SNP2TFBS - a database of regulatory SNPs affecting predicted transcription factor binding site affinity

Abstract

SNP2TFBS is a computational resource intended to support researchers investigating the molecular mechanisms underlying regulatory variation in the human genome. The database essentially consists of a collection of text files providing specific annotations for human single nucleotide polymorphisms (SNPs), namely whether they are predicted to abolish, create or change the affinity of one or several transcription factor (TF) binding sites. A SNP's effect on TF binding is estimated based on a position weight matrix (PWM) model for the binding specificity of the corresponding factor. These data files are regenerated at regular intervals by an automatic procedure that takes as input a reference genome, a comprehensive SNP catalogue and a collection of PWMs. SNP2TFBS is also accessible over a web interface, enabling users to view the information provided for an individual SNP, to extract SNPs based on various search criteria, to annotate uploaded sets of SNPs or to display statistics about the frequencies of binding sites affected by selected SNPs. Homepage: http://ccg.vital-it.ch/snp2tfbs/.

Figure 1.

SNP2TFBS data generation pipeline. The rectangular boxes represent data files. Duplicated frames indicate multiple files for each type, one for each position weight matrice (PWM). Encircled numbers refer to procedures: (1) Generation of the alternate human genome (hg19a) from reference genome (hg19) (2) Genome coordinates conversion of the reference single nucleotide polymorphisms (SNP) catalogue (VCF format) to the alternate genome. (3) Whole genome scan of both genomes with PWMs from JASPAR CORE 2014 at P-value threshold 10⁻⁵.(4) Extraction of SNPs overlapping PWM matches on the respective genomes. (5) Extraction of SNPs that disrupt, create or change score of overlapping PWM sites between the two genomes (6) Merging of essential information from single PWM files into master file, generation of gene-annotated and reformatted versions (e.g. BED) from primary data files. Variants annotation is carried out using an ANNOVAR input file (humandb/hg19_refGene.txt).

Figure 2.

Example of results page returned by the SNP2TFBS selection and annotation tool. Left side: upper part of the results page with three summary statistics plots. Right side: magnified TF enrichment plot. Input to the analysis was a set of SNPs known from multiple GWAS studies to be associated with diabetes.