LABS: linear amplification-based bisulfite sequencing for ultrasensitive cancer detection from cell-free DNA

Author:

Cui Xiao-Long,Nie Ji,Zhu Houxiang,Kowitwanich Krissana,Beadell Alana V.,West-Szymanski Diana C.,Zhang Zhou,Dougherty Urszula,Kwesi Akushika,Deng Zifeng,Li Yan,Meng Danqing,Roggin Kevin,Barry Teresa,Owyang Ryan,Fefferman Ben,Zeng Chang,Gao Lu,Zhao Carolyn W. T.,Malina Yuri,Wei Jiangbo,Weigert Melanie,Kang Wenjun,Goel Ajay,Chiu Brian C.-H.,Bissonnette Marc,Zhang Wei,Chen Mengjie,He Chuan

Abstract

AbstractMethylation-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.

Funder

Foundation for the National Institutes of Health

Publisher

Springer Science and Business Media LLC

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