Semi-Supervised Multi-View Learning for Gene Network Reconstruction

PLoS One. 2015 Dec 7;10(12):e0144031. doi: 10.1371/journal.pone.0144031. eCollection 2015.

Abstract

The task of gene regulatory network reconstruction from high-throughput data is receiving increasing attention in recent years. As a consequence, many inference methods for solving this task have been proposed in the literature. It has been recently observed, however, that no single inference method performs optimally across all datasets. It has also been shown that the integration of predictions from multiple inference methods is more robust and shows high performance across diverse datasets. Inspired by this research, in this paper, we propose a machine learning solution which learns to combine predictions from multiple inference methods. While this approach adds additional complexity to the inference process, we expect it would also carry substantial benefits. These would come from the automatic adaptation to patterns on the outputs of individual inference methods, so that it is possible to identify regulatory interactions more reliably when these patterns occur. This article demonstrates the benefits (in terms of accuracy of the reconstructed networks) of the proposed method, which exploits an iterative, semi-supervised ensemble-based algorithm. The algorithm learns to combine the interactions predicted by many different inference methods in the multi-view learning setting. The empirical evaluation of the proposed algorithm on a prokaryotic model organism (E. coli) and on a eukaryotic model organism (S. cerevisiae) clearly shows improved performance over the state of the art methods. The results indicate that gene regulatory network reconstruction for the real datasets is more difficult for S. cerevisiae than for E. coli. The software, all the datasets used in the experiments and all the results are available for download at the following link: http://figshare.com/articles/Semi_supervised_Multi_View_Learning_for_Gene_Network_Reconstruction/1604827.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Escherichia coli / physiology*
  • Gene Regulatory Networks / physiology*
  • Genes, Bacterial / physiology*
  • Genes, Fungal / physiology*
  • Machine Learning*
  • Saccharomyces cerevisiae / physiology*
  • Software*

Grants and funding

The authors acknowledge the financial support of the Slovenian Research Agency via the grant P2-0103, and the European Commission via the grants ICT-2013-612944 MAESTRA and ICT-2013-604102 HBP, as well as the grant CCI2007SI051PO001 through the European Social Fund for co-financing postgraduate studies in the context of the Operational Programme for Human Resources Development for the period 2007–2013. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.