Network legos: building blocks of cellular wiring diagrams

Journal of Computational Biology : a Journal of Computational Molecular Cell Biology
T M Murali, Corban G Rivera

Abstract

Publicly available datasets provide detailed and large-scale information on multiple types of molecular interaction networks in a number of model organisms. The wiring diagrams composed of these interaction networks capture a static view of cellular state. An important challenge in systems biology is obtaining a dynamic perspective on these networks by integrating them with gene expression measurements taken under multiple conditions. We present a top-down computational approach to identify building blocks of molecular interaction networks by: (i) integrating gene expression measurements for a particular disease state (e.g., leukemia) or experimental condition (e.g., treatment with growth serum) with molecular interactions to reveal an active network, which is the network of interactions active in the cell in that disease state or condition; and (ii) systematically combining active networks computed for different experimental conditions using set-theoretic formulae to reveal network legos, which are modules of coherently interacting genes and gene products in the wiring diagram. We propose efficient methods to compute active networks, systematically mine candidate legos, assess the statistical significance of these candidates, ...Continue Reading

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Citations

Jul 19, 2013·Annual Review of Biomedical Engineering·Padmavathy RajagopalanT M Murali
Jan 20, 2011·PloS One·Christopher D LasherT M Murali
Sep 25, 2010·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Rod K NibbeMark R Chance

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