ArticlePloS one2016
A Liver-Centric Multiscale Modeling Framework for Xenobiotics.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
28 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Application of Magnetic Resonance Imaging in Liver Biomechanics: A Systematic Review.Frontiers in physiology · 2021Pooled it
- Multiscale zonation-resolved modeling of dose-dependent determinants of acetaminophen-induced liver injury.Frontiers in pharmacology · 2026Article
- Predicting organoid morphology through a phase field model: Insights into cell division and lumenal pressure.PLoS computational biology · 2025Article
- Multiscale modeling of drug-induced liver injury from organ to lobule.NPJ digital medicine · 2025Article
- Article
- A virtual scalable model of the Hepatic Lobule for acetaminophen hepatotoxicity prediction.NPJ digital medicine · 2024Article
- A liver digital twin for in silico testing of cellular and inter-cellular mechanisms in regeneration after drug-induced damage.iScience · 2024Article
- SimService: a lightweight library for building simulation services in Python.Bioinformatics (Oxford, England) · 2024Article
- Illuminating HBV with multi-scale modeling.Frontiers in systems biology · 2023Article
- Unraveling the effect of intra- and intercellular processes on acetaminophen-induced liver injury.NPJ systems biology and applications · 2022Article
- A Negative Feedback Loop and Transcription Factor Cooperation Regulate Zonal Gene Induction by 2, 3, 7, 8-Tetrachlorodibenzo-p-Dioxin in the Mouse Liver.Hepatology communications · 2022Article
- Systems Biology in ELIXIR: modelling in the spotlight.F1000Research · 2022Article
- From Seeing to Simulating: A Survey of Imaging Techniques and Spatially-Resolved Data for Developing Multiscale Computational Models of Liver Regeneration.Frontiers in systems biology · 2022Article
- Generation of multicellular spatiotemporal models of population dynamics from ordinary differential equations, with applications in viral infection.BMC biology · 2021Article
- Patient-Specific Organoid and Organ-on-a-Chip: 3D Cell-Culture Meets 3D Printing and Numerical Simulation.Advanced biology · 2021Review
- Virtual metabolic human dynamic model for pathological analysis and therapy design for diabetes.iScience · 2021Article
- Impact of tumor-parenchyma biomechanics on liver metastatic progression: a multi-model approach.Scientific reports · 2021Article
- Hepatectomy-Induced Alterations in Hepatic Perfusion and Function - Toward Multi-Scale Computational Modeling for a Better Prediction of Post-hepatectomy Liver Function.Frontiers in physiology · 2021Review
- Quantitative prediction of human pharmacokinetic responses to drugs via fluidically coupled vascularized organ chips.Nature biomedical engineering · 2020Article
- Liver Bioreactor Design Issues of Fluid Flow and Zonation, Fibrosis, and Mechanics: A Computational Perspective.Journal of functional biomaterials · 2020Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
We describe a multi-scale, liver-centric in silico modeling framework for acetaminophen pharmacology and metabolism. We focus on a computational model to characterize whole body uptake and clearance, liver transport and phase I and phase II metabolism. We do this by incorporating sub-models that span three scales; Physiologically Based Pharmacokinetic (PBPK) modeling of acetaminophen uptake and distribution at the whole body level, cell and blood flow modeling at the tissue/organ level and metabolism at the sub-cellular level. We have used standard modeling modalities at each of the three scales. In particular, we have used the Systems Biology Markup Language (SBML) to create both the whole-body and sub-cellular scales. Our modeling approach allows us to run the individual sub-models separately and allows us to easily exchange models at a particular scale without the need to extensively rework the sub-models at other scales. In addition, the use of SBML greatly facilitates the inclusion of biological annotations directly in the model code. The model was calibrated using human in vivo data for acetaminophen and its sulfate and glucuronate metabolites. We then carried out extensive parameter sensitivity studies including the pairwise interaction of parameters. We also simulated population variation of exposure and sensitivity to acetaminophen. Our modeling framework can be extended to the prediction of liver toxicity following acetaminophen overdose, or used as a general purpose pharmacokinetic model for xenobiotics.
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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.