Identification of essential proteins based on ranking edge-weights in protein-protein interaction networks

PLoS One. 2014 Sep 30;9(9):e108716. doi: 10.1371/journal.pone.0108716. eCollection 2014.

Abstract

Essential proteins are those that are indispensable to cellular survival and development. Existing methods for essential protein identification generally rely on knock-out experiments and/or the relative density of their interactions (edges) with other proteins in a Protein-Protein Interaction (PPI) network. Here, we present a computational method, called EW, to first rank protein-protein interactions in terms of their Edge Weights, and then identify sub-PPI-networks consisting of only the highly-ranked edges and predict their proteins as essential proteins. We have applied this method to publicly-available PPI data on Saccharomyces cerevisiae (Yeast) and Escherichia coli (E. coli) for essential protein identification, and demonstrated that EW achieves better performance than the state-of-the-art methods in terms of the precision-recall and Jackknife measures. The highly-ranked protein-protein interactions by our prediction tend to be biologically significant in both the Yeast and E. coli PPI networks. Further analyses on systematically perturbed Yeast and E. coli PPI networks through randomly deleting edges demonstrate that the proposed method is robust and the top-ranked edges tend to be more associated with known essential proteins than the lowly-ranked edges.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computational Biology
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / metabolism*
  • Models, Molecular
  • Protein Interaction Maps*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • Escherichia coli Proteins
  • Saccharomyces cerevisiae Proteins

Grants and funding

This work was supported by the Natural Science Foundation of China [61272207, 61402194, 61472159], http://www.nsfc.gov.cn; Jilin Innovation Team Project [20122805], http://kjt.jl.gov.cn/kjt/4/tindex.shtml; Science-Technology Development Project from Jilin Province [20140101180JC], http://kjt.jl.gov.cn/kjt/4/tindex.shtml; Erasmus Nundus Programme, Action 2, ONE MORE STEP, http://www.one-more-step.eu/en/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.