Anomalous DNA methylation has wide-ranging implications, spanning from neurological disorders to cancer and cardiovascular complications. Current methods for single-cell DNA methylation analysis face limitations in coverage, leading to information loss and hampering our understanding of disease associations. The primary goal of this study is the imputation of CpG site methylation states in a given cell by leveraging the CpG states of other cells of the same type. To address this, we introduce CpGFuse, a novel methodology that combines information from diverse genomic features. Leveraging two benchmark datasets, we employed a careful preprocessing approach and conducted a comprehensive ablation study to assess the individual and collective contributions of DNA sequence, intercellular, and intracellular features. Our proposed model, CpGFuse, employs a convolutional neural network with an attention mechanism, surpassing existing models across HCCs and HepG2 datasets. The results highlight the effectiveness of our approach in enhancing accuracy and providing a robust tool for CpG site prediction in genomics. CpGFuse's success underscores the importance of integrating multiple genomic features for accurate identification of methylation states of CpG site.

MOTIVATION: The investigation of DNA methylation can shed light on the processes underlying human well-being and help determine overall human health. However, insufficient coverage makes it challenging to implement single-stranded DNA methylation sequencing technologies, highlighting the need for an efficient prediction model. Models are required to create an understanding of the underlying biological systems and to project single-cell (methylated) data accurately. RESULTS: In this study, we developed positional features for predicting CpG sites. Positional characteristics of the sequence are derived using data from CpG regions and the separation between nearby CpG sites. Multiple optimized classifiers and different ensemble learning approaches are evaluated. The OPTUNA framework is used to optimize the algorithms. The CatBoost algorithm followed by the stacking algorithm outperformed existing DNA methylation identifiers. AVAILABILITY AND IMPLEMENTATION: The data and methodologies used in this study are openly accessible to the research community. Researchers can access the positional features and algorithms used for predicting CpG site methylation patterns. To achieve superior performance, we employed the CatBoost algorithm followed by the stacking algorithm, which outperformed existing DNA methylation identifiers. The proposed iCpG-Pos approach utilizes only positional features, resulting in a substantial reduction in computational complexity compared to other known approaches for detecting CpG site methylation patterns. In conclusion, our study introduces a novel approach, iCpG-Pos, for predicting CpG site methylation patterns. By focusing on positional features, our model offers both accuracy and efficiency, making it a promising tool for advancing DNA methylation research and its applications in human health and well-being.