Identification of Drought Stress-Responsive Genes in Rice by Random Walk with Multi-Restart Probability on MultiPlex Biological Networks.

Exploring drought stress-responsive genes in rice is essential for breeding drought-resistant varieties. Rice drought resistance is controlled by multiple genes, and mining drought stress-responsive genes solely based on single omics data lacks stability and accuracy. Multi-omics correlation analysis and biological molecular network analysis provide robust solutions. This study proposed a random walk with a multi-restart probability (RWMRP) algorithm, based on the Restarted Random Walk (RWR) algorithm, to operate on rice MultiPlex biological networks. It explores the interactions between biological molecules across various levels and ranks potential genes. RWMRP uses eigenvector centrality to evaluate node importance in the network and adjusts the restart probabilities accordingly, diverging from the uniform restart probability employed in RWR. In the random walk process, it can be better to consider the global relationships in the network. Firstly, we constructed a MultiPlex biological network by integrating the rice protein-protein interaction, gene pathway, and gene co-expression network. Then, we employed RWMRP to predict the potential genes associated with rice tolerance to drought stress. Enrichment and correlation analyses resulted in the identification of 12 drought-related genes. We further conducted quantitative real-time polymerase chain reaction (qRT-PCR) analysis on these 12 genes, ultimately identifying 10 genes responsive to drought stress.