Ultra-mild bisulfite outperforms existing methods for 5-methylcytosine detection with low input DNA
We present Ultra-Mild Bisulfite Sequencing (UMBS-seq), a method for 5-methylcytosine (5mC) detection that minimizes DNA degradation and background noise. UMBS-seq outperforms conventional bisulfite and enzymatic methyl-sequencing (EM-seq) methods in library yield, complexity, and conversion efficiency when applied to low-input DNA samples. In particular, its effectiveness with low-input cell-free DNA (cfDNA) and hybridization-based target capture highlights its potential for clinical applications, including 5mC biomarker detection and early disease diagnosis.
Authors
- Ruitu Lyu (ORCID: https://orcid.org/0000-0003-4597-1604)
- Bryan C. Daniels (ORCID: https://orcid.org/0000-0002-5870-1059)
- Qing Dai (ORCID: https://orcid.org/0000-0002-8578-1568)
- Yushuai Liu (ORCID: https://orcid.org/0000-0002-2011-1926)
- Liane Lin (ORCID: https://orcid.org/0009-0006-6437-8565)
- Hubiao Chen (ORCID: https://orcid.org/0000-0003-0708-6073)
- Yiding Wang (ORCID: https://orcid.org/0000-0002-7172-8651)
- Chenyou Zhu (ORCID: https://orcid.org/0000-0003-2682-9565)
- Chuan He (ORCID: https://orcid.org/0000-0003-4319-7424)
- Daiming Fan (ORCID: https://orcid.org/0000-0002-2466-5002)
- Chang Ye (ORCID: https://orcid.org/0000-0003-0236-5671)
- Tanner Baldwin (ORCID: https://orcid.org/0009-0001-4603-1836)
Institutions
- Howard Hughes Medical Institute (US)
- University of Illinois Chicago (US)
- University of Chicago (US)
- Lake County Forest Preserves (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-11-13
- DOI
- https://doi.org/10.1038/s41467-025-66033-y
- Citations
- 2
- Primary Topic
- Epigenetics and DNA Methylation
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- National Institutes of Health