Constructing a Cancer Patient-Specific Network Based on Second-Order Partial Correlations of Gene Expression and DNA Methylation.

Abstract

Typically patient-specific gene networks are constructed with gene expression data only. Such networks cannot distinguish direct gene interactions from indirect interactions via others such as the effect of epigenetic events to gene activity. There is an increasing evidence of inter-individual variations not only in gene expression but also in epigenetic events such as DNA methylation. In this paper we propose a new method for constructing a cancer patient-specific gene correlation network using both gene expression and DNA methylation data. We derive a patient-specific network from differential second-order partial correlations of gene expression and DNA methylation between normal samples and the patient sample. The network represents direct interactions between genes by controlling the effect of DNA methylation. Using this method, we constructed 4,000 patient-specific networks for 10 types of cancer. The networks are highly effective in classifying different types of cancer and in deriving potential prognostic gene pairs. In particular, potential prognostic gene pairs derived from the networks were powerful in predicting the survival time of cancer patients. This approach will help identify patient-specific gene correlations and predict prognosis of cancer patients.