Inferring Subnetworks from Perturbed Expression Profiles

Dana Pe'er

Aviv Regev

Gal Elidan

Nir Friedman

International Conference on Intelligent Systems for Molecular Biology 2001


Genome-wide expression profiles of genetic mutants provide a wide variety of measurements of cellular responses to perturbations. Typical analysis of such data identifies genes affected by perturbation and uses clustering to group genes of similar function. In this paper we discover a finer structure of interactions between genes, such as causality, mediation, activation, and inhibition by using a Bayesian network framework. We extend this framework to correctly handle perturbations, and to identify significant subnetworks of interacting genes. We apply this method to expression data of S.~cerevisiae mutants and uncover a variety of structured metabolic, signaling and regulatory pathways.

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We applied our methodology to Rosetta Inpharmatics Compendium Dataset ( Hughes et. al. Cell 2000 ). The annotated results can be interactively viewed using Pathway Explorer We stress that no prior biological knowledge was used by our learning procedure when reconstructing the networks.