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ProKinO: a unified resource for mining the cancer kinome

Daniel Ian McSkimming1, Shima Dastgheib, Eric Talevich

  • 1Institute of Bioinformatics, University of Georgia, Athens, Georgia.

Human Mutation
|November 11, 2014
PubMed

Insights

This study introduces ProKinO, an ontological framework to analyze cancer-related protein kinase variants. It identifies a novel hotspot in EGFR, impacting its activity and drug sensitivity.

Area of Science:

  • Oncology
  • Bioinformatics
  • Molecular Biology

Background:

  • Protein kinases are crucial in human cancers, with numerous variants identified through genomic studies.
  • Translating vast genomic data into actionable biological insights for kinases remains a significant challenge.

Purpose of the Study:

  • To develop an ontological framework for integrating diverse kinase information.
  • To analyze the cancer kinome and generate testable hypotheses for cancer research.

Main Methods:

  • Developed an ontological framework for machine-readable integration of kinase data.
  • Utilized aggregate ontology querying and hypothesis generation.
  • Performed experimental validation of identified variants.

Main Results:

  • Identified a novel mutational hotspot in the αC-β4 loop of the kinase domain.
  • Demonstrated functional impact of variants on epidermal growth factor receptor (EGFR) activity.
  • Showed effects on EGFR constitutive activity and inhibitor sensitivity.

Conclusions:

  • The ProKinO framework facilitates analysis of the cancer kinome.
  • Identified a new hotspot in EGFR with functional implications for cancer therapy.
  • ProKinO serves as a unified resource for the kinase and cancer research communities.
Keywords:
big datacancer therapyconformationdatabasediseasedrug discoverykinasemutationpersonalized medicineregulationresistance

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