title: Toward accurate reconstruction of functional protein networks.
abstract: Genome-scale screening studies are gradually accumulating a wealth of data on the putative involvement of hundreds of genes/proteins in various cellular responses or functions. A fundamental challenge is to chart out the protein pathways that underlie these systems. Previous approaches to the problem have either employed a local optimization criterion, aiming to infer each pathway independently, or a global criterion, searching for the overall most parsimonious subnetwork. Here, we study the trade-off between the two approaches and present a new intermediary scheme that provides explicit control over it. We demonstrate its utility in the analysis of the apoptosis network in humans, and the telomere length maintenance (TLM) system in yeast. Our results show that in the majority of real-life cases, the intermediary approach provides the most plausible solutions. We use a new set of perturbation experiments measuring the role of essential genes in telomere length regulation to further study the TLM network. Surprisingly, we find that the proteasome plays an important role in telomere length regulation through its associations with transcription and DNA repair circuits.
authors.affiliation: The Blavatnik School of Computer Science, Tel-Aviv University, Tel-Aviv, Israel. niryosef@post.tau.ac.il
authors.forename: Nir
authors.initials: N
authors.lastname: Yosef
authors.forename: Lior
authors.initials: L
authors.lastname: Ungar
authors.forename: Einat
authors.initials: E
authors.lastname: Zalckvar
authors.forename: Adi
authors.initials: A
authors.lastname: Kimchi
authors.forename: Martin
authors.initials: M
authors.lastname: Kupiec
authors.forename: Eytan
authors.initials: E
authors.lastname: Ruppin
authors.forename: Roded
authors.initials: R
authors.lastname: Sharan
mesh_terms: D000465:Algorithms; D017209:Apoptosis; D030562:Databases, Protein; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D046988:Proteasome Endopeptidase Complex