Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Mutational oncogenic signatures on structurally resolved protein interacting interfaces

Luz Garcia-Alonso, Joaquin Dopazo
doi: https://doi.org/10.1101/016204
Luz Garcia-Alonso
Computational Genomics Department, Centro de Investigacion Principe Felipe (CIPF), Valencia, 46012, Spain.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joaquin Dopazo
Computational Genomics Department, Centro de Investigacion Principe Felipe (CIPF), Valencia, 46012, Spain.Bioinformatics of Rare Diseases (BIER), CIBER de Enfermedades Raras (CIBERER), Valencia, Spain.Functional Genomics Node at CIPF, (INB) CIPF, Valencia, 46012, Spain.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

The importance of the context of interactions in the proteins mutated in cancer is long known. However, our knowledge on how mutations affecting to protein-protein interactions (PPIs) are related to cancer occurrence and progression is still poor. Here, we extracted the missense somatic mutations from 5920 cancer patients of 33 different cancer types, taken from the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), and mapped them onto a structurally resolved interactome, which integrates three-dimensional atomic-level models of domain-domain interactions with experimentally determined PPIs, involving a total of 7580 unique interacting domains that participate in 13160 interactions connecting 4996 proteins. We observed that somatic nonsynonymous mutations tend to concentrate in ordered regions of the affected proteins and, within these, they have a clear preference for the interacting interfaces. Also, we have identified more than 250 interacting interfaces candidate to drive cancer. Examples demonstrate how mutations in the interacting interfaces are strongly associated with patient survival time, while similar mutations in other areas of the same proteins lack this association. Our results suggest that the perturbation caused by cancer mutations in protein interactions is an important factor in explaining the heterogeneity between cancer patients.

Footnotes

  • LG-A: luzgaral{at}ebi.ac.uk JD: jdopazo{at}cipf.es

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted March 07, 2015.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Mutational oncogenic signatures on structurally resolved protein interacting interfaces
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
Share
Mutational oncogenic signatures on structurally resolved protein interacting interfaces
Luz Garcia-Alonso, Joaquin Dopazo
bioRxiv 016204; doi: https://doi.org/10.1101/016204
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Mutational oncogenic signatures on structurally resolved protein interacting interfaces
Luz Garcia-Alonso, Joaquin Dopazo
bioRxiv 016204; doi: https://doi.org/10.1101/016204

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genomics
Subject Areas
All Articles
  • Animal Behavior and Cognition (1519)
  • Biochemistry (2473)
  • Bioengineering (1727)
  • Bioinformatics (9648)
  • Biophysics (3884)
  • Cancer Biology (2961)
  • Cell Biology (4173)
  • Clinical Trials (135)
  • Developmental Biology (2620)
  • Ecology (4084)
  • Epidemiology (2031)
  • Evolutionary Biology (6868)
  • Genetics (5195)
  • Genomics (6482)
  • Immunology (2176)
  • Microbiology (6909)
  • Molecular Biology (2746)
  • Neuroscience (17197)
  • Paleontology (125)
  • Pathology (425)
  • Pharmacology and Toxicology (703)
  • Physiology (1050)
  • Plant Biology (2478)
  • Scientific Communication and Education (642)
  • Synthetic Biology (828)
  • Systems Biology (2680)
  • Zoology (429)