Evidence map›Paper›PMID 38826316›Full record

ArticlebioRxiv : the preprint server for biology2025

Scalable Screening of Ternary-Code DNA Methylation Dynamics Associated with Human Traits.

David C Goldberg, Cameron Cloud, Sol Moe Lee, Bret Barnes, Steven Gruber, Elliot Kim, Anita Pottekat, Maximillian S Westphal, Luana McAuliffe, Elisa Majounie and 10 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors.

David C GoldbergCenter for Computational and Genomic Medicine, The Children's Hospital of Philadelphia, PA, 19104, USA.
Cameron CloudCenter for Computational and Genomic Medicine, The Children's Hospital of Philadelphia, PA, 19104, USA.
Sol Moe LeeCenter for Computational and Genomic Medicine, The Children's Hospital of Philadelphia, PA, 19104, USA.
Bret BarnesIllumina, Inc. San Diego, CA 92122, USA.
Steven GruberIllumina, Inc. San Diego, CA 92122, USA.
Elliot KimCenter for Computational and Genomic Medicine, The Children's Hospital of Philadelphia, PA, 19104, USA.
Anita PottekatIllumina, Inc. San Diego, CA 92122, USA.
Maximillian S WestphalIllumina, Inc. San Diego, CA 92122, USA.
Luana McAuliffeIllumina, Inc. San Diego, CA 92122, USA.
Elisa MajounieIllumina, Inc. San Diego, CA 92122, USA.
Manesh KalayilManianIllumina, Inc. San Diego, CA 92122, USA.
Qingdi ZhuIllumina, Inc. San Diego, CA 92122, USA.
Christine TranIllumina, Inc. San Diego, CA 92122, USA.
Mark HansenIllumina, Inc. San Diego, CA 92122, USA.
Jelena StojakovicIllumina, Inc. San Diego, CA 92122, USA.
Jared B ParkerDepartment of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Rahul M KohliDepartment of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Rishi PorechaIllumina, Inc. San Diego, CA 92122, USA.
Nicole RenkeIllumina, Inc. San Diego, CA 92122, USA.
Wanding ZhouCenter for Computational and Genomic Medicine, The Children's Hospital of Philadelphia, PA, 19104, USA.ORCID 0000-0001-9126-1932

Funding

UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Robert H. Vonderheide · 1985 to 2026
$222.3M
Virus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Ronald G Collman · 1999 to 2026
$78.6M
Ultra low-input epigenetic sequencing with combined enzymatic and long-read technologiesR01HG010646 · NHGRI · UNIVERSITY OF PENNSYLVANIA · PI Gang Fang, Rahul Manu Kohli · 2019 to 2026
$3.9M
Decoding Single-cell DNA Methylomes for Epigenetic Cell IdentityR35GM146978 · NIGMS · CHILDREN'S HOSP OF PHILADELPHIA · PI Wanding Zhou · 2022 to 2026
$2.2M
NCI NIH HHS P30 CA016520NHGRI NIH HHS R01 HG010646NIAID NIH HHS P30 AI045008NIGMS NIH HHS R35 GM146978
6 · The paper itself

Abstract

Epigenome-wide association studies (EWAS) are transforming our understanding of the interplay between epigenetics and complex human traits and phenotypes. We introduce the Methylation Screening Array (MSA), a new iteration of the Infinium technology for scalable and quantitative screening of trait associations of nuanced ternary-code cytosine modifications in larger, more inclusive, and stratified human populations. MSA integrates EWAS, single-cell, and cell-type-resolved methylome profiles, covering diverse human traits and diseases. Our first MSA applications yield multiple biological insights: we revealed a previously unappreciated role of 5-hydroxymethylcytosine (5hmC) in trait associations and epigenetic clocks. We demonstrated that 5hmCs complement 5-methylcytosines (5mCs) in defining tissues and cells' epigenetic identities. In-depth analyses highlighted the cell type context of EWAS and GWAS hits. Using this platform, we conducted a comprehensive human 5hmC aging EWAS, discovering tissue-invariant and tissue-specific aging dynamics, including distinct tissue-specific rates of mitotic hyper- and hypomethylation rates. These findings chart a landscape of the complex interplay of the two forms of cytosine modifications in diverse human tissues and their roles in health and disease.

Indexed as

DNA methylationEpigeneticsEpigenome-wide Association Study

Identifiers

PMID38826316
PMCPMC11142114

What OpenQuestion holds

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LicenceCC BY-ND
Read underepoch 390

Registered trials

None linked

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.