Fig. 1: Overview of the study.
From: Multimodal cell-free DNA whole-genome TAPS is sensitive and reveals specific cancer signals
We conducted a diagnostic accuracy study using a) cancer cases (GEL) from a cohort of symptomatic patients referred for urgent investigation for a possible gynaecological, lower GI, upper GI or renal cancer, and b) non-cancer controls with non-specific symptoms that might have been due to cancer from a rapid diagnostic centre (SCAN) or from Cambridge Bioscience (CBS). After collection of plasma samples, we conducted whole-genome sequencing at 80x or higher using TET-Assisted Pyridine Borane Sequencing (TAPS), aligned the generated reads against the human genome (GRCh38), and conducted analyses of copy number aberrations, methylation modifications, and somatic point mutations and indels, which included efficient denoising using the non-cancer SCAN controls. By integrating the analyses from all three data modalities, we generated sample-specific scores for the quantification of plasma ctDNA burden, which was used for cancer detection and post-treatment disease tracking. Matched tumour biopsies, if available, were used for validation, not for guiding the analysis. GEL Genomics England, SCAN Suspected Cancer Pathway, CBS Cambridge Biosciences Human Blood Products Supply Service.
