Bayesian graphical models for computational network biology

Yang Ni, Peter Müller, Lin Wei, Yuan Ji

Computational network biology is an emerging interdisciplinary research area. Among many other network approaches, probabilistic graphical models provide a comprehensive probabilistic characterization of interaction patterns between molecules and the associated uncertainties. In this article, we first review graphical models, including directed, undirected, and reciprocal graphs (RG), with an emphasis on the RG models that are curiously under-utilized in biostatistics and bioinformatics literature. RG's strictly contain chain graphs as a special case and are suitable to model reciprocal causality such as feedback mechanism in molecular networks. We then extend the RG approach to modeling molecular networks by integrating DNA-, RNA- and protein-level data. We apply the extended RG method to The Cancer Genome Atlas multi-platform ovarian cancer data and reveal several interesting findings. This study aims to review the basics of different probabilistic graphical models as well as recent development in RG approaches for network modeling. The extension presented in this paper provides a principled and efficient way of integrating DNA copy number, DNA methylation, mRNA gene expression and protein expression.