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When metabolism meets physiology: Harvey and Harvetta

Ines Thiele, Swagatika Sahoo, Almut Heinken, Laurent Heirendt, Maike K. Aurich, Alberto Noronha, Ronan M.T. Fleming
doi: https://doi.org/10.1101/255885
Ines Thiele
1Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Campus Belval, Esch-sur-Alzette, Luxembourg
2Faculty of Science, Technology and Communication, University of Luxembourg, Campus Belval, Esch-sur-Alzette, Luxembourg.
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  • For correspondence: ines.thiele@gmail.com ronan.mt.fleming@gmail.com
Swagatika Sahoo
1Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Campus Belval, Esch-sur-Alzette, Luxembourg
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Almut Heinken
1Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Campus Belval, Esch-sur-Alzette, Luxembourg
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Laurent Heirendt
1Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Campus Belval, Esch-sur-Alzette, Luxembourg
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Maike K. Aurich
1Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Campus Belval, Esch-sur-Alzette, Luxembourg
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Alberto Noronha
1Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Campus Belval, Esch-sur-Alzette, Luxembourg
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Ronan M.T. Fleming
1Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Campus Belval, Esch-sur-Alzette, Luxembourg
3Division of Analytical Biosciences, Leiden Academic Centre for Drug Research, Faculty of Science, University of Leiden, Leiden, The Netherlands.
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  • For correspondence: ines.thiele@gmail.com ronan.mt.fleming@gmail.com
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Abstract

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.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted January 29, 2018.
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When metabolism meets physiology: Harvey and Harvetta
Ines Thiele, Swagatika Sahoo, Almut Heinken, Laurent Heirendt, Maike K. Aurich, Alberto Noronha, Ronan M.T. Fleming
bioRxiv 255885; doi: https://doi.org/10.1101/255885
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When metabolism meets physiology: Harvey and Harvetta
Ines Thiele, Swagatika Sahoo, Almut Heinken, Laurent Heirendt, Maike K. Aurich, Alberto Noronha, Ronan M.T. Fleming
bioRxiv 255885; doi: https://doi.org/10.1101/255885

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