Aniceto - Paper - ABC transporters multi-label 2016-06-09 (plain text).pdf (1.64 MB)
Simultaneous prediction of four ATP-binding cassette transporters' substrates using multi-label QSAR
journal contribution
posted on 2023-06-09, 03:25 authored by Natália Aniceto, Alex Freitas, Andreas Bender, Taravat GhafourianEfflux by the ATP-binding cassette (ABC) transporters affects the pharmacokinetic profile of drugs and it has been implicated in drug-drug interactions as well as its major role in multi-drug resistance in cancer. It is therefore important for the pharmaceutical industry to be able to understand what phenomena rule ABC substrate recognition. Considering a high degree of substrate overlap between various members of ABC transporter family, it is advantageous to employ a multi-label classification approach where predictions made for one transporter can be used for modeling of the other ABC transporters. Here, we present decision tree-based QSAR classification models able to simultaneously predict substrates and non-substrates for BCRP1, P-gp/MDR1 and MRP1 and MRP2, using a dataset of 1493 compounds. To this end, two multi-label classification QSAR modelling approaches were adopted: Binary Relevance (BR) and Classifier Chain (CC). Even though both multi-label models yielded similar predictive performances in terms of overall accuracies (close to 70), the CC model overcame the problem of skewed performance towards identifying substrates compared with non-substrates, which is a common problem in the literature. The models were thoroughly validated by using external testing, applicability domain and activity cliffs characterization. In conclusion, a multi-label classification approach is an appropriate alternative for the prediction of ABC efflux. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Publication status
- Published
File Version
- Accepted version
Journal
Molecular InformaticsISSN
1868-1743Publisher
Wiley-VCH VerlagExternal DOI
Issue
10Volume
35Page range
514-528Department affiliated with
- Biochemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2017-11-30First Open Access (FOA) Date
2017-12-01First Compliant Deposit (FCD) Date
2017-11-30Usage metrics
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