Réactivité des glyconitriles vis-à-vis d'organométalliques ...
R-Vis - Cefic-Lricefic-lri.org/wp-content/uploads/2019/12/9.-George...2019/12/09 · Aims and...
Transcript of R-Vis - Cefic-Lricefic-lri.org/wp-content/uploads/2019/12/9.-George...2019/12/09 · Aims and...
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George Loizou, Alex Hogg and Kevin McNally
HSE Science and Research Centre
R-Vis
An Open Access PBPK Modelling Platform
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Aims and Objectives
• Further develop R-Vis, a prototype application for the analysis of structure and performance of physiologically based pharmacokinetic
(PBPK), and other models, written in the free, open source syntax, R
• Provide a common, transparent and independently auditable, free-to-use platform
• Provide a labour-saving application that also shifts emphasis away from mathematics and programming to mechanistic toxicology
LRI – R-Vis: An Open Access PBPK Modelling Platform
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LRI – R-Vis: An Open Access PBPK Modelling Platform
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A PBPK Model
R Syntax Viewed in RStudio
LRI – R-Vis: An Open Access PBPK Modelling Platform
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LRI – R-Vis: An Open Access PBPK Modelling Platform
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Home Page
Import Model
LRI – – R-Vis: An Open Access PBPK Modelling Platform
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LRI – R-Vis: An Open Access PBPK Modelling Platform
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Plotter
Select Parameters and Outputs
LRI – R-Vis: An Open Access PBPK Modelling Platform
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Parameters (constants)• Anatomical
• Physiological
• Metabolic
• Physicochemical
Outputs (calculated values)• Rates of uptake
• Dermal, oral, inhalation
• Concentrations:
• Venous, arterial, plasma, red blood cells
• Organs and tissues
• Urinary excretion
• exhalation
Plotter
LRI – R-Vis: An Open Access PBPK Modelling Platform
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Plotter
Plot Output
LRI – R-Vis: An Open Access PBPK Modelling Platform
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LRI – R-Vis: An Open Access PBPK Modelling Platform
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Plotter
Multiple Outputs
LRI – R-Vis: An Open Access PBPK Modelling Platform
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LRI – R-Vis: An Open Access PBPK Modelling Platform
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Evidence
Importing Data
LRI – R-Vis: An Open Access PBPK Modelling Platform
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LRI – R-Vis: An Open Access PBPK Modelling Platform
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Evidence
Tweaking Parameters
LRI – R-Vis: An Open Access PBPK Modelling Platform
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LRI – R-Vis: An Open Access PBPK Modelling Platform
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Evidence
Tweaking Parameters Using Ranges
LRI – R-Vis: An Open Access PBPK Modelling Platform
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Good Modelling Practice
Model Structure and Biological Plausibility
22/11/2019LRI – PRESENTATION TITLE
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Evaluating Variability and Uncertainty
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Morris Test – Elementary Parameter Screening
Sensitivity Analysis
LRI – R-Vis: An Open Access PBPK Modelling Platform
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LRI – R-Vis: An Open Access PBPK Modelling Platform
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Extended Fourier Amplitude Sensitivity Test - eFAST
Global Sensitivity Analysis
LRI – R-Vis: An Open Access PBPK Modelling Platform
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LRI – R-Vis: An Open Access PBPK Modelling Platform
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LRI – PRESENTATION TITLE
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LRI – R-Vis: An Open Access PBPK Modelling Platform
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Parameter configurations available to all modules
Shared State
LRI – R-Vis: An Open Access PBPK Modelling Platform
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Markov Chain Monte Carlo Sampling
Parameter Estimation – Reverse Dosimetry
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Bayesian Inference – Prior Knowledge
LRI – PRESENTATION TITLE
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LRI – R-Vis: An Open Access PBPK Modelling Platform
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LRI – R-Vis: An Open Access PBPK Modelling Platform
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Probabilistic Modelling
Monte Carlo Sampling
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Incorporating Inter-Individual Differences
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Incorporating Inter-Individual Differences: Organs/Tissue Distributions
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LRI – R-Vis: An Open Access PBPK Modelling Platform
Generating Virtual Humans
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Settings – User Preferences
Appearance
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LRI – R-Vis: An Open Access PBPK Modelling Platform
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Acknowledgements
• Alex Hogg – Programmer
• Kevin McNally – Statistical/Mathematical Modeller
• Cefic-LRI
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