Human domainome 1: A valuable resource for biomedical research and therapeutic development – a systematic review

Recent advances in large-scale proteomics and computational biology have enabled systematic mapping of protein domains across the human proteome, giving rise to integrative resources known as domainomes. Human Domainome 1 represents a comprehensive framework for annotating protein domains, domain–domain interactions, and associated biological functions. By capturing the modular organization of proteins, this resource provides critical insights into molecular mechanisms underlying health and disease, and offers a powerful platform for rational drug discovery and precision medicine. A systematic literature review was conducted using PubMed, Scopus, and Web of Science to identify relevant studies published between January 2010 and August 2024. Search terms included “Human Domainome 1”, “protein domains”, “domainome”, “biomedical research”, “therapeutic development”, and “drug target discovery”. Two independent reviewers screened titles, abstracts, and full texts according to predefined eligibility criteria. Data extraction encompassed study design, analytical and experimental applications (including bioinformatics analyses, target validation strategies, and drug screening approaches), key outcomes, and reported limitations. Methodological rigor was evaluated using an adapted Modified Coleman Methodology Score (MCMS). Following full-text assessment, 35 studies met the inclusion criteria. Human Domainome 1 was applied across a wide range of biomedical contexts, including protein-protein interaction mapping, pathway reconstruction, and identification of disease-associated domains in oncology, infectious diseases, and neurological disorders. Quantitative synthesis (Table 3) demonstrated a strong association between domain architecture-based analyses and successful identification of novel biomarkers. Furthermore, multiple studies (Table 4) reported that integration of Domainome data into drug discovery workflows significantly enhanced in silico screening efficiency and structure-guided drug design, resulting in higher hit rates and improved target prioritization. Human Domainome 1 emerges as a robust and versatile resource that substantially advances the understanding of protein function, regulation, and disease relevance. Its integration into contemporary biomedical research pipelines accelerates target identification and therapeutic development, supporting more precise and mechanism-driven drug discovery. Future efforts should prioritize the standardization of domain annotation methodologies and the expansion of functional validation across diverse biological systems to fully realize the translational potential of the Domainome.