Multipopulational Transcriptome Analysis of Post-Weaned Beef Cattle at Arrival Further Validates Candidate Biomarkers for Predicting Clinical Bovine Respiratory Disease

Scott, Matthew A.; Woolums, Amelia R.; Swiderski, Cyprianna E.; Perkins, Andy D.; Nanduri, Bindu; Smith, David; Karisch, Brandi B.; Epperson, William B.; Blanton, J. R.

doi:10.21203/rs.3.rs-600364/v1

Cited by 1 publication

(10 citation statements)

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“…While this study cannot elucidate the exact mechanistic components nor temporality of molecular events, it suggests that promotion of Th2-mediated T-cells at arrival shares a common mechanism with RBC elevation and risk of BRD development. Our previous research has indicated that genes elevated at arrival in cattle that eventually develop BRD interact, and may enhance, TLR-4 and IL-6 responses [20,40,72], which may contribute to the co-expressed pattern related to Th2-mediated T-cell development [73]. Overall, this pattern of Th2-mediated immunity is strongly associated with clinical BRD development and timing to first treatment, and may further strengthen the depiction that early Th2 responses indicate clinical disease development and lung pathology [74, 75].…”

Section: Discussionmentioning

confidence: 99%

“…Based on our previous work, it can be inferred that host gene expression captured at facility arrival is variable across BRD severity cohorts [20,40,41]. Therefore, we assessed whether the at-arrival co-expression patterns and modules found in this study were well preserved across an RNA-Seq data set from an independent population of cattle.…”

Section: Methodsmentioning

confidence: 95%

“…The gene-level raw count matrix generated from our previous research was utilized for this study [20]. Briefly, RNA was isolated via Tempus Spin RNA Isolation Kits (Thermo Fisher Scientific; Waltham, MA, USA), following manufacturer’s protocol.…”

Section: Methodsmentioning

confidence: 99%

“…When evaluating the relationships between cytokine gene expression and CBC data in cattle with concurrent BRD, Lindholm-Perry and colleagues discovered that cattle with BRD possessed a comparative increase in numbers of neutrophils, decrease in numbers of basophils, and increased expression of CCL16 , CXCR1 , and CCR1 [17]. Recent RNA sequencing studies, performed by both our group and others, have identified mechanisms and candidate biomarkers in whole blood associated with BRD development [18,19,20]. However, these studies primarily sought to identify differentially expressed genes (DEGs) between cattle that were or were not treated for BRD based on clinical signs.…”

Section: Introductionmentioning

confidence: 99%

“…This analysis approach falls into the field of systems biology, where, in contrast to reductionist biology, molecular components are pieced and scaled together to better understand disease and generate novel hypotheses [23, 24]. In this respect, we sought to build networks of co-expressed genes, utilizing the full structure of previously published gene expression data [20], and discover relationships between gene expression and cellular hematological components, which may elucidate and/or further confirm genes and mechanisms related to BRD development or resistance.…”

Section: Introductionmentioning

confidence: 99%

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Hematological and gene co-expression network analyses of high-risk beef cattle defines immunological mechanisms and biological complexes involved in bovine respiratory disease and weight gain

Scott

Woolums

Swiderski

et al. 2022

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Bovine respiratory disease (BRD), the leading disease complex in beef cattle production systems, remains highly elusive regarding diagnostics and disease prediction. Previous research has employed cellular and molecular techniques to describe hematological and gene expression variation that coincides with BRD development. Here, we utilized weighted gene co-expression network analysis (WGCNA) to leverage total gene expression patterns from cattle at arrival and generate hematological and clinical trait associations to describe mechanisms that may predict BRD development. Gene expression counts of previously published RNA-Seq data from 23 cattle (2017; n=11 Healthy, n=12 BRD) were used to construct gene co-expression modules and correlation patterns with complete blood count (CBC) and clinical datasets. Modules were further evaluated for cross-populational preservation of expression with RNA-Seq data from 24 cattle in an independent population (2019; n=12 Healthy, n=12 BRD). Genes within well-preserved modules were subject to functional enrichment analysis for significant Gene Ontology terms and pathways. Genes which possessed high module membership and association with BRD development, regardless of module preservation (“hub genes”), were utilized for protein-protein physical interaction network and clustering analyses. Five well-preserved modules of co-expressed genes were identified. One module (“steelblue”), involved in alpha-beta T-cell complexes and Th2-type immunity, possessed significant correlation with increased erythrocytes, platelets, and BRD development. One module (“purple”), involved in mitochondrial metabolism and rRNA maturation, possessed significant correlation with increased eosinophils, fecal egg count per gram, and weight gain over time. Fifty-two interacting hub genes, stratified into 11 clusters, may possess transient function involved in BRD development not previously described in literature. This study identifies co-expressed genes and coordinated mechanisms associated with BRD, which necessitates further investigation in BRD-prediction research.

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