Minimum curvilinearity to enhance topological prediction of protein interactions by network embedding

Carlo Cannistraci, Gregorio Alanis Lobato, Timothy Ravasi

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

Motivation: Most functions within the cell emerge thanks to protein-protein interactions (PPIs), yet experimental determination of PPIs is both expensive and time-consuming. PPI networks present significant levels of noise and incompleteness. Predicting interactions using only PPI-network topology (topological prediction) is difficult but essential when prior biological knowledge is absent or unreliable.Methods: Network embedding emphasizes the relations between network proteins embedded in a low-dimensional space, in which protein pairs that are closer to each other represent good candidate interactions. To achieve network denoising, which boosts prediction performance, we first applied minimum curvilinear embedding (MCE), and then adopted shortest path (SP) in the reduced space to assign likelihood scores to candidate interactions. Furthermore, we introduce (i) a new valid variation of MCE, named non-centred MCE (ncMCE); (ii) two automatic strategies for selecting the appropriate embedding dimension; and (iii) two new randomized procedures for evaluating predictions.Results: We compared our method against several unsupervised and supervisedly tuned embedding approaches and node neighbourhood techniques. Despite its computational simplicity, ncMCE-SP was the overall leader, outperforming the current methods in topological link prediction.Conclusion: Minimum curvilinearity is a valuable non-linear framework that we successfully applied to the embedding of protein networks for the unsupervised prediction of novel PPIs. The rationale for our approach is that biological and evolutionary information is imprinted in the non-linear patterns hidden behind the protein network topology, and can be exploited for predicting new protein links. The predicted PPIs represent good candidates for testing in high-throughput experiments or for exploitation in systems biology tools such as those used for network-based inference and prediction of disease-related functional modules. The Author 2013.
Original languageEnglish (US)
Pages (from-to)i199-i209
Number of pages1
JournalBioinformatics
Volume29
Issue number13
DOIs
StatePublished - Jun 19 2013

ASJC Scopus subject areas

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

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