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The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
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Phosphoproteomic Strategy for Profiling Osmotic Stress Signaling in Arabidopsis
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Synthesizing Signaling Pathways from Temporal Phosphoproteomic Data.

Ali Sinan Köksal1, Kirsten Beck2, Dylan R Cronin3

  • 1Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, Berkeley, CA, USA.

Cell Reports
|September 27, 2018
PubMed
Summary
This summary is machine-generated.

We developed a new algorithm, Temporal Pathway Synthesizer (TPS), to automatically discover cell signaling pathways using time-resolved phosphoproteomic data without protein perturbation. This method identifies novel pathway members and reconstructs known signaling cascades.

Keywords:
mass spectrometrynetwork algorithmprogram synthesisprotein-protein interactionstime series phosphorylation

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Area of Science:

  • Systems Biology
  • Computational Biology
  • Molecular Signaling

Background:

  • Understanding cell signaling pathways is crucial for deciphering cellular responses.
  • Traditional methods often require extensive experimental perturbations.
  • Time-resolved phosphoproteomic data offers a rich source for inferring dynamic pathway information.

Purpose of the Study:

  • To present an automated method for discovering signaling pathways from time-resolved phosphoproteomic data.
  • To develop an algorithm capable of identifying pathway members and reconstructing signaling cascades without direct experimental manipulation of proteins.

Main Methods:

  • The Temporal Pathway Synthesizer (TPS) algorithm was developed, employing constraint-solving techniques from formal verification.
  • TPS systematically analyzes temporal phosphoproteomic data to eliminate invalid pathway structures.
  • The algorithm models over 100,000 dynamic phosphosites and identifies non-differentially phosphorylated pathway members.

Main Results:

  • TPS successfully recovers known signaling pathways, including those involved in human epidermal growth factor and yeast osmotic stress responses.
  • The algorithm proposes novel pathway connections and identifies potential pathway members not detected by differential phosphorylation analysis.
  • Independent validation using kinase mutant studies confirmed predicted substrates in the yeast osmotic stress pathway.

Conclusions:

  • The Temporal Pathway Synthesizer (TPS) provides an effective computational approach for automated signaling pathway discovery.
  • TPS leverages temporal phosphoproteomic data to reconstruct signaling cascades, reducing the need for protein perturbation experiments.
  • This method advances systems biology by enabling more comprehensive and efficient pathway inference.