Toward the dynamic interactome: it's about time
Briefings in BioinformaticsPublished 1 January 2010Open access
Teresa M. Przytycka, Mona Singh, Donna K. Slonim
Citations260
SJR quartileQ1
SJR score2.39
SNIP1.72
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TL;DR
The beginnings of a new subfield within computational biology, one focused on the global inference and analysis of the dynamic interactome, are reviewed, which promises to be a major step forward in the ability to model and reason about cellular function and behavior.
Abstract
Dynamic molecular interactions play a central role in regulating the functioning of cells and organisms. The availability of experimentally determined large-scale cellular networks, along with other high-throughput experimental data sets that provide snapshots of biological systems at different times and conditions, is increasingly helpful in elucidating interaction dynamics. Here we review the beginnings of a new subfield within computational biology, one focused on the global inference and analysis of the dynamic interactome. This burgeoning research area, which entails a shift from static to dynamic network analysis, promises to be a major step forward in our ability to model and reason about cellular function and behavior.
Keywords
Biochemistry, Genetics and Molecular Biology
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NatureLethality and centrality in protein networks
5,398 Citations2001Hawoong Jeong, S. P. Mason +2 more
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NatureA comprehensive analysis of protein–protein interactions in Saccharomyces cerevisiae
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Graphs over time
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PubMedBiclustering of expression data.
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An efficient node-deletion algorithm is introduced to find submatrices in expression data that have low mean squared residue scores and it is shown to perform well in finding co-regulation patterns in yeast and human.
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The procedure identifies modules of coregulated genes, their regulators and the conditions under which regulation occurs, generating testable hypotheses in the form 'regulator X regulates module Y under conditions W'.
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