TY - JOUR
T1 - Use of nCounter mRNA profiling to identify at-arrival gene expression patterns for predicting bovine respiratory disease in beef cattle
AU - Scott, Matthew A.
AU - Woolums, Amelia R.
AU - Swiderski, Cyprianna E.
AU - Thompson, Alexis C.
AU - Perkins, Andy D.
AU - Nanduri, Bindu
AU - Karisch, Brandi B.
AU - Goehl, Dan R.
N1 - Funding Information:
This research was supported by the Animal Health and Disease Program [Grant no. 2020–67016-31469] from the USDA National Institute of Food and Agriculture.
Funding Information:
The authors would like to thank Elliot Sandhu, Lyra Griffiths, and Emory Integrated Genomic Core (EIGC) staff for their technical assistance and support. The authors additionally thank Marguerite Yelverton, William Crosby, Richard Wagner, Kirsten Midkiff, Merrilee Thoresen, Brianna Furman, Kelsey Shields, and the staff at the Mississippi Agriculture and Forestry Experiment Station (MAFES) and Professional Beef Services, LLC for their assistance in animal care, sample collection, and data preparation.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Background: Transcriptomics has identified at-arrival differentially expressed genes associated with bovine respiratory disease (BRD) development; however, their use as prediction molecules necessitates further evaluation. Therefore, we aimed to selectively analyze and corroborate at-arrival mRNA expression from multiple independent populations of beef cattle. In a nested case-control study, we evaluated the expression of 56 mRNA molecules from at-arrival blood samples of 234 cattle across seven populations via NanoString nCounter gene expression profiling. Analysis of mRNA was performed with nSolver Advanced Analysis software (p < 0.05), comparing cattle groups based on the diagnosis of clinical BRD within 28 days of facility arrival (n = 115 Healthy; n = 119 BRD); BRD was further stratified for severity based on frequency of treatment and/or mortality (Treated_1, n = 89; Treated_2+, n = 30). Gene expression homogeneity of variance, receiver operator characteristic (ROC) curve, and decision tree analyses were performed between severity cohorts. Results: Increased expression of mRNAs involved in specialized pro-resolving mediator synthesis (ALOX15, HPGD), leukocyte differentiation (LOC100297044, GCSAML, KLF17), and antimicrobial peptide production (CATHL3, GZMB, LTF) were identified in Healthy cattle. BRD cattle possessed increased expression of CFB, and mRNA related to granulocytic processes (DSG1, LRG1, MCF2L) and type-I interferon activity (HERC6, IFI6, ISG15, MX1). Healthy and Treated_1 cattle were similar in terms of gene expression, while Treated_2+ cattle were the most distinct. ROC cutoffs were used to generate an at-arrival treatment decision tree, which classified 90% of Treated_2+ individuals. Conclusions: Increased expression of complement factor B, pro-inflammatory, and type I interferon-associated mRNA hallmark the at-arrival expression patterns of cattle that develop severe clinical BRD. Here, we corroborate at-arrival mRNA markers identified in previous transcriptome studies and generate a prediction model to be evaluated in future studies. Further research is necessary to evaluate these expression patterns in a prospective manner.
AB - Background: Transcriptomics has identified at-arrival differentially expressed genes associated with bovine respiratory disease (BRD) development; however, their use as prediction molecules necessitates further evaluation. Therefore, we aimed to selectively analyze and corroborate at-arrival mRNA expression from multiple independent populations of beef cattle. In a nested case-control study, we evaluated the expression of 56 mRNA molecules from at-arrival blood samples of 234 cattle across seven populations via NanoString nCounter gene expression profiling. Analysis of mRNA was performed with nSolver Advanced Analysis software (p < 0.05), comparing cattle groups based on the diagnosis of clinical BRD within 28 days of facility arrival (n = 115 Healthy; n = 119 BRD); BRD was further stratified for severity based on frequency of treatment and/or mortality (Treated_1, n = 89; Treated_2+, n = 30). Gene expression homogeneity of variance, receiver operator characteristic (ROC) curve, and decision tree analyses were performed between severity cohorts. Results: Increased expression of mRNAs involved in specialized pro-resolving mediator synthesis (ALOX15, HPGD), leukocyte differentiation (LOC100297044, GCSAML, KLF17), and antimicrobial peptide production (CATHL3, GZMB, LTF) were identified in Healthy cattle. BRD cattle possessed increased expression of CFB, and mRNA related to granulocytic processes (DSG1, LRG1, MCF2L) and type-I interferon activity (HERC6, IFI6, ISG15, MX1). Healthy and Treated_1 cattle were similar in terms of gene expression, while Treated_2+ cattle were the most distinct. ROC cutoffs were used to generate an at-arrival treatment decision tree, which classified 90% of Treated_2+ individuals. Conclusions: Increased expression of complement factor B, pro-inflammatory, and type I interferon-associated mRNA hallmark the at-arrival expression patterns of cattle that develop severe clinical BRD. Here, we corroborate at-arrival mRNA markers identified in previous transcriptome studies and generate a prediction model to be evaluated in future studies. Further research is necessary to evaluate these expression patterns in a prospective manner.
KW - Beef cattle
KW - Bioinformatics
KW - Biomarkers
KW - Bovine respiratory disease
KW - Disease prediction
KW - Gene expression
KW - Host immunology
KW - Infectious disease
KW - NanoString
KW - mRNA
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U2 - 10.1186/s12917-022-03178-8
DO - 10.1186/s12917-022-03178-8
M3 - Article
C2 - 35197051
AN - SCOPUS:85125215724
VL - 18
JO - BMC Veterinary Research
JF - BMC Veterinary Research
SN - 1746-6148
IS - 1
M1 - 77
ER -