Skip to main content

New Tool Developed by Children’s Hospital of Philadelphia Researchers Decodes Complex DNA Methylation

News Brief
New Tool Developed by Children’s Hospital of Philadelphia Researchers Decodes Complex DNA Methylation
Findings unlock new approaches to uncovering how environment and biology shape health across tissues and populations
July 9, 2025
Wanding Zhou, PhD
Wanding Zhou, PhD

Researchers in the Center for Computational and Genomic Medicine at Children’s Hospital of Philadelphia (CHOP) developed a new tool called the Methylation Screening Array (MSA) to better understand how changes in DNA methylation-mediated regulation of genes, rather than changes in the genes themselves, affect complex human traits like aging and disease risk. This is the first data set to dissect the two forms of DNA methylation---5-methylcytosine and 5-hydroxymethylcytosine---to associate characteristics such as cell composition, gene regulatory mechanism, and epigenetic age in diverse human cell lines and tissues. The findings were reported in Cell Genomics.

Epigenome-wide association studies are transforming how researchers understand the interplay between epigenetics and complex human traits. These tools have become a powerful strategy to examine how changes in our DNA can affect traits like health, behavior, or risk for disease. Until now, prior versions of these types of tools were limited.

“Our dataset introduces a focused, scalable, and biologically nuanced tool for epigenetic screening,” said Wanding Zhou, PhD, a lead study author and computational scientist in CHOP’s Center for Computational and Genomic Medicine. “The MSA opens the door for exploring epigenetic mechanisms across tissues, aging, environmental exposures and diverse populations.”

In this study, researchers performed extensive meta-analyses of human EWASs to develop the MSA for screening trait epigenetic associations. The MSA is a fast, large-scale tool that measures subtle DNA changes, detecting three key forms of cytosine – unmodified, 5-methylcytosine (5mC), and 5-hydroxymethylcytosine (5hmC), in diverse groups of people. 

Based on the dataset, the researchers comprehensively characterized the tissue-specific methylation biology and the tissue context of trait associations with genetic and epigenetic variations. They integrated MSA data with existing models to accurately predict human traits, including age and mitotic history, a record of how many times a cell has divided, which helps researchers understand how old the cell is and how it’s been growing. 

The study also showed that the epigenetic marker 5hmC varies widely between tissues, aligns with gene expression, and plays a significant role in aging processes. The 5hmC-aging EWAS found both universal and tissue-specific methylation changes with age and demonstrated that resolving 5hmC improves epigenetic clock accuracy. 

CHOP conducted the product and experiment design, data analysis, software development, paper drafting, and revision with support from researchers in the Perelman School of Medicine at the University of Pennsylvania.

The research was supported in part by the National Institute of Health (P30 AI045008) and (P30 CA016520), (SCR 022380), (R35-GM146978) and (R01-HG010646). 

Goldberg et al. “Scalable Screening of Ternary-Code DNA Methylation Dynamics Associated with Human Traits.Journal. Online July 3, 2025. DOI: 10.1016/j.xgen.2025.100929.

Featured in this article

Experts

Research

Recommended reading

News Release

Algorithm Created By “Deep Learning” Identifies Potential Therapeutic Targets Throughout Genome

Researchers from NJIT and CHOP identified sites of methylation that could not be found with existing sequencing methods.

Learn more

Contact us

Jump back to top