Large scale computational analysis of cis-regulatory somatic mutations altering gene expression regulation

With the increasing availability of whole genome sequencing data, one has now access to a wealth of somatic mutation events specific to patients carrying a cancer. Classically, researchers focus on the events lying within protein-coding regions in order to extract the ones disruptive to protein structure and/or function. One can use whole-genome sequencing information to extract mutations lying within cis-regulatory regions with potential impact on gene regulation. We will present our study of 84 matched tumor-normal whole genomes of B-cell lymphomas where we specifically focused on mutations overlapping transcription factor binding sites (TFBSs) for their potential impact on gene expression regulation. We highlight the importance of moving beyond the protein-coding subset of the genome to analyze the cis-regulatory space. TFBSs representing the core of gene cis-regulation, we will finally introduce our transcription factor flexible models representing the next generation of TFBS prediction.