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Bayesian analysis of signaling networks governing embryonic stem cell fate decisions.

Publication ,  Journal Article
Woolf, PJ; Prudhomme, W; Daheron, L; Daley, GQ; Lauffenburger, DA
Published in: Bioinformatics
March 2005

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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Published In

Bioinformatics

DOI

ISSN

1367-4803

Publication Date

March 2005

Volume

21

Issue

6

Start / End Page

741 / 753

Location

England

Related Subject Headings

  • Transcription Factors
  • Stem Cells
  • Signal Transduction
  • Proteome
  • Models, Statistical
  • Models, Biological
  • Mice
  • Gene Expression Regulation
  • Gene Expression Profiling
  • Computer Simulation
 

Citation

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Woolf, P. J., Prudhomme, W., Daheron, L., Daley, G. Q., & Lauffenburger, D. A. (2005). Bayesian analysis of signaling networks governing embryonic stem cell fate decisions. Bioinformatics, 21(6), 741–753. https://doi.org/10.1093/bioinformatics/bti056
Woolf, Peter J., Wendy Prudhomme, Laurence Daheron, George Q. Daley, and Douglas A. Lauffenburger. “Bayesian analysis of signaling networks governing embryonic stem cell fate decisions.Bioinformatics 21, no. 6 (March 2005): 741–53. https://doi.org/10.1093/bioinformatics/bti056.
Woolf PJ, Prudhomme W, Daheron L, Daley GQ, Lauffenburger DA. Bayesian analysis of signaling networks governing embryonic stem cell fate decisions. Bioinformatics. 2005 Mar;21(6):741–53.
Woolf, Peter J., et al. “Bayesian analysis of signaling networks governing embryonic stem cell fate decisions.Bioinformatics, vol. 21, no. 6, Mar. 2005, pp. 741–53. Pubmed, doi:10.1093/bioinformatics/bti056.
Woolf PJ, Prudhomme W, Daheron L, Daley GQ, Lauffenburger DA. Bayesian analysis of signaling networks governing embryonic stem cell fate decisions. Bioinformatics. 2005 Mar;21(6):741–753.
Journal cover image

Published In

Bioinformatics

DOI

ISSN

1367-4803

Publication Date

March 2005

Volume

21

Issue

6

Start / End Page

741 / 753

Location

England

Related Subject Headings

  • Transcription Factors
  • Stem Cells
  • Signal Transduction
  • Proteome
  • Models, Statistical
  • Models, Biological
  • Mice
  • Gene Expression Regulation
  • Gene Expression Profiling
  • Computer Simulation