TY - JOUR
T1 - A high-resolution C. elegans essential gene network based on phenotypic profiling of a complex tissue
AU - Green, Rebecca A.
AU - Kao, Huey Ling
AU - Audhya, Anjon
AU - Arur, Swathi
AU - Mayers, Jonathan R.
AU - Fridolfsson, Heidi N.
AU - Schulman, Monty
AU - Schloissnig, Siegfried
AU - Niessen, Sherry
AU - Laband, Kimberley
AU - Wang, Shaohe
AU - Starr, Daniel A.
AU - Hyman, Anthony A.
AU - Schedl, Tim
AU - Desai, Arshad
AU - Piano, Fabio
AU - Gunsalus, Kristin C.
AU - Oegema, Karen
N1 - Funding Information:
This work was supported by grants from the American Cancer Society (PF-06-254-01-CCG, to RG), the Helen Hay Whitney Foundation (to A.A.), and the NIH (R01 GM074207 to K.O., R01 HD046236 to K.C.G. and FP; R01 GM085503 to K.C.G.; R01 GM085150 to TS; R01 GM088151 to A.A.; R01 GM073874 to D.A.S.) and by funding from the Ludwig Institute for Cancer Research to KO and AD. We thank Kahn Rhrissorrakrai for the MINE algorithm, Michael Volkmer for movie formatting, and the Caenorhabditis Genetics Center, funded by the NIH National Center for Research Resources, for strains. Author Contributions: Conceived and designed the experiments: KO, AD, RG, AA. Performed the experiments: RG, AA, SN, SA, TS, SW, HF, DS, JM. Scored the data: AA, RG, KO. Manually partitioned the genes into classes: RG, KO. Reworked Phenobank to include the gonad morphology data: SS, RG, KO, AH. Developed N-Browse: HK, MS, FP, KG. Developed CSI: KO, RG, HK, MS, FP, KG. Conceptualized and performed network analysis: HK, FP, KG. Contributed reagents/materials/analysis tools: KO, RG, AA, SN, KL, SA, TS, AD, HK, MS, KG, FP, HF, DS.
PY - 2011/4/29
Y1 - 2011/4/29
N2 - 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:
AB - 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:
UR - https://www.scopus.com/pages/publications/79955549678
U2 - 10.1016/j.cell.2011.03.037
DO - 10.1016/j.cell.2011.03.037
M3 - Article
C2 - 21529718
AN - SCOPUS:79955549678
SN - 0092-8674
VL - 145
SP - 470
EP - 482
JO - Cell
JF - Cell
IS - 3
ER -