The effect of pre-analytical and physiological variables on cell-free DNA fragmentation

Background: assays that account for the biological properties and fragmentation of cell-free DNA (cfDNA) can improve the performance of liquid biopsy. However, pre-analytic and physiological differences between individuals on fragmentomic analysis are poorly defined. Methods: we analyzed the impact of collection tube, plasma processing time and physiology on the size distribution of cfDNA, their genome-wide representation and sequence diversity at the cfDNA fragment-ends using shallow Whole Genome Sequencing. Results: we observed that using different stabilizing collection tubes, or processing times does not affect the cfDNA fragment sizes, but can impact the genome-wide fragmentation patterns and fragment-end sequences of cfDNA. In addition, beyond differences depending on the gender, the physiological conditions tested between 63 individuals (age, body mass index, use of medication and chronic conditions) minimally influenced the outcome of fragmentomic methods. Conclusions: our results highlight that fragmentomic approaches have potential for implementation in the clinic, pending clear traceability of analytical and physiological factors.

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
EGAD00001008322	The dataset contains 6 lung cancer and 60 healthy control plasma cfDNA samples collected in EDTA, PAXGene and Norgen blood collection tubes at various locations. Shallow WGS was performed on an Illumina Novaseq S4 PE150bp. Samples are provided as raw reads without any prior processing.	Illumina NovaSeq 6000	66
EGAD50000000213	The dataset contain 20 lung cancer and 20 healthy control cfDNA samples from plasma sequenced using 150bp PE sequencing.	Illumina NovaSeq 6000	40

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	2
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	0