Evidence map›Paper›PMID 38797520›Full record

ArticleNucleic acids research2024

Single-stranded pre-methylated 5mC adapters uncover the methylation profile of plasma ultrashort Single-stranded cell-free DNA.

Jordan C Cheng, Neeti Swarup, Marco Morselli, Wei-Lun Huang, Mohammad Aziz, Christa Caggiano, Misagh Kordi, Abhijit A Patel, David Chia, Yong Kim and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Ultrashort plasma cell-free DNA: a novel non-invasive marker for cancer diagnostics.American journal of clinical and experimental immunology · 2024
    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

17 authors.

Jordan C ChengSchool of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.ORCID 0000-0001-5352-4017
Neeti SwarupSchool of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Marco MorselliDepartment of Molecular, Cell, and Developmental Biology, Life Sciences Division, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Wei-Lun HuangCenter of Applied Nanomedicine, National Cheng Kung University, Tainan, Taiwan.
Mohammad AzizSchool of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Christa CaggianoDepartment of Computational Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Misagh KordiSchool of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Abhijit A PatelDepartment of Therapeutic Radiology, Yale University, New Haven, CT, USA.
David ChiaDepartment of Pathology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Yong KimSchool of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Feng LiSchool of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Fang WeiSchool of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Noah ZaitlenDepartment of Computational Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Kostyantyn KrysanDepartment of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Steve DubinettDepartment of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Matteo PellegriniDepartment of Molecular, Cell, and Developmental Biology, Life Sciences Division, University of California, Los Angeles, Los Angeles, CA 90095, USA.
David T W WongSchool of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Funding

UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
EFIRM Liquid Biopsy Research Laboratory: Early Lung Cancer AssessmentU01CA233370 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ABERLE, DENISE R., HSU, WILLIAM · 2018 to 2025
$8.0M
Advancing EFIRM-Liquid Biopsy (eLB) to a CLIA-Certified Laboratory Developed Test (eLB-LDT) for Detection of Actionable EGFR Mutations in NSCLC PatientsUH3CA206126 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHIA, DAVID S., SOO HOO, GUY · 2019 to 2021
$1.2M
UCLA Dentist-Scientist and Oral Health-Researcher Training ProgramR90DE031531 · NIDCR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TON-THAT, HUNG, WONG, DAVID T · 2021 to 2025
$858k
Novel ultra-short cell free DNA biomarkers for early detection of non-small cell lung cancer.R21CA283665 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LI, FENG, WONG, DAVID T · 2023 to 2024
$393k
Cell-free DNA Analysis for Liquid Biopsy of CancerK00CA264398 · NCI · STANFORD UNIVERSITY · PI Jordan C Cheng · 2023 to 2026
$389k
Ultra-short circulating tumor DNA (uctDNA) for liquid biopsy of non-small cell lung cancerR21CA239052 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LI, FENG, WONG, DAVID T · 2019 to 2020
$373k
Advancing EFIRM-Liquid Biopsy (eLB) to a CLIA-Certified Laboratory Developed Test (eLB-LDT) for Detection of Actionable EGFR Mutations in NSCLC PatientsUH2CA206126 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHIA, DAVID S., DAS, KINGSHUK · 2017 to 2018
$368k
Canadian Institute of Health Research Doctoral Foreign Study AwardHigher Education Sprout ProjectNCATS NIH HHS UL1 TR001881NCI NIH HHS K00 CA264398NCI NIH HHS R21 CA239052NCI NIH HHS R21 CA283665NCI NIH HHS U01 CA233370NCI NIH HHS UH2 CA206126NCI NIH HHS UH3 CA206126NIDCR NIH HHS 1R90DE031531NIDCR NIH HHS R90 DE031531NIH HHS UH2/UH3 CA206126Spectrum Solutions 20212918Tobacco-Related Disease Research Program (TRDRP) Predoctoral Fellowship, Jonsson Comprehensive Cancer Center Predoctoral Fellowship K00CA264398-03UCLA JCCC SEED/Ali Jassim Family Cancer Research Fund
6 · The paper itself

Abstract

Whole-genome bisulfite sequencing (BS-Seq) measures cytosine methylation changes at single-base resolution and can be used to profile cell-free DNA (cfDNA). In plasma, ultrashort single-stranded cfDNA (uscfDNA, ∼50 nt) has been identified together with 167 bp double-stranded mononucleosomal cell-free DNA (mncfDNA). However, the methylation profile of uscfDNA has not been described. Conventional BS-Seq workflows may not be helpful because bisulfite conversion degrades larger DNA into smaller fragments, leading to erroneous categorization as uscfDNA. We describe the '5mCAdpBS-Seq' workflow in which pre-methylated 5mC (5-methylcytosine) single-stranded adapters are ligated to heat-denatured cfDNA before bisulfite conversion. This method retains only DNA fragments that are unaltered by bisulfite treatment, resulting in less biased uscfDNA methylation analysis. Using 5mCAdpBS-Seq, uscfDNA had lower levels of DNA methylation (∼15%) compared to mncfDNA and was enriched in promoters and CpG islands. Hypomethylated uscfDNA fragments were enriched in upstream transcription start sites (TSSs), and the intensity of enrichment was correlated with expressed genes of hemopoietic cells. Using tissue-of-origin deconvolution, we inferred that uscfDNA is derived primarily from eosinophils, neutrophils, and monocytes. As proof-of-principle, we show that characteristics of the methylation profile of uscfDNA can distinguish non-small cell lung carcinoma from non-cancer samples. The 5mCAdpBS-Seq workflow is recommended for any cfDNA methylation-based investigations.

Indexed as

5-MethylcytosineCell-Free Nucleic AcidsCpG IslandsDNA MethylationDNA, Single-StrandedHumansLung NeoplasmsPromoter Regions, GeneticSequence Analysis, DNASulfitesWhole Genome Sequencing5-MethylcytosineCell-Free Nucleic AcidsDNA, Single-Strandedhydrogen sulfiteSulfites

Identifiers

PMID38797520
PMCPMC11194076

What OpenQuestion holds

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LicenceCC BY
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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.