New method cuts DNA sequencing prep costs by 90%, opening door to massive studies
Researchers have developed upSPLAT, a library preparation technique that slashes the cost of preparing DNA samples for sequencing by roughly tenfold. The breakthrough addresses a major bottleneck in genomics research and could enable large-scale population studies, disease screening programs, and clinical diagnostics that were previously too expensive to execute.
Originaltitel: upSPLAT: Early-Barcoded Library Preparation for Cost-Effective Population-Scale Genomics
Advances in high-throughput sequencing have substantially reduced sequencing costs, yet library preparation remains a major financial and logistical bottleneck, particularly for high-throughput applications or low-quality DNA inputs. Here, we introduce upscaled Splinted Ligation Adapter Tagging (upSPLAT), a library preparation strategy that combines early sample barcoding with single-stranded splinted ligation to enable highly multiplexed pooled sequencing at substancially reduced cost. upSPLAT supports flexible high-plex pooling and reduces per-sample library preparation costs by approximately 10-fold compared to conventional workflows. By leveraging single-strand ligation, upSPLAT is compatible with a wide range of DNA inputs, including degraded, damaged or denatured double stranded DNA, bisulfite or enzymatically converted DNA, and viral single-stranded DNA. We present two complementary workflows and evaluate their performance across multiple species and DNA qualities, demonstrating robust demultiplexing, uniform sample representation, and low barcode cross-assignment. Together, upSPLAT provides a scalable, cost-effective solution for sequencing-based studies requiring large sample numbers while preserving individual-level information.