Sonika Tyagi

Yao Li, Xikun Zhang, Xiaotao Shen et al.

Epigenetic clocks based on DNA methylation have emerged as powerful tools for estimating biological age, with broad applications in aging research, age-related disease studies, and longevity science. Despite advances across machine learning approaches to epigenetic age prediction, spanning penalised linear regression, deep feedforward networks, residual architectures, and graph neural networks, no existing method jointly models co-methylation graph structure and site-specific DNA sequence context within a unified framework. We propose a unified sequence--graph integration framework for epigenetic age prediction that addresses this gap, integrating eight-dimensional DNA sequence statistical features through a lightweight gated modulation mechanism that adaptively scales each site's methylation signal according to its sequence-determined biological relevance prior to graph convolution. Evaluated on 3,707 blood methylation samples against a comprehensive set of baselines, our method achieves a test MAE of 3.149 years, a 12.8\% improvement over the strongest graph-based baseline. Biologically informed statistical features outperform CNN-based sequence encoding, demonstrating that handcrafted sequence features are more effective than end-to-end learned representations in this data regime. Post-hoc interpretability analysis identifies CpG density and local adenine frequency as features with age-dependent importance shifts, consistent with known mechanisms of age-related hypermethylation at CpG-dense promoter regions. Our code is at https://github.com/yaoli2022/graphage-seq.

Falih Gozi Febrinanto, Adonia Simango, Chengpei Xu et al.

Graph neural networks (GNNs) have been developed to model the relationship between regions of interest (ROIs) in brains and have shown significant improvement in detecting brain diseases. However, most of these frameworks do not consider the intrinsic relationship of causality factor between brain ROIs, which is arguably more essential to observe cause and effect interaction between signals rather than typical correlation values. We propose a novel framework called CGB (Causal Graphs for Brains) for brain disease classification/detection, which models refined brain networks based on the causal discovery method, transfer entropy, and geometric curvature strategy. CGB unveils causal relationships between ROIs that bring vital information to enhance brain disease classification performance. Furthermore, CGB also performs a graph rewiring through a geometric curvature strategy to refine the generated causal graph to become more expressive and reduce potential information bottlenecks when GNNs model it. Our extensive experiments show that CGB outperforms state-of-the-art methods in classification tasks on brain disease datasets, as measured by average F1 scores.