Module cover - A new approach to genotype-phenotype studies

Yoo Ah Kim, Raheleh Salari, Stefan Wuchty, Teresa M. Przytycka

Research output: Contribution to journalConference article

13 Scopus citations

Abstract

Uncovering and interpreting phenotype/genotype relationships are among the most challenging open questions in disease studies. Set cover approaches are explicitly designed to provide a representative set for diverse disease cases and thus are valuable in studies of heterogeneous datasets. At the same time pathway-centric methods have emerged as key approaches that significantly empower studies of genotype-phenotype relationships. Combining the utility of set cover techniques with the power of network-centric approaches, we designed a novel approach that extends the concept of set cover to network modules cover. We developed two alternative methods to solve the module cover problem: (i) an integrated method that simultaneously determines network modules and optimizes the coverage of disease cases. (ii) a two-step method where we first determined a candidate set of network modules and subsequently selected modules that provided the best coverage of the disease cases. The integrated method showed superior performance in the context of our application. We demonstrated the utility of the module cover approach for the identification of groups of related genes whose activity is perturbed in a coherent way by specific genomic alterations, allowing the interpretation of the heterogeneity of cancer cases.

Original languageEnglish (US)
Pages (from-to)135-146
Number of pages12
JournalPacific Symposium on Biocomputing
StatePublished - Jan 1 2013
Event18th Pacific Symposium on Biocomputing, PSB 2013 - Kohala Coast, United States
Duration: Jan 3 2013Jan 7 2013

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ASJC Scopus subject areas

  • Biomedical Engineering
  • Computational Theory and Mathematics

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