Table 2 A list of open-access bioinformatics software tools or web servers that can perform batch annotation of genetic variants from whole-exome/genome sequencing data*

ANNOVAR

[http://www.openbioinformatics.org/annovar/]

A software tool written in Perl to perform gene-based, region-based and filter-based annotation

Rapid and up-to-date annotations for multiple species; thousands of annotation types are supported

Requires format conversion for VCF files; command line interface cannot be accessed by many biologists

AnnTools

[http://anntools.sourceforge.net/]

A software tool written in Python to annotate SNVs, indels and CNVs

Fast information retrieval by MySQL database engine; output in VCF format for easy downstream processing

Only supports human genome build 37; does not annotate variant effect on coding sequence

Mu2a

[http://code.google.com/p/mu2a/]

A Java web application for variant annotation

Web interface for users with limited bioinformatics expertise; output in Excel and text formats

Does not allow annotation of indels or CNVs

SeattleSeq

[http://snp.gs.washington.edu/SeattleSeqAnnotation/]

A web server that provides annotation on known and novel SNPs

Multiple input formats are supported; users can customize annotation tasks

Limited annotation on indels or CNVs

Sequence Variant Analyzer

[http://www.svaproject.org/]

A graphical Java software tool to annotate, visualize and organize variants

Intuitive graphical user interface; ability to prioritize candidate genes from multiple patients

Functionality is not very customizable; depends on ENSEMBL database for annotations

snpEff

[http://snpeff.sourceforge.net]

A command-line software tool to calculate the effects of variants on known genes such as amino acid changes

Rapid annotation on multiple species and genome builds; supports multiple codon table

Only supports gene-based annotation

TREAT

[http://ndc.mayo.edu/mayo/research/biostat/stand-alone-packages.cfm]

A command-line software tool with rich integration of publicly available and in-house developed annotations

An Amazon Cloud Image is available for users with limited bioinformatics infrastructure; offers a complete set of pipelines to process FASTQ files and generates annotation outputs

Only supports ENSEMBL gene definition and with limited sets of annotations

VAAST

[http://www.yandell-lab.org/software/vaast.html]

A command-line software tool implementing a probabilistic disease-gene finder to rank all genes

Prioritize candidate genes for Mendelian and complex diseases

Main focus is disease gene finding with limited set of annotations

VARIANT

[http://variant.bioinfo.cipf.es]

A Java web application for variant annotation and visualization

Intuitive interface with integrated genome viewer

Highly specific requirement for internet browser; slow performance

VarSifter

[http://research.nhgri.nih.gov/software/VarSifter/]

A graphical Java program to display, sort, filter and sift variation data

Nice graphical user interface; allows interaction with Integrative Genomics Viewer

Main focus is variant filtering and visualization with limited functionality in variant annotation

VAT

[http://vat.gersteinlab.org/]

A web application to annotate a list of variants with respect to genes or user-specified intervals

Application can also be deployed locally; can generate image for genes to visualize variant effects

Requires multiple other packages to work; only supports gene-based annotation by GENCODE

wANNOVAR

[http://wannovar.usc.edu/]

A web server to annotate user-supplied list of whole genome or whole exome variants with a set of pre-defined annotation tasks

Easy-to-use interface for users with limited bioinformatics skills

Limited set of annotation types are available