Evidence map›Paper›PMID 39576863›Full record

ArticleScience advances2024

Multiplex digital profiling of DNA methylation heterogeneity for sensitive and cost-effective cancer detection in low-volume liquid biopsies.

Yang Zhao, Christine M O'Keefe, Jiumei Hu, Conor M Allan, Weiwen Cui, Hanran Lei, Allyson Chiu, Kuangwen Hsieh, Sonali C Joyce, James G Herman and 2 more

Abstract read
In one paragraph

Article in Science advances, 2024. 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.

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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

12 authors.

Yang ZhaoDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.ORCID 0000-0002-8216-6420
Christine M O'KeefeDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.ORCID 0000-0002-7166-6972
Jiumei HuDepartment of Mechanical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Conor M AllanDepartment of Mechanical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.ORCID 0009-0000-6661-445X
Weiwen CuiDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Hanran LeiDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.ORCID 0009-0009-9813-515X
Allyson ChiuDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.ORCID 0009-0004-8390-8627
Kuangwen HsiehDepartment of Mechanical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.ORCID 0000-0003-3730-4406
Sonali C JoyceDivision of Hematology and Oncology, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA.
James G HermanDivision of Hematology and Oncology, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA.
Thomas R PisanicJohns Hopkins Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.
Tza-Huei WangDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.ORCID 0000-0002-3540-9354

Funding

SPORE in Ovarian CancerP50CA228991 · NCI · JOHNS HOPKINS UNIVERSITY · PI Amanda Nickles Fader · 2018 to 2026
$20.5M
Optimizing Ultrasensitive DNA methylation detection for lung cancer and other malignanciesU2CCA271885 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JAMES G. HERMAN · 2022 to 2026
$4.2M
Ultrasensitive Detection of Tumor Specific DNA Methylation Changes for the Early Detection of Lung Cancer U01CA214165 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI HERMAN, JAMES G., WANG, TZA-HUEI JEFF · 2016 to 2021
$3.1M
Development of a low-cost epigenetic screening assay for Pap specimen-based detection of early-stage ovarian cancer in high-risk womenR01CA260628 · NCI · JOHNS HOPKINS UNIVERSITY · PI PISANIC II, THOMAS RUSSELL, SHIH, IE-MING · 2021 to 2025
$2.1M
A low-cost, multiplexed digital high resolution melt platform for DNA methylation-based detection and identification of cancers in liquid biopsiesR33CA272321 · NCI · JOHNS HOPKINS UNIVERSITY · PI PISANIC II, THOMAS RUSSELL, WANG, TZA-HUEI JEFF · 2022 to 2024
$1.2M
Simple and Accessible Microfluidic Platform for Single Molecule Sequence Profiling of Tumor-derived DNA within Liquid BiopsiesR43CA281570 · NCI · HYPERMELT, LLC · PI O'KEEFE, CHRISTINE · 2023 to 2023
$276k
NCI NIH HHS P50 CA228991NCI NIH HHS R01 CA260628NCI NIH HHS R33 CA272321NCI NIH HHS R43 CA281570NCI NIH HHS U01 CA214165NCI NIH HHS U2C CA271885
6 · The paper itself

Abstract

Molecular alterations in cancerous tissues exhibit intercellular genetic and epigenetic heterogeneity, complicating the performance of diagnostic assays, particularly for early cancer detection. Conventional liquid biopsy methods have limited sensitivity and/or ability to assess epigenetic heterogeneity of rare epiallelic variants cost-effectively. We report an approach, named REM-DREAMing (Ratiometric-Encoded Multiplex Discrimination of Rare EpiAlleles by Melt), which leverages a digital microfluidic platform that incorporates a ratiometric fluorescence multiplex detection scheme and precise digital high-resolution melt analysis to enable low-cost, parallelized analysis of heterogeneous methylation patterns on a molecule-by-molecule basis for the detection of cancer in liquid biopsies. We applied the platform to simultaneously assess intermolecular epigenetic heterogeneity in five methylation biomarkers for improved, blood-based screening for early-stage non-small cell lung cancer. In a cohort of 48 low-volume liquid biopsy specimens from patients with indeterminant pulmonary nodules, we show that assessment of intermolecular methylation density distributions can notably improve the performance of multigene methylation biomarker panels for the early detection of cancer.

Indexed as

Biomarkers, TumorDNA MethylationLung NeoplasmsCarcinoma, Non-Small-Cell LungCost-Benefit AnalysisEarly Detection of CancerEpigenesis, GeneticHumansLiquid BiopsyNeoplasmsBiomarkers, Tumor

Identifiers

PMID39576863
PMCPMC11584010

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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.