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

Rebecca A. Green, Huey Ling Kao, Anjon Audhya, Swathi Arur, Jonathan R. Mayers, Heidi N. Fridolfsson, Monty Schulman, Siegfried Schloissnig, Sherry Niessen, Kimberley Laband, Shaohe Wang, Daniel A. Starr, Anthony A. Hyman, Tim Schedl, Arshad Desai, Fabio Piano, Kristin C. Gunsalus, Karen Oegema

Research output: Contribution to journalArticle

Abstract

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. PaperFlick:

Original languageEnglish (US)
Pages (from-to)470-482
Number of pages13
JournalCell
Volume145
Issue number3
DOIs
StatePublished - Apr 29 2011

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Gene Regulatory Networks
Essential Genes
Genes
Tissue
Gene Knockdown Techniques
Macromolecular Substances
Benchmarking
Gonads
Eukaryota
Computational methods
Screening
Imaging techniques

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Green, R. A., Kao, H. L., Audhya, A., Arur, S., Mayers, J. R., Fridolfsson, H. N., ... Oegema, K. (2011). A high-resolution C. elegans essential gene network based on phenotypic profiling of a complex tissue. Cell, 145(3), 470-482. https://doi.org/10.1016/j.cell.2011.03.037

A high-resolution C. elegans essential gene network based on phenotypic profiling of a complex tissue. / Green, Rebecca A.; Kao, Huey Ling; Audhya, Anjon; Arur, Swathi; Mayers, Jonathan R.; Fridolfsson, Heidi N.; Schulman, Monty; Schloissnig, Siegfried; Niessen, Sherry; Laband, Kimberley; Wang, Shaohe; Starr, Daniel A.; Hyman, Anthony A.; Schedl, Tim; Desai, Arshad; Piano, Fabio; Gunsalus, Kristin C.; Oegema, Karen.

In: Cell, Vol. 145, No. 3, 29.04.2011, p. 470-482.

Research output: Contribution to journalArticle

Green, RA, Kao, HL, Audhya, A, Arur, S, Mayers, JR, Fridolfsson, HN, Schulman, M, Schloissnig, S, Niessen, S, Laband, K, Wang, S, Starr, DA, Hyman, AA, Schedl, T, Desai, A, Piano, F, Gunsalus, KC & Oegema, K 2011, 'A high-resolution C. elegans essential gene network based on phenotypic profiling of a complex tissue', Cell, vol. 145, no. 3, pp. 470-482. https://doi.org/10.1016/j.cell.2011.03.037
Green RA, Kao HL, Audhya A, Arur S, Mayers JR, Fridolfsson HN et al. A high-resolution C. elegans essential gene network based on phenotypic profiling of a complex tissue. Cell. 2011 Apr 29;145(3):470-482. https://doi.org/10.1016/j.cell.2011.03.037
Green, Rebecca A. ; Kao, Huey Ling ; Audhya, Anjon ; Arur, Swathi ; Mayers, Jonathan R. ; Fridolfsson, Heidi N. ; Schulman, Monty ; Schloissnig, Siegfried ; Niessen, Sherry ; Laband, Kimberley ; Wang, Shaohe ; Starr, Daniel A. ; Hyman, Anthony A. ; Schedl, Tim ; Desai, Arshad ; Piano, Fabio ; Gunsalus, Kristin C. ; Oegema, Karen. / A high-resolution C. elegans essential gene network based on phenotypic profiling of a complex tissue. In: Cell. 2011 ; Vol. 145, No. 3. pp. 470-482.
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