Multipopulational transcriptome analysis of post-weaned beef cattle at arrival further validates candidate biomarkers for predicting clinical bovine respiratory disease

Bovine respiratory disease (BRD) remains the leading infectious disease in post-weaned beef cattle. The objective of this investigation was to contrast the at-arrival blood transcriptomes from cattle derived from two distinct populations that developed BRD in the 28 days following arrival versus cattle that did not. Forty-eight blood samples from two populations were selected for mRNA sequencing based on even distribution of development (n = 24) or lack of (n = 24) clinical BRD within 28 days following arrival; cattle which developed BRD were further stratified into BRD severity cohorts based on frequency of antimicrobial treatment: treated once (treated_1) or treated twice or more and/or died (treated_2+). Sequenced reads (~ 50 M/sample, 150 bp paired-end) were aligned to the ARS-UCD1.2 bovine genome assembly. One hundred and thirty-two unique differentially expressed genes (DEGs) were identified between groups stratified by disease severity (healthy, n = 24; treated_1, n = 13; treated_2+, n = 11) with edgeR (FDR ≤ 0.05). Differentially expressed genes in treated_1 relative to both healthy and treated_2+ were predicted to increase neutrophil activation, cellular cornification/keratinization, and antimicrobial peptide production. Differentially expressed genes in treated_2+ relative to both healthy and treated_1 were predicted to increase alternative complement activation, decrease leukocyte activity, and increase nitric oxide production. Receiver operating characteristic (ROC) curves generated from expression data for six DEGs identified in our current and previous studies (MARCO, CFB, MCF2L, ALOX15, LOC100335828 (aka CD200R1), and SLC18A2) demonstrated good-to-excellent (AUC: 0.800–0.899; ≥ 0.900) predictability for classifying disease occurrence and severity. This investigation identifies candidate biomarkers and functional mechanisms in at arrival blood that predicted development and severity of BRD.