Modeling and simulation for toxicity assessment
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 conc...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
AIMS Press
2017-05-01
|
| Series: | Mathematical Biosciences and Engineering |
| Subjects: | |
| Online Access: | https://www.aimspress.com/article/doi/10.3934/mbe.2017034 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832590052800069632 |
|---|---|
| author | Cristina Anton Jian Deng Yau Shu Wong Yile Zhang Weiping Zhang Stephan Gabos Dorothy Yu Huang Can Jin |
| author_facet | Cristina Anton Jian Deng Yau Shu Wong Yile Zhang Weiping Zhang Stephan Gabos Dorothy Yu Huang Can Jin |
| author_sort | Cristina Anton |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-67ded33a8ff646808a94aeb80504b306 |
| institution | Kabale University |
| issn | 1551-0018 |
| language | English |
| publishDate | 2017-05-01 |
| publisher | AIMS Press |
| record_format | Article |
| series | Mathematical Biosciences and Engineering |
| spelling | doaj-art-67ded33a8ff646808a94aeb80504b3062025-01-24T02:39:47ZengAIMS PressMathematical Biosciences and Engineering1551-00182017-05-0114358160610.3934/mbe.2017034Modeling and simulation for toxicity assessmentCristina Anton0Jian Deng1Yau Shu Wong2Yile Zhang3Weiping Zhang4Stephan Gabos5Dorothy Yu Huang6Can Jin7Department of Mathematics and Statistics, Grant MacEwan University, Edmonton, Alberta, T5P2P7, CanadaDepartment of Mathematical and statistical Sciences, University of Alberta, Edmonton, Alberta, T6G2G1, CanadaDepartment of Mathematical and statistical Sciences, University of Alberta, Edmonton, Alberta, T6G2G1, CanadaDepartment of Mathematical and statistical Sciences, University of Alberta, Edmonton, Alberta, T6G2G1, CanadaAlberta Health, Edmonton, Alberta, T5J1S6, CanadaDepartment of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, T6G2B7, CanadaAlberta Centre for Toxicology, University of Calgary, Calgary, Alberta, T2N4N1, CanadaACEA Biosciences Inc, San Diego, California, 92121, USAThe 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.https://www.aimspress.com/article/doi/10.3934/mbe.2017034mathematical modelcytotoxicityparameter estimationpersistence |
| spellingShingle | Cristina Anton Jian Deng Yau Shu Wong Yile Zhang Weiping Zhang Stephan Gabos Dorothy Yu Huang Can Jin Modeling and simulation for toxicity assessment Mathematical Biosciences and Engineering mathematical model cytotoxicity parameter estimation persistence |
| title | Modeling and simulation for toxicity assessment |
| title_full | Modeling and simulation for toxicity assessment |
| title_fullStr | Modeling and simulation for toxicity assessment |
| title_full_unstemmed | Modeling and simulation for toxicity assessment |
| title_short | Modeling and simulation for toxicity assessment |
| title_sort | modeling and simulation for toxicity assessment |
| topic | mathematical model cytotoxicity parameter estimation persistence |
| url | https://www.aimspress.com/article/doi/10.3934/mbe.2017034 |
| work_keys_str_mv | AT cristinaanton modelingandsimulationfortoxicityassessment AT jiandeng modelingandsimulationfortoxicityassessment AT yaushuwong modelingandsimulationfortoxicityassessment AT yilezhang modelingandsimulationfortoxicityassessment AT weipingzhang modelingandsimulationfortoxicityassessment AT stephangabos modelingandsimulationfortoxicityassessment AT dorothyyuhuang modelingandsimulationfortoxicityassessment AT canjin modelingandsimulationfortoxicityassessment |