A rice protein interaction network reveals high centrality nodes and candidate pathogen effector targets

Network science identifies key players in diverse biological systems including host-pathogen interactions. We demonstrated a scale-free network property for a comprehensive rice protein-protein interactome (RicePPInets) that exhibits nodes with increased centrality indices. While weighted k-shell decomposition was shown efficacious to predict pathogen effector targets in Arabidopsis, we improved its computational code for a broader implementation on large-scale networks including RicePPInets. We determined that nodes residing within the internal layers of RicePPInets are poised to be the most influential, central, and effective information spreaders. To identify central players and modules through network topology analyses, we integrated RicePPInets and co-expression networks representing susceptible and resistant responses to strains of the bacterial pathogens Xanthomonas oryzae pv. oryzae and X. oryzae pv. oryzicola (Xoc) and generated a RIce-Xanthomonas INteractome (RIXIN). This revealed that previously identified candidate targets of pathogen transcription activator-like (TAL) effectors are enriched in nodes with enhanced connectivity, bottlenecks, and information spreaders that are located in the inner layers of the network, and these nodes are involved in several important biological processes. Overall, our integrative multi-omics network-based platform provides a potentially useful approach to prioritizing candidate pathogen effector targets for functional validation, suggesting that this computational framework can be broadly translatable to other complex pathosystems.