Meta-analysis of drought-tolerant genotypes in Oryza sativa: A network-based approach

BACKGROUND: Drought is a severe environmental stress. It is estimated that about 50% of the world rice production is affected mainly by drought. Apart from conventional breeding strategies to develop drought-tolerant crops, innovative computational approaches may provide insights into the underlying molecular mechanisms of stress response and identify drought-responsive markers. Here we propose a network-based computational approach involving a meta-analytic study of seven drought-tolerant rice genotypes under drought stress. RESULTS: Co-expression networks enable large-scale analysis of gene-pair associations and tightly coupled clusters that may represent coordinated biological processes. Considering differentially expressed genes in the co-expressed modules and supplementing external information such as resistance/tolerance QTLs, transcription factors, network-based topological measures, we identify and prioritize drought-adaptive co-expressed gene modules and potential candidate genes. Using the candidate genes that are well-represented across the datasets as ‘seed’ genes, two drought-specific protein-protein interaction networks (PPINs) are constructed with up- and down-regulated genes. Cluster analysis of the up-regulated PPIN revealed ABA signalling pathway as a central process in drought response with a probable crosstalk with energy metabolic processes. Tightly coupled gene clusters representing up-regulation of core cellular respiratory processes and enhanced degradation of branched chain amino acids and cell wall metabolism are identified. Cluster analysis of down-regulated PPIN provides a snapshot of major processes associated with photosynthesis, growth, development and protein synthesis, most of which are shut down during drought. Differential regulation of phytohormones, e.g., jasmonic acid, cell wall metabolism, signalling and posttranslational modifications associated with biotic stress are elucidated. Functional characterization of topologically important, drought-responsive uncharacterized genes that may play a role in important processes such as ABA signalling, calcium signalling, photosynthesis and cell wall metabolism is discussed. Further transgenic studies on these genes may help in elucidating their biological role under stress conditions. CONCLUSION: Currently, a large number of resources for rice functional genomics exist which are mostly underutilized by the scientific community. In this study, a computational approach integrating information from various resources such as gene co-expression networks, protein-protein interactions and pathway-level information is proposed to provide a systems-level view of complex drought-responsive processes across the drought-tolerant genotypes.