From Coexpression to Coregulation: An Approach to Inferring Transcriptional Regulation among Gene Classes from Large-Scale Expression Data

Abstract

We provide preliminary evidence that existing algorithms for inferring small-scale gene regulation networks from gene expression data can be adapted to large-scale gene expression data coming from hybridization microarrays. The essential steps are (1) clustering many genes by their expression time-course data into a minimal set of clusters of co-expressed genes, (2) theoretically modeling the various conditions under which the time-courses are measured using a continious-time analog recurrent neural network for the cluster mean time-courses, (3) fitting such a regulatory model to the cluster mean time courses by simulated annealing with weight decay, and (4) analysing several such fits for commonalities in the circuit parameter sets including the connection matrices. This procedure can be used to assess the adequacy of existing and future gene expression time-course data sets for determining transcriptional regulatory relationships such as coregulation.