Integrative Transcriptomic and Network Based Framework for Designing Heat-Stress and Protective Topical Therapies in Mammals
Rihaan Sodhani and Nirupma Singh
21/07/2026
Anthropogenic climate change and the urban heat island effect have significantly increased the risk of heat stress in urban mammals. Existing cooling strategies for animals primarily focus on physiological management and often overlook molecular-level mitigation of heat-induced cellular damage. Therefore, this study aimed to employ bioinformatics and computational chemistry approaches to identify candidate bioactive compounds for heat stress mitigation in mammals.
A heat stress-related Bos taurus gene expression dataset was analyzed using differential expression analysis; a total of 6273 statistically significant DEGs were identified, of which 1202 were highly differentially expressed (|log₂FC| > 5). Protein–protein interaction network analysis and functional pathway enrichment analysis were subsequently performed to investigate functional relationships among these genes and associated biological pathways, leading to the identification of nine key DEGs. Several of these genes were also associated with heat stress pathways across multiple mammalian species, demonstrating the broader relevance of the findings.
Molecular docking analysis was conducted to evaluate the interaction potential of selected antioxidative and anti-inflammatory bioactive compounds with proteins corresponding to the top DEGs, UBA52 and RPS9, as well as HSP90, a well-established heat shock protein. Among the tested compounds, epigallocatechin gallate and quercetin demonstrated the strongest binding interactions, leading to the proposal of a formulation incorporating these compounds.
Overall, this study highlights the potential of integrating bioinformatics and computational approaches to identify candidate compounds for mitigating heat-induced cellular stress in urban animals. Further experimental validation is required to confirm these findings.