title: Predictive models of molecular machines involved in Caenorhabditis elegans early embryogenesis.
abstract: Although numerous fundamental aspects of development have been uncovered through the study of individual genes and proteins, system-level models are still missing for most developmental processes. The first two cell divisions of Caenorhabditis elegans embryogenesis constitute an ideal test bed for a system-level approach. Early embryogenesis, including processes such as cell division and establishment of cellular polarity, is readily amenable to large-scale functional analysis. A first step toward a system-level understanding is to provide 'first-draft' models both of the molecular assemblies involved and of the functional connections between them. Here we show that such models can be derived from an integrated gene/protein network generated from three different types of functional relationship: protein interaction, expression profiling similarity and phenotypic profiling similarity, as estimated from detailed early embryonic RNA interference phenotypes systematically recorded for hundreds of early embryogenesis genes. The topology of the integrated network suggests that C. elegans early embryogenesis is achieved through coordination of a limited set of molecular machines. We assessed the overall predictive value of such molecular machine models by dynamic localization of ten previously uncharacterized proteins within the living embryo.
authors.affiliation: Center for Comparative Functional Genomics, Department of Biology, New York University, New York, New York 10003, USA.
authors.forename: Kristin C
authors.initials: KC
authors.lastname: Gunsalus
authors.forename: Hui
authors.initials: H
authors.lastname: Ge
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Schetter
authors.forename: Debra S
authors.initials: DS
authors.lastname: Goldberg
authors.forename: Jing-Dong J
authors.initials: JD
authors.lastname: Han
authors.forename: Tong
authors.initials: T
authors.lastname: Hao
authors.forename: Gabriel F
authors.initials: GF
authors.lastname: Berriz
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bertin
authors.forename: Jerry
authors.initials: J
authors.lastname: Huang
authors.forename: Ling-Shiang
authors.initials: LS
authors.lastname: Chuang
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Ramamurthy
authors.initials: R
authors.lastname: Mani
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Hyman
authors.forename: Birte
authors.initials: B
authors.lastname: Sönnichsen
authors.forename: Christophe J
authors.initials: CJ
authors.lastname: Echeverri
authors.forename: Frederick P
authors.initials: FP
authors.lastname: Roth
authors.forename: Marc
authors.initials: M
authors.lastname: Vidal
authors.forename: Fabio
authors.initials: F
authors.lastname: Piano
mesh_terms: D000465:Algorithms; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D016764:Cell Polarity; D047108:Embryonic Development / Q000235:genetics; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D008954:Models, Biological; D010641:Phenotype; D011485:Protein Binding; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D049490:Systems Biology / Q000379:methods*
chemical_list: D011993:Recombinant Fusion Proteins