Evidence map›Paper›PMID 41422275›Full record

ArticleNature communications2025

Reconstructing the three-dimensional architecture of extrachromosomal DNA with ec3D.

Biswanath Chowdhury, Kaiyuan Zhu, Chaohui Li, Jessica Alsing, Jens Luebeck, Maria E Stefanova, Owen S Chapman, Katerina Kraft, Shu Zhang, Jun Yi Stanley Lim and 9 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Fast and accurate resolution of ecDNA sequence using Cycle-Extractor.bioRxiv : the preprint server for biology · 2026
    Article
  5. Article
  6. Review
  7. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Biswanath Chowdhury *Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-3465-7505
Kaiyuan Zhu *Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-9976-6505
Chaohui Li *Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0009-0009-6196-1191
Jessica AlsingDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.ORCID http://orcid.org/0000-0002-8558-6471
Jens LuebeckDepartment of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-4391-979X
Maria E StefanovaDepartment of Pediatric Hematology and Oncology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Owen S ChapmanDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Katerina KraftCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.
Shu ZhangCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.
Jun Yi Stanley LimChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Yipeng XieChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Yoon Jung KimChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Sihan WuChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0001-8329-7492
Lukas ChavezDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Guy NirDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.ORCID http://orcid.org/0000-0001-9268-6596
Anton G HenssenDepartment of Pediatric Hematology and Oncology, Charité-Universitätsmedizin Berlin, Berlin, Germany.ORCID http://orcid.org/0000-0003-1534-778X
Paul S MischelDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-4560-2211
Howard Y ChangCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-9459-4393
Vineet BafnaDepartment of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA. vbafna@ucsd.edu.ORCID http://orcid.org/0000-0002-5810-6241

Funding

eDyNAmiC - STANFORDOT2CA278688 · NCI · STANFORD UNIVERSITY · PI PAUL S MISCHEL · 2022 to 2026
$7.7M
Software and algorithms for elucidating the structure, function, and evolution of extrachromosomal DNAU24CA264379 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BAFNA, VINEET, MESIROV, JILL P. · 2021 to 2025
$3.5M
Computational methods for detecting patterns of complex genomic variationR01GM114362 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Vineet Bafna · 2016 to 2026
$3.1M
Investigation of ecDNA as a Driver of Intratumoral Heterogeneity and Treatment Resistance in High-Risk MedulloblastomaR01NS132780 · NINDS · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI Lukas Chavez · 2023 to 2026
$2.6M
eDyNAmiC-TEXASSWOT2CA278683 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI Zhijian J Chen · 2022 to 2026
$2.4M
eDyNAmiC - UCSDOT2CA278635 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Vineet Bafna · 2022 to 2026
$1.8M
American Cancer Society (American Cancer Society, Inc.) CAT-24-1379043-01-CATCancer Prevention and Research Institute of Texas (Cancer Prevention Research Institute of Texas) RP210041Cancer Prevention and Research Institute of Texas (Cancer Prevention Research Institute of Texas) RR210018Cancer Prevention and Research Institute of Texas (Cancer Prevention Research Institute of Texas) RR210034Cancer Research UK (CRUK) CGCATF-2021/100012Cancer Research UK (CRUK) CGCATF-2021/100023Cancer Research UK (CRUK) CGCATF-2021/100025Deutsche Krebshilfe (German Cancer Aid) Mildred Scheel Professorship program 70114107NCI NIH HHS OT2 CA278635NCI NIH HHS OT2 CA278683NCI NIH HHS OT2 CA278688NCI NIH HHS U24 CA264379NIGMS NIH HHS R01 GM114362NINDS NIH HHS R01 NS132780U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) OT2CA278635U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) OT2CA278683U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) OT2CA278688U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) U24CA264379U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) R01GM114362
6 · The paper itself

Abstract

Extrachromosomal DNAs (ecDNAs) are circular DNA molecules prevalent in human cancers that drive tumor evolution and drug resistance. Their circular topology, which disrupts topological domains and rewires regulatory circuits, has typically been studied via pairwise interactions. Here we develop ec3D, a computational method for reconstructing three-dimensional ecDNA structures from Hi-C data. Given a candidate ecDNA sequence and whole-genome Hi-C data, ec3D reconstructs spatial structures by maximizing the Poisson likelihood of observed interactions. We validate ec3D using simulated structures, previously characterized cancer cell lines, and microscopy imaging. Our reconstructions reveal that ecDNAs occupy spherical configurations and mediate unique long-range regulatory interactions involved in gene regulation. Through algorithmic innovations, ec3D can resolve complex structures with duplicated segments, identify multi-way interactions, and identify potential intermolecular (trans) interactions. Our findings provide insights into how ecDNA's spatial organization bypasses normal chromosomal constraints and contributes to increased oncogene expression.

Indexed as

DNA, CircularAlgorithmsCell Line, TumorHumansNeoplasmsNucleic Acid ConformationDNA, Circular

Identifiers

PMID41422275
PMCPMC12830899

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.