When metabolism meets physiology: Harvey and Harvetta

Precision medicine is an emerging paradigm that requires realistic, mechanistic models capturing the complexity of the human body. We present two comprehensive molecular to physiological-level, gender-specific whole-body metabolism (WBM) reconstructions, named Harvey, in recognition of William Harvey, and Harvetta. These validated, knowledge-based WBM reconstructions capture the metabolism of 20 organs, six sex organs, six blood cells, the gastrointestinal lumen, systemic blood circulation, and the blood-brain barrier. They represent 99% of the human body weight, when excluding the weight of the skeleton. Harvey and Harvetta can be parameterized based on physiological, dietary, and omics data. They correctly predict inter-organ metabolic cycles, basal metabolic rates, and energy use. We demonstrate the integration of microbiome data thereby allowing the assessment of individual-specific, organ-level modulation of host metabolism by the gut microbiota. The WBM reconstructions and the individual organ reconstructions are available under http://vmh.life. Harvey and Harvetta represent a pivotal step towards virtual physiological humans.