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

Nat Genet. 2008 Feb;40(2):181-8. doi: 10.1038/ng.2007.70. Epub 2008 Jan 27.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bayes Theorem
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / metabolism
  • Computational Biology / methods
  • Databases, Genetic
  • Dystrophin-Associated Protein Complex / genetics
  • Epidermal Growth Factor / metabolism
  • Female
  • Gene Expression Regulation, Developmental
  • Gene Regulatory Networks / genetics*
  • Genes, Helminth*
  • Genes, ras
  • Genetic Linkage
  • Helminth Proteins / genetics
  • Likelihood Functions
  • Mitogen-Activated Protein Kinases / metabolism
  • Models, Biological
  • Models, Genetic
  • Phenotype*
  • Predictive Value of Tests
  • Probability
  • Proteome / genetics
  • RNA Interference
  • RNA, Helminth / genetics
  • RNA, Messenger / metabolism
  • ROC Curve
  • Repressor Proteins / genetics
  • Reproducibility of Results
  • Retinoblastoma Protein / antagonists & inhibitors
  • Retinoblastoma Protein / genetics
  • Signal Transduction
  • Vulva / growth & development


  • Dystrophin-Associated Protein Complex
  • Helminth Proteins
  • Proteome
  • RNA, Helminth
  • RNA, Messenger
  • Repressor Proteins
  • Retinoblastoma Protein
  • Epidermal Growth Factor
  • Mitogen-Activated Protein Kinases