title: A high-resolution C. elegans essential gene network based on phenotypic profiling of a complex tissue.
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.
authors.affiliation: Ludwig Institute for Cancer Research, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, 92093, USA.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Green
authors.forename: Huey-Ling
authors.initials: HL
authors.lastname: Kao
authors.forename: Anjon
authors.initials: A
authors.lastname: Audhya
authors.forename: Swathi
authors.initials: S
authors.lastname: Arur
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Mayers
authors.forename: Heidi N
authors.initials: HN
authors.lastname: Fridolfsson
authors.forename: Monty
authors.initials: M
authors.lastname: Schulman
authors.forename: Siegfried
authors.initials: S
authors.lastname: Schloissnig
authors.forename: Sherry
authors.initials: S
authors.lastname: Niessen
authors.forename: Kimberley
authors.initials: K
authors.lastname: Laband
authors.forename: Shaohe
authors.initials: S
authors.lastname: Wang
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Starr
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Hyman
authors.forename: Tim
authors.initials: T
authors.lastname: Schedl
authors.forename: Arshad
authors.initials: A
authors.lastname: Desai
authors.forename: Fabio
authors.initials: F
authors.lastname: Piano
authors.forename: Kristin C
authors.initials: KC
authors.lastname: Gunsalus
authors.forename: Karen
authors.initials: K
authors.lastname: Oegema
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D019295:Computational Biology / Q000379:methods*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D055785:Gene Knockdown Techniques; D053263:Gene Regulatory Networks; D005821:Genetic Techniques; D006066:Gonads / Q000196:embryology; D010641:Phenotype