RIceNet: a systems approach to elucidating the biotic stress response

Rice is a staple food for half the world’s population and a model for other monocotyledonous species. Thus, efficient approaches for identifying key genes controlling simple or complex traits in rice have important biological, agricultural and economic consequences. To address this challenge, we have constructed RiceNet, the first experimentally-tested genome-scale gene network for a monocotyledonous species. Many different datasets, derived from five different organisms including plants, animals, yeast and humans, were evaluated and 24 of the most useful were integrated into a statistical framework that allowed for the prediction of functional linkages between pairs of genes. Genes could be linked to traits using guilt-by-association, predicting gene attributes on the basis of network neighbors. We applied RiceNet to an important agronomic trait, the biotic stress response. Using network guilt-by-association followed by focused protein-protein interaction assays, we identified and validated, in planta, two positive regulators, LOC_Os01g70580 (now Regulator of XA21; ROX1), LOC_Os02g21510 (ROX2) and one negative regulator, LOC_Os06g12530 (ROX3). These proteins control resistance mediated by rice XA21, a pattern recognition receptor. We also showed that RiceNet can accurately predict gene function in another major monocotyledonous crop species, maize. RiceNet thus enables the identification of genes regulating important crop traits, facilitating engineering of pathways critical to crop productivity.