残余物
计算生物学
微小残留病
错误检测和纠正
全基因组测序
基因组
生物
遗传学
计算机科学
算法
基因
白血病
作者
X. Li,Tao Liu,Antonella Bacchiocchi,Mengxing Li,Wen Cheng,Tobias Wittkop,Fernando L. Méndez,Yingyu Wang,Paul C. Tang,Qianqian Yao,Marcus Bosenberg,Mario Sznol,Qin Yan,Malek Faham,Li Weng,Ruth Halaban,Hai Jin,Zhiqian Hu
标识
DOI:10.1038/s44321-024-00115-0
摘要
Abstract While whole genome sequencing (WGS) of cell-free DNA (cfDNA) holds enormous promise for detection of molecular residual disease (MRD), its performance is limited by WGS error rate. Here we introduce AccuScan, an efficient cfDNA WGS technology that enables genome-wide error correction at single read-level, achieving an error rate of 4.2 × 10 −7 , which is about two orders of magnitude lower than a read-centric de-noising method. The application of AccuScan to MRD demonstrated analytical sensitivity down to 10 −6 circulating variant allele frequency at 99% sample-level specificity. AccuScan showed 90% landmark sensitivity (within 6 weeks after surgery) and 100% specificity for predicting relapse in colorectal cancer. It also showed 67% sensitivity and 100% specificity in esophageal cancer using samples collected within one week after surgery. When AccuScan was applied to monitor immunotherapy in melanoma patients, the circulating tumor DNA (ctDNA) levels and dynamic profiles were consistent with clinical outcomes. Overall, AccuScan provides a highly accurate WGS solution for MRD detection, empowering ctDNA detection at parts per million range without requiring high sample input or personalized reagents.
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