363: cfDNA size deconvolution reveals a 159‑bp nucleosomal pivot and tumor fragmentomic signatures

Zhou Z et al., Nature Communications - This study develops a Lorentzian deconvolution model of cfDNA fragment length distributions across bodily fluids, identifies a ~159 bp component that demarcates intra- vs inter-nucleosomal fragments, and shows that intra-nucleosomal fragmentation entropy distinguishes tumor-derived ctDNA from non-tumor shortening. Key terms: cell-free DNA, fragmentomics, nucleosome, ctDNA, size deconvolution. Study Highlights:The authors modeled cfDNA size profiles as sums of Cauchy–Lorentz distributions with ~10 bp periodicity and applied deconvolution across plasma, saliva, urine, CSF and lymphatic fluid. A distinct ~159 bp component emerged as a pivot between intra- and inter-nucleosomal fragments. Tumor-derived ctDNA shows increased intra-nucleosomal fragmentation entropy and inverse amplitude changes across the 159 bp boundary, whereas phagocytosis-associated shortening increases intra-nucleosomal amplitude without raising entropy. The intra/inter-nucleosomal entropy ratio improved cancer detection performance relative to standard size-ratio metrics across multiple cohorts. Conclusion:Size deconvolution using Lorentzian components reveals nucleosomal structure in cfDNA, identifies a 159 bp demarcation between fragmentation regimes, and provides an entropy-based metric that enhances ctDNA detection while separating tumor-associated fragmentation from phagocyte-related signals. Music:Enjoy the music based on this article at the end of the episode. Article title:Cell-free DNA size deconvolution resolves nucleosomal origins and reveals tumor-associated fragmentomic alterations First author:Zhou Z Journal:Nature Communications DOI:10.1038/s41467-026-72925-4 Reference:Zhou Z, Cooper WN, Cheng Z, et al. Cell-free DNA size deconvolution resolves nucleosomal origins and reveals tumor-associated fragmentomic alterations. Nat Commun (2026). https://doi.org/10.1038/s41467-026-72925-4 License:This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/ Support:Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com On PaperCast Base by Base you'll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Episode link: https://basebybase.com/episodes/cfdna-size-deconvolution-nucleosomal-origins QC:This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-05-09. QC Scope:- article metadata and core scientific claims from the narration- excludes analogies, intro/outro, and music- transcript coverage: Substantive auditing of the transcript's discussion of cfDNA fragmentology, Lorentzian deconvolution, the 159 bp pivot, entropy vs amplitude distinctions, Li-Fraumeni context, phagocytosis vs tumor fragmentation, and diagnostic performance metrics.- transcript topics: cfDNA fragmentomics basics; Lorentzian size deconvolution and nucleosome structure; 159 bp boundary between intra- and inter-nucleosomal cfDNA; intra-/inter-nucleosomal amplitude and entropy ratios; ctDNA fragmentation entropy as cancer signature; phagocytosis vs tumor-derived fragmentation QC Summary:- factual score: 10/10- metadata score: 10/10- supported core claims: 7- claims flagged for review: 0- metadata checks passed: 4- metadata issues found: 0 Metadata Audited:- article_doi- article_title- article_journal- license Factual Items Audited:- cfDNA size profiles deconvoluted into Lorentzian components across multiple fluids with ~10 bp periodicity- a ~159 bp component d...