Evidence map›Paper›PMID 34516908›Full record

ArticleScience advances2021

Cell-free DNA TAPS provides multimodal information for early cancer detection.

Paulina Siejka-Zielińska, Jingfei Cheng, Felix Jackson, Yibin Liu, Zahir Soonawalla, Srikanth Reddy, Michael Silva, Luminita Puta, Misti Vanette McCain, Emma L Culver and 8 more

Abstract read
In one paragraph

Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing 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

53 citing papers in PubMed.

  1. Review
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  4. Improving surgical treatments for hepatocellular carcinoma.Nature reviews. Gastroenterology & hepatology · 2026
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  14. Observational
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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

18 authors.

Paulina Siejka-ZielińskaLudwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID 0000-0003-3284-6249
Jingfei ChengLudwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Felix JacksonLudwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID 0000-0003-1767-8101
Yibin LiuLudwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID 0000-0003-3451-0212
Zahir SoonawallaOxford University Hospitals NHS Foundation Trust, Oxford, UK.
Srikanth ReddyOxford Transplant Centre, Churchill Hospital, Oxford, UK.ORCID 0000-0001-9074-2961
Michael SilvaDepartment of HPB Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.ORCID 0000-0003-4575-3519
Luminita PutaLudwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Misti Vanette McCainNewcastle University Translational and Clinical Research Institute, The Medical School, Newcastle University, Newcastle upon Tyne, UK.ORCID 0000-0002-1967-0421
Emma L CulverPeter Medawar Building and Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID 0000-0001-9644-8392
Noor BekkaliDepartment of Gastroenterology, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford, UK.
Benjamin Schuster-BöcklerLudwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID 0000-0002-8892-5133
Pier Francesco PalamaraDepartment of Statistics, University of Oxford, Oxford, UK.
Derek MannNewcastle University Translational and Clinical Research Institute, The Medical School, Newcastle University, Newcastle upon Tyne, UK.
Helen ReevesNewcastle University Translational and Clinical Research Institute, The Medical School, Newcastle University, Newcastle upon Tyne, UK.ORCID 0000-0003-0359-9795
Eleanor BarnesPeter Medawar Building and Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID 0000-0002-0860-0831
Shivan SivakumarDepartment of Oncology, University of Oxford, Oxford, UK.ORCID 0000-0002-5175-2697
Chun-Xiao SongLudwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID 0000-0002-7781-6521

Funding

Cancer Research UK 23390Cancer Research UK 26394Cancer Research UK 26813Cancer Research UK 27122Cancer Research UK 29725Medical Research Council MR/T04490X/1
6 · The paper itself

Abstract

Multimodal, genome-wide characterization of epigenetic and genetic information in circulating cell-free DNA (cfDNA) could enable more sensitive early cancer detection, but it is technologically challenging. Recently, we developed TET-assisted pyridine borane sequencing (TAPS), which is a mild, bisulfite-free method for base-resolution direct DNA methylation sequencing. Here, we optimized TAPS for cfDNA (cfTAPS) to provide high-quality and high-depth whole-genome cell-free methylomes. We applied cfTAPS to 85 cfDNA samples from patients with hepatocellular carcinoma (HCC) or pancreatic ductal adenocarcinoma (PDAC) and noncancer controls. From only 10 ng of cfDNA (1 to 3 ml of plasma), we generated the most comprehensive cfDNA methylome to date. We demonstrated that cfTAPS provides multimodal information about cfDNA characteristics, including DNA methylation, tissue of origin, and DNA fragmentation. Integrated analysis of these epigenetic and genetic features enables accurate identification of early HCC and PDAC.

Identifiers

PMID34516908
PMCPMC8442905

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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.