 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 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 KOD LOVD 3 0 Leiden Open Variation Database LOVD v 3 0 Build beta 04 o L 0 100 EEEE 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 O LOVD Leiden Open Variation Database Installing database tables Institute optional
43. t data contradicts their user level They will always be allowed to 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 LOVD LOVD Leiden Open Variation Database Fe ee aad one isovaleryl CoA dehydrogenase IVD Your account L Curator Ivo F A C Fokkema Genes NV de datar dl ii 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 t Curator O Save Cancel Powered by LOVD v 3 0 Build beta 10 Li University Medi 2004 2012 Leiden University Medical Center 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 Since the curator names are shown on the Required level Curator gene home
44. t implemented Force SSL only access to LOVD o0 Use data versioning of biological data Not yet implemented Disable LOVD uninstall ON Continue Figure 2 5 The system settings form with example data filled in 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 Done When everything has 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 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
45. ta 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 f icon up or down the list Release the mouse button in the preferred location Name Allow edit Shown t Ivo FA C Fokkema M Mx t Curator M e t Collaborator O x Enter your password for authorization Save curator list Cancel uild beta 10 Medical Center 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 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 27 5 Gene databases Assigning curators and collaborators bottom To add a user as a curator or collaborator search for the user in t
46. tively 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 Genomic reference sequence Select the genomic 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 23 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 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 c
47. 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 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 Th
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