Methods Mol Biol. 2025;2952:335-367. doi: 10.1007/978-1-0716-4690-8_20.
ABSTRACT
The convergence of next-generation sequencing and advanced computational methods has reshaped genomic analysis by enabling unprecedented volumes of molecular data to be generated and scrutinized. This chapter surveys the rapidly evolving landscape of deep genomics, highlighting how breakthroughs in deep learning frameworks-such as Convolutional Neural Networks, Recurrent Neural Networks, Transformers, and Graph Neural Networks-allow researchers to detect, characterize, and interpret complex genetic alterations. We begin by illustrating the progression from traditional bioinformatics to contemporary neural architectures capable of identifying fine-grained molecular signals. CNNs excel at discerning localized sequence motifs, RNNs capture dynamic expression patterns in sequential data, Transformers unveil long-range dependencies crucial for pinpointing regulatory variants, and GNNs trace systemic gene-gene and protein-protein interactions, clarifying how single mutations can ripple throughout biological networks.A central theme is the integration of diverse omic layers-encompassing epigenomic, transcriptomic, and proteomic profiles to offer a more comprehensive perspective on genomic regulation. While this approach amplifies the detection power for pathogenic variants and hidden biomarkers, it also poses significant methodological hurdles related to data harmonization and interpretability. Techniques such as saliency mapping, SHAP analysis, and gradient-based CAM illuminate the internal logic of these deep models, strengthening reliability in clinical diagnostics and fueling mechanistic insights in research settings. Beyond methodological innovations, the chapter underscores data privacy, systematic bias mitigation, and explainability protocols as foundational elements for the safe and ethical use of deep genomics tools in clinical and research environments. Regulatory compliance and transparent communication of model outputs are indispensable for cultivating public trust and ensuring equitable access to genomic medicine.Looking ahead, emerging technologies such as secure multi-institutional data analysis protocols, federated learning, and potential quantum computing applications offer promising avenues for scaling analysis to ever-larger datasets without jeopardizing patient privacy. As these advancements merge with more refined models, precision medicine stands to benefit from unprecedented accuracy in variant interpretation, timely disease diagnosis, and effective therapeutic strategies. By integrating cutting-edge computational methods with robust ethical frameworks, deep genomics is poised to transform our understanding of genetic variation and its implications for human health.
PMID:40553343 | DOI:10.1007/978-1-0716-4690-8_20
