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HIT’nDRIVE: Multi-driver Gene Prioritization Based on Hitting Time

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Research in Computational Molecular Biology (RECOMB 2014)

Abstract

A key challenge in cancer genomics is the identification and prioritization of genomic aberrations that potentially act as drivers of cancer. In this paper we introduce HIT’nDRIVE, a combinatorial method to identify aberrant genes that can collectively influence possibly distant “outlier” genes based on what we call the “random-walk facility location” (RWFL) problem on an interaction network. RWFL differs from the standard facility location problem by its use of “multi-hitting time”, the expected minimum number of hops in a random walk originating from any aberrant gene to reach an outlier. HIT’nDRIVE thus aims to find the smallest set of aberrant genes from which one can reach outliers within a desired multi-hitting time. For that it estimates multi-hitting time based on the independent hitting times from the drivers to any given outlier and reduces the RWFL to a weighted multi-set cover problem, which it solves as an integer linear program (ILP). We apply HIT’nDRIVE to identify aberrant genes that potentially act as drivers in a cancer data set and make phenotype predictions using only the potential drivers - more accurately than alternative approaches.

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Shrestha, R. et al. (2014). HIT’nDRIVE: Multi-driver Gene Prioritization Based on Hitting Time. In: Sharan, R. (eds) Research in Computational Molecular Biology. RECOMB 2014. Lecture Notes in Computer Science(), vol 8394. Springer, Cham. https://doi.org/10.1007/978-3-319-05269-4_23

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  • DOI: https://doi.org/10.1007/978-3-319-05269-4_23

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-05268-7

  • Online ISBN: 978-3-319-05269-4

  • eBook Packages: Computer ScienceComputer Science (R0)

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