SMOOTH-seq: single-cell genome sequencing of human cells on a third-generation sequencing platform
Xiaoying Fan, Cheng Yang, Wen Li, Xiuzhen Bai, Xin Zhou, Haoling Xie, Lu Wen, Fuchou Tang
Abstract
There is no effective way to detect structure variations (SVs) and extra-chromosomal circular DNAs (ecDNAs) at single-cell whole-genome level. Here, we develop a novel third-generation sequencing platform-based single-cell whole-genome sequencing (scWGS) method named SMOOTH-seq (single-molecule real-time sequencing of long fragments amplified through transposon insertion). We evaluate the method for detecting CNVs, SVs, and SNVs in human cancer cell lines and a colorectal cancer sample and show that SMOOTH-seq reliably and effectively detects SVs and ecDNAs in individual cells, but shows relatively limited accuracy in detection of CNVs and SNVs. SMOOTH-seq opens a new chapter in scWGS as it generates high fidelity reads of kilobases long.