LABS: linear amplification-based bisulfite sequencing for ultrasensitive cancer detection from cell-free DNA
Xiao‐Long Cui, Ji Nie, Houxiang Zhu, Krissana Kowitwanich, Alana V. Beadell, Diana C. West-Szymanski, Zhou Zhang, Urszula Dougherty, Akushika Kwesi, Zifeng Deng, Yan Li, Danqing Meng, Kevin K. Roggin, Teresa Barry, Ryan C. Owyang, Ben Fefferman, Chang Zeng, Lu Gao, Carolyn W. T. Zhao, Yuri Malina, Jiangbo Wei, Melanie Weigert, Wenjun Kang, Ajay Goel, Brian C.‐H. Chiu, Marc Bissonnette, Wei Zhang, Mengjie Chen, Chuan He
Abstract
Methylation-based liquid biopsies show promises in detecting cancer using circulating cell-free DNA; however, current limitations impede clinical application. Most assays necessitate substantial DNA inputs, posing challenges. Additionally, underrepresented tumor DNA fragments may go undetected during exponential amplification steps of traditional sequencing methods. Here, we report linear amplification-based bisulfite sequencing (LABS), enabling linear amplification of bisulfite-treated DNA fragments in a genome-wide, unbiased fashion, detecting cancer abnormalities with sub-nanogram inputs. Applying LABS to 100 patient samples revealed cancer-specific patterns, copy number alterations, and enhanced cancer detection accuracy by identifying tissue-of-origin and immune cell composition.