Article ; Online: Assessment of modelling strategies for drug response prediction in cell lines and xenografts.
2020 Volume 10, Issue 1, Page(s) 2849
Abstract: Data from several large high-throughput drug response screens have become available to the scientific community recently. Although many efforts have been made to use this information to predict drug sensitivity, our ability to accurately predict drug ... ...
| Abstract | Data from several large high-throughput drug response screens have become available to the scientific community recently. Although many efforts have been made to use this information to predict drug sensitivity, our ability to accurately predict drug response based on genetic data remains limited. In order to systematically examine how different aspects of modelling affect the resulting prediction accuracy, we built a range of models for seven drugs (erlotinib, pacliatxel, lapatinib, PLX4720, sorafenib, nutlin-3 and nilotinib) using data from the largest available cell line and xenograft drug sensitivity screens. We found that the drug response metric, the choice of the molecular data type and the number of training samples have a substantial impact on prediction accuracy. We also compared the tasks of drug response prediction with tissue type prediction and found that, unlike for drug response, tissue type can be predicted with high accuracy. Furthermore, we assessed our ability to predict drug response in four xenograft cohorts (treated either with erlotinib, gemcitabine or paclitaxel) using models trained on cell line data. We could predict response in an erlotinib-treated cohort with a moderate accuracy (correlation ≈ 0.5), but were unable to correctly predict responses in cohorts treated with gemcitabine or paclitaxel. |
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| MeSH term(s) | Animals ; Biomarkers, Pharmacological ; Cell Line, Tumor ; Erlotinib Hydrochloride/pharmacology ; Humans ; Imidazoles/pharmacology ; Indoles/pharmacology ; Lapatinib/pharmacology ; Machine Learning ; Mice ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/pathology ; Organ Specificity/drug effects ; Organ Specificity/genetics ; Paclitaxel/pharmacology ; Piperazines/pharmacology ; Prognosis ; Pyrimidines/pharmacology ; Sorafenib/pharmacology ; Sulfonamides/pharmacology ; Xenograft Model Antitumor Assays |
| Chemical Substances | Biomarkers, Pharmacological ; Imidazoles ; Indoles ; PLX 4720 ; Piperazines ; Pyrimidines ; Sulfonamides ; Lapatinib (0VUA21238F) ; nutlin 3 (53IA0V845C) ; Sorafenib (9ZOQ3TZI87) ; Erlotinib Hydrochloride (DA87705X9K) ; nilotinib (F41401512X) ; Paclitaxel (P88XT4IS4D) |
| Language | English |
| Publishing date | 2020-02-18 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2615211-3 |
| ISSN | 2045-2322 ; 2045-2322 |
| ISSN (online) | 2045-2322 |
| ISSN | 2045-2322 |
| DOI | 10.1038/s41598-020-59656-2 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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