Identification of diagnostic biomarkers of and immune cell infiltration analysis in bovine respiratory disease

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Background: Bovine respiratory disease (BRD) is a prevalent and costly condition in the cattle industry, impacting long-term productivity, antibioticusage, and global food safety. Thus, identifying reliable biomarkers for BRD is crucial for early diagnosis, effective treatment, and monitoring therapeutic outcomes. Methods: This study identified differentially expressed genes (DEGs) associated with BRD by analyzing a blood RNA-seq expression dataset associated with BRD, and conducted a Kyoto Encyclopedia of Genes and Genomes (KEGG) approach enrichment and Gene Ontology (GO) annotation analysis on these DEGs. Meanwhile, the key modules related to BRD were screened by weighted gene co-expression network analysis (WGCNA), and the genes in the module were intersected with DEGs. Subequently, least absolute shrinkage and selection operator (LASSO) and random forest (RF) analysis were employed to identify potential biomarkers. Finally, gene set enrichment analysis (GSEA) was performed to explore the potential mechanisms of the identified biomarkers, and their diagnostic significance was assessed using receiver operator characteristic (ROC) curve analysis and real-time fluorescent quantitative PCR (RT-qPCR). In addition, immune cell infiltration in BRD was evaluated using the CIBERSORT algorithm and the correlation between biomarkers and immune cell infiltration was analyzed. Results: The results showed that a total of 1,097 DEG were screened. GO and KEGG analysis showed that DEGs was mainly enriched in inflammatory response, defense response, Complement and coagulation cascades and Antigen processing and presentation pathways. WGCNA analysis determined that the cyan module had the highest correlation with BRD. A total of 833 overlapping genes were identified through Venn analysis of the differential and WGCNA results. Lasso and RF analyses identified five potential biomarkers for BRD. RT-qPCR testing and data set analysis showed that the expression levels of these five potential biomarkers in nasal mucus and blood of BRD cattle were significantly higher than those of healthy cattle. In addition, ROC curve analysis showed that potential biomarkers had high diagnostic value. GSEA analysis revealed that potential biomarkers are mainly involved in Neutrophil extracellular trap formation, Complement and coagulation cascades, T cell receptor signaling pathway, B cell receptor signaling pathway, Fc gamma R-mediated phagocytosis and IL-17 signaling pathway. The results from the CIBERSORT algorithm demonstrated a significant difference in immune cell composition between the BRD group and the healthy group, indicating that the diagnostic biomarkers were closely associated with immune cells. Conclusion: This study identified ADGRG3, CDKN1A, CA4, GGT5, and SLC26A8 as potential diagnostic markers for BRD, providing significant insights for the development of new immunotherapy targets and improving disease prevention and treatment strategies.

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