NIMEFI: gene regulatory network inference using multiple ensemble feature importance algorithms

PLoS One. 2014 Mar 25;9(3):e92709. doi: 10.1371/journal.pone.0092709. eCollection 2014.

Abstract

One of the long-standing open challenges in computational systems biology is the topology inference of gene regulatory networks from high-throughput omics data. Recently, two community-wide efforts, DREAM4 and DREAM5, have been established to benchmark network inference techniques using gene expression measurements. In these challenges the overall top performer was the GENIE3 algorithm. This method decomposes the network inference task into separate regression problems for each gene in the network in which the expression values of a particular target gene are predicted using all other genes as possible predictors. Next, using tree-based ensemble methods, an importance measure for each predictor gene is calculated with respect to the target gene and a high feature importance is considered as putative evidence of a regulatory link existing between both genes. The contribution of this work is twofold. First, we generalize the regression decomposition strategy of GENIE3 to other feature importance methods. We compare the performance of support vector regression, the elastic net, random forest regression, symbolic regression and their ensemble variants in this setting to the original GENIE3 algorithm. To create the ensemble variants, we propose a subsampling approach which allows us to cast any feature selection algorithm that produces a feature ranking into an ensemble feature importance algorithm. We demonstrate that the ensemble setting is key to the network inference task, as only ensemble variants achieve top performance. As second contribution, we explore the effect of using rankwise averaged predictions of multiple ensemble algorithms as opposed to only one. We name this approach NIMEFI (Network Inference using Multiple Ensemble Feature Importance algorithms) and show that this approach outperforms all individual methods in general, although on a specific network a single method can perform better. An implementation of NIMEFI has been made publicly available.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Gene Expression Regulation / physiology*
  • Gene Regulatory Networks / physiology*
  • Models, Genetic*

Grants and funding

This work was partially supported by the Interuniversity Attraction Poles Programme (IAP P6/25 BIOMAGNET), initiated by the Belgian State, Science Policy Office, by the French Community of Belgium (ARC REFRACT, ULg), and by a grant from the European Commission (FP7-PEOPLE-2011; CardiomiR-285991; Dr. Heymans). This work is supported by Ghent University Multidisciplinary Research Partnership Bioinformatics: from nucleotides to networks. This work was carried out using the Stevin Supercomputer Infrastructure at Ghent University, funded by Ghent University, the Hercules Foundation and the Flemish Government department EWI. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.