A platform for decoding regulatory somatic mutations in human cancers
Whole-exome and whole-genome sequencing have revealed millions of somatic mutations associated with different human cancers. The vast majority of identified somatic mutations are located outside of coding sequences, making it challenging to directly interpret their functional effects. With the rapid advances in high-throughput chromosome conformation capture (3C)-based technologies, genome-scale long-range chromatin interactions were detected, and distal target genes of regulatory elements were determined using three-dimensional (3D) chromatin looping. Herein, we present OncoBase, an integrated database for annotating regulatory noncoding somatic mutations in human cancers by exploring their roles in distal interactions between target genes and regulatory elements. OncoBase integrates local chromatin signatures, 3D chromatin interactions in different cell types and reconstruction of enhancer-target networks using state-of-the-art algorithms. OncoBase employs informative visualization tools to display the integrated local and 3D chromatin signatures and effects of somatic mutations on regulatory elements. Enhancer-promoter interactions estimated from chromatin interactions are integrated into a network diffusion system that quantitatively prioritizes somatic mutations and target genes to help select important candidates from a large pool. OncoBase is a useful resource for the functional annotation of regulatory noncoding sequences and systematically benchmarking the regulatory effects of embedded noncoding somatic mutations in human carcinogenesis. The OncoBase platform is available at http://www.oncobase.biols.ac.cn/.