Predicting the structures of metabolites formed in humans can provide advantageous insights for the development of drugs and other compounds. Here we present GLORYx, which integrates machine learning-based site of metabolism (SoM) prediction with reaction rule sets to predict and rank the structures of metabolites that could potentially be formed by phase 1 and/or phase 2 metabolism. GLORYx extends the approach from our previously developed tool GLORY, which predicted metabolite structures for cytochrome P450-mediated metabolism only. A robust approach to ranking the predicted metabolites is attained by using the SoM probabilities predicted by the FAME 3 machine learning models to score the predicted metabolites. On a manually curated test data set containing both phase 1 and phase 2 metabolites, GLORYx achieves a recall of 77% and an area under the receiver operating characteristic curve (AUC) of 0.79. Separate analysis of performance on a large amount of freely available phase 1 and phase 2 metabolite data indicates that achieving a meaningful ranking of predicted metabolites is more difficult for phase 2 than for phase 1 metabolites. GLORYx is freely available as a web server at https://nerdd.zbh.uni-hamburg.de/ and is also provided as a software package upon request. The data sets as well as all the reaction rules from this work are also made freely available.
GLORYx : Prediction of the metabolites resulting from phase 1 and phase 2 biotransformations of xenobiotics / C. de Bruyn Kops, M. Sicho, A. Mazzolari, J. Kirchmair. - In: CHEMICAL RESEARCH IN TOXICOLOGY. - ISSN 0893-228X. - 34:2(2021 Feb 15), pp. 286-299.
|Titolo:||GLORYx : Prediction of the metabolites resulting from phase 1 and phase 2 biotransformations of xenobiotics|
|Settore Scientifico Disciplinare:||Settore CHIM/08 - Chimica Farmaceutica|
|Data di pubblicazione:||15-feb-2021|
|Data ahead of print / Data di stampa:||26-ago-2020|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1021/acs.chemrestox.0c00224|
|Appare nelle tipologie:||01 - Articolo su periodico|