Leveraging protein quaternary structure to identify oncogenic driver mutations

Gregory Alexander Ryslik, Yuwei Cheng, Yorgo Modis, Hongyu Zhao

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Identifying key "driver" mutations which are responsible for tumorigenesis is critical in the development of new oncology drugs. Due to multiple pharmacological successes in treating cancers that are caused by such driver mutations, a large body of methods have been developed to differentiate these mutations from the benign "passenger" mutations which occur in the tumor but do not further progress the disease. Under the hypothesis that driver mutations tend to cluster in key regions of the protein, the development of algorithms that identify these clusters has become a critical area of research. Results: We have developed a novel methodology, QuartPAC (Quaternary Protein Amino acid Clustering), that identifies non-random mutational clustering while utilizing the protein quaternary structure in 3D space. By integrating the spatial information in the Protein Data Bank (PDB) and the mutational data in the Catalogue of Somatic Mutations in Cancer (COSMIC), QuartPAC is able to identify clusters which are otherwise missed in a variety of proteins. The R package is available on Bioconductor at: http://bioconductor.jp/packages/3.1/bioc/html/QuartPAC.html. Conclusion:QuartPAC provides a unique tool to identify mutational clustering while accounting for the complete folded protein quaternary structure.

Original languageEnglish (US)
Article number137
JournalBMC bioinformatics
Volume17
Issue number1
DOIs
StatePublished - Mar 22 2016

Fingerprint

Quaternary Protein Structure
Protein Structure
Driver
Mutation
Proteins
Protein
Cluster Analysis
Clustering
Cancer
Neoplasms
Oncology
Spatial Information
Differentiate
Amino Acids
Amino acids
Tumors
Tumor
Drugs
Carcinogenesis
Databases

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Applied Mathematics

Cite this

Ryslik, Gregory Alexander ; Cheng, Yuwei ; Modis, Yorgo ; Zhao, Hongyu. / Leveraging protein quaternary structure to identify oncogenic driver mutations. In: BMC bioinformatics. 2016 ; Vol. 17, No. 1.
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Leveraging protein quaternary structure to identify oncogenic driver mutations. / Ryslik, Gregory Alexander; Cheng, Yuwei; Modis, Yorgo; Zhao, Hongyu.

In: BMC bioinformatics, Vol. 17, No. 1, 137, 22.03.2016.

Research output: Contribution to journalArticle

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