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 | [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 | [12] | |
Bedops | Automatic high performance feature overlap and proximity | Command line tool | [13] | |
HaploReg | Web server identifying non-coding annotations for variants and haplotypes | Web server with pre-computed results for several GWAS | [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 | [17] | |
ANNOVAR | Annotation of genic variants, can also identify overlaps with other annotated elements | Downloadable software | [18] | |
VAT | Annotation of genic variants | Downloadable software | [20] | |
SnpEff | Annotation of genic variants, companion tool SnpSift can filter results by annotations | Downloadable software | [19] | |
RegulomeDB | Identifies overlaps with non-coding elements and applies heuristic rules to predict consequences | Web server | [24] | |
Annotation based on sequence motifs | ||||
JASPAR | Open access database of TF binding PWMs | Queryable interface and database downloads | [26] | |
MEME suite | Several tools for handling PWMs | Web services and downloadable tools | [27] | |
MOODS | Tool for aligning PWMs to sequences | Command line tool | [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 | [31] | |
PHAST package | Suite of tools for phylogenetic analyses, including phastCons and phyloP | Downloadable software and R package | ||
SCONE | Position-specific conservation scores | Downloadable software | [34] | |
SIFT | Predicts deleterious AASs) based on conservation and physico-chemical principles | Downloadable software and web server | [35] | |
FATHMM | Uses a hidden Markov model to identify AASs likely to be deleterious | Downloadable software and web server, VEP plugin | [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 | [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 | [44] | |
PhD-SNP | Predicts deleterious AASs based on protein sequence information | Downloadable software and web server | [45] | |
Condel | Tool that integrates predictions from multiple AAS prediction tools | Downloadable software and web server, VEP plugin | [46] | |
CAROL | Tool that integrates scores from SIFT and PolyPhen using a weighted Z method | Downloadable R script, VEP plugin | [47] | |
GWAVA | Classifier identifying likely functional regulatory variants | Downloadable software and database of pre-computed scores and annotations for known variants, VEP plugin | [48] | |
CADD | Integrated classifier that can score all classes of variants | Web server, pre-computed scores for all possible SNVs, VEP plugin | [51] | |
Phenotype association techniques that can incorporate functional information | ||||
fgwas | Command line tool for incorporating functional information into a GWAS | Downloadable software | [52] | |
SKAT | A test for association between a set of variants and dichotomous or quantitative phenotypes | Downloadable software | [53] | |
VT | Tests for pooled association of multiple rare variants and phenotypes | Downloadable software | [54] | |
VAAST | Probabilistic tool to identify causal genes and variants in disease | Downloadable software, free for academic use, license required for commercial usage |