Dataset Information

Diagnosis of Bovine Respiratory Disease in feedlot cattle using blood ¹H NMR metabolomics.

ABSTRACT: Current diagnosis methods for Bovine Respiratory Disease (BRD) in feedlots have a low diagnostic accuracy. The current study aimed to search for blood biomarkers of BRD using ¹H NMR metabolomics and determine their accuracy in diagnosing BRD. Animals with visual signs of BRD (n?=?149) and visually healthy (non-BRD; n?=?148) were sampled for blood metabolomics analysis. Lung lesions indicative of BRD were scored at slaughter. Non-targeted ¹H NMR metabolomics was used to develop predictive algorithms for disease classification using classification and regression trees. In the absence of a gold standard for BRD diagnosis, six reference diagnosis methods were used to define an animal as BRD or non-BRD. Sensitivity (Se) and specificity (Sp) were used to estimate diagnostic accuracy (Acc). Blood metabolomics demonstrated a high accuracy at diagnosing BRD when using visual signs of BRD (Acc?=?0.85), however was less accurate at diagnosing BRD using rectal temperature (Acc?=?0.65), lung auscultation score (Acc?=?0.61) and lung lesions at slaughter as reference diagnosis methods (Acc?=?0.71). Phenylalanine, lactate, hydroxybutyrate, tyrosine, citrate and leucine were identified as metabolites of importance in classifying animals as BRD or non-BRD. The blood metabolome classified BRD and non-BRD animals with high accuracy and shows potential for use as a BRD diagnosis tool.

SUBMITTER: Blakebrough-Hall C

PROVIDER: S-EPMC6954258 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Diagnosis of Bovine Respiratory Disease in feedlot cattle using blood 1H NMR metabolomics.

Blakebrough-Hall C C Dona A A D'occhio M J MJ McMeniman J J González L A LA

Scientific reports 20200110 1

Current diagnosis methods for Bovine Respiratory Disease (BRD) in feedlots have a low diagnostic accuracy. The current study aimed to search for blood biomarkers of BRD using 1H NMR metabolomics and determine their accuracy in diagnosing BRD. Animals with visual signs of BRD (n = 149) and visually healthy (non-BRD; n = 148) were sampled for blood metabolomics analysis. Lung lesions indicative of BRD were scored at slaughter. Non-targeted 1H NMR metabolomics was used to deve ...[more]

PMID: 31924818

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Project description:Bovine respiratory disease (BRD) is the most important cause of clinical disease and death in feedlot cattle. Respiratory viral infections are key components in predisposing cattle to the development of this disease. To quantify the contribution of four viruses commonly associated with BRD, a case-control study was conducted nested within the National Bovine Respiratory Disease Initiative project population in Australian feedlot cattle. Effects of exposure to Bovine viral diarrhoea virus 1 (BVDV-1), Bovine herpesvirus 1 (BoHV-1), Bovine respiratory syncytial virus (BRSV) and Bovine parainfluenza virus 3 (BPIV-3), and to combinations of these viruses, were investigated. Based on weighted seroprevalences at induction (when animals were enrolled and initial samples collected), the percentages of the project population estimated to be seropositive were 24% for BoHV-1, 69% for BVDV-1, 89% for BRSV and 91% for BPIV-3. For each of the four viruses, seropositivity at induction was associated with reduced risk of BRD (OR: 0.6-0.9), and seroincrease from induction to second blood sampling (35-60 days after induction) was associated with increased risk of BRD (OR: 1.3-1.5). Compared to animals that were seropositive for all four viruses at induction, animals were at progressively increased risk with increasing number of viruses for which they were seronegative; those seronegative for all four viruses were at greatest risk (OR: 2.4). Animals that seroincreased for one or more viruses from induction to second blood sampling were at increased risk (OR: 1.4-2.1) of BRD compared to animals that did not seroincrease for any viruses. Collectively these results confirm that prior exposure to these viruses is protective while exposure at or after feedlot entry increases the risk of development of BRD in feedlots. However, the modest increases in risk associated with seroincrease for each virus separately, and the progressive increases in risk with multiple viral exposures highlights the importance of concurrent infections in the aetiology of the BRD complex. These findings indicate that, while efficacious vaccines could aid in the control of BRD, vaccination against one of these viruses would not have large effects on population BRD incidence but vaccination against multiple viruses would be expected to result in greater reductions in incidence. The findings also confirm the multifactorial nature of BRD development, and indicate that multifaceted approaches in addition to efficacious vaccines against viruses will be required for substantial reductions in BRD incidence.

Project description:Bovine respiratory disease (BRD) is the most common and costly infectious disease affecting the wellbeing and productivity of beef cattle in North America. BRD is a complex disease whose development is dependent on environmental factors and host genetics. Due to the polymicrobial nature of BRD, our understanding of the genetic and molecular mechanisms underlying the disease is still limited. This knowledge would augment the development of better genetic/genomic selection strategies and more accurate diagnostic tools to reduce BRD prevalence. Therefore, this study aimed to utilize multi-omics data (genomics, transcriptomics, and metabolomics) analyses to study the genetic and molecular mechanisms of BRD infection. Blood samples of 143 cattle (80 BRD; 63 non-BRD animals) were collected for genotyping, RNA sequencing, and metabolite profiling. Firstly, a genome-wide association study (GWAS) was performed for BRD susceptibility using 207,038 SNPs. Two SNPs (Chr5:25858264 and BovineHD1800016801) were identified as associated (p-value <1 × 10-5) with BRD susceptibility. Secondly, differential gene expression between BRD and non-BRD animals was studied. At the significance threshold used (log2FC>2, logCPM>2, and FDR<0.01), 101 differentially expressed (DE) genes were identified. These DE genes significantly (p-value <0.05) enriched several immune responses related functions such as inflammatory response. Additionally, we performed expression quantitative trait loci (eQTL) analysis and identified 420 cis-eQTLs and 144 trans-eQTLs significantly (FDR <0.05) associated with the expression of DE genes. Interestingly, eQTL results indicated the most significant SNP (Chr5:25858264) identified via GWAS was a cis-eQTL for DE gene GPR84. This analysis also demonstrated that an important SNP (rs209419196) located in the promoter region of the DE gene BPI significantly influenced the expression of this gene. Finally, the abundance of 31 metabolites was significantly (FDR <0.05) different between BRD and non-BRD animals, and 17 of them showed correlations with multiple DE genes, which shed light on the interactions between immune response and metabolism. This study identified associations between genome, transcriptome, metabolome, and BRD phenotype of feedlot crossbred cattle. The findings may be useful for the development of genomic selection strategies for BRD susceptibility, and for the development of new diagnostic and therapeutic tools.

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Diagnosis of Bovine Respiratory Disease in feedlot cattle using blood ¹H NMR metabolomics.

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Diagnosis of Bovine Respiratory Disease in feedlot cattle using blood <sup>1</sup>H NMR metabolomics.

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