title: Dynamics of the discovery process of protein-protein interactions from low content studies.
abstract: BACKGROUND
  Thousands of biological and biomedical investigators study of the functional role of single genes and their protein products in normal physiology and in disease. The findings from these studies are reported in research articles that stimulate new research. It is now established that a complex regulatory networks's is controlling human cellular fate, and this community of researchers are continually unraveling this network topology. Attempts to integrate results from such accumulated knowledge resulted in literature-based protein-protein interaction networks (PPINs) and pathway databases. These databases are widely used by the community to analyze new data collected from emerging genome-wide studies with the assumption that the data within these literature-based databases is the ground truth and contain no biases. While suspicion for research focus biases is growing, a concrete proof for it is still missing. It is difficult to prove because the real PPINs are mostly unknown.
  
  
  RESULTS
  Here we analyzed the longitudinal discovery process of literature-based mammalian and yeast PPINs to observe that these networks are discovered non-uniformly. The pattern of discovery is related to a theoretical concept proposed by Kauffman called "expanding the adjacent possible". We introduce a network discovery model which explicitly includes the space of possibilities in the form of a true underlying PPIN.
  
  
  CONCLUSIONS
  Our model strongly suggests that research focus biases exist in the observed discovery dynamics of these networks. In summary, more care should be placed when using PPIN databases for analysis of newly acquired data, and when considering prior knowledge when designing new experiments.
authors.affiliation: Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place Box 1215, New York, NY, 10029, USA. zichen.wang@mssm.edu.|BD2K-LINCS Data Coordination and Integration Center, New York, USA. zichen.wang@mssm.edu.|Knowledge Management Center for the Illuminating the Druggable Genome project, New York, USA. zichen.wang@mssm.edu.
authors.forename: Zichen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place Box 1215, New York, NY, 10029, USA. neil.clark@mssm.edu.|BD2K-LINCS Data Coordination and Integration Center, New York, USA. neil.clark@mssm.edu.|Knowledge Management Center for the Illuminating the Druggable Genome project, New York, USA. neil.clark@mssm.edu.
authors.forename: Neil R
authors.initials: NR
authors.lastname: Clark
authors.affiliation: Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place Box 1215, New York, NY, 10029, USA. avi.maayan@mssm.edu.|BD2K-LINCS Data Coordination and Integration Center, New York, USA. avi.maayan@mssm.edu.|Knowledge Management Center for the Illuminating the Druggable Genome project, New York, USA. avi.maayan@mssm.edu.
authors.forename: Avi
authors.initials: A
authors.lastname: Ma'ayan
mesh_terms: D000818:Animals; D019295:Computational Biology / Q000379:methods*; D006801:Humans; D051379:Mice; D025941:Protein Interaction Mapping; D012441:Saccharomyces cerevisiae / Q000378:metabolism