CNA2Subpathway: identification of dysregulated subpathway driven by copy number alterations in cancer

Yuqi Sheng1, Ying Jiang2, Yang Yang1

  • 1College of Bioinformatics Science and Technology, Harbin Medical University, China.

Insights

We developed CNA2Subpathway, a network-based tool to identify dysfunctional subpathways (SPs) in cancer by analyzing somatic copy number alterations (CNAs) and their interactions. This method reveals cancer-relevant SPs linked to patient prognosis and immune response.

Area of Science:

  • * Computational biology and bioinformatics.
  • * Cancer genomics and systems biology.

Background:

  • * Biological pathways are crucial for understanding disease states and drug responses.
  • * Subpathways (SPs), localized pathway regions, are implicated in cancer development.
  • * Identifying dysfunctional SPs using multi-omics data is increasingly feasible.

Purpose of the Study:

  • * To propose a novel network-based method, CNA2Subpathway, for identifying cancer-associated dysfunctional SPs driven by somatic copy number alterations (CNAs).
  • * To integrate pathway topology, multi-omics data, and SP crosstalk for a systems-level analysis.
  • * To validate the method's effectiveness in identifying cancer-relevant SPs and their association with patient outcomes.

Main Methods:

  • * Developed CNA2Subpathway, a network-based computational method.
  • * Integrated somatic copy number alteration (CNA) data, multi-omics data, and subpathway (SP) crosstalk information.
  • * Utilized pathway topology and SP interaction networks.

Main Results:

  • * Validated CNA2Subpathway using breast and head and neck cancer datasets.
  • * Identified cancer-relevant SPs driven by CNAs, correlating with patient immune profiles and prognosis.
  • * Demonstrated superior performance compared to methods ignoring SP crosstalk.

Conclusions:

  • * CNA2Subpathway effectively uncovers dysfunctional SPs in cancer by leveraging SP crosstalk.
  • * The tool provides a novel approach for SP analysis at a systems biological level.
  • * CNA2Subpathway is available as an R-based tool on GitHub for broader research application.

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