Ultra-mild bisulfite outperforms existing methods for 5-methylcytosine detection with low input DNA
- Qing Dai
- Tanner Baldwin
- Ruitu Lyu
- Bryan Daniels
- Chang Ye
- Chen Cao
- Chenyou Zhu
- Diwen Fan
- Liane Lin
- Yushuai Liu
- Yiding Wang
- Chuan He
2025-11-13
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.