Efficient genetic value prediction using incomplete omics data.

KEY MESSAGE: Covering a subset of individuals with a quantitative predictor, while imputing records for all others using pedigree or genomic data, could improve the precision of predictions while controlling for costs. Predicting genetic values with high accuracy is pivotal for effective candidate selection in animal and plant breeding. Novel 'omics'-based predictors have been shown to improve upon established genome-based predictions of important complex traits but require laborious and expensive assays. As a consequence, there are various datasets with full genetic marker coverage of all studied individuals but incomplete coverage with other 'omics' data. In animal breeding, single-step prediction was introduced to efficiently combine pedigree information, collected on a large number of animals, with genomic information, collected on a smaller subset of animals, for breeding value estimation without bias. Using two maize datasets of inbred lines and hybrids, we show that the single-step framework facilitates imputing transcriptomic data, boosting forecasts when their predictive ability exceeds that of pedigree or genomic data. Our results suggest that covering only a subset of inbred lines with 'omics' predictors and imputing all others using pedigree or genomic data could enable breeders to improve trait predictions while keeping costs under control. Employing 'omics' predictors could particularly improve candidate selection in hybrid breeding because the success of forecasts is a strongly convex function of predictive ability.

Omics-based hybrid prediction in maize.

KEY MESSAGE: Complementing genomic data with other "omics" predictors can increase the probability of success for predicting the best hybrid combinations using complex agronomic traits. Accurate prediction of traits with complex genetic architecture is crucial for selecting superior candidates in animal and plant breeding and for guiding decisions in personalized medicine. Whole-genome prediction has revolutionized these areas but has inherent limitations in incorporating intricate epistatic interactions. Downstream "omics" data are expected to integrate interactions within and between different biological strata and provide the opportunity to improve trait prediction. Yet, predicting traits from parents to progeny has not been addressed by a combination of "omics" data. Here, we evaluate several "omics" predictors-genomic, transcriptomic and metabolic data-measured on parent lines at early developmental stages and demonstrate that the integration of transcriptomic with genomic data leads to higher success rates in the correct prediction of untested hybrid combinations in maize. Despite the high predictive ability of genomic data, transcriptomic data alone outperformed them and other predictors for the most complex heterotic trait, dry matter yield. An eQTL analysis revealed that transcriptomic data integrate genomic information from both, adjacent and distant sites relative to the expressed genes. Together, these findings suggest that downstream predictors capture physiological epistasis that is transmitted from parents to their hybrid offspring. We conclude that the use of downstream "omics" data in prediction can exploit important information beyond structural genomics for leveraging the efficiency of hybrid breeding.

Genomic prediction of unordered categorical traits: an application to subpopulation assignment in German Warmblood horses.

BACKGROUND: Categorical traits without ordinal representation of classes do not qualify for threshold models. Alternatively, the multinomial problem can be assessed by a sequence of independent binary contrasts using schemes such as one-vs-all or one-vs-one. Class probabilities can be arrived at by normalization or pair-wise coupling strategies. We assessed the predictive ability of whole-genome regression models and support vector machines for the classification of horses into four German Warmblood breeds. RESULTS: Prediction accuracies of leave-one-out cross-validation were high and ranged from 0.75 to 0.97 depending on the binary classifier and breeds incorporated in the training. An analysis of the population structure using eigenvectors of the genomic relationship matrix revealed clustering of individuals beyond the given breed labels. Admixture between two breeds became apparent which had substantial impact on the prediction accuracies between those two breeds and also influenced the contrasts between other breeds. CONCLUSIONS: Genomic prediction of unordered categorical traits was successfully applied to subpopulation assignment of German Warmblood horses. The applied methodology is a straightforward extension of existing binary threshold models for genomic prediction.

Polymorphisms within the APOBR gene are highly associated with milk levels of prognostic ketosis biomarkers in dairy cows.

Essentially all high-yielding dairy cows experience a negative energy balance during early lactation leading to increased lipomobilization, which is a normal physiological response. However, a severe energy deficit may lead to high levels of ketone bodies and, subsequently, to subclinical or clinical ketosis. It has previously been reported that the ratio of glycerophosphocholine to phosphocholine in milk is a prognostic biomarker for the risk of ketosis in dairy cattle. It was hypothesized that this ratio reflects the ability to break down blood phosphatidylcholine as a fatty acid resource. In the current study, 248 animals from a previous study were genotyped with Illumina BovineSNP50 BeadChip, and genome-wide association studies were carried out for the milk levels of phosphocholine, glycerophosphocholine, and the ratio of both metabolites. It was demonstrated that the latter two traits are heritable with h2 = 0.43 and h2 = 0.34, respectively. A major quantitative trait locus was identified on cattle chromosome 25. The APOBR gene, coding for the apolipoprotein B receptor, is located within this region and was analyzed as a candidate gene. The analysis revealed highly significant associations of polymorphisms within the gene with glycerophosphocholine as well as the metabolite ratio. These findings support the hypothesis that differences in the ability to take up blood phosphatidylcholine from low-density lipoproteins play an important role in early lactation metabolic stability of dairy cows and indicate APOBR to contain a causative variant.

Novel use of derived genotype probabilities to discover significant dominance effects for milk production traits in dairy cattle.

The estimation of dominance effects requires the availability of direct phenotypes, i.e., genotypes and phenotypes in the same individuals. In dairy cattle, classical QTL mapping approaches are, however, relying on genotyped sires and daughter-based phenotypes like breeding values. Thus, dominance effects cannot be estimated. The number of dairy bulls genotyped for dense genome-wide marker panels is steadily increasing in the context of genomic selection schemes. The availability of genotyped cows is, however, limited. Within the current study, the genotypes of male ancestors were applied to the calculation of genotype probabilities in cows. Together with the cows' phenotypes, these probabilities were used to estimate dominance effects on a genome-wide scale. The impact of sample size, the depth of pedigree used in deriving genotype probabilities, the linkage disequilibrium between QTL and marker, the fraction of variance explained by the QTL, and the degree of dominance on the power to detect dominance were analyzed in simulation studies. The effect of relatedness among animals on the specificity of detection was addressed. Furthermore, the approach was applied to a real data set comprising 470,000 Holstein cows. To account for relatedness between animals a mixed-model two-step approach was used to adjust phenotypes based on an additive genetic relationship matrix. Thereby, considerable dominance effects were identified for important milk production traits. The approach might serve as a powerful tool to dissect the genetic architecture of performance and functional traits in dairy cattle.