Blended Length Genome Sequencing (blend-seq): Combining Short Reads with Low-Coverage Long Reads to Maximize Variant Discovery.

ABSTRACT: We introduce blend-seq, a workflow for combining data from traditional short-read sequencing pipelines with low-coverage long reads, to improve variant discovery for single samples without the full cost of high-coverage long reads. We demonstrate that with only 4x long-read coverage augmenting 30x short reads, we can improve SNP discovery across the genome, exceeding performance beyond even high-coverage short reads (60x). For genotype-agnostic discovery of structural variants, we see a threefold improvement in recall while maintaining precision by using the low-coverage long reads on their own, and show how we can improve genotyping accuracy by adding in the short-read data. In addition, we demonstrate how the long reads can better phase these variants, incorporating long-context informat

SUBMITTER: Magner R 

PROVIDER: S-EPMC12424989 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature