Uncovering the molecular mechanisms of bovine tuberculosis through meta-analysis of differentially expressed genes

Abstract

Bovine tuberculosis (BTB) is a chronic bacterial disease, caused by Mycobacterium bovis. It is a globally significant disease affecting cattle production and health. In the present meta-analysis study, alveolar macrophage tissue from three independent studies was analyzed, comprising 21 biological replicates (100 RNA-Seq data) from BTB infected and non-infected cattle. RNA-Seq analysis was performed on individual studies to obtain count matrices, followed by meta-analysis using one-sided NOISeq method. Fisher’s and Stouffer’s methods yielded 5904 and 2631 DEGs respectively. Functional annotation and pathway enrichment analysis revealed key biological, molecular, and cellular functions involved in pathogenesis. A protein interaction network identified ten hub genes that were mainly associated with the proteasome complex playing role in host immune response. JAK/STAT signaling pathway, Notable pathways included Pentose phosphate pathway, Ubiquitin proteasome pathway, Toll receptor signaling pathway, Interleukin signaling pathway among the 36 enriched pathways. The findings highlighted the role of immunological pathways and genes upregulated during BTB in cattle. Meta-analysis improved statistical power and robustness compared to individual studies, offering insights into potential biomarkers compared to individual studies. The findings enhance the understanding of BTB pathogenesis and offer direction to bovine breeders in endeavour of improved production and management.

Keywords

• Bovine tuberculosis, Cattle, Hub genes, Meta-analysis, Transcriptome