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Analysis of plasma DNA fragmentation patterns from dried blood spots

Stephens, M. D.; Dietmann, E. C.; McDonald, B. R.; Nkadori, E. N.; Zafar, S. N.; McGregor, S. M.; Murtaza, M.

2024-12-26 genetic and genomic medicine
10.1101/2024.12.22.24319522 medRxiv
Show abstract

Circulating tumor DNA analysis holds promise for early detection of cancer. However, costs and complexity of genomic methods, and logistical requirements for blood collection and processing limit large scale implementation. Here, we evaluated the feasibility of genome-wide analysis of fragmentation patterns in plasma DNA obtained from dried blood spots (DBS). Across 75 individuals including 25 patients with cancer, we prepared conventional DBS, and plasma-separating DBS (psDBS) from whole blood samples, prior to plasma separation. In paired comparisons of plasma DNA between psDBS and blood tubes, we observed correlated concentrations, similar distributions of fragment lengths, correlated genome-wide fragmentation features, and equivalent performance of machine learning algorithms for cancer detection. Our results provide proof-of-principle that plasma DNA fragmentation analysis can be performed from small amounts of DNA obtained from psDBS. With further development and validation, this approach can expand the reach and impact of blood-based early cancer detection, particularly for resource constrained environments such as low- and middle-income countries and rural healthcare systems.

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