️ 70: Scalable Screening of Ternary-Code DNA Methylation Dynamics Associated with Human Traits

️ Episode 70: Scalable Screening of Ternary-Code DNA Methylation Dynamics Associated with Human Traits In this episode of Base por Base, we delve into a methodological breakthrough reported by Goldberg et al. (2025) in Cell Genomics, where the authors introduce the methylation screening array (MSA) — a next-generation Infinium BeadChip designed for large-scale, high-throughput profiling of DNA cytosine modifications across human populations. By integrating curated trait-associated loci from epigenome-wide association studies with novel cell-type discriminants, the MSA provides a compact yet comprehensive platform to measure ternary-code methylation (5mC, 5hmC, and unmodified cytosine) at base resolution across diverse tissues . Highlights of the study:The authors demonstrate that the MSA enables scalable and quantitative profiling of human epigenomes, overcoming the coverage–cost trade-offs of previous array designs; they construct a base-resolution atlas of matched total modifications (5modC) and 5hmC landscapes across multiple human tissues; they uncover how distinct patterns of 5modC and 5hmC correlate with gene expression to regulate tissue identity; and they reveal underappreciated roles for 5hmC in aging dynamics and the performance of epigenetic clocks . Conclusion:By consolidating extant EWAS discoveries and leveraging advances in whole-genome methylation profiling, the MSA inaugurates a scalable approach for trait-focused methylation screening in large cohorts. This tool promises to dissect cell-type-specific epigenetic mechanisms underlying human traits, improve the annotation of disease-associated loci, and inform genomics-driven strategies for prevention and precision medicine. Reference:Goldberg, D. C., Cloud, C., Lee, S. M., Barnes, B., Gruber, S., Kim, E., Pottekat, A., Westphal, M. S., McAuliffe, L., Majounie, E., Kalayil Manian, M., Zhu, Q., Tran, C., Hansen, M., Stojakovic, J., Parker, J. B., Kohli, R. M., Porecha, R., Renke, N., & Zhou, W. (2025). Scalable screening of ternary-code DNA methylation dynamics associated with human traits. Cell Genomics, 5, 100929. https://doi.org/10.1016/j.xgen.2025.100929 License:This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

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