ArticleProceedings of the National Academy of Sciences of the United States of America2026
Toward the simultaneous detection of multiple diseases with a highly cost-effective cell-free DNA methylome test.
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Article in Proceedings of the National Academy of Sciences of the United States of America, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4citing papers in PubMed
–field-weighted citation impact
What it found
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Who cites it
4 citing papers in PubMed.
- Consolidated Evidence and New Frontiers of Liquid Biopsy in Lung Cancer: A Narrative Review.Cells · 2026Review
- Methylation plus alpha-fetoprotein blood test for early detection of HCC in at-risk populations.Hepatology communications · 2026Article
- Reducing demographic bias in biomedical machine learning for cancer detection using cfDNA methylation.Genome biology · 2026Article
- Recent advances in biomarkers for cardiac fibrosis.Frontiers in cardiovascular medicine · 2026Review
Corrections and comments
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Authors and funding
54 authors.
Weihua Zeng *Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.ORCID 0009-0006-8727-0055
Chun-Chi Liu *EarlyDiagnostics Inc., Agoura Hills, CA 91301.ORCID 0000-0001-5532-8589
Shuo Li *Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.ORCID 0000-0002-1960-6016
Yonggang Zhou *Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.
Mary L StackpoleEarlyDiagnostics Inc., Agoura Hills, CA 91301.
Ying XiaoEarlyDiagnostics Inc., Agoura Hills, CA 91301.
Ran HuDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.ORCID 0000-0002-0563-8957
Caitlin TangDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.
Qiao LiuDepartment of Statistics, Stanford University, Stanford, CA 94305.ORCID 0000-0002-9781-3360
Wanwen ZengDepartment of Statistics, Stanford University, Stanford, CA 94305.
Angela YehDepartment of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.
Andrew MelehyDepartment of Surgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.
Benjamin TranDepartment of Surgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.ORCID 0000-0001-8602-5134
Zorawar NoorDepartment of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.
Megumi YokomizoDepartment of Radiological Sciences, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.ORCID 0009-0008-9983-9549
Dominic AmaraDepartment of Surgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.
Shreya GumateDepartment of Surgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.ORCID 0009-0007-0606-2439
Preeti AhujaDepartment of Radiological Sciences, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.ORCID 0009-0006-2559-8733
David Yuanze LiThousand Oaks High School, Thousand Oaks, CA 91360.
Junting ZhaoSage Hill School, Newport Coast, CA 92657.
Inga RoseReference Medicine, Phoenix, AZ 85040.
Cattlena WalkerCrown Bioscience, San Diego, CA 92127.
Sadaf MalikCrown Bioscience, San Diego, CA 92127.
Yazhen ZhuDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.
Hsian-Rong TsengJonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA 90095.
Edward B GaronDepartment of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.ORCID 0000-0001-7077-8801
Samuel W FrenchDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.ORCID 0000-0002-7611-881X
Clara E MagyarDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.
Sarah M DryDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.
Clara M LajonchereJonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA 90095.
Daniel GeschwindInstitute for Precision Health, University of California at Los Angeles, Los Angeles, CA 90095.
Gina ChoiDepartment of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.
Sammy SaabDepartment of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.
Akshay ShettyDepartment of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.
Carrie R WongVatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, University of California, Los Angeles, CA 90095.ORCID 0000-0002-2052-3701
Kevin G KingDepartment of Radiological Sciences, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.ORCID 0000-0002-9107-2207
David S LuDepartment of Radiological Sciences, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.ORCID 0000-0002-3263-4476
Steven S RamanDepartment of Radiological Sciences, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.
Xiyan XiangThe Institute for Bioelectronic Medicine, Feinstein Institutes for Medical Research and Cold Spring Harbor Laboratory, Department of Medicine, Division of Gastroenterology and Hepatology, Northwell Health, NY 11030.
Kirti ShettyDivision of Gastroenterology and Hepatology, School of Medicine, University of Maryland, Baltimore, MD 21201.
Lopa MishraThe Institute for Bioelectronic Medicine, Feinstein Institutes for Medical Research and Cold Spring Harbor Laboratory, Department of Medicine, Division of Gastroenterology and Hepatology, Northwell Health, NY 11030.
Sanaz MemarzadehJonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA 90095.
Yan LiuDepartment of Computer Science, University of Southern California, Los Angeles, CA 90089.
Frank AlberDepartment of Microbiology, Immunology and Molecular Genetics, University of California at Los Angeles, Los Angeles, CA 90095.
William HsuDepartment of Radiological Sciences, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.ORCID 0000-0002-5168-070X
Kostyantyn KrysanDepartment of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.
Steven M DubinettDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.
Denise R AberleDepartment of Radiological Sciences, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.
Vatche AgopianDepartment of Surgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.ORCID 0000-0003-0130-9838
Steven-Huy B HanDepartment of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.
Wing Hung WongDepartment of Statistics, Stanford University, Stanford, CA 94305.ORCID 0000-0001-7466-2339
Xiaohui NiEarlyDiagnostics Inc., Agoura Hills, CA 91301.
Wenyuan LiDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.ORCID 0000-0002-5029-8525
Xianghong Jasmine ZhouDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.ORCID 0000-0002-4522-7490
Funding
Special EquipmentP50HG007735 · NHGRI · STANFORD UNIVERSITY · PI WONG, WING H. · 2014 to 2018
$15.2MMultiscale Analyses of 4D Nucleome Structure and Function by Comprehensive Multimodal Data IntegrationUM1HG011593 · NHGRI · CARNEGIE-MELLON UNIVERSITY · PI ALBER, FRANK, BELMONT, ANDREW STEVEN · 2020 to 2024
$10.4MThe UCLA Center in Early Detection of Liver CancerU01CA230705 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Vatche Agopian, Samuel Wheeler French · 2018 to 2026
$6.6MThe Boston University - UCLA Lung Cancer Biomarker Characterization CenterU2CCA271898 · NCI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI Steven M. Dubinett · 2022 to 2026
$5.5MHCC EV Digital Scoring Assay for assessing treatment response in HCC patientsR01CA253651 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TSENG, HSIAN-RONG, ZHU, YAZHEN · 2020 to 2024
$3.3MMulti-cancer early detection using cell-free DNA methylome analysisU01CA285010 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ROBERT S BRESALIER, Wenyuan Li · 2023 to 2026
$3.3MDetecting and locating cancer for patients with CT-detected lung nodulesR01CA264864 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ZHOU, XIANGHONG JASMINE · 2022 to 2025
$3.2MExtracellular Vesicle-Based Digital Scoring Assay for Detecting Early-stage Hepatocellular CarcinomaR01CA255727 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ZHU, YAZHEN · 2021 to 2025
$3.2MMolecular and Imaging Biomarkers for Early Lung Cancer Detection in the Setting of Indeterminate Pulmonary NodulesR01CA210360 · NCI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI ABERLE, DENISE R., LENBURG, MARC ELLIOTT · 2016 to 2021
$3.1MThe Boston University-UCLA Lung Cancer Biomarker Development LabU01CA214182 · NCI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI ABERLE, DENISE R., DUBINETT, STEVEN M. · 2016 to 2021
$3.1MHLA B44 motif neoepitopes in NSCLC: Evaluating their effects on the TME and adding them to established markers in a model to predict durable benefit from PD- 1 inhibition with and without chemotherapyR01CA276917 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI EDWARD B GARON · 2023 to 2026
$2.9MIntegrated analysis of HCC CTCs for Liver Transplant Candidate SelectionR01CA246304 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AGOPIAN, VATCHE, TSENG, HSIAN-RONG · 2020 to 2024
$2.8MBLRD VA I01 BX006019BLRD VA I01 BX006411California Tobacco-Related Disease Research Program California Tobacco-Related Disease Research Program of the University of California T32DT4721HHS | NIH | National Cancer Institute (NCI) K99CA290092HHS | NIH | National Cancer Institute (NCI) R01CA210360HHS | NIH | National Cancer Institute (NCI) R01CA246304HHS | NIH | National Cancer Institute (NCI) R01CA246329HHS | NIH | National Cancer Institute (NCI) R01CA253651HHS | NIH | National Cancer Institute (NCI) R01CA255727HHS | NIH | National Cancer Institute (NCI) R01CA264864HHS | NIH | National Cancer Institute (NCI) R01CA276917HHS | NIH | National Cancer Institute (NCI) R21CA240887HHS | NIH | National Cancer Institute (NCI) R43CA246941HHS | NIH | National Cancer Institute (NCI) U01CA214182HHS | NIH | National Cancer Institute (NCI) U01CA230705HHS | NIH | National Cancer Institute (NCI) U01CA237711HHS | NIH | National Cancer Institute (NCI) U01CA285010HHS | NIH | National Cancer Institute (NCI) U2CCA271898HHS | NIH | National Human Genome Research Institute (NHGRI) P50HG007735HHS | NIH | National Human Genome Research Institute (NHGRI) R01HG010359HHS | NIH | National Human Genome Research Institute (NHGRI) UM1HG011593NCI NIH HHS K99 CA290092NCI NIH HHS R01 CA210360NCI NIH HHS R01 CA246304NCI NIH HHS R01 CA246329NCI NIH HHS R01 CA253651NCI NIH HHS R01 CA255727NCI NIH HHS R01 CA264864NCI NIH HHS R01 CA276917NCI NIH HHS R21 CA240887NCI NIH HHS R43 CA246941NCI NIH HHS U01 CA214182NCI NIH HHS U01 CA230705NCI NIH HHS U01 CA237711NCI NIH HHS U01 CA285010NCI NIH HHS U2C CA271898NHGRI NIH HHS P50 HG007735NHGRI NIH HHS R01 HG010359NHGRI NIH HHS UM1 HG011593NSF (NSF) DMS1952386NSF | NSF Graduate Research Fellowship Program (GRFP) DGE-1418060Stand Up To Cancer-LUNGevity-American Lung Association SU2C-AACR-DT23-17
Abstract
Plasma cell-free DNA (cfDNA), originating from multiple organs, holds significant potential for noninvasive diagnostics and prognostics. Current cfDNA methylation assays primarily focus on single clinical indications by targeting specific genomic loci. In contrast, comprehensive profiling of cfDNA methylome can enable simultaneous detection of multiple diseases by capturing organ-specific methylation signatures, thereby offering a holistic view of health, when disease etiology is unclear or when conventional biochemical diagnostics are unavailable. However, deep sequencing required for sensitive detection of methylation abnormalities remains prohibitively expensive, limiting widespread clinical use. To overcome this barrier, we developed
Indexed as
Cell-Free Nucleic AcidsDNA MethylationEpigenomeNeoplasmsBiomarkers, TumorCost-Benefit AnalysisFemaleHumansLiver NeoplasmsBiomarkers, TumorCell-Free Nucleic Acidscancer detectioncell-free DNAdisease detectionDNA methylationliquid biopsy
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