A crowd-sourcing approach for the construction of species-specific cell signaling networks

Erhan Bilal, Theodore Sakellaropoulos, Challenge Participantsz, Ioannis N. Melas, Dimitris E. Messinis, Vincenzo Belcastro, Kahn Rhrissorrakrai, Pablo Meyer, Raquel Norel, Anita Iskandar, Elise Blaese, John J. Rice, Manuel C. Peitsch, Julia Hoeng, Gustavo Stolovitzky, Leonidas G. Alexopoulos, Carine Poussin

Research output: Contribution to journalArticle

Abstract

Motivation: 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.

Original languageEnglish (US)
Pages (from-to)484-491
Number of pages8
JournalBioinformatics
Volume31
Issue number4
DOIs
StatePublished - Feb 15 2015

ASJC Scopus subject areas

  • Statistics and Probability
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Computational Theory and Mathematics
  • Computational Mathematics

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  • Cite this

    Bilal, E., Sakellaropoulos, T., Participantsz, C., Melas, I. N., Messinis, D. E., Belcastro, V., Rhrissorrakrai, K., Meyer, P., Norel, R., Iskandar, A., Blaese, E., Rice, J. J., Peitsch, M. C., Hoeng, J., Stolovitzky, G., Alexopoulos, L. G., & Poussin, C. (2015). A crowd-sourcing approach for the construction of species-specific cell signaling networks. Bioinformatics, 31(4), 484-491. https://doi.org/10.1093/bioinformatics/btu659