ArticlePLoS computational biology2012
Integrating cellular metabolism into a multiscale whole-body model.
Article in PLoS computational biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
55 citing papers in PubMed, 126 citations in OpenAlex.
- Metabolic dysfunction over a life course key to healthy ageing inequality.Aging clinical and experimental research · 2025Review
- Safety evaluation of irinotecan: a real-world disproportionality analysis using FAERS and JADER databases during the time period 2004-2024.Frontiers in pharmacology · 2025Article
- Mitochondria: the gatekeepers between metabolism and immunity.Frontiers in immunology · 2024Review
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- Dissecting the human gut microbiome to better decipher drug liability: A once-forgotten organ takes center stage.Journal of advanced research · 2023Review
- Genome-scale metabolic reconstruction of 7,302 human microorganisms for personalized medicine.Nature biotechnology · 2023Article
- Quantitative systems pharmacology of the eye: Tools and data for ocular QSP.CPT: pharmacometrics & systems pharmacology · 2023Review
- Prediction ofFrontiers in pharmacology · 2023Article
- Mathematical modeling of regulatory networks of intracellular processes - Aims and selected methods.Computational and structural biotechnology journal · 2023Review
- Does seasonality of the microbiota contribute to the seasonality of acute gout flare?Clinical and experimental rheumatology · 2022Review
- Genome-scale metabolic modeling in antimicrobial pharmacology.Engineering microbiology · 2022Review
- Article
- A dynamic multi-tissue model to study human metabolism.NPJ systems biology and applications · 2021Article
- Metabolic modelling approaches for describing and engineering microbial communities.Computational and structural biotechnology journal · 2021Review
- Advances in flux balance analysis by integrating machine learning and mechanism-based models.Computational and structural biotechnology journal · 2021Review
- Systemic Immunometabolism: Challenges and Opportunities.Immunity · 2020Review
- Metabolic Modelling as a Framework for Metabolomics Data Integration and Analysis.Metabolites · 2020Review
- Integration of Placental Transfer in a Fetal-Maternal Physiologically Based Pharmacokinetic Model to Characterize Acetaminophen Exposure and Metabolic Clearance in the Fetus.Clinical pharmacokinetics · 2020Article
- Insights from pharmacokinetic models of host-microbiome drug metabolism.Gut microbes · 2020Article
- Personalized whole-body models integrate metabolism, physiology, and the gut microbiome.Molecular systems biology · 2020Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cellular metabolism continuously processes an enormous range of external compounds into endogenous metabolites and is as such a key element in human physiology. The multifaceted physiological role of the metabolic network fulfilling the catalytic conversions can only be fully understood from a whole-body perspective where the causal interplay of the metabolic states of individual cells, the surrounding tissue and the whole organism are simultaneously considered. We here present an approach relying on dynamic flux balance analysis that allows the integration of metabolic networks at the cellular scale into standardized physiologically-based pharmacokinetic models at the whole-body level. To evaluate our approach we integrated a genome-scale network reconstruction of a human hepatocyte into the liver tissue of a physiologically-based pharmacokinetic model of a human adult. The resulting multiscale model was used to investigate hyperuricemia therapy, ammonia detoxification and paracetamol-induced toxication at a systems level. The specific models simultaneously integrate multiple layers of biological organization and offer mechanistic insights into pathology and medication. The approach presented may in future support a mechanistic understanding in diagnostics and drug development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.