Genome-wide cell-free DNA termini in patients with cancer

The structure, fragmentation patterns and terminal sequences of cell-free DNA (cfDNA) are altered by nucleases and biological mechanisms in the blood of cancer patients. The cfDNA fragment-end composition recovered from low coverage WGS (<1 fold coverage) using a bespoke software (FrEIA) is aberrant in the plasma from cancer patient (n = 418, 655 samples) compared to controls (n = 117). As a standalone test FrEIA allows detection down to ~0.2% tumor fraction in vitro and in silico at 95% specificity, leading to a sensitivity of ~71% for detecting lung cancer (14/22 stage I-II, 27/38 stage III, 92/127 stage IV) and ~68% for detecting esophageal adenocarcinoma (26/44 stage II, 46/62 stage III). Additional cfDNA biological patterns can be combined with FrEIA increasing the diagnostic potential of low coverage WGS at minimal cost (mean AUROC = 0.96). Integrating multiple cfDNA biological signal augments the diagnostic performance of liquid biopsy.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

2 Datasets 2 Publications

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001008666	The dataset contains 90 lung cancer and 5 non-cancerous lung lesion plasma cfDNA samples collected in EDTA blood collection tubes. Shallow WGS was performed on an Illumina Novaseq S4 PE150bp. Samples are provided as raw reads without any prior processing.	Illumina NovaSeq 6000	95
EGAD00001009780	Plasma from lung cancer patients from EDTA tubes was fractionated using size exclusion chromatography. Fractions 1-5, 7-11, 12-15, 16-20 were pooled, cfDNA was extracted from the fractions and paired unfractionated samples and PE150bp sequencing was performed on an Illumina Novaseq S4 flowcell. Samples are provided as raw reads without any prior processing.	Illumina NovaSeq 6000	64

Publications	Citations
The landscape of cell-free mitochondrial DNA in liquid biopsy for cancer detection. van der Pol Y, Moldovan N, Ramaker J, Bootsma S, Lenos KJ, Vermeulen L, Sandhu S, Bahce I, Pegtel DM, Wong SQ, Dawson SJ, Chandrananda D, Mouliere F. Genome Biol 24: 2023 229	8
Multi-modal cell-free DNA genomic and fragmentomic patterns enhance cancer survival and recurrence analysis. Moldovan N, van der Pol Y, van den Ende T, Boers D, Verkuijlen S, Creemers A, Ramaker J, Vu T, Bootsma S, Lenos KJ, Vermeulen L, Fransen MF, Pegtel M, Bahce I, van Laarhoven H, Mouliere F. Cell Rep Med 5: 2024 101349	3