A Local Poisson Graphical Model for Inferring Networks From Sequencing Data

Gaussian graphical models, a class of undirected graphs or Markov Networks, are often used to infer gene networks based on microarray expression data. Many scientists, however, have begun using high-throughput sequencing technologies such as RNA-sequencing or next generation sequencing to measure gene expression. As the resulting data consists of counts of sequencing reads for each gene, Gaussian graphical models are not optimal for this discrete data. In this paper, we propose a novel method for inferring gene networks from sequencing data: the Local Poisson Graphical Model. Our model assumes a Local Markov property where each variable conditional on all other variables is Poisson distributed. We develop a neighborhood selection algorithm to fit our model locally by performing a series of l₁ penalized Poisson, or log-linear, regressions. This yields a fast parallel algorithm for estimating networks from next generation sequencing data. In simulations, we illustrate the effectiveness of our methods for recovering network structure from count data. A case study on breast cancer microRNAs (miRNAs), a novel application of graphical models, finds known regulators of breast cancer genes and discovers novel miRNA clusters and hubs that are targets for future research.