Computational inference of gene regulatory networks: Approaches, limitations and opportunities*

•The basic concepts and methodologies used for gene expression based regulatory network inference are introduced•The limitations of network inference based on transcriptional datasets only are described•The data types and strategies used for integrative gene regulatory network inference and causal link prediction are presented•The caveats and solutions for the selection of statistically and biologically relevant regulatory interactions are discussed

Gene regulatory networks lie at the core of cell function control. In E. coli and S. cerevisiae, the study of gene regulatory networks has led to the discovery of regulatory mechanisms responsible for the control of cell growth, differentiation and responses to environmental stimuli. In plants, computational rendering of gene regulatory networks is gaining momentum, thanks to the recent availability of high-quality genomes and transcriptomes and development of computational network inference approaches.Here, we review current techniques, challenges and trends in gene regulatory network inference and highlight challenges and opportunities for plant science. We provide plant-specific application examples to guide researchers in selecting methodologies that suit their particular research questions.Given the interdisciplinary nature of gene regulatory network inference, we tried to cater to both biologists and computer scientists to help them engage in a dialogue about concepts and caveats in network inference. Specifically, we discuss problems and opportunities in heterogeneous data integration for eukaryotic organisms and common caveats to be considered during network model evaluation. This article is part of a Special Issue entitled: Plant Gene Regulatory Mechanisms and Networks, edited by Dr. Erich Grotewold and Dr. Nathan Springer.