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SSA-ME Detection of cancer driver genes using mutual exclusivity by small subnetwork analysis

Sergio Pulido Tamayo (UGent) , Bram Weytjens (UGent) , Dries De Maeyer (UGent) and Kathleen Marchal (UGent)
Author
Organization
Project
Bioinformatics: from nucleotids to networks (N2N)
Abstract
Because of its clonal evolution a tumor rarely contains multiple genomic alterations in the same pathway as disrupting the pathway by one gene often is sufficient to confer the complete fitness advantage. As a result, many cancer driver genes display mutual exclusivity across tumors. However, searching for mutually exclusive gene sets requires analyzing all possible combinations of genes, leading to a problem which is typically too computationally complex to be solved without a stringent a priori filtering, restricting the mutations included in the analysis. To overcome this problem, we present SSA-ME, a network-based method to detect cancer driver genes based on independently scoring small subnetworks for mutual exclusivity using a reinforced learning approach. Because of the algorithmic efficiency, no stringent upfront filtering is required. Analysis of TCGA cancer datasets illustrates the added value of SSA-ME: well-known recurrently mutated but also rarely mutated drivers are prioritized. We show that using mutual exclusivity to detect cancer driver genes is complementary to state-of-the art approaches. This framework, in which a large number of small subnetworks are being analyzed in order to solve a computationally complex problem (SSA), can be generically applied to any problem in which local neighborhoods in a network hold useful information.
Keywords
IBCN, MUTATIONS, LUNG-CANCER, PATHWAYS, NETWORK, COMBINATIONS, EXPRESSION, SIGNATURES, DISCOVERY, PATTERNS, SERVER

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Citation

Please use this url to cite or link to this publication:

Chicago
Pulido Tamayo, Sergio, Bram Weytjens, Dries De Maeyer, and Kathleen Marchal. 2016. “SSA-ME Detection of Cancer Driver Genes Using Mutual Exclusivity by Small Subnetwork Analysis.” Scientific Reports 6.
APA
Pulido Tamayo, S., Weytjens, B., De Maeyer, D., & Marchal, K. (2016). SSA-ME Detection of cancer driver genes using mutual exclusivity by small subnetwork analysis. SCIENTIFIC REPORTS, 6.
Vancouver
1.
Pulido Tamayo S, Weytjens B, De Maeyer D, Marchal K. SSA-ME Detection of cancer driver genes using mutual exclusivity by small subnetwork analysis. SCIENTIFIC REPORTS. 2016;6.
MLA
Pulido Tamayo, Sergio, Bram Weytjens, Dries De Maeyer, et al. “SSA-ME Detection of Cancer Driver Genes Using Mutual Exclusivity by Small Subnetwork Analysis.” SCIENTIFIC REPORTS 6 (2016): n. pag. Print.
@article{8173862,
  abstract     = {Because of its clonal evolution a tumor rarely contains multiple genomic alterations in the same pathway as disrupting the pathway by one gene often is sufficient to confer the complete fitness advantage. As a result, many cancer driver genes display mutual exclusivity across tumors. However, searching for mutually exclusive gene sets requires analyzing all possible combinations of genes, leading to a problem which is typically too computationally complex to be solved without a stringent a priori filtering, restricting the mutations included in the analysis. To overcome this problem, we present SSA-ME, a network-based method to detect cancer driver genes based on independently scoring small subnetworks for mutual exclusivity using a reinforced learning approach. Because of the algorithmic efficiency, no stringent upfront filtering is required. Analysis of TCGA cancer datasets illustrates the added value of SSA-ME: well-known recurrently mutated but also rarely mutated drivers are prioritized. We show that using mutual exclusivity to detect cancer driver genes is complementary to state-of-the art approaches. This framework, in which a large number of small subnetworks are being analyzed in order to solve a computationally complex problem (SSA), can be generically applied to any problem in which local neighborhoods in a network hold useful information.},
  articleno    = {36257},
  author       = {Pulido Tamayo, Sergio and Weytjens, Bram and De Maeyer, Dries and Marchal, Kathleen},
  issn         = {2045-2322},
  journal      = {SCIENTIFIC REPORTS},
  keyword      = {IBCN,MUTATIONS,LUNG-CANCER,PATHWAYS,NETWORK,COMBINATIONS,EXPRESSION,SIGNATURES,DISCOVERY,PATTERNS,SERVER},
  language     = {eng},
  pages        = {12},
  title        = {SSA-ME Detection of cancer driver genes using mutual exclusivity by small subnetwork analysis},
  url          = {http://dx.doi.org/10.1038/srep36257},
  volume       = {6},
  year         = {2016},
}

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