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

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OncoBase annotates millions of noncoding somatic mutations in 68 cancer types by integrating 3D chromatin interactions. This database helps understand how these mutations affect gene regulation and contribute to human carcinogenesis.

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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.