Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Nat Genet. 2008 Feb;40(2):181-8. doi: 10.1038/ng.2007.70. Epub 2008 Jan 27.

A single gene network accurately predicts phenotypic effects of gene perturbation in Caenorhabditis elegans.

Author information

  • 1Center for Systems and Synthetic Biology, Department of Chemistry and Biochemistry, Institute for Cellular and Molecular Biology, University of Texas, 2500 Speedway, MBB 3.210, Austin, Texas 78712, USA.

Abstract

The fundamental aim of genetics is to understand how an organism's phenotype is determined by its genotype, and implicit in this is predicting how changes in DNA sequence alter phenotypes. A single network covering all the genes of an organism might guide such predictions down to the level of individual cells and tissues. To validate this approach, we computationally generated a network covering most C. elegans genes and tested its predictive capacity. Connectivity within this network predicts essentiality, identifying this relationship as an evolutionarily conserved biological principle. Critically, the network makes tissue-specific predictions-we accurately identify genes for most systematically assayed loss-of-function phenotypes, which span diverse cellular and developmental processes. Using the network, we identify 16 genes whose inactivation suppresses defects in the retinoblastoma tumor suppressor pathway, and we successfully predict that the dystrophin complex modulates EGF signaling. We conclude that an analogous network for human genes might be similarly predictive and thus facilitate identification of disease genes and rational therapeutic targets.

PMID:
18223650
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group
    Loading ...
    Write to the Help Desk