Below we provide a basic description of the annotations, delineated by class, provided by SG-ADVISER. The relevant annotations refer to the annotation columns presented in the output file. See Results Description for a more detailed description of the specific annotation columns, the implemented tools, and their output formats.
Physical and Gene-Relative Mapping and Characteristics
The most basic level of annotation including user provided information about the type and location of variants, the nearest gene and location and distance from that gene, as well as variant identifiers. These annotations include:
- Haplotype - A user defined parameter if phasing information is available.
Relevant Annotations - Haplotype
- Physical Location - The chromosome and position of the variant. User defined.
Relevant Annotations - Chromosome, Begin, End.
- Variant Information - The variant type and reference and variant alleles. User defined.
Relevant Annotations - VarType, Reference, Allele.
- Gene Information - The nearest gene(s) and gene type (coding vs. non-coding).
Relevant Annotations - Gene, Gene_Type, Gene_Symbol
- Gene-Relative Mapping - The distance from the nearest gene(s) and location relative to the gene (exonic, intronic, upstream, etc.)
Relevant Annotations - Location, Distance
- Identifiers - dbSNP identifiers assigned to the variant.
Relevant Annotations - dbSNP_ID
Coding Gene Impact, Inferred and Predicted
The impact of variants on protein coding genes - including a basic impact inferred from the reading frame and the predicted functional impact based on a variety of tools. These annotations include:
- Coding Impact - Impact of the variant on the coding frame (nonsynonymous, synonymous, frameshift, etc.).
Relevant Annotations - Coding_Impact
- Protein Impact - Location of the variant within the protein and relative to the start-stop codons of the protein and induced amino acid changes.
Relevant Annotations - Protein_Pos, Original_AA, Allele_AA, Start~Stop_Dist, Protein_Domains
- Functional Impact Predictions - Predictions as to whether the variant coding impact significantly impacts the protein function.
Relevant Annotations - Protein_Impact_Prediction(Polyphen), Protein_Impact_Probability(Polyphen), Protein_Impact_Prediction(SIFT), Prop_Cons_Affected_Upstream, Prop_Cons_Affected_Downstream, Protein_Impact_Score(SIFT), Protein_Impact_Prediction(Condel), Protein_Impact_Score(Condel), Protein_Domains_Impact(LogRE), Trunc_Prediction.
Splicing Impact, Inferred and Predicted
The impact of variants on splicing of genes - including a basic impact inferred from canonical splice site donors/acceptor sequences and the predicted functional impact of variants. These annotations include:
- Splicing Impact - Variants landing in splice site donor/acceptor positions.
Relevant Annotations - Splice_Site_Pred
- Splicing Impact Predictions - Predictions as to whether the variant significantly impacts splicing.
Relevant Annotations - splicing_Prediction(MaxENT), ESE_sites, ESS_sites
Information about the genomic region in which the variant resides. These annotations include:
- Conservation - Determination whether the variant resides in a conserved element and nucleotide level conservation.
Relevant Annotations - Conserved46way, Conserved46wayPlacental, Conserved46wayPrimates
- Segmental Duplications - Variant residence within a segmental duplication.
Relevant Annotations - SegDup_Region
Population genetics annotations. These annotations include:
- Allele Frequency - Allele frequency of variants in Hapmap, 1000 genomes, Complete Genomics, and Wellderly genomes.
Relevant Annotations - ASW_minallele, CEU_minallele, CHB_minallele, CHD_minallele, GIH_minallele, JPT_minallele, LWK_minallele, MEX_minallele, MKK_minallele, TSI_minallele, YRI_minallele, 1000GENOMES_AF, CG_69_AF, CG_WELLDERLY_AF
Known and predicted impacts of variants on gene regulation. These annotations include:
- Transcription Factor Binding Sites - Variant residence and predicted impact on transcription factor binding sites.
Relevant Annotations - TFBS, TFBS_DeltaS
- microRNA Binding Sites - Variant residence and predicted impact on microRNA binding sites in 3’ UTRs of genes.
Relevant Annotations - miRNA_BS_influenced, miRNA_BS_impact, miRNA_BS_direct, miRNA_BS_deltaG
- Known Regulatory Variants - Variants known to change gene expression levels.
Relevant Annotations - eQTL_genes
Disease-based, Drug-based and other Clinical Annotations
Gene and variant based information that is relevant to diseases and/or drugs. These annotations include.
- Disease Causitive and Risk Genes - Determination of whether the variant resides in a gene(s) previously observed to carry disease causative or risk variants or otherwise associated with disease.
Relevant Annotations - omimGene_ID~omimGene_association, HGMD_Gene~disease_association, Disease_Ontology
- Disease Causitive and Risk Variants - Variants previously observed or predicted to be disease causative. Variants known to elevate the risk of disease.
Relevant Annotations - HGMD_Variant~PubMedID, Genetic_Association_Database~PubMedID, Inheritance~Penetrance, Severity~Treatability, ADVISER_Score_Clinical~Disease_Entry~Explanation, ADVISER_Score_Research~Disease_Entry~Explanation
- Cancer Genes - Determination of whether the variants resides in a gene(s) considered to be oncogenes or tumor suppressors.
Relevant Annotations - COSMIC_Variant~NumSamples, COSMIC_Gene~NumSamples, MSKCC_CancerGenes, Atlas_Oncology, Sanger_CancerGenes, Sanger_Germline_CancerGenes, Sanger_network-informed_CancerGenes~Pval
- Drug Targets - Determinat of whether the variant resides in a known drug target.
Relevant Annotations - DrugBank
- Pharmacogenetic Variants - Variants known to influence the efficacy or adverse response to drugs.
Relevant Annotations - PharmGKB_Database~Drug
Gene Networks, Pathways, Biological Process and Molecular Functions
Annotations that link genes to one another based upon shared participation in biological pathways, processes, or molecular functions.
- Biological Pathways - Known biological pathways of genes impacted by a variant.
Relevant Annotations - Reactome_Pathway
- Biological Processes - Known biological processes of genes impacted by a variant.
Relevant Annotations - Gene_Ontology
- Molecular Functions - Known molecular functions of genes impacted by a variant.
Relevant Annotations - Protein_Domain_Gene_Ontology
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