Inferring Signaling Pathway Topologies from Multiple Perturbation Measurements of Specific Biochemical Species

Science Signaling  16 Mar 2010:
Vol. 3, Issue 113, pp. ra20
DOI: 10.1126/scisignal.2000517

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Picking the Right Path

Signaling networks have become increasingly complex as large-scale analysis and experiments in multiple systems add new potential connections and players. Xu et al. present a mathematical approach to rank the possible paths through a signaling pathway and develop hypotheses that can be rationally tested. They call their approach BIBm for Bayesian inference–based modeling and apply BIBm to explore the signaling pathways by which epidermal growth factor (EGF) stimulates extracellular signal–regulated kinase (ERK). Using a limited set of biochemical experiments, the authors tested four models and found that the one that relied on two Raf family members ranked the highest. This model was then experimentally validated in two cell lines to show that both Raf-1 and B-Raf contribute to ERK activation in response to EGF.

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