Modeling and simulation for toxicity assessment
| Autor: | Cristina Anton, Jian Deng, Can Jin, Stephan Gabos, Dorothy Yu Huang, Yile Zhang, Yau Shu Wong, Weiping Zhang |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cell Survival Hazardous Substances Modeling and simulation 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Expectation–maximization algorithm Toxicity Tests Extracellular Humans Computer Simulation Logistic function Concentration Response Chemistry Estimation theory Applied Mathematics Reproducibility of Results General Medicine Models Theoretical Computational Mathematics Kinetics 030104 developmental biology 030220 oncology & carcinogenesis Modeling and Simulation General Agricultural and Biological Sciences Biological system Intracellular Algorithms Toxicant |
| Zdroj: | Mathematical biosciences and engineering : MBE. 14(3) |
| ISSN: | 1551-0018 |
| Popis: | The effect of various toxicants on growth/death and morphology of human cells is investigated using the xCELLigence Real-Time Cell Analysis High Troughput in vitro assay. The cell index is measured as a proxy for the number of cells, and for each test substance in each cell line, time-dependent concentration response curves (TCRCs) are generated. In this paper we propose a mathematical model to study the effect of toxicants with various initial concentrations on the cell index. This model is based on the logistic equation and linear kinetics. We consider a three dimensional system of differential equations with variables corresponding to the cell index, the intracellular concentration of toxicant, and the extracellular concentration of toxicant. To efficiently estimate the model's parameters, we design an Expectation Maximization algorithm. The model is validated by showing that it accurately represents the information provided by the TCRCs recorded after the experiments. Using stability analysis and numerical simulations, we determine the lowest concentration of toxin that can kill the cells. This information can be used to better design experimental studies for cytotoxicity profiling assessment. |
| Databáze: | OpenAIRE |
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