Genevar (GENe Expression VARiation)
Genevar is a database and Java tool designed to integrate multiple datasets, and provides analysis and visualization of associations between sequence variation and gene expression in eQTL studies.
Genevar allows researchers to investigate eQTL (expression quantitative trait loci) associations within a gene locus of interest in real time. The database and application can be installed on a standard computer in database mode and, in addition, on a server to share discoveries among affiliations or the broader community over the internet via web services protocols.
Default services at the Sanger Institute currently contain gene expression profiling and genotypic data from the following datasets:
[Genome Research Limited]
Features
cis-eQTL - Gene
Gene-centric cis-eQTL analysis
To identify eQTLs centred on the gene of interest in different populations or across tissues:
- Observed eQTLs are visualized in a scatter plot; where the dotted line represents the user-defined p-value threshold
- A list of significant eSNPs are shown in a table (figure cis-eQTL - Gene)
- Query results are organized in a tree node structure and can be easily browsed
- Plots can be saved as PNG images; and tables can be exported to tab-delimited files
- External links to three genome browsers
- Quick Start: cis-eQTL - Gene (new to Genevar?)
cis-eQTL - SNP
SNP-centric cis-eQTL analysis
To investigate SNP-gene associations surrounding SNPs of interest in different populations or across tissues:
- Observed associations are displayed in a line chart; where the dotted line represents the p-value threshold
- Genes located within the region are listed in a table: only significant genes their check boxes will be selected
- Query results are organized in a tree node structure and can be easily browsed (figure cis-eQTL - SNP)
- Plots can be saved as PNG images
- Quick Start: cis-eQTL - SNP
eQTL - SNP-Gene
SNP-gene association analysis
To illustrate SNP-probe associations in different populations or across cell types:
- SNP-probe association plots (figure eQTL - SNP-Gene)
- Spearman's rho / linear's r, observed and permutation p-values are shown in each plot
- Each plot can be saved as PNG format
- Quick Start: eQTL - SNP-Gene
Launch application
Multiple connections in the web-services mode
Genevar web-services mode
Genevar 3.1.1 
- Java Web Start automatically downloads and installs the most current version of Genevar when you click on launch.
- After launched, Genevar is initially in the web-services mode connecting to the Sanger Institute.
- There is no need to download any raw datasets and no prior local database is needed in this mode.
Multiple services connections
- This system design allows users to switch between different servers in the same interface (see figure).
- Separate, password-protected servers enable researchers to share unpublished data among collaborators in a secure fashion.
System requirements
- Java SE 6 or above is required - Download Java now if it is not installed.
- Genevar is a cross-platform application and has been tested successfully on Linux, Mac and Windows machines.
License
Genevar and database is freely available under the terms of the GNU Lesser General Public License.
Database installation
Genevar database mode
Genevar database mode
- Users are able to upload, manage and analyze their studies locally in this mode.
- This system design allows users to switch between public servers and local database in the same interface (see figure).
- Genevar can be run completely offline in this mode as there is no communication between the tool and our servers.
Installing MySQL on Windows
The easiset way to run Genevar database with template tables is to download the noinstall, portable package:
- Download the compressed file here genevar-mysql-noinstall-5.1.46-win32.tar.gz and extract it into any your preferable directory (as it is portable!);
- Double click on the startup.bat under the package directory to start your MySQL instance;
- Connect to your MySQL database based on the version downloaded (see figure); and
- Double click on the shutdown.bat to stop your MySQL instance when finish analysis.
Installing MySQL on Windows, Mac or Linux from scratch
If an existing MySQL database is installed or not using Windows system:
- Download suitable package from MySQL Downloads and install MySQL, see the online manual Installation Guidance;
- Change to the MySQL installation directory (represented by BASEDIR) and start your MySQL instance;
shell> cd BASEDIR shell> bin/mysqld --standalone
- Create Genevar database and user tpy (password ypt) and grant SELECT, INSERT, UPDATE, CREATE, DROP, ALTER privileges to tpy;
shell> bin/mysql -u root -p mysql> CREATE DATABASE tpy_team16_genevar_2_0_0; mysql> CREATE USER 'tpy'@'localhost' IDENTIFIED BY 'ypt'; mysql> GRANT SELECT, INSERT, UPDATE, CREATE, DROP, ALTER ON tpy_team16_genevar_2_0_0.* TO 'tpy'@'localhost';
- Download the backup file here tpy_team16_genevar_2_0_0.sql.tar.gz and unzip it into BASEDIR;
- Restore Genevar database with emtpy, template tables;
shell> bin/mysql -u tpy -p tpy_team16_genevar_2_0_0 < tpy_team16_genevar_2_0_0_20100519.sql
- Stop your MySQL instance when finish analysis.
shell> bin/mysqladmin -u root shutdown
Upload formats
Users are able to upload, manage and analyze their studies locally in the database mode
Genevar database mode currently supports the following upload data formats.
Expression profiling data
Illumina HumanRef-8 v3, HumanWG-6 v2, v3 and HumanHT-12 v3 BeadChips:
- TXT example (tab-delimited; including header)
PROBE_ID SMP001 SMP002 ILMN_0000001 7.26 7.1 ILMN_0000002 12.73 11.58
Genotype data
PLINK formats:
- BIM example (not MAP; how to create *.bim)
7 rs0001 0 12345 A T 7 rs0002 0 56789 C G
- PED example
FAM001 SMP001 0 0 0 0 A A G G FAM002 SMP002 0 0 0 0 A T C G
Team16 merged format:
- TXT example (tab-delimited; including header)
Chr Position SNP_ID Alleles SMP001 SMP002 7 12345 rs0001 A/T AA AT 7 56789 rs0002 C/G GG CG
Development
System design and architecture
Develop
- The Genevar software package is powered by MySQL, Hibernate, Apache CXF, JFreeChart and Maven.
- Source code is available from the SourceForge project site.
- Web services protocols provide an additional security layer for Genevar's public database (see figure).
License
Genevar and database is freely available under the terms of the GNU Lesser General Public License.
Release notes
3.1.1, released on 15 December 2011
[Whats new]
- Added a new Database 3.0.0 option in the "New Data Connection" menu
- Added a new "No limit" option in the P-vaule threshold drop-down list
- Improved table sorting in Java SE 6
- Fixed several incompatibly issues when connecting to Database 2.0.0
- Fixed "Export List" in Cis-eQTL - Gene
3.1.0, released on 7 December 2011
[Whats new]
- Added support for external algorithms and pre-uploaded results
- Added support for space-delimited PLINK formats
- Added auto selection for "Reference" drop-down list when a study is chosen
- Fixed a "Data not found error message" when having null QTL results
[Known issues]
- Cannot properly display "Reference" drop-down list when a study is chosen in Database 2.0.0
3.0.2, released on 15 July 2011
[Whats new]
- Fixed several upload issues in database mode.
3.0.1 (was 3.5.0), released on 14 February 2011
[Known issues]
If you have ever encountered an error message Data not found exception whilst accessing your local database then this might affect you:
- When uploading data via the interface onto both expression and genotype table (for your local v2.0.0 database). It looks like the upload was successful from the summary panel but actually these two tables remained empty.
- Please re-upload your files via the latest 3.0.2 interface (3.5.0 became 3.0.1 internally) if you have been using this version to upload your studies. Uploads before February via the older versions will be unaffected by the bug!
- It is not necessary to re-create all your study names and attributes at this stage. Follow the same steps in both Genotype Manager and Expression Manager to specify your previous uploads and submit. When prompted Study already exists. Would you like to re-submit again? in the confirmation dialogue, then select Yes to re-direct the previous unsuccessfully uploads to the new ones.
Publications
Citations
Genevar: a database and Java application for the analysis and visualization of SNP-gene associations in eQTL studies.
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK.
Genevar (GENe Expression VARiation) is a database and Java tool designed to integrate multiple datasets, and provides analysis and visualization of associations between sequence variation and gene expression. Genevar allows researchers to investigate expression quantitative trait loci (eQTL) associations within a gene locus of interest in real time. The database and application can be installed on a standard computer in database mode and, in addition, on a server to share discoveries among affiliations or the broader community over the Internet via web services protocols. AVAILABILITY: http://www.sanger.ac.uk/resources/software/genevar.
Funded by: Wellcome Trust
Bioinformatics (Oxford, England)2010;26;19;2474-6
PUBMED: 20702402; PMC: 2944204; DOI: 10.1093/bioinformatics/btq452
Data release
The architecture of gene regulatory variation across multiple human tissues: the MuTHER study.
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom.
While there have been studies exploring regulatory variation in one or more tissues, the complexity of tissue-specificity in multiple primary tissues is not yet well understood. We explore in depth the role of cis-regulatory variation in three human tissues: lymphoblastoid cell lines (LCL), skin, and fat. The samples (156 LCL, 160 skin, 166 fat) were derived simultaneously from a subset of well-phenotyped healthy female twins of the MuTHER resource. We discover an abundance of cis-eQTLs in each tissue similar to previous estimates (858 or 4.7% of genes). In addition, we apply factor analysis (FA) to remove effects of latent variables, thus more than doubling the number of our discoveries (1,822 eQTL genes). The unique study design (Matched Co-Twin Analysis--MCTA) permits immediate replication of eQTLs using co-twins (93%-98%) and validation of the considerable gain in eQTL discovery after FA correction. We highlight the challenges of comparing eQTLs between tissues. After verifying previous significance threshold-based estimates of tissue-specificity, we show their limitations given their dependency on statistical power. We propose that continuous estimates of the proportion of tissue-shared signals and direct comparison of the magnitude of effect on the fold change in expression are essential properties that jointly provide a biologically realistic view of tissue-specificity. Under this framework we demonstrate that 30% of eQTLs are shared among the three tissues studied, while another 29% appear exclusively tissue-specific. However, even among the shared eQTLs, a substantial proportion (10%-20%) have significant differences in the magnitude of fold change between genotypic classes across tissues. Our results underline the need to account for the complexity of eQTL tissue-specificity in an effort to assess consequences of such variants for complex traits.
Funded by: Wellcome Trust: 077016/Z/05/Z, 085235
PLoS genetics2011;7;2;e1002003
PUBMED: 21304890; PMC: 3033383; DOI: 10.1371/journal.pgen.1002003
Common regulatory variation impacts gene expression in a cell type-dependent manner.
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, CB10 1HH, Cambridge, UK.
Studies correlating genetic variation to gene expression facilitate the interpretation of common human phenotypes and disease. As functional variants may be operating in a tissue-dependent manner, we performed gene expression profiling and association with genetic variants (single-nucleotide polymorphisms) on three cell types of 75 individuals. We detected cell type-specific genetic effects, with 69 to 80% of regulatory variants operating in a cell type-specific manner, and identified multiple expressive quantitative trait loci (eQTLs) per gene, unique or shared among cell types and positively correlated with the number of transcripts per gene. Cell type-specific eQTLs were found at larger distances from genes and at lower effect size, similar to known enhancers. These data suggest that the complete regulatory variant repertoire can only be uncovered in the context of cell-type specificity.
Funded by: Wellcome Trust: 077011, 077046
Science (New York, N.Y.)2009;325;5945;1246-50
PUBMED: 19644074; PMC: 2867218; DOI: 10.1126/science.1174148
Contact
- For questions and requests about Genevar, please contact Professor Emmanouil Dermitzakis
- Please report any bugs or error messages you observe to Genevar developer Tsun-Po Yang
- We thank ex-Team16 members' consistent support in this project
