---
title: "Pan-cancer nucleosome atlas from 410 tumors informs cfDNA cancer detection"
id: "biorxiv-12-pan-cancer-nucleosome-landscapes-reveal-tumor-heterogeneity-and-inform-cell"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-12-pan-cancer-nucleosome-landscapes-reveal-tumor-heterogeneity-and-inform-cell"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.10.12.758417v1?rss=1"
published_at: "2026-10-18T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Pan-cancer nucleosome atlas from 410 tumors informs cfDNA cancer detection
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-12-pan-cancer-nucleosome-landscapes-reveal-tumor-heterogeneity-and-inform-cell
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.10.12.758417v1?rss=1)
- **Published At:** 2026-10-18T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The study generated a pan-cancer **nucleosome** atlas using **ATAC-seq** on 410 primary tumors representing 23 cancer types; independent **MNase-seq** data validated the atlas. - Investigators identified both shared nucleosome positions and cancer-type-enriched nucleosomes linked to distinct regulatory programs and genomic features. - The authors reported that nucleosome occupancy provided information complementary to chromatin accessibility for tumor stratification, offering an orthogonal epigenomic signal. - Analysis revealed molecular heterogeneity within individual cancers; the cohort showed subgroups tied to Basal-like breast cancer among other intra-cancer clusters. - In hepatocellular carcinoma, differential nucleosome analysis indicated cancer-associated chromatin remodeling involving regulatory pathways, transcription factor motifs, and candidate genes — the study team observed locus-specific changes. - The group evaluated tissue-derived nucleosome signatures in circulating **cell-free DNA (cfDNA)** and achieved multi-class and single-cancer classification performance: AUROC 0.877 for three-way cancer classification and AUROC 0.930 for **colorectal cancer** detection in the discovery set, with AUROC 0.773 in an independent validation cohort. - Data indicated that tissue nucleosome signatures are detectable in cfDNA, suggesting potential utility for noninvasive detection and tissue-of-origin classification. - The authors created OncoNucAtlas, a publicly accessible database to explore the nucleosome landscapes; the team is applying for a software copyright for the resource. - The manuscript is a preprint and has not undergone peer review; the source did not report additional methodological specifics such as exact sequencing depth, normalization procedures, or sample demographics in the abstract.
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Shen Yang 1 Soochow University; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Shen%2BYang%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Yang%20S&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AShen%2BYang%2B) Jialuo Ye 1 Soochow University; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Jialuo%2BYe%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Ye%20J&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AJialuo%2BYe%2B) Jinqi Yuan 1 Soochow University; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Jinqi%2BYuan%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Yuan%20J&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AJinqi%2BYuan%2B) Xiaoqian Huang 1 Soochow University; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Xiaoqian%2BHuang%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Huang%20X&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AXiaoqian%2BHuang%2B) Yue Yin 1 Soochow University; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Yue%2BYin%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Yin%20Y&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AYue%2BYin%2B) Zhaoying Liu 1 Soochow University; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Zhaoying%2BLiu%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Liu%20Z&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AZhaoying%2BLiu%2B) Wei Li 2 University of California, Irvine * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Wei%2BLi%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Li%20W&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AWei%2BLi%2B) Yumei Li 1 Soochow University; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Yumei%2BLi%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Li%20Y&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AYumei%2BLi%2B) * For correspondence: ymli12@suda.edu.cn * [Abstract](https://www.biorxiv.org/content/10.64898/2026.10.12.758417v1)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_art/node:5880789/1) * [Info/History](https://www.biorxiv.org/content/10.64898/2026.10.12.758417v1.article-info)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_info/node:5880789/1) * [Metrics](https://www.biorxiv.org/content/10.64898/2026.10.12.758417v1.article-metrics)[](https://www.biorxiv.org/panels_ajax_tab/article_tab_metrics/node:5880789/1) * [Supplementary material](https://www.biorxiv.org/content/10.64898/2026.10.12.758417v1.supplementary-material)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_data/node:5880789/1) * [ Preview PDF](https://www.biorxiv.org/content/10.64898/2026.10.12.758417v1.full.pdf+html)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_pdf/node:5880789/1) ![Loading](https://www.biorxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif) ## Abstract Background: Nucleosome positioning and occupancy are fundamental features of chromatin organization, yet their variation across human cancers and potential utility for noninvasive cancer detection remain poorly characterized. Methods: We systematically characterized nucleosome organization across 410 primary tumors spanning 23 cancer types using ATAC-seq, establishing a high-confidence pan-cancer nucleosome atlas validated by independent MNase-seq data. We characterized shared and cancer-type-enriched nucleosome patterns, investigated their associations with tumor heterogeneity and regulatory alterations, and evaluated tissue-derived nucleosome signatures for cancer classification and detection using circulating cell-free DNA (cfDNA). Results: The atlas identified shared and cancer-type-enriched nucleosomes associated with distinct regulatory programs. Notably, nucleosome occupancy provided information complementary to chromatin accessibility for tumor stratification and revealed molecular heterogeneity within individual cancers, including subgroups associated with Basal-like breast cancer. In hepatocellular carcinoma, differential nucleosome analysis revealed cancer-associated chromatin remodeling involving regulatory pathways, transcription factor motifs, and candidate genes. Importantly, tissue-derived nucleosome signatures were detectable in cfDNA, enabling classification among three cancer types (AUROC = 0.877) and colorectal cancer detection (AUROC = 0.930), with an AUROC of 0.773 in an independent validation cohort. We also developed OncoNucAtlas, a publicly accessible database facilitating exploration of these nucleosome landscapes. Conclusions: Our study cancer-associated nucleosome organization as a complementary source of epigenomic information and demonstrates the potential of tissue-derived nucleosome signatures for cfDNA-based cancer detection. The pan-cancer atlas provides a resource for investigating tumor heterogeneity and developing noninvasive cancer detection approaches. ### Competing Interest Statement The authors are in the process of applying for a software copyright for the database OncoNucAtlas described in this manuscript. The authors declare no other competing interests. ## Funder Information Declared National Natural Science Foundation of China, 82402740, 32570770 Natural Science Foundation of Jiangsu Province, BK20240783 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a [CC-BY-NC-ND 4.0 International license](http://creativecommons.org/licenses/by-nc-nd/4.0/). bioRxiv and medRxiv thank the following for their generous financial support: > The Chan Zuckerberg Initiative, Cold Spring Harbor Laboratory, the Sergey Brin Family Foundation, California Institute of Technology, Centre National de la Recherche Scientifique, Fred Hutchinson Cancer Center, Imperial College London, Massachusetts Institute of Technology, Stanford University, The University of Edinburgh, University of Washington, and Vrije Universiteit Amsterdam. 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[ Download PDF](https://www.biorxiv.org/content/10.64898/2026.10.12.758417v1.full.pdf) Print/Save Options [Download PDF](https://www.biorxiv.org/content/biorxiv/early/2026/10/18/2026.10.12.758417.full.pdf)Full Text & In-line FiguresXML [More Info](https://www.biorxiv.org/about/FAQ#PrintOptions "More Information on Print/Save Options") [Supplementary Material ](https://www.biorxiv.org/content/10.64898/2026.10.12.758417v1.supplementary-material) [ Email](https://www.biorxiv.org/ "Email this Article") [ Share](https://www.biorxiv.org/) Pan-cancer nucleosome landscapes reveal tumor heterogeneity and inform cell-free DNA-based detection Shen Yang, Jialuo Ye, Jinqi Yuan, Xiaoqian Huang, Yue Yin, Zhaoying Liu, Wei Li, Yumei Li bioRxiv 2026.10.12.758417; doi: https://doi.org/10.64898/2026.10.12.758417 This article is a preprint and has not been certified by peer review [[what does this mean?](https://www.biorxiv.org/about/FAQ#unrefereed)]. 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