Inferring functional relationships and causal network structure from gene expression profiles

Inferring functional relationships and network structure from the observed gene expression profiles can provide a novel insight into the working of the genes as a system or network as opposed to independent entities. Such networks may also represent possible causal relationships between a given set of genes, hence can prove to be a convenient abstraction of the underlying signaling mechanism. The discovery of functional relationships from the observed gene expression profiles does not rely on prior literature, hence useful in identifying undocumented relationships between a given set of genes. Several techniques have been proposed in the literature. The present study investigates the choice Granger causality (GC) and its extensions in modeling the network structure between a given pair of genes from their expression profiles. The impact of noise variance on GC relationships is investigated. VAR parameter estimation is proposed to obtain a finer insight into the functional relationships inferred using GC tests. The results are presented on synthetic networks generated from known vector-autoregressive (VAR) models and those from cell-cycle gene expression profiles that can be modeled as a first-order bivariate VAR.