Table 1 A summary of selected computational tools and their applications

Ensembl Genome Browser

Manual variant annotation and genomic context

Web server, data also available via Perl and REST APIs

http://www.ensembl.org

[10]

UCSC Genome Browser

Manual variant annotation and genomic context

Web server, data also available for download using the UCSC table browser

http://www.genome.ucsc.edu

[11]

Bedtools

Automatic high performance feature overlap and proximity

Command line tool and Python interface

http://bedtools.readthedocs.org

[12]

Bedops

Automatic high performance feature overlap and proximity

Command line tool

http://bedops.readthedocs.org

[13]

HaploReg

Web server identifying non-coding annotations for variants and haplotypes

Web server with pre-computed results for several GWAS

http://www.broadinstitute.org/mammals/haploreg/

[14]

Ensembl Variant Effect Predictor (VEP)

Wide support for variant annotation, emphasis on genic variants, but also incorporates regulatory elements and TF motifs from JASPAR

Downloadable software, web server, Perl and REST APIs, plugin system to add functionality

http://www.ensembl.org/vep

[17]

ANNOVAR

Annotation of genic variants, can also identify overlaps with other annotated elements

Downloadable software

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

[18]

VAT

Annotation of genic variants

Downloadable software

http://vat.gersteinlab.org

[20]

SnpEff

Annotation of genic variants, companion tool SnpSift can filter results by annotations

Downloadable software

http://snpeff.sourceforge.net

[19]

RegulomeDB

Identifies overlaps with non-coding elements and applies heuristic rules to predict consequences

Web server

http://regulome.stanford.edu

[24]

JASPAR

Open access database of TF binding PWMs

Queryable interface and database downloads

http://jaspar.genereg.net

[26]

MEME suite

Several tools for handling PWMs

Web services and downloadable tools

http://meme.nbcr.net

[27]

MOODS

Tool for aligning PWMs to sequences

Command line tool

http://www.cs.helsinki.fi/group/pssmfind/

[28]

Human Splicing Finder

Tool for computing the effects of mutations on splicing

Web server

http://www.umd.be/HSF/

[29]

GERP

Nucleotide resolution conservation scores

Downloadable software, pre-computed scores and elements for human and mouse genomes

http://mendel.stanford.edu/SidowLab/downloads/gerp/

[31]

PHAST package

Suite of tools for phylogenetic analyses, including phastCons and phyloP

Downloadable software and R package

http://compgen.bscb.cornell.edu/phast/

[32],[33]

SCONE

Position-specific conservation scores

Downloadable software

http://genetics.bwh.harvard.edu/scone/

[34]

SIFT

Predicts deleterious AASs) based on conservation and physico-chemical principles

Downloadable software and web server

http://sift.bii.a-star.edu.sg

[35]

FATHMM

Uses a hidden Markov model to identify AASs likely to be deleterious

Downloadable software and web server, VEP plugin

http://fathmm.biocompute.org.uk

[39]

PolyPhen

Predicts deleterious AASs based on several sequence and structural features

Downloadable software and web server, pre-computed predictions for all possible substitutions

http://genetics.bwh.harvard.edu/pph2/

[41]

MutationTaster

Classifier which can predict deleterious variants in genic regions, including coding regions and splice sites

Web server

http://www.mutationtaster.org

[42]

MutationAssessor

Predicts deleterious AASs based on evolutionary conservation

Web server, pre-computed scores for all possible substitutions

http://www.mutationassessor.org

[43]

SNAP

Predicts deleterious AASs based on a range of protein level information

Downloadable software and web server

http://www.rostlab.org/services/SNAP/

[44]

PhD-SNP

Predicts deleterious AASs based on protein sequence information

Downloadable software and web server

http://snps.biofold.org/phd-snp/

[45]

Condel

Tool that integrates predictions from multiple AAS prediction tools

Downloadable software and web server, VEP plugin

http://bg.upf.edu/fannsdb/

[46]

CAROL

Tool that integrates scores from SIFT and PolyPhen using a weighted Z method

Downloadable R script, VEP plugin

http://www.sanger.ac.uk/resources/software/carol/

[47]

GWAVA

Classifier identifying likely functional regulatory variants

Downloadable software and database of pre-computed scores and annotations for known variants, VEP plugin

http://www.sanger.ac.uk/resources/software/gwava/

[48]

CADD

Integrated classifier that can score all classes of variants

Web server, pre-computed scores for all possible SNVs, VEP plugin

http://cadd.gs.washington.edu

[51]

fgwas

Command line tool for incorporating functional information into a GWAS

Downloadable software

http://www.github.com/joepickrell/fgwas

[52]

SKAT

A test for association between a set of variants and dichotomous or quantitative phenotypes

Downloadable software

http://www.hsph.harvard.edu/skat/

[53]

VT

Tests for pooled association of multiple rare variants and phenotypes

Downloadable software

http://genetics.bwh.harvard.edu/vt/dokuwiki/start

[54]

VAAST

Probabilistic tool to identify causal genes and variants in disease

Downloadable software, free for academic use, license required for commercial usage

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

[55],[56]