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Enhanced Reduced Representation Bisulfite Sequencing for Assessment of DNA Methylation at Base Pair Resolution
Published on: February 24, 2015
Electrostatic-Driven Nucleobase Discrimination by Covalent Organic Framework Nanosheets for Deoxyribonucleic Acid
Rongjie Yang1, Jinze Li1, Chuanyu Li1
1CAS Key Lab of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China.
Journal of the American Chemical Society
|June 1, 2026
Summary
We developed a novel fluorescent biosensor using triphenylamine-based covalent organic framework nanosheets (TPA CONs) for precise nucleobase discrimination and DNA methylation analysis. This method enables sensitive detection of epigenetic modifications in cancer cells.
Area of Science:
- Materials Science
- Biotechnology
- Analytical Chemistry
Background:
- Nucleotide base abnormalities are linked to various diseases.
- Accurate discrimination of nucleotide bases is crucial but challenging due to structural similarities.
- Epigenetic modifications, like DNA methylation, play a significant role in disease development.
Purpose of the Study:
- To develop a novel fluorescent biosensor for nucleobase discrimination.
- To enable quantitative profiling of DNA methylation.
- To investigate the potential of triphenylamine-based covalent organic framework nanosheets (TPA CONs) for epigenetic detection.
Main Methods:
- Fabrication of triphenylamine-based covalent organic framework nanosheets (TPA CONs).
- Utilizing TPA CONs as a fluorescent biosensor for nucleobase discrimination based on electrostatic potential.
- Quantitative DNA methylation analysis using the TPA CONs platform in cancer cell lines and patient specimens.
- Experimental and computational studies to elucidate the interaction mechanism between CONs and nucleobases.
Main Results:
- TPA CONs exhibit electrostatic potential-mediated base selectivity, with affinity order T > G > A > C.
- Efficient fluorescence quenching via photoinduced electron transfer observed for T-rich sequences.
- Restoration of fluorescence observed for C-rich sequences.
- Successful detection of estrogen receptor α (ERα) gene methylation in breast cancer cells with a 2.4% limit of detection.
- High consistency between TPA CONs platform and pyrosequencing for eyes absent homologue 2 (EYA2) gene methylation analysis in hepatocellular carcinoma (HCC) specimens.
Conclusions:
- Triphenylamine-based covalent organic framework nanosheets (TPA CONs) serve as an effective fluorescent biosensor for direct nucleobase discrimination.
- The developed platform enables sensitive and quantitative DNA methylation analysis.
- This work highlights the potential of TPA CONs for epigenetic detection and disease diagnostics.
