Generalized Additive Mixed-Models for Pharmacology Using Integrated Discrete Multiple Organ Co-Culture
Autor: | Stephanie Cole, Russell M. Dorsey, Harry Salem, Lamont Booker, Janna S. Madren-Whalley, Thomas Ingersoll, Albert P. Li |
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Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
lcsh:Medicine Pharmacology Toxicology Pathology and Laboratory Medicine Mice Mathematical and Statistical Techniques 0302 clinical medicine Animal Cells Medicine and Health Sciences lcsh:Science Connective Tissue Cells Staining Multidisciplinary Mathematical model Mathematical Models Linear model Drugs Cell Staining Liver Connective Tissue 030220 oncology & carcinogenesis Physical Sciences Coculture Technique Cellular Types Anatomy Statistics (Mathematics) Research Article Mixed model Biology Research and Analysis Methods Models Biological 03 medical and health sciences 3T3-L1 Cells Confidence Intervals Animals Humans Cyclophosphamide Independence (probability theory) lcsh:R Biology and Life Sciences Cell Biology Fibroblasts Coculture Techniques Nuclear Staining Maxima and minima Cell staining Biological Tissue 030104 developmental biology Specimen Preparation and Treatment Hepatocytes IdMOC lcsh:Q Mathematics |
Zdroj: | PLoS ONE, Vol 11, Iss 4, p e0152985 (2016) PLoS ONE |
ISSN: | 1932-6203 |
Popis: | Integrated Discrete Multiple Organ Co-culture (IDMOC) is emerging as an in-vitro alternative to in-vivo animal models for pharmacology studies. IDMOC allows dose-response relationships to be investigated at the tissue and organoid levels, yet, these relationships often exhibit responses that are far more complex than the binary responses often measured in whole animals. To accommodate departure from binary endpoints, IDMOC requires an expansion of analytic techniques beyond simple linear probit and logistic models familiar in toxicology. IDMOC dose-responses may be measured at continuous scales, exhibit significant non-linearity such as local maxima or minima, and may include non-independent measures. Generalized additive mixed-modeling (GAMM) provides an alternative description of dose-response that relaxes assumptions of independence and linearity. We compared GAMMs to traditional linear models for describing dose-response in IDMOC pharmacology studies. |
Databáze: | OpenAIRE |
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