OncoBase: a platform for decoding regulatory somatic mutations in human cancers

Area of Science:

• Genomics
• Cancer Biology
• Bioinformatics

Background:

• Millions of somatic mutations in human cancers occur outside coding sequences, complicating functional interpretation.
• Advances in sequencing and 3D chromatin looping enable determination of distal gene targets for regulatory elements.

Purpose of the Study:

• To present OncoBase, an integrated database for annotating somatic mutations by exploring their roles in distal gene-regulatory element interactions.
• To provide a resource for functional annotation of noncoding regulatory regions and benchmarking of noncoding somatic mutation effects in carcinogenesis.

Main Methods:

• Integration of 81,385,242 somatic mutations from 68 cancer types and over 120 projects.
• Incorporation of local chromatin signatures, 3D chromatin interactions, and enhancer-target network reconstruction.
• Utilizing a network diffusion system to prioritize mutations and target genes based on enhancer-promoter interactions.

Main Results:

• OncoBase integrates diverse data, including local and 3D chromatin signatures, and visualizes mutation effects on regulatory elements.
• The database quantitatively prioritizes somatic mutations and target genes by analyzing enhancer-promoter interactions.
• It facilitates the systematic analysis of noncoding somatic mutations' regulatory effects.

Conclusions:

• OncoBase serves as a valuable resource for understanding the functional impact of noncoding somatic mutations in cancer.
• The database aids in the systematic annotation and benchmarking of regulatory elements and their associated mutations in human carcinogenesis.