title: Finding undetected protein associations in cell signaling by belief propagation.
abstract: External information propagates in the cell mainly through signaling cascades and transcriptional activation, allowing it to react to a wide spectrum of environmental changes. High-throughput experiments identify numerous molecular components of such cascades that may, however, interact through unknown partners. Some of them may be detected using data coming from the integration of a protein-protein interaction network and mRNA expression profiles. This inference problem can be mapped onto the problem of finding appropriate optimal connected subgraphs of a network defined by these datasets. The optimization procedure turns out to be computationally intractable in general. Here we present a new distributed algorithm for this task, inspired from statistical physics, and apply this scheme to alpha factor and drug perturbations data in yeast. We identify the role of the COS8 protein, a member of a gene family of previously unknown function, and validate the results by genetic experiments. The algorithm we present is specially suited for very large datasets, can run in parallel, and can be adapted to other problems in systems biology. On renowned benchmarks it outperforms other algorithms in the field.
authors.affiliation: Laboratoire de Biometrie et Biologie Evolutive, Centre National de la Recherche Scientifique, Unite Mixte de Recherche 5558, Université Lyon 1, Villeurbanne, France.
authors.forename: M
authors.initials: M
authors.lastname: Bailly-Bechet
authors.forename: C
authors.initials: C
authors.lastname: Borgs
authors.forename: A
authors.initials: A
authors.lastname: Braunstein
authors.forename: J
authors.initials: J
authors.lastname: Chayes
authors.forename: A
authors.initials: A
authors.lastname: Dagkessamanskaia
authors.forename: J-M
authors.initials: JM
authors.lastname: François
authors.forename: R
authors.initials: R
authors.lastname: Zecchina
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry; D000465:Algorithms; D000483:Alleles; D001703:Biophysics / Q000379:methods; D019295:Computational Biology / Q000379:methods*; D056827:Endosomal Sorting Complexes Required for Transport / Q000737:chemistry; D008954:Models, Biological; D015233:Models, Statistical; D010675:Pheromones; D010957:Plasmids / Q000378:metabolism; D025941:Protein Interaction Mapping; D012333:RNA, Messenger / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry; D015398:Signal Transduction / Q000502:physiology*; D012984:Software; D014158:Transcription, Genetic
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D010675:Pheromones; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; C107528:VPS4 protein, S cerevisiae; D000251:Adenosine Triphosphatases