51 - "From the Virtual Metabolic Human to Digital Metabolic Twins"
ABSTRACT:
Metabolism plays a crucial role in health and disease and depends on intrinsic (e.g., genetics) and extrinsic (e.g., microbiome, nutrition, lifestyle) factors. A Digital Metabolic Twin (DMT) is therefore required to systematically interrelate these constituting factors. In this endeavour, we have created the Virtual Metabolic Human (VMH, www.vmh.life), which interconnects state-of-the-art resources on human and microbiome metabolism, diet, and disease. Specifically, the VMH focuses on enabling constraint-based reconstruction and analysis (COBRA), which leverages mathematical descriptions of an organism, i.e., genome-scale metabolic reconstructions, to enable a mechanistically accurate representation of cellular and physiological properties.
Extensive manual curation protocols enabled the complete computational representation, for both human and associated microbes, of known metabolism in relation to the underlying gene, protein, and biochemical networks. The VMH currently captures 5,607 unique metabolites, 19,313 unique reactions, 3,695 human genes, 255 Mendelian diseases, 818 microbes, and 8,790 food items. The VMH’s unique features are (i) the hosting of the metabolic reconstructions of human and gut microbes amenable for metabolic modelling; (ii) seven human metabolic maps for data visualisation; (iii) a nutrition designer; (iv) a user-friendly webpage and application-programming interface to access its content; (v) user feedback option for community engagement and (vi) the connection of its entities to 57 other web resources.
Ongoing efforts include the further development and integration of the reconstructions, such as sex-specific and organ-resolved whole-body models for both adults and infants, and expansion of the microbiome resource, which is now approaching a quarter million species identified from 34 countries and spanning five body sites. The models have been validated in a diverse range of applications, including, e.g., mechanism-derived hypothesis generation for neurodegenerative diseases, cancer, and inherited metabolic diseases. Ultimately, our aim is to position the VMH to catalyse the creation of DMTs to enable better health through personalised, real-time coaching derived from one’s own, holistic, and longitudinal data.
SHORT BIO:
Cyrille Thinnes is a co-chair of the Public & Patient Involvement (PPI) taskforce of the Avicenna Alliance Policy Development working group. Currently based at the University Galway as a member of the Molecular Systems Physiology group and Digital Metabolic Twin Centre, he is the Engagement Manager for the Virtual Metabolic Human (VMH). His focus is to accelerate Digital Health research outcome into societal benefit through systematic stakeholder involvement. He designed and leads Virtuome, the fully virtual VMH flagship undergraduate summer school in Digital Health with Engaged Research as a core pillar, now counting 84 alumni in 5 consecutive years, and over 2,000 community partners. Cyrille is also a member of the School of Medicine, Nursing & Health Sciences Civic Engagement Committee, the national PPI Ignite network working group on establishing PPI in the lab-based environment, and an academic mentor for the Irish University of Sanctuary network. Cyrille holds a doctorate in Chemical Biology from the University of Oxford and an Executive MBA from NUI Galway, and has worked in Ireland, the UK, the USA, and Luxembourg.
