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Public Library of Science, PLoS Computational Biology, 6(13), p. e1005573, 2017

DOI: 10.1371/journal.pcbi.1005573

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NetNorM: capturing cancer-relevant information in somatic exome mutation data with gene networks for cancer stratification and prognosis

Journal article published in 2016 by Marine Le Morvan ORCID, Andrei Zinovyev ORCID, Jean-Philippe Vert ORCID
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Postprint: archiving allowed
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Data provided by SHERPA/RoMEO

Abstract

Genome-wide somatic mutation profiles of tumours can now be assessed efficiently and promise to move precision medicine forward. Statistical analysis of mutation profiles is however challenging due to the low frequency of most mutations, the varying mutation rates across tumours , and the presence of a majority of passenger events that hide the contribution of driver events. Here we propose a method, NetNorM, to represent whole-exome somatic mutation data in a form that enhances cancer-relevant information using a gene network as background knowledge. We evaluate its relevance for two tasks: survival prediction and unsupervised patient stratification. Using data from 8 cancer types from The Cancer Genome Atlas (TCGA), we show that it improves over the raw binary mutation data and network diffusion for these two tasks. In doing so, we also provide a thorough assessment of somatic mutations prognostic power which has been overlooked by previous studies because of the sparse and binary nature of mutations.