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Table 1 A summary of selected computational tools and their applications

From: Computational approaches to interpreting genomic sequence variation

Tool Application Comments URL Reference
Annotation based on overlap with and proximity to functional elements
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]
Biologically informed rule-based annotation
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]
Annotation based on sequence motifs
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]
Annotation based on constraint estimated from multiple sequence alignments
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]
Integrative approaches using supervised learning algorithms
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]
Phenotype association techniques that can incorporate functional information
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]
  1. Abbreviations: AAS amino acid substitution, API application programming interface, GWAS genome-wide association studies, PWM position weight matrix, REST representational state transfer (an architecture style for designing networked applications), TF transcription factor, UCSC University of California Santa Cruz, VEP Variant Effect Predictor.