ArticleCommunications biology2025
Transformer-based deep learning for accurate detection of multiple base modifications using single molecule real-time sequencing.
Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- HPRC2: A human pangenome reference with near-complete coverage of common genetic variation.bioRxiv : the preprint server for biology · 2026Article
- From Spatial Epigenomes to Clinical Diagnostics: Integrative Methylomics Across Scales and Modalities.International journal of molecular sciences · 2026Review
- From multi-omics to deep learning: advances in cfDNA-based liquid biopsy for multi-cancer screening.Biomarker research · 2025Review
- EM-DeepSD: A Deep Neural Network Model Based on Cell-Free DNA End-Motif Signal Decomposition for Cancer Diagnosis.Diagnostics (Basel, Switzerland) · 2025Article
- Pioneering contribution of Professor Bruce Ames to early development in biochemical aspects of oxidatively generated damage to DNA.Frontiers in molecular biosciences · 2025Review
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20 authors.
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Abstract
We had previously reported a convolutional neural network (CNN) based approach, called the holistic kinetic model (HK model 1), for detecting 5-methylcytosine (5mC) by single molecule real-time sequencing (Pacific Biosciences). In this study, we constructed a hybrid model with CNN and transformer layers, named HK model 2. We improve the area under the receiver operating characteristic curve (AUC) for 5mC detection from 0.91 for HK model 1 to 0.99 for HK model 2. We further demonstrate that HK model 2 can detect other types of base modifications, such as 5-hydroxymethylcytosine (5hmC) and N6-methyladenine (6mA). Using HK model 2 to analyze 5mC patterns of cell-free DNA (cfDNA) molecules, we demonstrate the enhanced detection of patients with hepatocellular carcinoma, with an AUC of 0.97. Moreover, HK model 2-based detection of 6mA enables the detection of jagged ends of cfDNA and the delineation of cellular chromatin structures. HK model 2 is thus a versatile tool expanding the applications of single molecule real-time sequencing in liquid biopsies.
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