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A high-resolution C. elegans essential gene network based on phenotypic profiling of a complex tissue.

Cell | Apr 29, 2011

http://www.ncbi.nlm.nih.gov/pubmed/21529718

High-content screening for gene profiling has generally been limited to single cells. Here, we explore an alternative approach-profiling gene function by analyzing effects of gene knockdowns on the architecture of a complex tissue in a multicellular organism. We profile 554 essential C. elegans genes by imaging gonad architecture and scoring 94 phenotypic features. To generate a reference for evaluating methods for network construction, genes were manually partitioned into 102 phenotypic classes, predicting functions for uncharacterized genes across diverse cellular processes. Using this classification as a benchmark, we developed a robust computational method for constructing gene networks from high-content profiles based on a network context-dependent measure that ranks the significance of links between genes. Our analysis reveals that multi-parametric profiling in a complex tissue yields functional maps with a resolution similar to genetic interaction-based profiling in unicellular eukaryotes-pinpointing subunits of macromolecular complexes and components functioning in common cellular processes.

Pubmed ID: 21529718 RIS Download

Mesh terms: Animals | Caenorhabditis elegans | Computational Biology | Embryo, Nonmammalian | Gene Knockdown Techniques | Gene Regulatory Networks | Genetic Techniques | Gonads | Phenotype

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Associated grants

  • Agency: NIGMS NIH HHS, Id: R01 GM073874
  • Agency: NIGMS NIH HHS, Id: R01 GM074207
  • Agency: NIGMS NIH HHS, Id: R01 GM074207
  • Agency: NIGMS NIH HHS, Id: R01 GM074207-05
  • Agency: NIGMS NIH HHS, Id: R01 GM085150
  • Agency: NIGMS NIH HHS, Id: R01 GM085150
  • Agency: NIGMS NIH HHS, Id: R01 GM085150-04
  • Agency: NIGMS NIH HHS, Id: R01 GM085503
  • Agency: NIGMS NIH HHS, Id: R01 GM085503
  • Agency: NIGMS NIH HHS, Id: R01 GM085503-04
  • Agency: NIGMS NIH HHS, Id: R01 GM088151
  • Agency: NIGMS NIH HHS, Id: R01 GM088151
  • Agency: NIGMS NIH HHS, Id: R01 GM088151-02
  • Agency: NICHD NIH HHS, Id: R01 HD046236
  • Agency: NICHD NIH HHS, Id: R01 HD046236
  • Agency: NICHD NIH HHS, Id: R01 HD046236-09

WormBase (Data, Gene Expression)

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