Abstract
Interpreting the functional impact of noncoding variants is an ongoing challenge in the field of genome analysis. With most noncoding variants associated with complex traits and disease residing in regulatory regions, altered transcription factor (TF) binding has been proposed as a mechanism of action. It is therefore imperative to develop methods that predict the impact of noncoding variants at TF binding sites (TFBSs). Here, we describe the update of our MANTA database that stores: 1) TFBS predictions in the human genome, and 2) the potential impact on TF binding for all possible single nucleotide variants (SNVs) at these TFBSs. TFBSs were predicted by combining experimental ChIP-seq data from ReMap and computational position weight matrices (PWMs) derived from JASPAR. Impact of SNVs at these TFBSs was assessed by means of PWM scores computed on the alternate alleles. The updated database, MANTA2, provides the scientific community with a critical map of TFBSs and SNV impact scores to improve the interpretation of noncoding variants in the human genome.
Highlights
Background & SummaryUnderstanding the relationship between DNA sequence variation and observable traits and diseases is one of the central paradigms of the post-genomics era
In 2015, we developed MANTA, a Mongo database for the analysis of TF binding sites (TFBSs) alterations, to study the impact of regulatory mutations in B-cell lymphomas[20]
MANTA2 provides the scientific community with a critical map of TFBSs and single nucleotide variants (SNVs) impact scores for the interpretation of noncoding variants in the human genome
Summary
Understanding the relationship between DNA sequence variation (genotype) and observable traits and diseases (phenotype) is one of the central paradigms of the post-genomics era. Bioinformatics methods have been developed for scoring the impact of noncoding variants based on their pathogenicity and regulatory capacity (Table 1). These methods vary both in their algorithmic approaches and the underlying genomic features used. Building on the recent updates of both the JASPAR and ReMap databases, we have largely expanded MANTA This second release of the database, MANTA2, hosts over 48 million TFBS predictions within ChIP-seq regions of 225 human TFs, covering about 8% of the human genome, together with computed impact scores for all Method CADD CpGenie DANN DeepSEA deltaSVM Eigen FATHMM fitCons FunSeq[2] GWAVA LINSIGHT MANTA RegulomeDB ReMM RVSP SNP2TFBS. MANTA2 provides the scientific community with a critical map of TFBSs and SNV impact scores for the interpretation of noncoding variants in the human genome
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