Oncotarget

Research Papers:

Identification of driver modules in pan-cancer via coordinating coverage and exclusivity

Bo Gao, Guojun Li _, Juntao Liu, Yang Li and Xiuzhen Huang

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Oncotarget. 2017; 8:36115-36126. https://doi.org/10.18632/oncotarget.16433

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Abstract

Bo Gao1,2,*, Guojun Li1,2,*, Juntao Liu1, Yang Li1, Xiuzhen Huang2,3

1School of Mathematics, Shandong University, Jinan, Shandong, 250100, China

2Department of Computer Science, Arkansas State University, Jonesboro, Arkansas, 72401, USA

3Molecular Biosciences Program, Arkansas State University, Jonesboro, Arkansas, 72401, USA

*These authors contributed equally to this work

Correspondence to:

Guojun Li, email: guojunsdu@gmail.com

Xiuzhen Huang, email: xhuang@astate.edu

Keywords: pan-cancer, coverage, exclusivity, driver gene, network module

Received: February 04, 2017     Accepted: March 13, 2017     Published: March 21, 2017

ABSTRACT

It is widely accepted that cancer is driven by accumulated somatic mutations during the lifetime of an individual. Cancer mutations may target relatively small number of cell functional modules. The heterogeneity in different cancer patients makes it difficult to identify driver mutations or functional modules related to cancer. It is biologically desired to be capable of identifying cancer pathway modules through coordination between coverage and exclusivity. There have been a few approaches developed for this purpose, but they all have limitations in practice due to their computational complexity and prediction accuracy. We present a network based approach, CovEx, to predict the specific patient oriented modules by 1) discovering candidate modules for each considered gene, 2) extracting significant candidates by harmonizing coverage and exclusivity and, 3) further selecting the patient oriented modules based on a set cover model. Applying CovEx to pan-cancer datasets spanning 12 cancer types collecting from public database TCGA, it demonstrates significant superiority over the current leading competitors in performance. It is published under GNU GENERAL PUBLIC LICENSE and the source code is available at: https://sourceforge.net/projects/cancer-pathway/files/.


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