GSE186007
LABS: linear amplification-based bisulfite sequencing for ultrasensitive cancer detection from cell-free DNA
Methylation-based liquid biopsies show promise in detecting cancer from circulating cell-free DNA, but current limitations impede clinical application. Most assays necessitate substantial DNA inputs, posing challenges. Underrepresented tumor DNA fragments may go undetected during exponential amplification steps of traditional sequencing methods. Here we report LABS (Linear Amplification based Bisulfite Sequencing), 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. Overall design: For method validation, we compared our LABS method with two commonly used commercial methods: EpiGnome and MethylC-seq. For clinical usage, we collected cfDNA samples from 50 CRC, 16 PDAC, and 34 control patients.