Toward accurate reconstruction of functional protein networks
Open Access
- 1 January 2009
- journal article
- Published by Springer Science and Business Media LLC in Molecular Systems Biology
- Vol. 5 (1), 248
- https://doi.org/10.1038/msb.2009.3
Abstract
Genome‐scale screening studies are gradually accumulating a wealth of data on the putative involvement of hundreds of genes/proteins in various cellular responses or functions. A fundamental challenge is to chart out the protein pathways that underlie these systems. Previous approaches to the problem have either employed a local optimization criterion, aiming to infer each pathway independently, or a global criterion, searching for the overall most parsimonious subnetwork. Here, we study the trade‐off between the two approaches and present a new intermediary scheme that provides explicit control over it. We demonstrate its utility in the analysis of the apoptosis network in humans, and the telomere length maintenance (TLM) system in yeast. Our results show that in the majority of real‐life cases, the intermediary approach provides the most plausible solutions. We use a new set of perturbation experiments measuring the role of essential genes in telomere length regulation to further study the TLM network. Surprisingly, we find that the proteasome plays an important role in telomere length regulation through its associations with transcription and DNA repair circuits.This publication has 43 references indexed in Scilit:
- A systems‐level approach to mapping the telomere length maintenance gene circuitryMolecular Systems Biology, 2008
- Network‐based classification of breast cancer metastasisMolecular Systems Biology, 2007
- Large‐scale mapping of human protein–protein interactions by mass spectrometryMolecular Systems Biology, 2007
- Global landscape of protein complexes in the yeast Saccharomyces cerevisiaeNature, 2006
- Proteome survey reveals modularity of the yeast cell machineryNature, 2006
- Exploration of the Function and Organization of the Yeast Early Secretory Pathway through an Epistatic Miniarray ProfileCell, 2005
- Towards a proteome-scale map of the human protein–protein interaction networkNature, 2005
- Conserved patterns of protein interaction in multiple speciesProceedings of the National Academy of Sciences of the United States of America, 2005
- Development of Human Protein Reference Database as an Initial Platform for Approaching Systems Biology in HumansGenome Research, 2003
- Structure of 20S proteasome from yeast at 2.4Å resolutionNature, 1997