Whole blood transcriptomic analysis of beef cattle at arrival identifies potential predictive molecules and mechanisms that indicate animals that naturally resist bovine respiratory disease

Objectives: Identify gene products that characterize the biological status of typical calves which have been recently weaned, transported, and co-mingled prior to arrival at stocker facilities in order to identify gene products associated with BRD resistance. Methods: Whole blood RNA profiles were generated via NGS approach, using an Illumina HiSeq 3000. Individual samples were processed using an adaptation of the Revised Tuxedo Suite protocol (Tuxedo 2), then analyzed in R using edgeR and DESeq2 with likelihood-ratio testing. Genes were considered differentially expressed with an FDR cutoff of 0.10. qRT-PCR validation was performed using a SYBR green assay. Results: 135 differentially expressed genes were identified between healthy and BRD animals; 36 were shared between edgeR and DESeq2. Biological processes, using the 36 DEGs, were identified to be involved with inflammation, defense response, macrophage function, and lipoxin metabolism/biosynthesis. Enriched pathways of the 36 DEGs were involving SPM synthesis and angiotensinogen metabolism to angiotensins. Genes increased in diseased animals had known function towards anitmicrobial activity. Conlusions: Our analysis has provided, for the first time, a list of whole blood molecular biomarkers that may predict disease risk in the first 28 days of stocker cattle arrival. We identified pathways related to immune response, inflammatory mediation, metabolic processes, and stress regulation. Using whole blood transcriptomic analysis, this study provides an insight to host immunity in response to BRD. Overall design: Whole blood mRNA of stocker cattle at facility arrival were generated through next-generation sequencing utilizing an Illumina HiSeq 3000.