TY - JOUR A1 - Chen, Zhoutao A1 - Pham, Long A1 - Wu, Tsai-Chin A1 - Mo, Guoya A1 - Xia, Yu A1 - Chang, Peter L. A1 - Porter, Devin A1 - Phan, Tan A1 - Che, Huu A1 - Tran, Hao A1 - Bansal, Vikas A1 - Shaffer, Justin A1 - Belda-Ferre, Pedro A1 - Humphrey, Greg A1 - Knight, Rob A1 - Pevzner, Pavel A1 - Pham, Son A1 - Wang, Yong A1 - Lei, Ming T1 - Ultralow-input single-tube linked-read library method enables short-read second-generation sequencing systems to routinely generate highly accurate and economical long-range sequencing information Y1 - 2020/06/01 JF - Genome Research JO - Genome Research SP - 898 EP - 909 DO - 10.1101/gr.260380.119 VL - 30 IS - 6 UR - http://genome.cshlp.org/content/30/6/898.abstract N2 - Long-range sequencing information is required for haplotype phasing, de novo assembly, and structural variation detection. Current long-read sequencing technologies can provide valuable long-range information but at a high cost with low accuracy and high DNA input requirements. We have developed a single-tube Transposase Enzyme Linked Long-read Sequencing (TELL-seq) technology, which enables a low-cost, high-accuracy, and high-throughput short-read second-generation sequencer to generate over 100 kb of long-range sequencing information with as little as 0.1 ng input material. In a PCR tube, millions of clonally barcoded beads are used to uniquely barcode long DNA molecules in an open bulk reaction without dilution and compartmentation. The barcoded linked-reads are used to successfully assemble genomes ranging from microbes to human. These linked-reads also generate megabase-long phased blocks and provide a cost-effective tool for detecting structural variants in a genome, which are important to identify compound heterozygosity in recessive Mendelian diseases and discover genetic drivers and diagnostic biomarkers in cancers. ER -