System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Review Ahead of print

PubMed: 42482117 DOI: 10.1186/s40246-026-01014-w

ExposoGenomics: integrating genome and exposome as jointly dynamic systems for causal discovery and precision health.

Hum Genomics

Authors: Vasilis Vasiliou, Nicholas Katsanis, Giuseppe Novelli, Juergen K V Reichardt, Bassam R Ali, Maria Gazouli, Sek Won Kong, Hongyu Zhao, Kiril Veselkov, Bhramar Mukherjee, Dimosthenis Sarigiannis

Affiliations

  • Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA.
  • Galatea Bio, Miami, FL, and Institute of Molecular Biology and Biotechnology (IMBB), Foundation for Research and Technology-Hellas (FORTH), Heraklion, Crete, Greece.
  • Department of Biomedicine and Prevention, Tor Vergata University of Rome, Rome, Italy.
  • Australian Institute of Tropical Health and Medicine, James Cook University, Smithfield, QLD, Australia.
  • Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.
  • Department of Basic Medical Science, Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
  • Computational Health Informatics Program, Boston Children's Hospital, Boston, MA, USA.
  • Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
  • Department of Biostatistics, Yale School of Public Health, New Haven, CT, USA.
  • Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA.
  • Department of Surgery and Cancer, Imperial College London, London, UK.
  • Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA. Center of Excellence on Cancer Theranostics, National Hellenic Research Foundation, Athens, Greece. Environmental Engineering Lab, School of Chemical Engineering, and HERACLES Research Center on Health and the Exposome, Center for Interdisciplinary Research and Innovation, Aristotle University of Thessaloniki, Thessaloniki, Greece. Department of Urology, Medical School, Johns Hopkins University, Baltimore, MD, USA.

Abstract

The past decade has witnessed an unprecedented convergence of exposomic technologies, population-scale genomics, and AI-enabled data science, creating the conditions for a new integrative discipline. Here we introduce ExposoGenomics, defined as the integrative study of how the genome and exposome, treated as jointly dynamic systems, interact across the life course to shape health and disease. ExposoGenomics moves beyond classical gene-environment interaction models by embedding high-dimensional, temporally resolved exposure data within a multi-omic and AI-enabled analytical architecture oriented toward causal discovery, mechanistic understanding, and translational application. We describe the conceptual foundations of this framework, its mechanistic architecture linking external exposures to genomic responses through physiologically based kinetic models and adverse outcome networks, and the analytical approaches, including causal machine learning, graph-based integration, and foundation models, required to realize its potential. We emphasize that computational prediction must be accompanied by rigorous empirical validation, and that findings must be grounded in biologically plausible, causally supported mechanisms. In conjunction with this Perspective, Human Genomics formally launches ExposoGenomics as a dedicated article category and invites submissions that advance this integrative agenda.

MeSH

Genomics, Genome, Foundations, Exposome