Capitalizing genebank core collections for rare and novel disease resistance loci to enhance barley resilience.

In the realm of agricultural sustainability, the utilization of plant genetic resources (PGRs) for enhanced disease resistance is paramount. Preservation efforts in genebanks are justified by their potential contributions to future crop improvement. To capitalize on the potential of PGRs, we focused on a barley core collection from the German ex situ genebank, and contrasted it with a European elite collection. The phenotypic assessment included 812 PGRs and 298 elites with a particular emphasis on four disease traits (Puccinia hordei, Blumeria graminis hordei, Ramularia collo-cygni, and Rhynchosporium commune). An integrated genome-wide association study, employing both Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (BLINK) and a linear mixed model, was performed to unravel the genetic underpinnings of disease resistance. A total of 932 marker-trait associations were identified and assigned to 49 quantitative trait loci. The accumulation of novel and rare resistance alleles significantly bolstered the overall resistance level in PGRs. Three PGR donors with high counts of novel/rare alleles and exhibited exceptional resistance to leaf rust and powdery mildew were identified, offering promise for targeted pre-breeding goals and enhanced resilience in forthcoming varieties. Our findings underscore the critical contribution of PGRs to strengthening crop resilience and advancing sustainable agricultural practices.

Maximization through optimization? On the relationship between hybrid performance and parental genetic distance.

Heterosis is the improved performance of hybrids compared with their parental components and is widely exploited in agriculture. According to quantitative genetic theory, genetic distance between parents at heterotic quantitative trait loci is required for heterosis, but how heterosis varies with genetic distance has remained elusive, despite intensive research on the topic. Experimental studies have often found a positive association between heterosis and genetic distance that, however, varied in strength. Most importantly, it has remained unclear whether heterosis increases continuously with genetic distance or whether there is an optimum genetic distance after which heterosis declines again. Here, we revisit the relationship between heterosis and genetic distance and provide perspectives on how to maximize heterosis and hybrid performance in breeding, as well as the consequences for the design of heterotic groups and the utilization of more exotic material and genetic resources.

Genetic control and prospects of predictive breeding for European winter wheat's Zeleny sedimentation values and Hagberg-Perten falling number.

KEY MESSAGE: Sedimentation values and falling number in the last decades have helped maintain high baking quality despite rigorous selection for grain yield in wheat. Allelic combinations of major loci sustained the bread-making quality while improving grain yield. Glu-D1, Pinb-D1, and non-gluten proteins are associated with sedimentation values and falling number in European wheat. Zeleny sedimentation values (ZSV) and Hagberg-Perten falling number (HFN) are among the most important parameters that help determine the baking quality classes of wheat and, thus, influence the monetary benefits for growers. We used a published data set of 372 European wheat varieties evaluated in replicated field trials in multiple environments. ZSV and HFN traits hold a wide and significant genotypic variation and high broad-sense heritability. The genetic correlations revealed positive and significant associations of ZSV and HFN with each other, grain protein content (GPC) and grain hardness; however, they were all significantly negatively correlated with grain yield. Besides, GPC appeared to be the major predictor for ZSV and HFN. Our genome-wide association analyses based on high-quality SSR, SNP, and candidate gene markers revealed a strong quantitative genetic nature of ZSV and HFN by explaining their total genotypic variance as 41.49% and 38.06%, respectively. The association of known Glutenin (Glu-1) and Puroindoline (Pin-1) with ZSV provided positive analytic proof of our studies. We report novel candidate loci associated with globulins and albumins-the non-gluten monomeric proteins in wheat. In addition, predictive breeding analyses for ZSV and HFN suggest using genomic selection in the early stages of breeding programs with an average prediction accuracy of 81 and 59%, respectively.

Deciphering the genetic basis of resistance to soybean cyst nematode combining IBD and association mapping.

KEY MESSAGE: IBD analysis clarified the dynamics of chromosomal recombination during the ZP pedigree breeding process and identified ten genomic regions resistant to SCN race3 combining association mapping. Soybean cyst nematode (SCN, Heterodera glycines Ichinohe) is one of the most devastating pathogens for soybean production worldwide. The cultivar Zhongpin03-5373 (ZP), derived from SCN-resistant progenitor parents, Peking, PI 437654 and Huipizhi Heidou, is an elite line with high resistance to SCN race3. In the current study, a pedigree variation map was generated for ZP and its ten progenitors using 3,025,264 high-quality SNPs identified from an average of 16.2 × re-sequencing for each genome. Through identity by decent (IBD) tracking, we showed the dynamic change of genome and detected important IBD fragments, which revealed the comprehensively artificial selection of important traits during ZP breeding process. A total of 2,353 IBD fragments related to SCN resistance including SCN-resistant genes rhg1, rhg4 and NSFRAN07 were identified based on the resistant-related genetic paths. Moreover, 23 genomic regions underlying resistance to SCN race3 were identified by genome-wide association study (GWAS) in 481 re-sequenced cultivated soybeans. Ten common loci were found by both IBD tracking and GWAS analysis. Haplotype analysis of 16 potential candidate genes suggested a causative SNP (C/T, - 1065) located in the promoter of Glyma.08G096500 and encoding a predicted TIFY5b-related protein on chr8 was highly correlated with SCN race3 resistance. Our results more thoroughly elucidated the dynamics of genomic fragments during ZP pedigree breeding and the genetic basis of SCN resistance, which will provide useful information for gene cloning and the development of resistant soybean cultivars using a marker-assisted selection approach.

A catalogue of resistance gene homologs and a chromosome-scale reference sequence support resistance gene mapping in winter wheat.

A resistance gene atlas is an integral component of the breeder's arsenal in the fight against evolving pathogens. Thanks to high-throughput sequencing, catalogues of resistance genes can be assembled even in crop species with large and polyploid genomes. Here, we report on capture sequencing and assembly of resistance gene homologs in a diversity panel of 907 winter wheat genotypes comprising ex situ genebank accessions and current elite cultivars. In addition, we use accurate long-read sequencing and chromosome conformation capture sequencing to construct a chromosome-scale genome sequence assembly of cv. Attraktion, an elite variety representative of European winter wheat. We illustrate the value of our resource for breeders and geneticists by (i) comparing the resistance gene complements in plant genetic resources and elite varieties and (ii) conducting genome-wide associations scans (GWAS) for the fungal diseases yellow rust and leaf rust using reference-based and reference-free GWAS approaches. The gene content under GWAS peaks was scrutinized in the assembly of cv. Attraktion.

Choosing the right tool: Leveraging of plant genetic resources in wheat (Triticum aestivum L.) benefits from selection of a suitable genomic prediction model.

KEY MESSAGE: Genomic prediction of genebank accessions benefits from the consideration of additive-by-additive epistasis and subpopulation-specific marker effects. Wheat (Triticum aestivum L.) and other species of the Triticum genus are well represented in genebank collections worldwide. The substantial genetic diversity harbored by more than 850,000 accessions can be explored for their potential use in modern plant breeding. Characterization of these large number of accessions is constrained by the required resources, and this fact limits their use so far. This limitation might be overcome by engaging genomic prediction. The present study compared ten different genomic prediction approaches to the prediction of four traits, namely flowering time, plant height, thousand grain weight, and yellow rust resistance, in a diverse set of 7745 accession samples from Germany's Federal ex situ genebank at the Leibniz Institute of Plant Genetics and Crop Plant Research in Gatersleben. Approaches were evaluated based on prediction ability and robustness to the confounding influence of strong population structure. The authors propose the wide application of extended genomic best linear unbiased prediction due to the observed benefit of incorporating additive-by-additive epistasis. General and subpopulation-specific additive ridge regression best linear unbiased prediction, which accounts for subpopulation-specific marker-effects, was shown to be a good option if contrasting clusters are encountered in the analyzed collection. The presented findings reaffirm that the trait's genetic architecture as well as the composition and relatedness of the training set and test set are major driving factors for the accuracy of genomic prediction.

SoySNP618K array: A high-resolution single nucleotide polymorphism platform as a valuable genomic resource for soybean genetics and breeding.

Innovations in genomics have enabled the development of low-cost, high-resolution, single nucleotide polymorphism (SNP) genotyping arrays that accelerate breeding progress and support basic research in crop science. Here, we developed and validated the SoySNP618K array (618,888 SNPs) for the important crop soybean. The SNPs were selected from whole-genome resequencing data containing 2,214 diverse soybean accessions; 29.34% of the SNPs mapped to genic regions representing 86.85% of the 56,044 annotated high-confidence genes. Identity-by-state analyses of 318 soybeans revealed 17 redundant accessions, highlighting the potential of the SoySNP618K array in supporting gene bank management. The patterns of population stratification and genomic regions enriched through domestication were highly consistent with previous findings based on resequencing data, suggesting that the ascertainment bias in the SoySNP618K array was largely compensated for. Genome-wide association mapping in combination with reported quantitative trait loci enabled fine-mapping of genes known to influence flowering time, E2 and GmPRR3b, and of a new candidate gene, GmVIP5. Moreover, genomic prediction of flowering and maturity time in 502 recombinant inbred lines was highly accurate (>0.65). Thus, the SoySNP618K array is a valuable genomic tool that can be used to address many questions in applied breeding, germplasm management, and basic crop research.

Genomics and breeding innovations for enhancing genetic gain for climate resilience and nutrition traits.

KEY MESSAGE: Integrating genomics technologies and breeding methods to tweak core parameters of the breeder's equation could accelerate delivery of climate-resilient and nutrient rich crops for future food security. Accelerating genetic gain in crop improvement programs with respect to climate resilience and nutrition traits, and the realization of the improved gain in farmers' fields require integration of several approaches. This article focuses on innovative approaches to address core components of the breeder's equation. A prerequisite to enhancing genetic variance (σ2g) is the identification or creation of favorable alleles/haplotypes and their deployment for improving key traits. Novel alleles for new and existing target traits need to be accessed and added to the breeding population while maintaining genetic diversity. Selection intensity (i) in the breeding program can be improved by testing a larger population size, enabled by the statistical designs with minimal replications and high-throughput phenotyping. Selection priorities and criteria to select appropriate portion of the population too assume an important role. The most important component of breeder's equation is heritability (h2). Heritability estimates depend on several factors including the size and the type of population and the statistical methods. The present article starts with a brief discussion on the potential ways to enhance σ2g in the population. We highlight statistical methods and experimental designs that could improve trait heritability estimation. We also offer a perspective on reducing the breeding cycle time (t), which could be achieved through the selection of appropriate parents, optimizing the breeding scheme, rapid fixation of target alleles, and combining speed breeding with breeding programs to optimize trials for release. Finally, we summarize knowledge from multiple disciplines for enhancing genetic gains for climate resilience and nutritional traits.

Genomic prediction models trained with historical records enable populating the German ex situ genebank bio-digital resource center of barley (Hordeum sp.) with information on resistances to soilborne barley mosaic viruses.

KEY MESSAGE: Genomic prediction with special weight of major genes is a valuable tool to populate bio-digital resource centers. Phenotypic information of crop genetic resources is a prerequisite for an informed selection that aims to broaden the genetic base of the elite breeding pools. We investigated the potential of genomic prediction based on historical screening data of plant responses against the Barley yellow mosaic viruses for populating the bio-digital resource center of barley. Our study includes dense marker data for 3838 accessions of winter barley, and historical screening data of 1751 accessions for Barley yellow mosaic virus (BaYMV) and of 1771 accessions for Barley mild mosaic virus (BaMMV). Linear mixed models were fitted by considering combinations for the effects of genotypes, years, and locations. The best linear unbiased estimations displayed a broad spectrum of plant responses against BaYMV and BaMMV. Prediction abilities, computed as correlations between predictions and observed phenotypes of accessions, were low for the marker-assisted selection approach amounting to 0.42. In contrast, prediction abilities of genomic best linear unbiased predictions were high, with values of 0.62 for BaYMV and 0.64 for BaMMV. Prediction abilities of genomic prediction were improved by up to ~ 5% using W-BLUP, in which more weight is given to markers with significant major effects found by association mapping. Our results outline the utility of historical screening data and W-BLUP model to predict the performance of the non-phenotyped individuals in genebank collections. The presented strategy can be considered as part of the different approaches used in genebank genomics to valorize genetic resources for their usage in disease resistance breeding and research.

Exome association analysis sheds light onto leaf rust (Puccinia triticina) resistance genes currently used in wheat breeding (Triticum aestivum L.).

Resistance breeding is crucial for a sustainable control of leaf rust (Puccinia triticina) in wheat (Triticum aestivum L.) while directly targeting functional variants is the Holy Grail for efficient marker-assisted selection and map-based cloning. We assessed the limits and prospects of exome association analysis for severity of leaf rust in a large hybrid wheat population of 1574 single-crosses plus their 133 parents. After imputation and quality control, exome sequencing revealed 202 875 single-nucleotide polymorphisms (SNPs) covering 19.7% of the high-confidence annotated gene space. We performed intensive data mining and found significant associations for 2171 SNPs corresponding to 50 different loci. Some of these associations mapped in the proximity of the already known resistance genes Lr21, Lr34-B, Lr1 and Lr10, while other associated genomic regions, such as those on chromosomes 1A and 3D, harboured several annotated genes putatively involved in resistance. Validation with an independent population helped to narrow down the list of putative resistance genes that should be targeted by fine-mapping. We expect that the proposed strategy of intensive data mining coupled with validation will significantly influence research in plant genetics and breeding.

Enabling reusability of plant phenomic datasets with MIAPPE 1.1.

Enabling data reuse and knowledge discovery is increasingly critical in modern science, and requires an effort towards standardising data publication practices. This is particularly challenging in the plant phenotyping domain, due to its complexity and heterogeneity. We have produced the MIAPPE 1.1 release, which enhances the existing MIAPPE standard in coverage, to support perennial plants, in structure, through an explicit data model, and in clarity, through definitions and examples. We evaluated MIAPPE 1.1 by using it to express several heterogeneous phenotyping experiments in a range of different formats, to demonstrate its applicability and the interoperability between the various implementations. Furthermore, the extended coverage is demonstrated by the fact that one of the datasets could not have been described under MIAPPE 1.0. MIAPPE 1.1 marks a major step towards enabling plant phenotyping data reusability, thanks to its extended coverage, and especially the formalisation of its data model, which facilitates its implementation in different formats. Community feedback has been critical to this development, and will be a key part of ensuring adoption of the standard.

Haplotype-based genome-wide association increases the predictability of leaf rust (Puccinia triticina) resistance in wheat.

Resistance breeding is crucial for sustainable control of wheat leaf rust and single nucleotide polymorphism (SNP)-based genome-wide association studies (GWAS) are widely used to dissect leaf rust resistance. Unfortunately, GWAS based on SNPs often explained only a small proportion of the genetic variation. We compared SNP-based GWAS with a method based on functional haplotypes (FH) considering epistasis in a comprehensive hybrid wheat mapping population composed of 133 parents plus their 1574 hybrids and characterized with 626 245 high-quality SNPs. In total, 2408 and 1 139 828 significant associations were detected in the mapping population by using SNP-based and FH-based GWAS, respectively. These associations mapped to 25 and 69 candidate regions, correspondingly. SNP-based GWAS highlighted two already-known resistance genes, Lr22a and Lr34-B, while FH-based GWAS detected associations not only on these genes but also on two additional genes, Lr10 and Lr1. As revealed by a second hybrid wheat population for independent validation, the use of detected associations from SNP-based and FH-based GWAS reached predictabilities of 11.72% and 22.86%, respectively. Therefore, FH-based GWAS is not only more powerful for detecting associations, but also improves the accuracy of marker-assisted selection compared with the SNP-based approach.

The potential of hybrid breeding to enhance leaf rust and stripe rust resistance in wheat.

KEY MESSAGE: Hybrid wheat breeding is a promising strategy to improve the level of leaf rust and stripe rust resistance in wheat. Leaf rust and stripe rust belong to the most important fungal diseases in wheat production. Due to a dynamic development of new virulent races, epidemics appear in high frequency and causes significant losses in grain yield and quality. Therefore, research is needed to develop strategies to breed wheat varieties carrying highly efficient resistances. Stacking of dominant resistance genes through hybrid breeding is such an approach. Within this study, we investigated the genetic architecture of leaf rust and stripe rust resistance of 1750 wheat hybrids and their 230 parental lines using a genome-wide association study. We observed on average a lower rust susceptibility for hybrids in comparison to their parental inbred lines and some hybrids outperformed their better parent with up to 56%. Marker-trait associations were identified on chromosome 3D and 4A for leaf rust and on chromosome 2A, 2B, and 6A for stripe rust resistance by using a genome-wide association study with a Bonferroni-corrected threshold of P < 0.10. Detected loci on chromosomes 4A and 2A were located within previously reported genomic regions affecting leaf rust and stripe rust resistance, respectively. The degree of dominance was for most associations favorable in the direction of improved resistance. Thus, resistance can be increased in hybrid wheat breeding by fixing complementary leaf rust and stripe rust resistance genes with desired dominance effects in opposite parental pools.

Reciprocal recurrent genomic selection: an attractive tool to leverage hybrid wheat breeding.

KEY MESSAGE: Using a two-part breeding strategy based on a population improvement and a product development component can leverage hybrid wheat breeding. Despite the technological advance of methods to facilitate hybrid breeding in self-pollinating crops, line breeding is still the dominating breeding strategy. This is likely due to a higher long-term selection gain in line compared to hybrid breeding. In this respect, recent studies on two-part strategies splitting the breeding program into a population improvement and a product development component could mark a trend reversal. Here, an overview of experimental and simulation-based studies exploring the possibilities to integrate genome-wide prediction into recurrent selection is given. Furthermore, possibilities to make use of recurrent selection for inter-population improvement are discussed. Current findings of simulation studies and quantitative genetic considerations suggest that long-term selection gain of hybrid breeding can be increased by implementing a two-part selection strategy based on reciprocal recurrent genomic selection. This would strengthen the competitiveness of hybrid versus line breeding facilitating to develop outstanding hybrid varieties also for self-pollinating plants such as wheat.

Genetic variation of growth dynamics in maize (Zea mays L.) revealed through automated non-invasive phenotyping.

Hitherto, most quantitative trait loci of maize growth and biomass yield have been identified for a single time point, usually the final harvest stage. Through this approach cumulative effects are detected, without considering genetic factors causing phase-specific differences in growth rates. To assess the genetics of growth dynamics, we employed automated non-invasive phenotyping to monitor the plant sizes of 252 diverse maize inbred lines at 11 different developmental time points; 50 k SNP array genotype data were used for genome-wide association mapping and genomic selection. The heritability of biomass was estimated to be over 71%, and the average prediction accuracy amounted to 0.39. Using the individual time point data, 12 main effect marker-trait associations (MTAs) and six pairs of epistatic interactions were detected that displayed different patterns of expression at various developmental time points. A subset of them also showed significant effects on relative growth rates in different intervals. The detected MTAs jointly explained up to 12% of the total phenotypic variation, decreasing with developmental progression. Using non-parametric functional mapping and multivariate mapping approaches, four additional marker loci affecting growth dynamics were detected. Our results demonstrate that plant biomass accumulation is a complex trait governed by many small effect loci, most of which act at certain restricted developmental phases. This highlights the need for investigation of stage-specific growth affecting genes to elucidate important processes operating at different developmental phases.

Genome-wide association analyses of plant growth traits during the stem elongation phase in wheat.

One of the primary objectives of wheat breeding was to increase grain yield. Floral abortion during the stem elongation phase (SEP) leads to a loss of more than 50% of the grain number potential. In this study, we quantified 75 plant growth-associated traits at seven stages during the SEP and mapped 15 696 single nucleotide polymorphism (SNP) markers in 210 accessions of wheat (Triticum aestivum). Our genomewide association study identified trait-associated SNPs that are shared among various stages of the SEP, as well as SNPs that are shared between plant growth traits and grain yield in the field. The genomic selection analysis shows variation among the prediction abilities of various traits and stages. Furthermore, we found that the allelic variants of Ppd-D1 (chromosome 2D) and Rht-D1 (chromosome 4D) loci affect some plant growth traits (e.g. leaf area and spike length). These results have identified a narrow time window within the SEP in which plant growth traits can be manipulated to alter grain yield. This suggests that there may be multiple ways to regulate plant growth during the SEP, to ultimately influence grain number in wheat.

Advantages and limitations of multiple-trait genomic prediction for Fusarium head blight severity in hybrid wheat (Triticum aestivum L.).

KEY MESSAGE: Predictabilities for wheat hybrids less related to the estimation set were improved by shifting from single- to multiple-trait genomic prediction of Fusarium head blight severity. Breeding for improved Fusarium head blight resistance (FHBr) of wheat is a very laborious and expensive task. FHBr complexity is mainly due to its highly polygenic nature and because FHB severity (FHBs) is greatly influenced by the environment. Associated traits plant height and heading date may provide additional information related to FHBr, but this is ignored in single-trait genomic prediction (STGP). The aim of our study was to explore the benefits in predictabilities of multiple-trait genomic prediction (MTGP) over STGP of target trait FHBs in a population of 1604 wheat hybrids using information on 17,372 single nucleotide polymorphism markers along with indicator traits plant height and heading date. The additive inheritance of FHBs allowed accurate hybrid performance predictions using information on general combining abilities or average performance of both parents without the need of markers. Information on molecular markers and indicator trait(s) improved FHBs predictabilities for hybrids less related to the estimation set. Indicator traits must be observed on the predicted individuals to benefit from MTGP. Magnitudes of genetic and phenotypic correlations along with improvements in predictabilities made plant height a better indicator trait for FHBs than heading date. Thus, MTGP having only plant height as indicator trait already maximized FHBs predictabilities. Provided a good indicator trait was available, MTGP could reduce the impacts of genotype environment [Formula: see text] interaction on STGP for hybrids less related to the estimation set.

Exploiting the Rht portfolio for hybrid wheat breeding.

KEY MESSAGE: The portfolio of available Reduced height loci (Rht-B1, Rht-D1, and Rht24) can be exploited for hybrid wheat breeding to achieve the desired heights in the female and male parents, as well as in the hybrids, without adverse effects on other traits relevant for hybrid seed production. Plant height is an important trait in wheat line breeding, but is of even greater importance in hybrid wheat breeding. Here, the height of the female and male parental lines must be controlled and adjusted relative to each other to maximize hybrid seed production. In addition, the height of the resulting hybrids must be fine-tuned to meet the specific requirements of the farmers in the target regions. Moreover, this must be achieved without adversely impacting traits relevant for hybrid seed production. In this study, we explored Reduced height (Rht) loci effective in elite wheat and exploited their utilization for hybrid wheat breeding. We performed association mapping in a panel of 1705 wheat hybrids and their 225 parental lines, which besides the Rht-B1 and Rht-D1 loci revealed Rht24 as a major QTL for plant height. Furthermore, we found that the Rht-1 loci also reduce anther extrusion and thus cross-pollination ability, whereas Rht24 appeared to have no adverse effect on this trait. Our results suggest different haplotypes of the three Rht loci to be used in the female or male pool of a hybrid breeding program, but also show that in general, plant height is a quantitative trait controlled by numerous small-effect QTL. Consequently, marker-assisted selection for the major Rht loci must be complemented by phenotypic selection to achieve the desired height in the female and male parents as well as in the wheat hybrids.

Unlocking historical phenotypic data from an ex situ collection to enhance the informed utilization of genetic resources of barley (Hordeum sp.).

Key message Historical data generated during seed regeneration are valuable to populate a bio-digital resource center for barley (Hordeum sp.). Precise estimates of trait performance of genetic resources are considered as an intellectually challenging, complex, costly and time-consuming step needed to exploit the phenotypic and genetic diversity maintained in genebanks for breeding and research. Using barley (Hordeum sp.) as a model, we examine strategies to tap into historical data available from regeneration trials. This is a first step toward extending the Federal ex situ Genebank into a bio-digital resource center facilitating an informed choice of barley accessions for research and breeding. Our study is based on historical data of seven decades collected for flowering time, plant height, and thousand grain weight during the regeneration of 12,872 spring and winter barley accessions. Linear mixed models were implemented in conjunction with routines for assessment of data quality. A resampling study highlights the potential risk of biased estimates in second-order statistics when grouping accessions for regeneration according to the year of collection or geographic origin. Based on rigorous quality assessment, we obtained high heritability estimates for the traits under consideration exceeding 0.8. Thus, the best linear unbiased estimations for the three traits are a valuable source to populate a bio-digital resource center for the IPK barley collection. The proposed strategy to leverage historical data from regeneration trials is not crop specific and can be used as a blueprint for other ex situ collections.

Genome-based establishment of a high-yielding heterotic pattern for hybrid wheat breeding.

Hybrid breeding promises to boost yield and stability. The single most important element in implementing hybrid breeding is the recognition of a high-yielding heterotic pattern. We have developed a three-step strategy for identifying heterotic patterns for hybrid breeding comprising the following elements. First, the full hybrid performance matrix is compiled using genomic prediction. Second, a high-yielding heterotic pattern is searched based on a developed simulated annealing algorithm. Third, the long-term success of the identified heterotic pattern is assessed by estimating the usefulness, selection limit, and representativeness of the heterotic pattern with respect to a defined base population. This three-step approach was successfully implemented and evaluated using a phenotypic and genomic wheat dataset comprising 1,604 hybrids and their 135 parents. Integration of metabolomic-based prediction was not as powerful as genomic prediction. We show that hybrid wheat breeding based on the identified heterotic pattern can boost grain yield through the exploitation of heterosis and enhance recurrent selection gain. Our strategy represents a key step forward in hybrid breeding and is relevant for self-pollinating crops, which are currently shifting from pure-line to high-yielding and resilient hybrid varieties.