LOVD 3.0 user manual

Build 3.0-21

Ivo F.A.C. Fokkema

Daan Asscheman

Leiden University Medical Center

Last updated: February 27, 2018

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

1 Introduction 3

2 View and search data in an LOVD installation 5

2.1 Searching and sorting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

2.2 Genes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

2.3 Transcripts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

2.4 Variants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

2.5 Individuals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

2.6 Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

2.7 Screenings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

3 Installing LOVD 11

3.1 Before you install . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

3.2 Install process . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

4 LOVD Setup 17

4.1 LOVD system settings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

4.2 System logs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

4.3 Announcements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

4.4 Uninstalling LOVD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

5 Authorized users 24

5.1 Registering a new account . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

5.2 Creating new user accounts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

5.3 Editing user accounts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28

5.4 Locking users out of the system . . . . . . . . . . . . . . . . . . . . . . . . . . . 29

5.5 Sharing access with other users . . . . . . . . . . . . . . . . . . . . . . . . . . . 29

6 Gene databases 31

6.1 Creating a new gene database . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

6.2 The gene homepage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

6.3 Editing a gene database . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

6.4 Deleting a gene database . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36

6.5 Assigning curators and collaborators . . . . . . . . . . . . . . . . . . . . . . . . 36

7 Gene transcripts 39

7.1 Which transcript(s) should I pick? . . . . . . . . . . . . . . . . . . . . . . . . . . 39

7.2 Creating new transcripts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39

7.3 Editing a transcript . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40

7.4 Deleting a transcript . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40

8 Custom columns 41

8.1 Custom column categories . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41

8.2 Creating a new custom column . . . . . . . . . . . . . . . . . . . . . . . . . . . 42

8.3 Enabling custom columns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

Contents

8.4 Editing custom column settings . . . . . . . . . . . . . . . . . . . . . . . . . . . 47

8.5 Changing the order of custom columns . . . . . . . . . . . . . . . . . . . . . . . 49

8.6 Disabling custom columns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50

8.7 Deleting custom columns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52

8.8 Downloading custom column data to text ﬁles . . . . . . . . . . . . . . . . . . . 52

8.9 Importing custom column data from text ﬁles . . . . . . . . . . . . . . . . . . . 53

9 Adding data to LOVD 54

9.1 Starting a submission by creating an individual . . . . . . . . . . . . . . . . . . 54

9.2 Continuing an unﬁnished submission . . . . . . . . . . . . . . . . . . . . . . . . 58

9.3 Submitting summary variant data . . . . . . . . . . . . . . . . . . . . . . . . . . 58

9.4 Adding data to already ﬁnished submissions . . . . . . . . . . . . . . . . . . . . 59

10 Downloading & importing data 60

10.1 The LOVD3 import format . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60

10.2 Downloading & importing data . . . . . . . . . . . . . . . . . . . . . . . . . . . 69

10.3 Downloading & importing the complete data . . . . . . . . . . . . . . . . . . . . 71

10.4 Downloading & importing the custom column data . . . . . . . . . . . . . . . . 71

10.5 Downloading & importing own data . . . . . . . . . . . . . . . . . . . . . . . . . 72

10.6 Downloading & importing a gene’s data . . . . . . . . . . . . . . . . . . . . . . 73

11 The LOVD APIs 74

11.1 Data retrieval API . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74

11.2 Data submission API . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79

12 Keeping your data secure 82

12.1 Built-in security measures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82

12.2 What you can do to protect your data . . . . . . . . . . . . . . . . . . . . . . . 83

13 Updating LOVD 84

14 Troubleshooting 85

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 platform-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

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

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

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, and the ﬁrst stable release was in December

of that year. Currently, the latest release is 3.0-21. 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. View and search data in an LOVD

installation

To navigate in an LOVD installation you can use the tabs on the top of the page. Which tabs

you can see depends on whether you are logged in or not, and your user level. When you are

not logged in or you are logged in as a submitter, you see the following tabs: Genes, Tran-

scripts, Variants, Individuals, Diseases, Screenings, Submit and Documentation. Additionally,

Curator-level users and up can see the Conﬁguration tab and only Managers and the Database

administrator can see the Users and Setup tabs.

Each tab has a dropdown menu and the tab itself has a default page to which you will go

when you click on the tab. The options of the dropdown menus depend on your user level.

2.1 Searching and sorting

All list views have search ﬁelds which can be used to search data. You can search for a complete

word or you can search for a part of a search term. For example, when you search for “AAM”

in the Symbol ﬁeld of the genes listing, LOVD will not only ﬁnd genes starting with “AAM”,

but also containing “AAM”, like “DAAM1” and “DAAM2”.

Figure 2.1: Results when searching for a gene symbol containing “AAM”. Note that the search is case insen-

sitive, so “aam” gives the same result.

To sort on a certain column, click on the column header or on the arrows. If that column

is already selected to sort on, the sort order will be swapped. The column currently sorted on

has a darker blue background color than the other columns. The up and down arrows next to

the column name indicate the current sorting direction. When sorting on any ﬁeld other than

the default, LOVD will sort secondarily on the default sort column.

LOVD allows boolean search terms, meaning you can construct complex queries with AND,

OR and NOT logic. Typing a space between search terms is treated as AND. OR is indicated

with a pipe ’|’ with no spaces around it and NOT is indicated by an exclamation mark ’!’, not

followed by a space. If you enclose two or more words in double quotes, LOVD will search for

the combination of those words only exactly in the order you specify. Note that search terms

are case-insensitive and that wildcards such as * are treated as normal text!

2. View and search data in an LOVD installation Genes

You can use diﬀerent operators to specify your search request:

Operator Example Description

space AM DA This gives results where both AM and DA are occuring.

| AM|DA This gives results where either AM or DA occurs.

="" ="AM" Returns results which exactly matches AM.

! !AM Returns results which does not contain AM.

!="" !="AM" Returns results which does not exactly match AM.

> >23 Filter for values higher than 23 (numeric and date columns).

< <23 Filter for values lower than 23 (numeric and date columns).

Some more advanced examples:

Asian Shows “Asian”, but also “Caucasian” entries.

Asian !Caucasian Shows “Asian”, but no “Caucasian” entries.

Asian|African !Caucasian Shows “Asian” or “African”, but no “Caucasian” entries.

"South Asian" Shows “South Asian”, but no “South East Asian” entries.

2.2 Genes

Figure 2.2: Gene menu.

When no gene is selected, the default page of the genes

tab shows all genes. When a gene is selected (shown

in the page header), the default page of the gene tab

is the gene homepage.

View all genes

Here you can see all the genes for this instal-

lation. When you click on a gene entry, you’re

taken to the gene homepage.

View gene homepage

Here you can see the details of a gene. For more information, see section “The gene

homepage”. This menu item is not available when no gene has been selected.

View graphs

This displays the statistics of the variants within a gene. This menu item is not available

when no gene has been selected.

Create a new gene entry

This menu item is only available for Managers or higher. See section “Creating a new

gene database” on how to add a new gene.

2.3 Transcripts

Figure 2.3: Transcript menu.

When no gene is selected, the default page of the tran-

scripts tab shows all transcripts. When a gene is se-

lected (shown in the page header), the default page of

the transcripts tab shows all transcripts of the selected

gene.

2. View and search data in an LOVD installation Variants

View all transcripts

View all transcripts stored in the database. Click on the transcript to view the transcript’s

details and variant overview.

View all transcripts of a gene

View all transcripts of the currently selected gene. Click on the transcript to view the

transcript’s details and variant overview. This menu item is not available when no gene

has been selected.

Create a new transcript information entry

This menu item is only available for Curators or higher. See section “Creating new

transcripts” on how to add a new transcript to a gene.

Transcript detailed view

When clicking a transcript from one of the transcript data listings, the transcript’s details

are shown. Below the transcript’s details, a variant listing is shown of all variants found

on this transcript. Click on a variants to view the variant’s details.

2.4 Variants

Figure 2.4: Variants menu.

When no gene is selected, the default page of the vari-

ants tab shows all genomic variants. When a gene is

selected (shown in the page header), the default page

of the variants tab shows all unique variants in the

selected gene.

View all genomic variants

This view displays all genomic variants in this

LOVD installation. Variants within, but also

outside of genes are shown. You can click on a

variant to view its details.

View all variants aﬀecting transcripts

This view displays all variants in this LOVD in-

stallation that are found within a gene, and have

been mapped to a transcript. You can click on

the a variant to view its details.

View unique variants in a gene

This view displays the gene’s unique variants. Each variant is shown only once, regardless

of the number of observations. The number of times a variant is found is displayed in the

ﬁeld “Reported”. The information in other ﬁelds are summarized and not all information

for the variants may be displayed. Click on a variant to see all reported observations.

This menu item is not available when no gene has been selected.

View all variants in a gene

View of all variants reported in the selected gene. Variants are not grouped like in the

unique variant view. Click on a variant to see the variant’s details. This menu item is

not available when no gene has been selected.

Full data view for a gene

This view shows all variant observations together with the variant screening(s) and the

individual in which the variant has been reported. Although this data view is very wide, it

2. View and search data in an LOVD installation Individuals

allows searching for variants only found in individuals with certain characteristics. Click

on a variant to see the variant’s details. This menu item is not available when no gene

has been selected.

Create a new data submission

This menu item is only available when logged in. See chapter “Adding data to LOVD”

on how to create a new data submission.

View active genomic custom columns

This menu item is only available for Managers or higher. See chapter “Custom columns”

for more information on custom columns.

Enable more genomic custom columns

This menu item is only available for Managers or higher. See section “Enabling custom

columns” on how to enable custom columns.

Variant detailed view

When clicking on a variant from one of the variant data listings, its details are shown.

If the variant is aﬀecting any transcripts, a listing is shown below the variant’s genomic

details. Click on any of the entries to view the data in a tabular view. If the variant

has been found in an individual, at the bottom of the page the listing for the variant

screenings used to identify the variant is shown. On the top of the page a link is shown

to the individual in which the variant is found.

2.5 Individuals

Figure 2.5: Individuals menu.

When no gene is selected, the default page of the in-

dividuals tab shows all individuals. When a gene is

selected (shown in the page header), the default page

of the individuals tab shows all individuals with vari-

ants in the selected gene.

View all individuals

This view shows all individuals in this LOVD

installation. You can click on an individual to

view its details.

View all individuals with variants in a gene

This view displays all individuals with variants in the currently selected gene. You can

click on an individual to view its details. This menu item is not available when no gene

has been selected.

Create a new data submission

This menu item is only available when logged in. See chapter “Adding data to LOVD”

on how to create a new data submission.

View active custom columns

This menu item is only available for Managers or higher. See chapter “Custom columns”

for more information on custom columns.

Enable more custom columns

This menu item is only available for Managers or higher. See section “Enabling custom

columns” on how to enable custom columns.

2. View and search data in an LOVD installation Diseases

Individual detailed view

When clicking on an individual from one of the data listings, the individual’s details

are shown. Below the individual’s details, the phenotype entries are shown if any are

stored. Also variant screenings performed are listed, and variants found in this individual.

Clicking on any of these entries will show the respective details.

2.6 Diseases

Figure 2.6: Diseases menu.

When no gene is selected, the default page of the dis-

eases tab shows all diseases. When a gene is selected

(shown in the page header), the default page of the

diseases tab shows all diseases associated with the se-

lected gene.

View all diseases

This view shows all the diseases in the database.

Also the number of individuals reported with

this disease is displayed and the number of phe-

notypes reported. You can click on a disease to

view its details.

View all diseases associated with a gene

This view displays all diseases associated with the currently selected gene. Also the num-

ber of individuals reported with this disease is displayed and the number of phenotypes

reported. You can click on a disease to view its details. This menu item is not available

when no gene has been selected.

Create a new data submission

This menu item is only available when logged in. See chapter “Adding data to LOVD”

on how to create a new data submission.

View available phenotype columns

This menu item is only available for Curators or higher. See chapter “Custom columns”

for more information on custom columns.

Disease detailed view

On the disease’s detailed view, all individuals diagnosed with this disease are listed. From

the table, a link is provided to view all phenotype entries for this disease.

2.7 Screenings

Figure 2.7: Screenings menu.

When no gene is selected, the default page of the

screenings tab shows all screenings. When a gene is se-

lected (shown in the page header), the default page of

the screenings tab shows all screenings that screened

for variants in the selected gene.

View all screenings

This view shows all the screenings in the

database. You can click on a screening to view

its details.

2. View and search data in an LOVD installation Screenings

View all screenings for a gene

This view displays all screenings that screened for variants in the currently selected gene.

You can click on a screening to view its details. This menu item is not available when no

gene has been selected.

Create a new data submission

This menu item is only available when logged in. See chapter “Adding data to LOVD”

on how to create a new data submission.

View active custom columns

This menu item is only available for Managers or higher. See chapter “Custom columns”

for more information on custom columns.

Enable more custom columns

This menu item is only available for Managers or higher. See section “Enabling custom

columns” on how to enable custom columns.

Screening detailed view

On the screening’s detailed view, all genes screened for variants are listed, as well as any

variants found.

3. 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.

3.1 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, 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.

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 & 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,

3. 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 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 “AllowOverride” 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”.

3.2 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.

3. Installing LOVD Install process

Figure 3.1: 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.

Figure 3.2: 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 *.

3. Installing LOVD Install process

Figure 3.3: 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 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 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

3. Installing LOVD Install process

Figure 3.4: 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

3. Installing LOVD Install process

Figure 3.5: The system settings form, with example data ﬁlled in.

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!

4. 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

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).

4.1 LOVD system settings

Required level: Manager

Available from: LOVD 3.0 Build 01

The LOVD system settings allow you to adapt

your LOVD installation to your preferences. For

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 not speciﬁed,

LOVD will use the (autodetected) website name LOVD has been installed on.

4. 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 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 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.

4. 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 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 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.

Allow submitter registration?

Enabling this setting allows submitters to create their own accounts in your LOVD in-

stallation. Having it enabled is the default setting, and this could not be disabled prior

to LOVD 3.0-17.

Note, that submitters can never register when your LOVD installation is set to read-

only because of an active announcement with the read-only setting enabled. See the

Announcements section for more information.

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.

4. LOVD Setup System logs

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.

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.

4.2 System logs

Required level: Manager

Available from: LOVD 3.0 Build 01

System logs were introduced in LOVD 2.0 to al-

low authorized users to keep track of events in

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

4. LOVD Setup System logs

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.

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,

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

Delete log entry

Options menu button

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.

4. LOVD Setup Announcements

4.3 Announcements

For messages meant for visitors and users of your LOVD installation, you can create announce-

ments. They will appear on the top of every page, can automatically appear and disappear on

a requested date and time, and can optionally make LOVD read-only, disallowing submitter

registrations and users lower than Managers to log into LOVD.

Creating a new announcement

Required level: Manager

Available from: LOVD 3.0 Build 17

To create a new announcement, click the “Create

a new announcement, optionally making LOVD

read-only” link in the Setup area, or click the

“Create a new system announcement” link in the Setup tab drop-down menu.

Announcement details

Creating an announcement does not require many ﬁelds.

Announcement type

This deﬁnes the icon next to the announcement. An Information dialog has an informa-

tion icon, a Question dialog has a question mark, a Warning dialog has an exclamation

mark.

Announcement text

Type here the announcement itself. If you choose to make LOVD read-only as well, be

sure to let users know from when they will be able to log in again.

Start date

Use this ﬁeld to create an announcement before it should be online. The announcement

will be active only after this date and time. If you leave this ﬁeld empty, the current

time will be selected, and the announcement will be shown immediately. To deactivate

an announcement, put a date in the future, like 9999-12-31.

End date

Use this ﬁeld to automatically let an announcement disappear at a certain date or time.

If you leave this ﬁeld empty, the end date will be set to 9999-12-31 23:59:59. To deactivate

an announcement, put a date in the past here.

Make LOVD read-only?

Enabling this feature blocks logins and submitter registrations when this announcement

is active. Only Managers and up will still be able to log into LOVD. Users of a lower level

that are active when this announcement activates, will be logged out. A true read-only

state is currently not enforced; Managers can still make changes to all data. Use this

feature when the server is undergoing maintenance, for instance. If you want to make

LOVD read-only, but only in the future, set a date in the future in “Start date”, and

make sure you make an extra announcement that introduces the downtime.

After completing the form, click the “Create announcement” button. If the “Start date”

ﬁeld was empty or a day in the past, and the “End date” was empty or a date in the future, the

announcement will be visible immediately. For Manager level users and up, announcements

are clickable, and they link to their detailed view, making it easy for Managers to ﬁnd active

announcements.

4. LOVD Setup Uninstalling LOVD

Editing an announcement

Required level: Manager

Available from: LOVD 3.0 Build 17

To edit an announcement, click the announce-

ment on the top of the page if it’s active to go to

its detailed view directly, or go to the list of an-

nouncements by using the “Manage system announcements” link in the Setup area or the “View

system announcements” in the Setup tab drop-down menu, after which you can click the an-

nouncement. On the detailed view, open the “Options” menu, and click “Edit announcement”.

Complete the form to update the announcement. If you wish to disable to announcement, edit

the “Start date” ﬁeld to be a date in the future, or edit the “End date” ﬁeld to be a date in

the past. For details on all ﬁelds, see section “Creating a new announcement”.

Deleting an announcement

Required level: Manager

Available from: LOVD 3.0 Build 17

To delete an announcement, click the announce-

ment on the top of the page if it’s active to go

to its detailed view directly, or go to the list of

announcements by using the “Manage system announcements” link in the Setup area or the

“View system announcements” in the Setup tab drop-down menu, after which you can click the

announcement. On the detailed view, open the “Options” menu, and click “Delete announce-

ment”. Fill in your password and submit the form to delete the announcement. Note, that you

can also disable an announcement without deleting it, for instance if you know in the future

you’ll make a similar announcement. To disable an announcement, edit the announcement

instead of deleting it, and either set the “Start date” ﬁeld to be a date in the future, or edit

the “End date” ﬁeld to be a date in the past.

4.4 Uninstalling LOVD

Required level: Database administrator

Available from: LOVD 3.0 Build 01

Only the database administrator can uninstall

LOVD, provided the uninstall lock has not been

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 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.

5. 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 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).

5. 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.

5.1 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 can

only be used by humans, and not by spam bots.

Required level: None (public)

Available from: LOVD 3.0 Build 01

To register a new submitter account, click

the “Register as submitter” link on the top right

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.

5. 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

“<First name> <Last name>”.

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 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.

5. 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 registration 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.

5.2 Creating new user accounts

Required level: Manager

Available from: LOVD 3.0 Build 01

Besides the public registration form, managers

can also create new users. This oﬀers the ad-

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 not be able to work with LOVD until he has changed

his password.

5. 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.

5.3 Editing user accounts

Required level: Submitter

Available from: LOVD 3.0 Build 01

Every user in LOVD can edit their own account.

Editing other user’s accounts requires you to

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.

5. Authorized users Locking users out of the system

5.4 Locking users out of the system

Required level: Manager

Available from: LOVD 3.0 Build 01

A user is automatically locked if a wrong pass-

word is used three times while logging in with

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.

5.5 Sharing access with other users

Required level: Submitter

Available from: LOVD 3.0 Build 16

An authorized user can share access to their data

with other users. The other users can then see

any non-public data entries owned by the shar-

ing user, and if speciﬁed, they can also edit those entries. Additionally, all non-public ﬁelds of

all entries owned by the sharing user, become available to this user, too.

A user can manage the people with whom they share their data from their account page.

When logged in, there is a link named “Share access to your entries with other users” under

the options menu on the user account page. When clicking this link, the user is presented with

a page similar to that of Figure 5.1. This page shows in the bottom table the users to whom

access is shared and whether they have edit permissions. The checkbox under “Allow edit”

denotes whether the user has edit permissions on the shared data. One can remove users from

this list by clicking the red cross next to their name, or add new users by ﬁnding and clicking

their name in the top table. Finally, one can save changes to the bottom table by verifying

their password and clicking “Save access permissions”.

5. Authorized users Sharing access with other users

Figure 5.1: The “Sharing access” page, with a list of users one can select on top and a list of users previously

selected on bottom.

6. 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. 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.

6.1 Creating a new gene database

Required level: Manager

Available from: LOVD 3.0 Build 01

Creating a new gene database in LOVD is largely

automated. Click the “Create a new gene entry”

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 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.

6. 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.

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.

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 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.

6. 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 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 <URL>”, such as “Other LOVDs on this gene <http://DMD.LOVD.nl/>”.

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”.

6. 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 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.

6. 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.

6.2 The gene homepage

Required level: None (public)

Available from: LOVD 3.0 Build 01

LOVD automatically generates a gene homepage

for every gene created within LOVD. The gene

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 behavior, simply move your mouse

over a tab, and select a diﬀerent option from the dropdown menu.

6.3 Editing a gene database

Required level: Curator

Available from: LOVD 3.0 Build 01

Curators, appointed to a gene database, have the

rights to edit its settings. Managers and up can

edit all gene databases in the LOVD installation.

To edit the gene’s settings, ﬁrst proceed to the gene’s homepage.

Options menu button

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 “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.

6. Gene databases Deleting a gene database

6.4 Deleting a gene database

Required level: Manager

Available from: LOVD 3.0 Build 01

Only managers and up can delete gene databases

from LOVD. To delete the gene database in

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 remove 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.

6.5 Assigning curators and collaborators

Required level: Manager

Available from: LOVD 3.0 Build 01

Managers and up can assign curators and col-

laborators to gene databases, as well as revoke

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 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 edit data contradicts their user level. They will always be allowed to

6. Gene databases Assigning curators and collaborators

Figure 6.1: 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.

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

Figure 6.2: 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.

Required level: Curator

Available from: LOVD 3.0 Build 01

Since the curator names are shown on the

gene homepage and on the page headers, it is

sometimes necessary to sort the curator names

6. Gene databases Assigning curators and collaborators

in a speciﬁc order. This can be done on the “Authorize curators” form (see ﬁgure 6.1 on page

37). 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 6.2 on page 37).

Drag/sort handle

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!

7. 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 pick 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.

7.1 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).

7.2 Creating new transcripts

Required level: Curator

Available from: LOVD 3.0 Build 01

The simplest way to create a gene transcript

in LOVD, is to select it when creating a gene

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.

7. Gene transcripts Editing a transcript

7.3 Editing a transcript

Required level: Curator

Available from: LOVD 3.0 Build 01

Because LOVD standardizes the transcript in-

formation, there is very little information that

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. Alternatively, 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.

7.4 Deleting a transcript

Required level: Curator

Available from: LOVD 3.0 Build 01

Deleting a transcript removes all information re-

lated to the transcript in question from all vari-

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 “Options” 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.

8. 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.

8.1 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

Information 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”.

8. Custom columns Creating a new custom column

8.2 Creating a new custom column

Required level: Manager

Available from: LOVD 3.0 Build 01

By creating a new custom column, you can de-

ﬁne what kind of information you want to store

in the database. Please note that deﬁning this

type of information, does not automatically make LOVD store this information. 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 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.

8. 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.

Integer 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 ﬁlling 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.

8. 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 only)

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 available 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.

8. 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

has 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. Your 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.

8. Custom columns Enabling custom columns

8.3 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

Required level: Manager

Available from: LOVD 3.0 Build 01

The non-shared, system-wide custom column

types are Individual, Screening and Variant On

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:

• 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.

• 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. 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 columns now.

Enabling shared custom columns

Required level: Curator

Available from: LOVD 3.0 Build 01

The shared custom column types are Phenotype

and Variant On Transcript. Before enabling

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:

8. Custom columns Editing custom column settings

• 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.

• 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 “Category” 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 already enabled ones, you may want to review or

change the object-speciﬁc order of shared custom columns.

8.4 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

Required level: Manager

Available from: LOVD 3.0 Build 01

Both shared and non-shared columns have sys-

tem-wide settings that can be changed by a man-

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

8. 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 custom 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

settings. All other ﬁelds on this form are explained in the section “Creating a new custom

column”.

Editing object-speciﬁc (shared) custom column settings

Required level: Curator

Available from: LOVD 3.0 Build 01

The object-speciﬁc settings, editable per gene or

disease, are (also see section “Creating a new

custom column”):

• 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 Transcript 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.

8. Custom columns Changing the order of custom columns

8.5 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-wide custom column order

Required level: Manager

Available from: LOVD 3.0 Build 01

For non-shared columns, changing the system-

wide custom column order will eﬀectively change

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 click the “Re-order

all «category» columns” link.

Drag/sort handle

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!

8. Custom columns Disabling custom columns

Changing the object-speciﬁc order of shared custom columns

Required level: Curator

Available from: LOVD 3.0 Build 01

When a new gene or disease is created, the cur-

rent system-wide order of Variant On Transcript

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 menu. 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.

Drag/sort handle

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!

8.6 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 system-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

Required level: Manager

Available from: LOVD 3.0 Build 01

To disable a non-shared custom column, you

should start from the list of currently active

columns. You can get there in two ways:

• 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.

• 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

8. 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 the “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

Required level: Curator

Available from: LOVD 3.0 Build 01

Shared custom columns can be disabled for one

parent object only, or from multiple parent ob-

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”, 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.

• 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.

• 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 “Category” column ﬁlter box, and

press the “Enter” key.

8. 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 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.

8.7 Deleting custom columns

Required level: Manager

Available from: LOVD 3.0 Build 01

Custom columns, which are created by users

(managers or the database administrator), can

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 not be removed.

8.8 Downloading custom column data to text ﬁles

Required level: Manager

Available from: LOVD 3.0 Build 04

LOVD supports exporting the custom data col-

umns, including the columns’ system-wide set-

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.

8. 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”.

8.9 Importing custom column data from text ﬁles

Required level: Manager

Available from: LOVD 3.0 Build 05

Custom columns downloaded in the LOVD im-

port format can be reimported into LOVD.

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 in the database or not.

Please see section “Importing data into LOVD” on how to import data into LOVD.

9. 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.

This chapter describes adding data to LOVD using the web forms. If you are a curator or

up and you wish to add data to LOVD using a tab-delimited ﬁle upload, please see chapter

“Downloading & importing data”. If you’re a programmer and you would like to submit data

in JSON format directly from your application using the LOVD3 submission API, please see

chapter “The LOVD APIs”.

9.1 Starting a submission by creating an individual

Required level: Submitter

Available from: LOVD 3.0 Build 01

You can submit new data by clicking the “Sub-

mit” tab, or by selecting the option “Create a

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, 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 9.1, where you can choose how to proceed.

9. Adding data to LOVD Starting a submission by creating an individual

Figure 9.1: After completing the data entry form, you can choose to add phenotype information (if a disease

or “healthy/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.

Adding phenotype information to the individual

Required level: Submitter

Available from: LOVD 3.0 Build 01

When you created an individual, and this in-

dividual has been diagnosed with one or more

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 9.1), 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

Required level: Submitter

Available from: LOVD 3.0 Build 01

By selecting “I want to add a variant screen-

ing to this individual” you can add a screen-

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 as displayed in ﬁgure 9.2, where you can choose how to

proceed.

Adding a variant to a screening

Required level: Submitter

Available from: LOVD 3.0 Build 01

After adding a screening, you can add a variant

to this screening. It is possible to add more than

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.

9. Adding data to LOVD Starting a submission by creating an individual

Figure 9.2: 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.

Figure 9.3: Creating a new variant entry. Note: Only managers and up have the option “I want to upload a

ﬁle with genomic variant data” available.

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

the currently selected screening (see ﬁgure 9.4). Click the checkmarks left of the variants that

you would like to mark as conﬁrmed, and click “Save variant list”.

Adding a variant located within a gene

After choosing this option, you are shown a list of genes (see ﬁgure 9.5). 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” column. Then click

the gene for which you want add a variant to proceed to the variant entry form. 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. Complete the form, and when ready, click the “Create variant entry”

9. Adding data to LOVD Starting a submission by creating an individual

Figure 9.4: Select a variant to conﬁrm. Shown are the variants already linked to other screenings of the

individual, but not to the currently selected screening.

button. If successful, you are redirected to the options to submit more variants, or return to

the individual.

Figure 9.5: 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 the 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

9. Adding data to LOVD Continuing an unﬁnished submission

two formats are supported: Variant Call Format (VCF) version 4.0 or higher and SeattleSeq

Annotation ﬁles.

Adding a variant to the individual

Required level: Submitter

Available from: LOVD 3.0 Build 01

The option “Add a variant to this individual”

as displayed in ﬁgure 9.1 is only available when

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”.

Finishing the submission

Required level: Submitter

Available from: LOVD 3.0 Build 01

The option “I want to ﬁnish this submission” is

enabled for submitters when they completed a

submission, i.e., an individual, screening and at

least one variant have been added. Finishing a submission will send 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.

9.2 Continuing an unﬁnished submission

Required level: Submitter

Available from: LOVD 3.0 Build 01

If, for whatever reason, a data submission has

not been ﬁnished, it is stored in the list of un-

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.

9.3 Submitting summary variant data

Required level: Curator

Available from: LOVD 3.0 Build 01

If you are a curator or higher, you can choose to

submit only summary variant data. This means

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.

9. Adding data to LOVD Adding data to already ﬁnished submissions

9.4 Adding data to already ﬁnished submissions

Required level: Submitter

Available from: LOVD 3.0 Build 01

It is still possible for the submitter to add data

to an individual or a screening when a submitter

ﬁnished the submission, regardless of whether

the curator published the data or not.

Adding a variant to a screening

Options menu button

To add a variant to an existing screening, click on the “Screen-

ings” tab and select a screening for which you are authorized.

Click on the “Options” menu button to open up the screening

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

“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

Options menu button

To add a screening to an existing individual, click on the “Indivi-

duals” tab and select an individual for which you are authorized.

Click on the “Options” menu button to open up the 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 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

Options menu button

To add phenotype information to an existing individual, click on

the “Individuals” tab and select an individual for which you are

authorized. Click on the “Options” menu button to open up the

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 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.

10. Downloading & importing data

10.1 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 id 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" "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}}" "{{owned_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 10.1: 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 geneid 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

10. Downloading & 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.

Please NOTE that spreadsheets are well known for introducing errors in import-

ing/exporting text ﬁles, due to automatic interpretation of the values. When using

a spreadsheet program to edit a downloaded ﬁle, format all cells to "Text" before

importing/pasting the downloaded data.

Also some cases have been reported where MS Excel removed contents of large text

ﬁelds (> 255 characters).

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 sections 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 their 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.

10. Downloading & importing data The LOVD3 import format

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.

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 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 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.

10. Downloading & importing data The LOVD3 import format

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

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 imply 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 values.

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.

10. Downloading & importing data The LOVD3 import format

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 YYYY-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,

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 during an import.

eﬀectid (from sections Variants_On_Genome and Variants_On_Transcripts)

The variant’s eﬀect on a protein’s function. The ﬁrst digit indicates the variant’s eﬀect

as reported by the source. 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 aﬀect 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

11 -/-

13 -/-?

15 -/?

17 -/+?

19 -/+

ID Name

31 -?/-

33 -?/-?

35 -?/?

37 -?/+?

39 -?/+

ID Name

51 ?/-

53 ?/-?

55 ?/?

57 ?/+?

59 ?/+

ID Name

71 +?/-

73 +?/-?

75 +?/?

77 +?/+?

79 +?/+

ID Name

91 +/-

93 +/-?

95 +/?

97 +/+?

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; The internal ID of the individual in the database that is the father of this

individual.

10. Downloading & importing data The LOVD3 import format

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”.

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)

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.

10. Downloading & importing data The LOVD3 import format

Possible values:

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 importing; 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 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.

10. Downloading & 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. 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 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

10. Downloading & 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 import.

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 Data entry has been submitted, awaiting 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”, value 1, can not be imported. Instead, there are 3 options:

1. Ask the submitter to ﬁnish the submission.

2. Change the statusid value to a valid value, being 4 or higher.

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.

10. Downloading & importing data Downloading & importing data

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 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”.

10.2 Downloading & importing data

Downloading data from LOVD

Required level: Submitter

Available from: LOVD 3.0 Build 01

For backup purposes or to move data sets from

one LOVD into another, LOVD supports diﬀer-

ent download options. All downloaded ﬁle types

lack the LOVD system settings, registered user accounts, and object-speciﬁc custom column

settings.

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 spreadsheet software

such as OpenOﬃce.org Calc or MS Excel, you could use the download ﬁles as a starting point.

10. Downloading & importing data Downloading & importing data

In that case, read the instructions at “Downloading & importing the complete data” before

you begin.

Importing data sets into LOVD

Required level: Curator

Available from: LOVD 3.0 Build 01

For managers it is possible to import data di-

rectly into LOVD, using the LOVD3 import for-

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 & Import”. Curators can import data from the Conﬁguration area. Click

the “Import data using the LOVD import format” link listed under “Download & 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 their 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

Required level: Curator

Available from: LOVD 3.0 Build 01

The option “add only” on the import page will

insert all data in the import ﬁle as new, also

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

Required level: Curator

Available from: LOVD 3.0 Build 14

For managers and higher it is possible to update

certain data via an import (curators can run a

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

the section “Speciﬁc ﬁelds explained” to check which ﬁelds you are not allowed to update.

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.

10. Downloading & importing data Downloading & importing the complete data

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.

10.3 Downloading & importing the complete data

Downloading the complete data set from LOVD

Required level: Manager

Available from: LOVD 3.0 Build 01

LOVD supports a full download that contains

most (currently not all) data stored in LOVD.

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 failure, 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 & 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

Required level: Manager

Available from: LOVD 3.0 Build 01

A complete data set downloaded from the LOVD

can be imported into a LOVD. This can only be

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.

10.4 Downloading & importing the custom column

data

Downloading custom columns data from LOVD

Required level: Manager

Available from: LOVD 3.0 Build 04

Managers can download a data ﬁle with only the

custom columns which are added to an LOVD

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

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.

10. Downloading & importing data Downloading & importing own data

Importing a custom columns data set into LOVD

Required level: Manager

Available from: LOVD 3.0 Build 05

The custom column data set downloaded by a

manager can be uploaded to the same or any

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.

10.5 Downloading & importing own data

Downloading own data set from LOVD

Required level: Submitter

Available from: LOVD 3.0 Build 01

LOVD allows you to collect a ﬁle containing all

information in LOVD that has been submitted

by you, or is currently owned 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

Required level: Manager

Available from: LOVD 3.0 Build 13

The own data set downloaded by a submitter

can also be reuploaded into LOVD. But as with

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” 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”.

10. Downloading & importing data Downloading & importing a gene’s data

10.6 Downloading & importing a gene’s data

Downloading a gene’s data set from LOVD

Required level: Curator

Available from: LOVD 3.0 Build 02

Curators can download a ﬁle containing all infor-

mation related to a gene they have authorization

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 reported, which are not aﬀecting this gene and therefore

not shown in this ﬁle.

Importing a gene’s data set into LOVD

Required level: Manager

Available from: LOVD 3.0 Build 01

The gene data set downloaded can be uploaded

without modiﬁcations into the same or any other

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.

11. The LOVD APIs

LOVD3 contains an LOVD2-style data retrieval API, useful for simple queries and retrieval

of basic gene and variant information, and a new data submission API, introduced in LOVD

3.0-21, useful for submitting data from other software tools without the need of using the web

forms.

11.1 Data retrieval 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 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.

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.

• 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.

• Limit your requests to a maximum of 5 per second per server/domain name.

• 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.

• 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.

Format

When searching for genes, an Atom feed is returned with zero or more entries. When requesting

a speciﬁc entry, just the Atom entry is returned. The Atom format is described in detail on

Wikipedia.

11. The LOVD APIs Data retrieval API

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.

Genes

<?xml version="1.0" encoding="UTF-8"?>

<title>

Results for your query of the database

</title>

<id>tag:databases.lovd.nl,2012-05-02:web01:shared/REST_api</id>

Leiden Open Variation Database

</generator>

<rights>Copyright (c), the curators of this database</rights>

<id>tag:databases.lovd.nl,2011-04-05:IVD</id>

<name>Gerard Schaafsma</name>

</author>

<name>Ivo F.A.C. Fokkema</name>

</contributor>

id:IVD

entrez_id:3712

symbol:IVD

name:isovaleryl-CoA dehydrogenase

chromosome_location:15q14-q15

position_start:chr15:40697686

position_end:chr15:40713512

refseq_genomic:NG_011986.1

refseq_mrna:NM_002225.3

refseq_build:hg19

</content>

</entry>

</feed>

Figure 11.1: 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).

11. The LOVD APIs Data retrieval API

The oﬃcial gene symbol is mentioned twice, because in LOVD2 multiple 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.

Variants

<?xml version="1.0" encoding="UTF-8"?>

<title>

Results for your query of the IVD gene database

</title>

<id>tag:databases.lovd.nl,2012-05-02:web01:shared/REST_api</id>

Leiden Open Variation Database

</generator>

<rights>Copyright (c), the curators of this database</rights>

<id>tag:databases.lovd.nl,1970-01-01:IVD/0000000563</id>

<name>Unknown</name>

</author>

<name>Unknown</name>

</contributor>

symbol:IVD

id:0000000563

position_mRNA:NM_002225.3:c.860

position_genomic:chr15:40707154

Variant/DNA:c.860G>A

Variant/DBID:IVD_000001

Times_reported:1

</content>

</entry>

</feed>

Figure 11.2: 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).

11. The LOVD APIs Data retrieval API

If the variant could not be interpreted by Mutalyzer, the position ﬁelds will 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.

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=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&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&position_match=partial

11. The LOVD APIs Data retrieval API

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 c.157+? and c.157_158 will match c.157+?_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_40710410&position_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_40710410&position_match=partial

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>T) or c.157C>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.

11. The LOVD APIs Data submission API

11.2 Data submission API

Required level: Submitter

Available from: LOVD 3.0 Build 18/21

LOVD3 includes a data submission API, use-

ful for submitting JSON data ﬁles directly into

LOVD3 without the need of web forms. This is

especially useful for diagnostic labs that wish to submit their found variants to LOVD3 without

the hassle of having to submit them manually or to construct LOVD3 import ﬁles.

Note that this API was introduced in LOVD 3.0-18, but was only fully functional from

LOVD 3.0-21.

The submission format

The format used by the submission API is a JSON implementation of the VarioML format. For

an example ﬁle, please see http://LOVD.nl/3.0/submission_api_format.json. Since Vario-

ML is originally an XML format, all XML attributes have been preﬁxed by an ‘@’ character,

and text nodes are stored in ‘#text’ elements. The JSON format allows for multiple individuals

to be submitted at once; the ﬁle is required to contain at least one individual with each at least

one variant. The mandatory columns are the same as otherwise mandatory in LOVD3. For

ﬁelds that require a ﬁxed set of options, such as the individual’s gender, the possible options

are mentioned in a comment next to the ﬁeld. JSON oﬃcially can’t contain comments so a

JSON parser might fail on the example ﬁle, but LOVD3 is OK with them.

Do note that not all ﬁelds that may be conﬁgured in LOVD3 will be representable (yet) in

this format. All ﬁelds currently supported are present in the example ﬁle (see above). If you

have more data that you’d like to submit using this format, please contact us. We aim to map

as many LOVD3 ﬁelds as possible to VarioML.

Mandatory ﬁelds to set before submission

Before you can submit your data using this example ﬁle, you’ll have to change the values of

some of the ﬁelds. The ‘lsdb’ element has an ‘@id’ and an ‘@uri’ ﬁeld that needs to be set.

The ‘@id’ is the LOVD’s ID, which can be found by the database administrator in the API

authorization token dialog (see “Getting your authorization token”. If you do not know who

the LOVD’s administrator is, submit the ﬁle without a valid ID (see “Submitting the JSON

ﬁle”) and LOVD will respond with the administrator’s contact information.

The ‘source’ element under ‘lsdb’ also requires a few ﬁelds to be ﬁlled in. For ‘name’, ﬁll

in the name of the lab that is submitting the data. Under ‘contact’, ﬁll in your name under

‘name’, and your email under ‘email’. The ‘db_xref’ ﬁelds are also required, and are explained

below.

Getting your authorization token

To submit data to LOVD3 using the submission API, you need to create an authorization

token for your submitter account. To do so, log into LOVD3 and proceed to your account page

by clicking the “Your account” link in the top right side of the screen. In the “API token”

ﬁeld, click “Show / More information”. In the new dialog, click the “Create new token” button

to create a token. Select the desired validity and click “Create new token”. If the token was

created successfully, click “Back” and copy your token from the bottom of the information

dialog (see ﬁgure 11.3). In the JSON data, under ‘lsdb’ / ‘source’ / ‘contact’ / ‘db_xref’,

ﬁll in both ‘@accession’ ﬁelds. Where ‘@source’ is ‘lovd’, ﬁll in your numeric account ID

11. The LOVD APIs Data submission API

(on the top of your account page). Where ‘@source’ is ‘lovd_auth_token’, ﬁll in your created

token.

Figure 11.3: The authorization token dialog, showing your current token at the bottom and including buttons

to create a new token or just revoking the current one. The database administrator also can ﬁnd

the LOVD’s ID at the top of this dialog.

Submitting the JSON ﬁle

To submit your JSON ﬁle, POST it to /api/submissions for the intended LOVD instance. In

case the intended LOVD is located at https://databases.lovd.nl/shared/, then POST your

ﬁle to https://databases.lovd.nl/shared/api/submissions. Before submitting though,

please read the information under “Diﬀerent versions of this API”. See ﬁgure 11.4 for an example

on how to submit using curl.

curl --data @submission.json "https://databases.lovd.nl/shared/api/submissions"

Figure 11.4: Example of how to submit a VarioML JSON ﬁle to the submission API, using curl. In this ex-

ample, the JSON ﬁle is named submission.json and is located in the current working directory.

The submission API will respond in JSON, sending its version, a messages array, a warnings

array, an errors array, and a data array (see ﬁgure 11.5).

The ‘messages’ array is for information of successful submissions. The ‘warnings’ array is

for output of information you should review because it might be a potential problem, although

it will not prevent a successful submission. The ‘errors’ array contain fatal errors. The ‘data’

array is reserved for returning data and not used in POST requests.

A successful submission results in an LOVD3 import ﬁle being created on the server. This

ﬁle then needs to be imported into LOVD3. In LOVD 3.0-21, submissions done through the API

are not yet scheduled for import automatically, it requires manual intervention of a manager.

See the INSTALL.txt ﬁle that is shipped with LOVD for more information.

11. The LOVD APIs Data submission API

{

"version": 1,

"messages": [],

"warnings": [],

"errors": [

"VarioML error: LSDB root element not found, or has no ID."

"data": []

}

Figure 11.5: Example submission API output, when sending “{"lsdb":{}}”. All arrays shown are always

present, but can be empty.

Diﬀerent versions of this API

Before you submit, make sure you read this information, to prevent unexpected

problems if we would update the API.

To allow easy further development of this API, we might change the way the API works or

change the way the API returns data. To make sure this doesn’t harm your application, you

can instruct LOVD to use a ﬁxed version of the API. To do so, you must include the APIs

version in the URL. For instance, to always use version 1 of the API, even when version 2 is

already released, use /api/v1/submissions instead of /api/submissions. When you’re not

supplying a version number in the URL you POST to, LOVD will automatically use the latest

version of the API. Make a decision based on what works best for you in your situation.

12. 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.

12.1 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 LOVD 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 reason 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.

12. Keeping your data secure What you can do to protect your data

12.2 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.

2. 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 remember your

password for you. Once you’re done using LOVD, log out.

3. 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.

4. 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.

5. 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.

13. Updating LOVD

Several times a year, a new LOVD build is released. An update may contain bug ﬁxes, new

features, new custom columns and such. Therefore, each update has a priority setting to

indicate how important it is to update your LOVD installation to the new release.

Depending on whether or not LOVD has found that there is an update available, an update

icon appears at the bottom right-hand side of the screen:

There is an update available.

There is no update available.

There was an error while checking for updates.

If you are logged in as an authorized user, you can click the update notiﬁcation icon for

more information on the status of the update. If an update is available, detailed information

is presented:

Last checked for updates: Shows the date LOVD last checked for a new update.

Latest version: Shows the detected update.

Release date: The date this update has been released.

Priority level: Shows how important the LOVD developers consider this update. Can contain

“Optional”, “Common”, “Suggested”, “Recommended”, “Important” or “Critical”, with

increasing priority.

Release info: Information on the changes that have been done in this release. Please note

that this is usually only a very short list of updates. A more elaborate description can

always be found in the news section of the LOVD website, and the full list can be found

in the LOVD changelog.

If you choose to upgrade LOVD, follow these steps:

1. Download the new build. Either using the direct link to it from the update window, or

from the website.

2. Unpack the new build and overwrite the LOVD ﬁles.

3. If you’re working from your local machine, upload the updated ﬁles to your webserver.

4. Log into LOVD. This is an important step. If you are already logged in, perform some

activity, like clicking on the Setup tab. LOVD will then upgrade the database tables to

make sure the database backend has the same version as the ﬁles. Skipping this step may

result in serious errors occurring.

5. You’re done!

14. 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, please 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.