biostudies-literatureUnknownMagner RNICHD NIH HHSNIH HHSWe 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 informatbioRxiv : the preprint server for biology2024.11.01.621515https://www.ebi.ac.uk/biostudies/studies/S-EPMC12424989biostudies-literatureBlended Length Genome Sequencing (blend-seq): Combining Short Reads with Low-Coverage Long Reads to Maximize Variant Discovery.PMC12424989U24 HD090743OT2 OD038121Lennon NSaponas SBasu SShand MPaulsen RCunial FMagner RBanks EfalseBlended Length Genome Sequencing (blend-seq): Combining Short Reads with Low-Coverage Long Reads to Maximize Variant Discovery.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 informat2025-01-01T00:00:00Z2025 Sep2026-05-26T17:03:35.384Z2026-05-26T03:06:12.738ZS-EPMC124249894095001910.1101/2024.11.01.621515