Predicting tumour content of liquid biopsies from cell-free DNA

• Published in: BMC bioinformatics Vol. 24; no. 1; p. 368
• Main Authors: Cardner, Mathias, Marass, Francesco, Gedvilaite, Erika, Yang, Julie L, Tsui, Dana W Y, Beerenwinkel, Niko
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 30.09.2023; BioMed Central; BMC
• Subjects: Biomarkers, Tumor - genetics; Biopsy; Body fluids; Cancer; Cell-free DNA; Cell-Free Nucleic Acids - genetics; Circulating tumour DNA; Datasets; Deoxyribonucleic acid; Diagnosis; Dilution; DNA; Estimates; Extrachromosomal DNA; Fourier transforms; Fragmentomics; Genetic aspects; Health aspects; Humans; Liquid biopsy; Liquid Biopsy - methods; Measurement; Methods; Mutation; Neoplasms - genetics; Neoplasms - pathology; Patients; Plasma; Tumors; Tumour content; Wavelet transforms; Switzerland; Cell-free DNA; Liquid biopsy; Tumour content; Circulating tumour DNA; Fragmentomics
• ISSN: 1471-2105; 1471-2105
• DOI: 10.1186/s12859-023-05478-8

Liquid biopsy is a minimally-invasive method of sampling bodily fluids, capable of revealing evidence of cancer. The distribution of cell-free DNA (cfDNA) fragment lengths has been shown to differ between healthy subjects and cancer patients, whereby the distributional shift correlates with the sample's tumour content. These fragmentomic data have not yet been utilised to directly quantify the proportion of tumour-derived cfDNA in a liquid biopsy. We used statistical learning to predict tumour content from Fourier and wavelet transforms of cfDNA length distributions in samples from 118 cancer patients. The model was validated on an independent dilution series of patient plasma. This proof of concept suggests that our fragmentomic methodology could be useful for predicting tumour content in liquid biopsies.