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Table 2 Partial list of tools and resources to annotate DNA sequence variants
From: Rare variant association studies: considerations, challenges and opportunities
| Tool/resource | Description | URL | Reference |
|---|---|---|---|
| CADD | A framework that integrates multiple annotations into one metric by contrasting variants that survived natural selection with simulated mutations | http://cadd.gs.washington.edu/ | [88] |
| ENCODE | Annotation of potential functional elements (for example, histone tail modifications) in several cell lines | https://www.encodeproject.org/ | [89] |
| Epigenomics Roadmap | Annotation of potential functional elements (for example, DNAse I hypersensitive sites) in many human tissues and primary cells | http://www.roadmapepigenomics.org/ | [90] |
| FANTOM5 | Annotation of transcriptional enhancers in many human tissues and primary cells through detection of bidirectional capped transcription | http://enhancer.binf.ku.dk/ | [91] |
| GERP | Identifies constrained elements in multiple alignments by quantifying substitution deficits | http://mendel.stanford.edu/SidowLab/downloads/gerp/ | [92] |
| HaploReg | Visualization of DNA polymorphisms along with their predicted chromatin state, their sequence conservation across mammals, and their effect on regulatory motifs | http://www.broadinstitute.org/mammals/haploreg/haploreg.php | [93] |
| Phen-Gen | Method that combines patients' disease symptoms and sequencing data with prior domain knowledge to identify the causative genes for rare disorders | http://phen-gen.org/about.html | [94] |
| PolyPhen-2 | A tool that predicts the possible impact of an amino acid substitution on the structure and function of a human protein using straightforward physical and comparative considerations | http://genetics.bwh.harvard.edu/pph2/ | [95] |
| RegulomeDB | A database that annotates SNPs with known and predicted regulatory elements in the intergenic regions of the human genome using gene expression, ENCODE and literature-mining data | http://regulomedb.org/ | [96] |
| RVIS | This score is designed to rank genes in terms of whether they have more or less common functional genetic variation relative to the genome-wide expectation given the amount of apparently neutral variation the gene has | http://chgv.org/GenicIntolerance/ | [97] |
| SIFT | Predicts whether an amino acid substitution affects protein function based on the degree of conservation of amino acid residues in sequence alignments derived from closely related sequences | http://sift.jcvi.org/ | [98] |
| VEP | Determines the effect of your variants (SNPs, insertions, deletions, CNVs or structural variants) on genes, transcripts and protein sequence, as well as regulatory regions. | http://useast.ensembl.org/info/docs/tools/vep/index.html?redirect=no | [99] |
