Computational prediction of immune cell cytotoxicity
Autor: | Janette Nickel-Seeber, Robert Preissner, Nadin Schultze, Paula Zwicker, Beate Haertel, Malgorzata N. Drwal, Anna K. Schrey |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
B-Lymphocytes T-Lymphocytes Computational Biology General Medicine Computational biology Gold standard (test) Biology Toxicology Bioinformatics Xenobiotics 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Immune system Cell cytotoxicity Immune System 030220 oncology & carcinogenesis Humans Food Science |
Zdroj: | Food and Chemical Toxicology. 107:150-166 |
ISSN: | 0278-6915 |
DOI: | 10.1016/j.fct.2017.05.041 |
Popis: | Immunotoxicity, defined as adverse effects of xenobiotics on the immune system, is gaining increasing attention in the approval process of industrial chemicals and drugs. In-vivo and ex-vivo experiments have been the gold standard in immunotoxicity assessment so far, so the development of in-vitro and in-silico alternatives is an important issue. In this paper we describe a widely applicable, easy-to use computational approach which can serve as an initial immunotoxicity screen of new chemical entities. Molecular fingerprints describing chemical structure were used as parameters in a machine-learning approach based on the Naïve-Bayes learning algorithm. The model was trained using blood-cell growth inhibition data from the NCI database and validated externally with several in-house and literature-derived data sets tested in cytotoxicity assays on different types on immune cells. Both cross-validations and external validations resulted in areas under the receiver operator curves (ROC/AUC) of 75% or higher. The classification of the validation data sets occurred with excellent specificities and fair to excellent selectivities, depending on the data set. This means that the probability of actual immunotoxicity is very high for compounds classified as immunotoxic, while the fraction of false negative predictions might vary. Thus, in a multistep immunotoxicity screening scheme, the classification as immunotoxic can be accepted without additional confirmation, while compounds classified as not immunotoxic will have to be subjected to further investigation. |
Databáze: | OpenAIRE |
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