Inferring time-varying network topologies from gene expression data

Authors:
Arvind Rao;Alfred O. Hero, III;David J. States;James Douglas Engel
Affiliations:
Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, MI and Bioinformatics Graduate Program, Center for Computational Medicine and Biology, School of Medic ...;Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, MI and Bioinformatics Graduate Program, Center for Computational Medicine and Biology, School of Medic ...;Bioinformatics Graduate Program, Center for Computational Medicine and Biology, School of Medicine, University of Michigan, Ann Arbor, MI and Department of Human Genetics, School of Medicine, Univ ...;Department of Cell and Developmental Biology, School of Medicine, University of Michigan, Ann Arbor, MI
Venue:
EURASIP Journal on Bioinformatics and Systems Biology
Year:
2007

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Abstract

Most current methods for gene regulatory network identification lead to the inference of steady-state networks, that is, networks prevalent over all times, a hypothesis which has been challenged. There has been a need to infer and represent networks in a dynamic, that is, time-varying fashion, in order to account for different cellular states affecting the interactions amongst genes. In this work, we present an approach, regime-SSM, to understand gene regulatory networks within such a dynamic setting. The approach uses a clustering method based on these underlying dynamics, followed by system identification using a state-space model for each learnt cluster--to infer a network adjacency matrix. We finally indicate our results on the mouse embryonic kidney dataset as well as the T-cell activation-based expression dataset and demonstrate conformity with reported experimental evidence.