Diagnostic milk biomarkers for predicting the metabolic health status of dairy cattle during early lactation.

Data on metabolic profiles of blood sampled at d 3, 6, 9, and 21 in lactation from 117 lactations (99 cows) were used for unsupervised k-means clustering. Blood metabolic parameters included β-hydroxybutyrate (BHB), nonesterified fatty acids, glucose, insulin-like growth factor-1 (IGF-1) and insulin. Clustering relied on the average and range of the 5 blood parameters of all 4 sampling days. The clusters were labeled as imbalanced (n = 42) and balanced (n = 72) metabolic status based on the values of the blood parameters. Various random forest models were built to predict the metabolic cluster of cows during early lactation from the milk composition. All the models were evaluated using a leave-group-out cross-validation, meaning data from a single cow were always present in either train or test data to avoid any data leakage. Features were either milk fatty acids (MFA) determined by gas chromatography (MFA [GC]) or features that could be determined during a routine dairy herd improvement (DHI) analysis, such as concentration of fat, protein, lactose, fat/protein ratio, urea, and somatic cell count (determined and reported routinely in DHI registrations), either or not in combination with MFA and BHB determined by mid-infrared (MIR), denoted as MFA [MIR] and BHB [MIR], respectively, which are routinely analyzed but not routinely reported in DHI registrations yet. Models solely based on fat, protein, lactose, fat/protein ratio, urea and somatic cell count (i.e., DHI model) were characterized by the lowest predictive performance [area under the receiver operating characteristic curve (AUCROC) = 0.69]. The combination of the features of the DHI model with BHB [MIR] and MFA [MIR] powerfully increased the predictive performance (AUCROC = 0.81). The model based on the detailed MFA profile determined by GC analysis did not outperform (AUCROC = 0.81) the model using the DHI-features in combination with BHB [MIR] and MFA [MIR]. Predictions solely based on samples at d 3 were characterized by lower performance (AUCROC DHI + BHB [MIR] + MFA [MIR] model at d 3: 0.75; AUCROC MFA [GC] model at d 3: 0.73). High predictive performance was found using samples from d 9 and 21. To conclude, overall, the DHI + BHB [MIR] + MFA [MIR] model allowed to predict metabolic status during early lactation. Accordingly, these parameters show potential for routine prediction of metabolic status.

[1]  M. Hostens,et al.  Predicting physiological imbalance in Holstein dairy cows by three different sets of milk biomarkers. , 2020, Preventive veterinary medicine.

[2]  Kohske Takahashi,et al.  Welcome to the Tidyverse , 2019, J. Open Source Softw..

[3]  J. Bewley,et al.  On-farm use of disease alerts generated by precision dairy technology. , 2019, Journal of dairy science.

[4]  R. Bruckmaier,et al.  Prediction of metabolic status of dairy cows in early lactation with on-farm cow data and machine learning algorithms. , 2019, Journal of dairy science.

[5]  M. De Marchi,et al.  Invited review: β-hydroxybutyrate concentration in blood and milk and its associations with cow performance. , 2019, Animal : an international journal of animal bioscience.

[6]  M. T. Sorensen,et al.  Potential of milk mid-IR spectra to predict metabolic status of cows through blood components and an innovative clustering approach. , 2019, Animal : an international journal of animal bioscience.

[7]  C Baumgartner,et al.  Prediction model optimization using full model selection with regression trees demonstrated with FTIR data from bovine milk. , 2019, Preventive veterinary medicine.

[8]  M. Hostens,et al.  Prediction of metabolic clusters in early-lactation dairy cows using models based on milk biomarkers. , 2019, Journal of dairy science.

[9]  V. Fievez,et al.  Susceptibility of dairy cows to subacute ruminal acidosis is reflected in milk fatty acid proportions, with C18:1 trans-10 as primary and C15:0 and C18:1 trans-11 as secondary indicators. , 2018, Journal of dairy science.

[10]  J. Gross,et al.  Prevalence of subclinical ketosis and production diseases in dairy cows in Central and South America, Africa, Asia, Australia, New Zealand, and Eastern Europe1 , 2018, Translational animal science.

[11]  J. Gross,et al.  Prevalence of subclinical ketosis and production diseases in dairy cows in Central and South America, Africa, Asia, Australia and New Zealand, and Eastern Europe , 2018 .

[12]  D. Döpfer,et al.  Identifying poor metabolic adaptation during early lactation in dairy cows using cluster analysis. , 2018, Journal of dairy science.

[13]  Per B. Brockhoff,et al.  lmerTest Package: Tests in Linear Mixed Effects Models , 2017 .

[14]  L. Armentano,et al.  Use of milk fatty acids to estimate plasma nonesterified fatty acid concentrations as an indicator of animal energy balance. , 2017, Journal of dairy science.

[15]  D. Nydam,et al.  Short communication: Association of milk fatty acids with early lactation hyperketonemia and elevated concentration of nonesterified fatty acids. , 2016, Journal of dairy science.

[16]  J. Dijkstra,et al.  Prediction of methane emission from lactating dairy cows using milk fatty acids and mid-infrared spectroscopy. , 2016, Journal of the science of food and agriculture.

[17]  Andreas Ziegler,et al.  ranger: A Fast Implementation of Random Forests for High Dimensional Data in C++ and R , 2015, 1508.04409.

[18]  B. De Baets,et al.  Milk fatty acids as possible biomarkers to diagnose hyperketonemia in early lactation. , 2015, Journal of dairy science.

[19]  Max Kuhn,et al.  caret: Classification and Regression Training , 2015 .

[20]  B. De Baets,et al.  Milk fatty acids as possible biomarkers to early diagnose elevated concentrations of blood plasma nonesterified fatty acids in dairy cows. , 2014, Journal of dairy science.

[21]  D. Bates,et al.  Fitting Linear Mixed-Effects Models Using lme4 , 2014, 1406.5823.

[22]  J. Stegeman,et al.  Routine detection of hyperketonemia in dairy cows using Fourier transform infrared spectroscopy analysis of β-hydroxybutyrate and acetone in milk in combination with test-day information. , 2012, Journal of dairy science.

[23]  V. Fievez,et al.  Milk odd- and branched-chain fatty acids as biomarkers of rumen function—An update , 2012 .

[24]  P. Dardenne,et al.  Mid-infrared prediction of bovine milk fatty acids across multiple breeds, production systems, and countries. , 2011, Journal of dairy science.

[25]  J. Dijkstra,et al.  Update of the Dutch protein evaluation system for ruminants: the DVE/OEB2010 system , 2010, The Journal of Agricultural Science.

[26]  D. Nydam,et al.  Evaluation of nonesterified fatty acids and beta-hydroxybutyrate in transition dairy cattle in the northeastern United States: Critical thresholds for prediction of clinical diseases. , 2010, Journal of dairy science.

[27]  S. LeBlanc Monitoring metabolic health of dairy cattle in the transition period. , 2010, The Journal of reproduction and development.

[28]  H. Bovenhuis,et al.  Predicting bovine milk fat composition using infrared spectroscopy based on milk samples collected in winter and summer. , 2009, Journal of dairy science.

[29]  Hadley Wickham,et al.  ggplot2 - Elegant Graphics for Data Analysis (2nd Edition) , 2017 .

[30]  Haibo He,et al.  Learning from Imbalanced Data , 2009, IEEE Transactions on Knowledge and Data Engineering.

[31]  M. Lucy,et al.  Functional differences in the growth hormone and insulin-like growth factor axis in cattle and pigs: implications for post-partum nutrition and reproduction. , 2008, Reproduction in domestic animals = Zuchthygiene.

[32]  B. De Baets,et al.  Effect of lactation stage on the odd- and branched-chain milk fatty acids of dairy cattle under grazing and indoor conditions. , 2008, Journal of dairy science.

[33]  T. Hothorn,et al.  Simultaneous Inference in General Parametric Models , 2008, Biometrical journal. Biometrische Zeitschrift.

[34]  R. Dewhurst,et al.  Milk odd- and branched-chain fatty acids in relation to the rumen fermentation pattern. , 2006, Journal of dairy science.

[35]  Thomas Lengauer,et al.  ROCR: visualizing classifier performance in R , 2005, Bioinform..

[36]  G. Oetzel Monitoring and testing dairy herds for metabolic disease. , 2004, The Veterinary clinics of North America. Food animal practice.

[37]  S. Godden,et al.  Evaluation and use of three cowside tests for detection of subclinical ketosis in early postpartum cows. , 2004, Journal of dairy science.

[38]  J. Drackley,et al.  ADSA Foundation Scholar Award. Biology of dairy cows during the transition period: the final frontier? , 1999, Journal of dairy science.

[39]  R. Wolff,et al.  Evaluation of sequential methods for the determination of butterfat fatty acid composition with emphasis ontrans-18:1 acids. Application to the study of seasonal variations in french butters , 1995 .

[40]  J. A. Hartigan,et al.  A k-means clustering algorithm , 1979 .

[41]  A.J.H. Van Es,et al.  Feed evaluation for dairy cows , 1975 .

[42]  R. G. Ackman,et al.  Application of specific response factors in the gas chromatographic analysis of methyl esters of fatty acids with flame ionization detectors , 1964 .

[43]  R. Mendes R: The R Project for Statistical Computing , 2016 .

[44]  Proteintech Supplemental Tables and Figures for , 2011 .