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| Bayesian analysis of signaling networks governing embryonic stem cell fate decisions |
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| Author(s): Woolf PJ, Prudhomme W, Daheron L, Daley GQ, Lauffenburger DA |
| Source: BIOINFORMATICS Volume: 21 Issue: 6 Pages: 741-753 Published: MAR 15 2005 |
| Times Cited: 38 References: 56 |
| Abstract: Motivation: Signaling events that direct mouse embryonic stem (ES) cell self-renewal and differentiation are complex and accordingly difficult to understand in an integrated manner. We address this problem by adapting a Bayesian network learning algorithm to model proteomic signaling data for ES cell fate responses to external cues. Using this model we were able to characterize the signaling pathway influences as quantitative, logic-circuit type interactions. Our experimental dataset includes measurements for 28 signaling protein phosphorylation states across 16 different factorial combinations of cytokine and matrix stimuli as reported previously. Results: The Bayesian network modeling approach allows us to uncover previously reported signaling activities related to mouse ES cell self-renewal, such as the roles of LIF and STAT3 in maintaining undifferentiated ES cell populations. Furthermore, the network predicts novel influences such as between ERK phosphorylation and differentiation, or RAF phosphorylation and differentiated cell proliferation. Visualization of the influences detected by the Bayesian network provides intuition about the underlying physiology of the signaling pathways. We demonstrate that the Bayesian networks can capture the linear, nonlinear and multistate logic interactions that connect extracellular cues, intracellular signals and consequent cell functional responses.
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| Document Type: Article |
| Language: English |
| Reprint Address: Woolf, PJ (reprint author), Univ Michigan, Dept Chem Engn, Room 3320,GG Brown Bldg,2300 Hayward St, Ann Arbor, MI 48109 USA |
Addresses:
1. Univ Michigan, Dept Chem Engn, Ann Arbor, MI 48109 USA 2. Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA 3. MIT, Biol Engn Div, Cambridge, MA 02139 USA 4. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA |
| Publisher: OXFORD UNIV PRESS, GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND |
| Subject Category: Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability |
| IDS Number: 905IQ |
| ISSN: 1367-4803 |
| DOI: 10.1093/bioinformatics/bti056 |
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