title: A crowd-sourcing approach for the construction of species-specific cell signaling networks.
abstract: BACKGROUND
  Animal models are important tools in drug discovery and for understanding human biology in general. However, many drugs that initially show promising results in rodents fail in later stages of clinical trials. Understanding the commonalities and differences between human and rat cell signaling networks can lead to better experimental designs, improved allocation of resources and ultimately better drugs.
  
  
  RESULTS
  The sbv IMPROVER Species-Specific Network Inference challenge was designed to use the power of the crowds to build two species-specific cell signaling networks given phosphoproteomics, transcriptomics and cytokine data generated from NHBE and NRBE cells exposed to various stimuli. A common literature-inspired reference network with 220 nodes and 501 edges was also provided as prior knowledge from which challenge participants could add or remove edges but not nodes. Such a large network inference challenge not based on synthetic simulations but on real data presented unique difficulties in scoring and interpreting the results. Because any prior knowledge about the networks was already provided to the participants for reference, novel ways for scoring and aggregating the results were developed. Two human and rat consensus networks were obtained by combining all the inferred networks. Further analysis showed that major signaling pathways were conserved between the two species with only isolated components diverging, as in the case of ribosomal S6 kinase RPS6KA1. Overall, the consensus between inferred edges was relatively high with the exception of the downstream targets of transcription factors, which seemed more difficult to predict.
  
  
  BACKGROUND
  ebilal@us.ibm.com or gustavo@us.ibm.com.
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: IBM Research, Computational Biology Center, Yorktown Heights, NY 10598, USA, ProtATonce Ltd, Scientific Park Lefkippos, Patriarchou Grigoriou & Neapoleos 15343 Ag. Paraskevi, Attiki, Greece, National Technical University of Athens, Heroon Polytechniou 9, Zografou, 15780, Greece and Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors.forename: Erhan
authors.initials: E
authors.lastname: Bilal
authors.affiliation: IBM Research, Computational Biology Center, Yorktown Heights, NY 10598, USA, ProtATonce Ltd, Scientific Park Lefkippos, Patriarchou Grigoriou & Neapoleos 15343 Ag. Paraskevi, Attiki, Greece, National Technical University of Athens, Heroon Polytechniou 9, Zografou, 15780, Greece and Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland IBM Research, Computational Biology Center, Yorktown Heights, NY 10598, USA, ProtATonce Ltd, Scientific Park Lefkippos, Patriarchou Grigoriou & Neapoleos 15343 Ag. Paraskevi, Attiki, Greece, National Technical University of Athens, Heroon Polytechniou 9, Zografou, 15780, Greece and Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors.forename: Theodore
authors.initials: T
authors.lastname: Sakellaropoulos
authors.affiliation: IBM Research, Computational Biology Center, Yorktown Heights, NY 10598, USA, ProtATonce Ltd, Scientific Park Lefkippos, Patriarchou Grigoriou & Neapoleos 15343 Ag. Paraskevi, Attiki, Greece, National Technical University of Athens, Heroon Polytechniou 9, Zografou, 15780, Greece and Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland IBM Research, Computational Biology Center, Yorktown Heights, NY 10598, USA, ProtATonce Ltd, Scientific Park Lefkippos, Patriarchou Grigoriou & Neapoleos 15343 Ag. Paraskevi, Attiki, Greece, National Technical University of Athens, Heroon Polytechniou 9, Zografou, 15780, Greece and Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors.forename: Ioannis N
authors.initials: IN
authors.lastname: Melas
authors.affiliation: IBM Research, Computational Biology Center, Yorktown Heights, NY 10598, USA, ProtATonce Ltd, Scientific Park Lefkippos, Patriarchou Grigoriou & Neapoleos 15343 Ag. Paraskevi, Attiki, Greece, National Technical University of Athens, Heroon Polytechniou 9, Zografou, 15780, Greece and Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland IBM Research, Computational Biology Center, Yorktown Heights, NY 10598, USA, ProtATonce Ltd, Scientific Park Lefkippos, Patriarchou Grigoriou & Neapoleos 15343 Ag. Paraskevi, Attiki, Greece, National Technical University of Athens, Heroon Polytechniou 9, Zografou, 15780, Greece and Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors.forename: Dimitris E
authors.initials: DE
authors.lastname: Messinis
authors.affiliation: IBM Research, Computational Biology Center, Yorktown Heights, NY 10598, USA, ProtATonce Ltd, Scientific Park Lefkippos, Patriarchou Grigoriou & Neapoleos 15343 Ag. Paraskevi, Attiki, Greece, National Technical University of Athens, Heroon Polytechniou 9, Zografou, 15780, Greece and Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Belcastro
authors.affiliation: IBM Research, Computational Biology Center, Yorktown Heights, NY 10598, USA, ProtATonce Ltd, Scientific Park Lefkippos, Patriarchou Grigoriou & Neapoleos 15343 Ag. Paraskevi, Attiki, Greece, National Technical University of Athens, Heroon Polytechniou 9, Zografou, 15780, Greece and Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors.forename: Kahn
authors.initials: K
authors.lastname: Rhrissorrakrai
authors.affiliation: IBM Research, Computational Biology Center, Yorktown Heights, NY 10598, USA, ProtATonce Ltd, Scientific Park Lefkippos, Patriarchou Grigoriou & Neapoleos 15343 Ag. Paraskevi, Attiki, Greece, National Technical University of Athens, Heroon Polytechniou 9, Zografou, 15780, Greece and Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors.forename: Pablo
authors.initials: P
authors.lastname: Meyer
authors.affiliation: IBM Research, Computational Biology Center, Yorktown Heights, NY 10598, USA, ProtATonce Ltd, Scientific Park Lefkippos, Patriarchou Grigoriou & Neapoleos 15343 Ag. Paraskevi, Attiki, Greece, National Technical University of Athens, Heroon Polytechniou 9, Zografou, 15780, Greece and Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors.forename: Raquel
authors.initials: R
authors.lastname: Norel
authors.affiliation: IBM Research, Computational Biology Center, Yorktown Heights, NY 10598, USA, ProtATonce Ltd, Scientific Park Lefkippos, Patriarchou Grigoriou & Neapoleos 15343 Ag. Paraskevi, Attiki, Greece, National Technical University of Athens, Heroon Polytechniou 9, Zografou, 15780, Greece and Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors.forename: Anita
authors.initials: A
authors.lastname: Iskandar
authors.affiliation: IBM Research, Computational Biology Center, Yorktown Heights, NY 10598, USA, ProtATonce Ltd, Scientific Park Lefkippos, Patriarchou Grigoriou & Neapoleos 15343 Ag. Paraskevi, Attiki, Greece, National Technical University of Athens, Heroon Polytechniou 9, Zografou, 15780, Greece and Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors.forename: Elise
authors.initials: E
authors.lastname: Blaese
authors.affiliation: IBM Research, Computational Biology Center, Yorktown Heights, NY 10598, USA, ProtATonce Ltd, Scientific Park Lefkippos, Patriarchou Grigoriou & Neapoleos 15343 Ag. Paraskevi, Attiki, Greece, National Technical University of Athens, Heroon Polytechniou 9, Zografou, 15780, Greece and Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors.forename: John J
authors.initials: JJ
authors.lastname: Rice
authors.affiliation: IBM Research, Computational Biology Center, Yorktown Heights, NY 10598, USA, ProtATonce Ltd, Scientific Park Lefkippos, Patriarchou Grigoriou & Neapoleos 15343 Ag. Paraskevi, Attiki, Greece, National Technical University of Athens, Heroon Polytechniou 9, Zografou, 15780, Greece and Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors.forename: Manuel C
authors.initials: MC
authors.lastname: Peitsch
authors.affiliation: IBM Research, Computational Biology Center, Yorktown Heights, NY 10598, USA, ProtATonce Ltd, Scientific Park Lefkippos, Patriarchou Grigoriou & Neapoleos 15343 Ag. Paraskevi, Attiki, Greece, National Technical University of Athens, Heroon Polytechniou 9, Zografou, 15780, Greece and Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors.forename: Julia
authors.initials: J
authors.lastname: Hoeng
authors.affiliation: IBM Research, Computational Biology Center, Yorktown Heights, NY 10598, USA, ProtATonce Ltd, Scientific Park Lefkippos, Patriarchou Grigoriou & Neapoleos 15343 Ag. Paraskevi, Attiki, Greece, National Technical University of Athens, Heroon Polytechniou 9, Zografou, 15780, Greece and Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Stolovitzky
authors.affiliation: IBM Research, Computational Biology Center, Yorktown Heights, NY 10598, USA, ProtATonce Ltd, Scientific Park Lefkippos, Patriarchou Grigoriou & Neapoleos 15343 Ag. Paraskevi, Attiki, Greece, National Technical University of Athens, Heroon Polytechniou 9, Zografou, 15780, Greece and Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland IBM Research, Computational Biology Center, Yorktown Heights, NY 10598, USA, ProtATonce Ltd, Scientific Park Lefkippos, Patriarchou Grigoriou & Neapoleos 15343 Ag. Paraskevi, Attiki, Greece, National Technical University of Athens, Heroon Polytechniou 9, Zografou, 15780, Greece and Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors.forename: Leonidas G
authors.initials: LG
authors.lastname: Alexopoulos
authors.affiliation: IBM Research, Computational Biology Center, Yorktown Heights, NY 10598, USA, ProtATonce Ltd, Scientific Park Lefkippos, Patriarchou Grigoriou & Neapoleos 15343 Ag. Paraskevi, Attiki, Greece, National Technical University of Athens, Heroon Polytechniou 9, Zografou, 15780, Greece and Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors.forename: Carine
authors.initials: C
authors.lastname: Poussin
mesh_terms: D000465:Algorithms; D000818:Animals; D001980:Bronchi / Q000166:cytology / Q000378:metabolism; D002450:Cell Communication; D002478:Cells, Cultured; D063045:Crowdsourcing; D016207:Cytokines / Q000378:metabolism*; D016208:Databases, Factual; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D023421:Models, Animal; D020411:Oligonucleotide Array Sequence Analysis; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D015398:Signal Transduction; D012984:Software; D013045:Species Specificity; D049490:Systems Biology / Q000379:methods*
chemical_list: D016207:Cytokines; D010750:Phosphoproteins