DPImpute: A Genotype Imputation Framework for Ultra-Low Coverage Whole-Genome Sequencing and its Application in...

Whole-genome sequencing is pivotal for elucidating the complex relationships between genotype and phenotype. However, its widespread application is hindered by the high sequencing depth and large sample sizes required, especially for genomic selection (GS) reliant on precise phenotype prediction from high-density genotype data. To address this, DPImpute (Dual-Phase Impute) is developed, an two-step imputation pipeline enabling accurate whole-genome SNP genotyping under ultra-low coverage whole-genome sequencing (ulcWGS) depths, small testing sample sizes, and limited reference populations. DPImpute achieved 98.06% SNP imputation accuracy with minimal testing samples (≤10), reference samples (≤100), and an ultra-low sequencing depth of 0.3X, surpassing the accuracy of existing imputation methods. Moreover, this high accuracy is maintained across multi-ancestry human populations. Remarkably, DPImpute demonstrated accurate SNP imputation from low-coverage sequencing data from single blood cells and single blastocyst cells, highlighting its potential in embryo GS. To enhance the accessibility of DPImpute, a user-friendly web server (https://agdb.ecenr.com/DPImpute/home) is developed and a Docker container for seamless implementation. In summary, DPImpute can significantly expedite breeding programs through precise and cost-effective genotyping and serve as a valuable tool for diverse population genotyping, encompassing both human and animal studies.