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A DNA methylation network interaction measure, and detection of network oncomarkers

Bartlett, TE; Olhede, SC; Zaikin, A; (2014) A DNA methylation network interaction measure, and detection of network oncomarkers. PLoS One , 9 (1) , Article e84573. 10.1371/journal.pone.0084573. Green open access

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Abstract

Epigenetic processes-including DNA methylation-are increasingly seen as having a fundamental role in chronic diseases like cancer. DNA methylation patterns offer a route to develop prognostic measures based directly on DNA measurements, rather than less-stable RNA measurements. A novel DNA methylation-based measure of the co-ordinated interactive behaviour of genes is developed, in a network context. It is shown that this measure reflects well the co-regulatory behaviour linked to gene expression (at the mRNA level) over the same network interactions. This measure, defined for pairs of genes in a single patient/sample, associates with overall survival outcome independent of known prognostic clinical features, in several independent data sets relating to different cancer types. In total, more than half a billion CpGs in over 1600 samples, taken from nine different cancer entities, are analysed. It is found that groups of gene-pair interactions which associate significantly with survival identify statistically significant subnetwork modules. Many of these subnetwork modules are shown to be biologically relevant by strong correlation with pre-defined gene sets, such as immune function, wound healing, mitochondrial function and MAP-kinase signalling. In particular, the wound healing module corresponds to an increase in co-ordinated interactive behaviour between genes for worse prognosis, and the immune module corresponds to a decrease in co-ordinated interactive behaviour between genes for worse prognosis. This measure has great potential for defining DNA-based cancer biomarkers. Such biomarkers could naturally be developed further, by drawing on the rapidly expanding knowledge base of network science.

Type: Article
Title: A DNA methylation network interaction measure, and detection of network oncomarkers
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0084573
Publisher version: http://dx.doi.org/10.1371/journal.pone.0084573
Language: English
Additional information: © 2014 Bartlett et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. PMCID: PMC3882261
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Mathematics
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Statistical Science
URI: http://discovery.ucl.ac.uk/id/eprint/1417662
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