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TOXTREE: TOXIC HAZARD ESTIMATION BY A DECISION TREE APPROACH - THE FIRST SEVEN YEARS
Nina Jeliazkova (a), Silvia Lapenna (b), Andrew Worth (b)
a) Ideaconsult Ltd, Sofia , Bulgaria
b) European Commission, Joint Research Centre, Via E. Fermi 2749, 21027 Ispra, Italy
Toxtree is a flexible and user-friendly open-source application that predicts various kinds of toxic effects, mostly by applying structural alerts, arranged in a decision tree fashion. Toxtree was initially commissioned by the European Commission’s Joint Research Centre (JRC) and the first version (v. 1.0) was released in 2005. It implemented the Cramer structural rules for estimating the threshold of toxicological concern. During the following years, more than 10 major releases have been made available, and the number of plug-ins had risen from one to fifteen. Toxtree was designed with flexible capabilities for future extensions, providing a core platform, implementing the user interface and common functionalities as input and output, and standardized Java interfaces for the prediction modules (or plug-ins). This architecture allows the development of prediction modules to concentrate on the model specifics, and facilitates the collaboration of independent developers. Toxtree modules have been developed by the JRC in collaboration with various consultants, in particular Ideaconsult Ltd (Sofia, Bulgaria), who also maintain the core as an open source (GPL license) project at http://toxtree.sf.net.
key feature of Toxtree is the transparent reporting of the rationale underlying each prediction. This is supported by keeping track of the path through the decision tree and reporting the result of applying the rules. Since version 2.1.0 (2010), Toxtree supports structural alerts highlighting. Some of the prediction modules also use descriptor calculation procedures and QSAR models. The SMARTCyp plugin was extended in 2011 to enable metabolite predictions, in addition to predicting sites of metabolism. While the earlier versions supported only input by SMILES and common chemical file formats, since version 2.2.0 (2010), Toxtree accepts InChI and chemical names as input. Version 2.5.0 (2011) introduced a chemical identifier lookup via remote OpenTox web service. Besides being used as downloadable standalone application, Toxtree was reported to be embedded in various workflow systems and exposed as a web service as early as 2007. Since 2010, Toxtree has been available as an OpenTox API compatible web service and also embedded in the online application ToxPredict. We report validation statistics for several plug-ins, as well as predicted class distribution statistics for several endpoints, based on the application of Toxtree to large scale public datasets.