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Quantification of Protein Interaction Network Dynamics using Multiplexed Co-Immunoprecipitation
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Aberration hubs in protein interaction networks highlight actionable targets in cancer

Mehran Karimzadeh1,2, Pouria Jandaghi1,2, Andreas I Papadakis3

  • 1Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada.

Oncotarget
|June 5, 2018
PubMed

Insights

Identifying targetable cancer genes is challenging due to tumor heterogeneity. Aberration Hub Analysis for Cancer (AbHAC) pinpoints key proteins interacting with mutated genes, revealing novel therapeutic targets like spleen tyrosine kinase in renal cancer.

Area of Science:

  • Oncology
  • Bioinformatics
  • Genomics

Background:

  • Cancer molecular characterization efforts like the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) face challenges in identifying actionable targets.
  • Tumor heterogeneity and limited understanding of protein function complicate gene targeting.

Purpose of the Study:

  • To introduce Aberration Hub Analysis for Cancer (AbHAC), a novel integrative approach to identify targetable genes.
  • To pinpoint "aberration hubs"—proteins extensively interacting with genes exhibiting aberrant mutations or expression.

Main Methods:

  • Developed and applied the Aberration Hub Analysis for Cancer (AbHAC) method.
  • Analyzed breast cancer data from TCGA and renal cancer data from ICGC.
  • Integrated mutation/expression data with biological network information.

Main Results:

  • AbHAC identified aberration hubs involved in key cancer pathways, such as cell cycle and DNA replication in basal-like breast tumors.
  • In renal carcinoma, identified hubs linked to Src kinase and VEGF signaling.
  • Uncovered novel, actionable targets, including experimentally validated abnormal spleen tyrosine kinase splicing crucial for renal cancer cell proliferation.

Conclusions:

  • AbHAC offers an effective strategy for discovering novel disease factors.
  • The approach highlights the importance of analyzing genomic data within biological network contexts.
  • Identified spleen tyrosine kinase as a potential therapeutic target in renal cancer.
Keywords:
cancercomputational biologygenomicssystems biologytarget discovery

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