Computational identification of key genes and regulatory miRNAs responsible for differential regulation of host-pathogen response during early and late blight diseases in tomato

Abstract

Early blight, caused by Alternaria solani, and late blight, caused by the Phytophthora infestans, are the two fungal diseases in tomato (Solanum lycopersicum) that largely hamper the crop yield and are responsible for significant economic losses, thus making tomato production challenging. While various candidate genes/proteins have been characterized to provide a significant understanding of disease pathogenesis, a significant success in developing resistant varieties is not achieved yet. Therefore, alternatively, we integrative multiple omics data to elucidate the topological differences in regulatory networks of early blight and late blight infected tomato to predict novel candidate genes and corresponding miRNAs that potentially regulate the distinct behavior of host-pathogen responses in both diseases. The overall approach comprises (i) obtaining and pre-processing the gene expression profiles, (ii) data merging and differential expression studies, (iii) gene co-expression network construction and modules identification, (iv) differential network analysis, and (v) enriching the gene co-expression networks with miRNA-gene interactions. Comparison of disease networks identified five potential candidate genes (Solyc09g014440, Solyc05g008380, Solyc04g072640, Solyc06g054580 and Solyc02g070580) having significant differences in the overall network connectivity, and are presumed to regulate differential host-pathogen responses between both fungal diseases. Also, miRNAs Sly-miRN4423 and Sly-miRN3104 were identified to regulate the top-candidate gene of PHD TF family, thus acting as regulators of rewiring in host-pathogen interactions to modulate the phenotypic plasticity during pathogen-mediated stress. Apart, the analyses also provided various systems-level insights into the network characteristics and biological processes regulating the underlying pathogenesis-associated mechanisms. The identified candidates are potential targets for further experimental analysis that will help plant biologists and researchers to well-understand the molecular basis of differences in onset of disease occurrence and phenotypic plasticity of both diseases.