Systems Biology and Multi-Omics in Asthma and COPD: A Systematic Review of Computational Approaches (2010-2024)

Systems biology approaches have contributed to advancing our understanding of complex respiratory diseases including asthma and chronic obstructive pulmonary disease (COPD). This systematic review evaluates the application of systems biology methodologies in respiratory medicine, focusing on multi-omics data integration and computational techniques for biomarker discovery and mechanistic understanding. Following PRISMA 2020 guidelines, we conducted a comprehensive literature search across Web of Science and Scopus databases, identifying 117 peer-reviewed documents published from 2010 to 2024. The review methodology employed bibliometric analysis combined with qualitative synthesis of included studies. Results demonstrate steady growth in systems biology applications for asthma and COPD research, with publication rates increasing by approximately 0.5 articles per year (<i>R²</i> = 0.73, p < 0.001). Bibliometric analysis identified five major research clusters: systems biology as a foundational methodological framework (Basic Theme), COPD-focused research as the most developed area (Motor Theme), gene expression analysis, disease classification approaches, and specialized lung disease investigations (Niche Theme). Multi-omics integration studies achieved 82-91% accuracy in disease classification tasks, with transcriptomics-based asthma endotyping validated in over 1500 patients across multiple cohorts. Network analysis approaches identified hub genes (IL-6, TNF-α, MMP9) replicated across three independent studies. Machine learning applications demonstrated 80-90% accuracy for diagnostic and prognostic tasks, though external validation remains limited, with only 15% of reviewed studies including independent validation cohorts. Significant challenges persist in data integration, computational reproducibility, and clinical translation. Most studies employed modest sample sizes (median n=89), and population diversity was limited, with 89% conducted in European-ancestry populations. This review provides a comprehensive assessment of systems biology progress in respiratory medicine, identifies methodological gaps, and highlights the need for standardized protocols, larger collaborative studies, and rigorous external validation to advance clinical implementation of systems biology findings in asthma and COPD management.