TY - JOUR
T1 - Serum 1H nuclear magnetic resonance-based metabolomics of sole lesion development in Holstein cows
AU - Barden, Matthew
AU - Phelan, Marie M
AU - Hyde, Robert
AU - Anagnostopoulos, Alkiviadis
AU - Griffiths, Bethany E
AU - Bedford, Cherry
AU - Green, Martin
AU - Psifidi, Androniki
AU - Banos, Georgios
AU - Oikonomou, Georgios
N1 - Funding Information:
This study was part of a wider project funded by the UK Biotechnology and Biological Sciences Research Council (BBSRC, Swindon, UK; Council References: BB/S002960/1, BB/S002944/1, BB/S003614/1), with additional funding from the Technology Directorate Strategy Group, University of Liverpool (Liverpool, UK), and constitutes part of a PhD funded by the School of Veterinary Science, University of Liverpool. Mollie Rudd, Amy Russon, Kerry Long, Theologia Menka, Konstantinos Georgakoudis, Konstantina Kasiora, Charlotte Smith, Aiglyne Chaperone, Ioanna Soumtaki (Department of Livestock and One Health, University of Liverpool), and all farm staff are gratefully acknowledged for assisting with data collection. The authors thank the reviewers for their insightful and constructive comments. The authors have not stated any conflicts of interest.
Publisher Copyright:
© 2023 American Dairy Science Association
PY - 2023/4
Y1 - 2023/4
N2 - Sole hemorrhage and sole ulcers, referred to as sole lesions, are important causes of lameness in dairy cattle. We aimed to compare the serum metabolome of dairy cows that developed sole lesions in early lactation with that of cows that remained unaffected. We prospectively enrolled a cohort of 1,169 Holstein dairy cows from a single dairy herd and assessed animals at 4 time points: before calving, immediately after calving, early lactation, and late lactation. Sole lesions were recorded by veterinary surgeons at each time point, and serum samples were collected at the first 3 time points. Cases were defined by the presence of sole lesions in early lactation and further subdivided by whether sole lesions had been previously recorded; unaffected controls were randomly selected to match cases. Serum samples from a case-control subset of 228 animals were analyzed with proton nuclear magnetic resonance spectroscopy. Spectral signals, corresponding to 34 provisionally annotated metabolites and 51 unlabeled metabolites, were analyzed in subsets relating to time point, parity cohort, and sole lesion outcome. We used 3 analytic methods (partial least squares discriminant analysis, least absolute shrinkage and selection operator regression, and random forest) to determine the predictive capacity of the serum metabolome and identify informative metabolites. We applied bootstrapped selection stability, triangulation, and permutation to support the inference of variable selection. The average balanced accuracy of class prediction ranged from 50 to 62% depending on the subset. Across all 17 subsets, 20 variables had a high probability of being informative; those with the strongest evidence of being associated with sole lesions corresponded to phenylalanine and 4 unlabeled metabolites. We conclude that the serum metabolome, as characterized by proton nuclear magnetic resonance spectroscopy, does not appear able to predict sole lesion presence or future development of lesions. A small number of metabolites may be associated with sole lesions although, given the poor prediction accuracies, these metabolites are likely to explain only a small proportion of the differences between affected and unaffected animals. Future metabolomic studies may reveal underlying metabolic mechanisms of sole lesion etiopathogenesis in dairy cows; however, the experimental design and analysis need to effectively control for interanimal and extraneous sources of spectral variation.
AB - Sole hemorrhage and sole ulcers, referred to as sole lesions, are important causes of lameness in dairy cattle. We aimed to compare the serum metabolome of dairy cows that developed sole lesions in early lactation with that of cows that remained unaffected. We prospectively enrolled a cohort of 1,169 Holstein dairy cows from a single dairy herd and assessed animals at 4 time points: before calving, immediately after calving, early lactation, and late lactation. Sole lesions were recorded by veterinary surgeons at each time point, and serum samples were collected at the first 3 time points. Cases were defined by the presence of sole lesions in early lactation and further subdivided by whether sole lesions had been previously recorded; unaffected controls were randomly selected to match cases. Serum samples from a case-control subset of 228 animals were analyzed with proton nuclear magnetic resonance spectroscopy. Spectral signals, corresponding to 34 provisionally annotated metabolites and 51 unlabeled metabolites, were analyzed in subsets relating to time point, parity cohort, and sole lesion outcome. We used 3 analytic methods (partial least squares discriminant analysis, least absolute shrinkage and selection operator regression, and random forest) to determine the predictive capacity of the serum metabolome and identify informative metabolites. We applied bootstrapped selection stability, triangulation, and permutation to support the inference of variable selection. The average balanced accuracy of class prediction ranged from 50 to 62% depending on the subset. Across all 17 subsets, 20 variables had a high probability of being informative; those with the strongest evidence of being associated with sole lesions corresponded to phenylalanine and 4 unlabeled metabolites. We conclude that the serum metabolome, as characterized by proton nuclear magnetic resonance spectroscopy, does not appear able to predict sole lesion presence or future development of lesions. A small number of metabolites may be associated with sole lesions although, given the poor prediction accuracies, these metabolites are likely to explain only a small proportion of the differences between affected and unaffected animals. Future metabolomic studies may reveal underlying metabolic mechanisms of sole lesion etiopathogenesis in dairy cows; however, the experimental design and analysis need to effectively control for interanimal and extraneous sources of spectral variation.
KW - lameness
KW - claw horn lesions
KW - metabolomics
KW - nuclear magnetic resonance (NMR) spectroscopy
U2 - 10.3168/jds.2022-22681
DO - 10.3168/jds.2022-22681
M3 - Article
C2 - 36870845
SN - 0022-0302
VL - 106
SP - 2667
EP - 2684
JO - Journal of Dairy Science
JF - Journal of Dairy Science
IS - 4
ER -