A Network Biology Approach for Understanding Foot-and-Mouth Disease Vaccination Response in Cattle using High-Throughput Gene Expression Data

Background: Foot-and-mouth disease (FMD) is a serious viral disease in cattle, causing an estimated economic loss of 6.5-21 billion USD. It is usually controlled through vaccination. The gene-gene association mechanisms underlying the response to FMD vaccination are currently poorly understood and remain of significant interest to researchers. Further, little amount of bioin-formatic work has been carried out to understand FMD vaccination response in cattle at the molec-ular level using publicly available gene expression data. Therefore, this study aims to identify key gene markers, gene networks, and hub genes associated with FMD vaccination response in cattle using gene selection and network biology methods. Methods: In this study, computational tools, including network biology techniques, were used to understand the FMD vaccination response in cattle using publicly available large gene expression data. Five different gene selection methods were employed to select informative genes from the high-dimensional gene expression data. Then, gene co-expression network analysis was carried out to construct gene-gene association networks and identify various gene modules. Next, hub genes, housekeeping hub genes, and unique hub genes were identified in the constructed networks through our earlier developed DHGA approach. Results: We identified 666 unique genes commonly selected by the gene selection methods that were informative to the vaccination condition. Two gene co-expression networks under vaccination and non-vaccination conditions were constructed, which revealed the association among the se-lected genes. Further, the selected genes were grouped into 10 and 13 gene modules under the vaccinated and non-vaccinated conditions, respectively. In the gene networks, we identified 193 and 94 genes as hubs for vaccinated and non-vaccinated conditions, respectively. The detected hub genes were classified into housekeeping hubs (49), unique hubs to vaccinated (144), and unique hubs to non-vaccinated conditions (45) based on their connection strengths. The enrichment anal-ysis of gene modules, genes, and various hub genes indicated that functions, including protein bind-ing, catalytic activity, transcription regulation, and transporter activity, were predominantly acti-vated in response to vaccination. Conclusion: These identified genes and their key roles can act as potential biomarkers for maxim-izing FMD vaccination response in cattle. The findings of this study may provide new inputs and hypotheses for future immunological studies.