Detecting Cancer Through cfDNA Methylation

Join Simon Pearce as he discusses the use of circulating cell-free DNA (cfDNA) methylation to detect and subtype cancer. Discover the Nextflow pipelines developed for demultiplexing, alignment, and classifier creation, achieving high sensitivity and accuracy in predicting cancer type from liquid biopsies. Title: Using cfDNA methylation to detect and subtype cancer Speaker: Simon Pearce, Cancer Biomarker Centre, Cancer Research UK Abstract: Circulating cell-free DNA (cfDNA) is a biomarker for cancer, as tumour-released DNA is detectable in blood plasma. We have established an MBD-protein enrichment method (T7-MBD-Seq) to investigate genome-wide cfDNA methylation, and have developed 2 Nextflow pipelines for demultiplexing, alignment, and creation of analysis objects, applied to over 3000 samples. We created a Nextflow pipeline to build classifiers, using data augmentation to simulate the wide range of tumour content found in cfDNA, and created a classifier to predict cancer type across 29 tumour classes. When tested on 143 cfDNA samples from patients, we achieve 84% sensitivity and 96% accuracy. This classifier was applied to 41 patients with Cancer of Unknown Primary; patients diagnosed with metastatic cancer but the primary cancer cannot be determined. Predictions were made in 32/41 cases (23/26 clinically consistent), showing we can predict tissue-of-origin from a liquid biopsy, increasing treatment options.