Maximum entropy reconstructions of dynamic signaling networks from quantitative proteomics data.

Published online

Journal Article

Advances in mass spectrometry among other technologies have allowed for quantitative, reproducible, proteome-wide measurements of levels of phosphorylation as signals propagate through complex networks in response to external stimuli under different conditions. However, computational approaches to infer elements of the signaling network strictly from the quantitative aspects of proteomics data are not well established. We considered a method using the principle of maximum entropy to infer a network of interacting phosphotyrosine sites from pairwise correlations in a mass spectrometry data set and derive a phosphorylation-dependent interaction network solely from quantitative proteomics data. We first investigated the applicability of this approach by using a simulation of a model biochemical signaling network whose dynamics are governed by a large set of coupled differential equations. We found that in a simulated signaling system, the method detects interactions with significant accuracy. We then analyzed a growth factor mediated signaling network in a human mammary epithelial cell line that we inferred from mass spectrometry data and observe a biologically interpretable, small-world structure of signaling nodes, as well as a catalog of predictions regarding the interactions among previously uncharacterized phosphotyrosine sites. For example, the calculation places a recently identified tumor suppressor pathway through ARHGEF7 and Scribble, in the context of growth factor signaling. Our findings suggest that maximum entropy derived network models are an important tool for interpreting quantitative proteomics data.

Full Text

Duke Authors

Cited Authors

  • Locasale, JW; Wolf-Yadlin, A

Published Date

  • August 26, 2009

Published In

Volume / Issue

  • 4 / 8

Start / End Page

  • e6522 -

PubMed ID

  • 19707567

Pubmed Central ID

  • 19707567

Electronic International Standard Serial Number (EISSN)

  • 1932-6203

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0006522

Language

  • eng

Conference Location

  • United States