Mini-Galaxy: Rethinking Complex Human Diseases Through the Lens of Systems Biology and Multilayered AI Network Perspectives
Human diseases are complex and arise from the coordinated action of multiple genes and their protein products. Genes' behaviors extend beyond genetic variants, mutations, and differential expressions. Their coordinated activity across biological scales (molecules, cells, tissues, organs) produces emergent behaviors that shape health and disease. These emergent behaviors span time and space and are often hard to measure directly from observation when using standard experimental measurements. Yet these "hidden" or latent gene characteristics can be powerful drivers of disease. We propose a Mini-Galaxy Model (MGM), a systems-level AI-driven network framework that models cells as "mini-galaxies" composed of multilayered biological information, with each layer encoding a different dimension of genes' behavior. Here, we delineate a strategy on how to construct and compare MGMs across health and disease and map their etiological relatedness. We also operationalize the MGM as a discovery platform for translational medicine, offering modules to allow target prioritization and editing. By reframing human diseases as the result of emergent behavior of multilayered multimode biological networks and their perturbations, the MGM yields actionable rules to streamline biomarker discovery, guide target selection and enable rational design of combinatorial interventions, and accelerate drug repurposing.
Authors
- Shizhen Zhu (ORCID: https://orcid.org/0000-0002-2929-3279)
- Cristina Belo Correia (ORCID: https://orcid.org/0000-0002-8220-6592)
- Choong Yong Ung (ORCID: https://orcid.org/0000-0002-9876-3473)
- Yuin‐Han Loh (ORCID: https://orcid.org/0000-0002-4715-6454)
- Daniel D. Billadeau (ORCID: https://orcid.org/0000-0002-2296-9547)
- Z Zhang
- Easton Blissenbach
- Hu Li
Institutions
- Agency for Science, Technology and Research (SG)
- Mayo Clinic (US)
- National University of Singapore (SG)
- University of Minnesota Rochester (US)
- Mayo Clinic in Arizona (US)
- Mayo Clinic in Florida (US)
- Institute of Molecular and Cell Biology (SG)
Publication Details
- Journal
- International Journal of Molecular Sciences
- Published
- 2026-03-31
- DOI
- https://doi.org/10.3390/ijms27073161
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Glenn Foundation for Medical Research
- Fondation pour la Recherche Médicale
- National Institutes of Health
- Center for Individualized Medicine, Mayo Clinic
- Center for Cell Signaling in Gastroenterology, Mayo Clinic
- NIH Clinical Center
- Susan Morrow Legacy Foundation