Learning global transcriptional dynamics with the Inferelator and cMonkey
Speaker: Richard Bonneau
Authors: David Reiss, Vesteinn Thorsson, Nitin Baliga, Aviv Madar, Peter Waltman, Thadeous Kacmarczyk, Richard Bonneau
Our system for network inference and modeling consists of two major components: cMonkey (a method for learning co-regulated biclusters and pathways), the Inferelator (regulatory network inference). We describe their integration into a functioning integrated system applied to several prokaryotic organisms.
cMonkey: We have developed an integrative biclustering algorithm, cMonkey, which groups genes and conditions into biclusters on the basis of 1) coherence in expression data across subsets of experimental conditions, 2) co-occurrence of putative cis-acting regulatory motifs in the regulatory regions of bicluster members and 3) the presence of highly connected sub-graphs in metabolic and functional association networks. We describe the algorithm and the results of extensive tests of several previously described methods, showing that cMonkey has several advantages in the context of regulatory network inference.
The Inferelator: We have described a network inference algorithm, the Inferelator, which infers regulatory influences for genes and/or gene clusters from mRNA and/or protein expression levels. The procedure can simultaneously model equilibrium and time-course expression levels, such that both kinetic and equilibrium expression levels may be predicted by the resulting models. Through the explicit inclusion of time, and gene-knockout information, the method is capable of learning causal relationships. It also includes a novel solution to the problem of encoding interactions between predictors. We discuss the results from an initial application of this method to the halophilic archaeon, Halobacterium NRC-1. We have found the network to be predictive of 130 newly collected microarray datasets and have also validated parts of the network using ChIP-chip. This network offers a means of deciphering how this organism maintains homeostasis and responds to wide varieties of metabolic, genetic and environmental states.
For Background on our integrated system see:
http://genomebiology.com/2006/7/5/R36
http://www.biomedcentral.com/1471-2105/7/280
http://www.biomedcentral.com/1471-2105/7/176