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The utilization of heterosis is a successful strategy in increasing yield for many crops. However, it consumes tremendous manpower to test the combining ability of the parents in fields. Here, we applied the genomic-selection (GS) strategy and developed models that significantly increase the predictability of heterosis by introducing the concept of a regional parental genetic-similarity index (PGSI) and reducing dimension in the calculation matrix in a machine-learning approach. Overall, PGSI negatively affected grain yield and several other traits but positively influenced the thousand-seed weight of the hybrids. It was found that the C subgenome of rapeseed had a greater impact on heterosis than the A subgenome. We drew maps with overviews of quantitative-trait loci that were responsible for the heterosis (h-QTLs) of various agronomic traits. Identifications and annotations of genes underlying high impacting h-QTLs were provided. Using models that we elaborated, combining abilities between an Ogu-CMS-pool member and a potential restorer can be simulated in silico, sidestepping laborious work, such as testing crosses in fields. The achievements here provide a case of heterosis prediction in polyploid genomes with relatively large genome sizes. Author summary: Oilseed rape (Brassica napus) is of significant economic interest worldwide, providing high-quality oil with excellent health-promoting properties. It represents an excellent model of a successful recent polyploid that rapidly became an important crop worldwide. The utilization of hybridization, leading to hybrid vigor, or heterosis, is a successful strategy in increasing yield and vigor for many field crops including rapeseed (Brassica napus). However, the procedure of using classical breeding methods remains slow and laborious, illustrating the need for predictive and innovative methods. Here, we have achieved a significant breakthrough by using genome selection and significantly advanced models to predict the heterosis by pairing genome-wide nucleotides of parents. We provided maps with overviews of quantitative trait loci that were responsible for the heterosis of various agronomic traits. The research used deep resequencing (>30x) data of the entire polyploidy rapeseed genome, providing a successful case for the prediction of heterosis in polyploid genomes with relatively large genome sizes. Moreover, we provided the genetic information (SNPs) of 1007 core accessions of this species in the public domain for testing combinations with high heterosis using our predicting model for rapeseed breeders all over the world. [ABSTRACT FROM AUTHOR]