toxtree: toxic hazard estimation by a decision tree approach
DESCRIPTION
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 e-mail: [email protected] 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.TRANSCRIPT
For developers
TOXTREE: TOXIC HAZARD ESTIMATION BY DECISION TREE APPROACH
Nina Jeliazkova a, Silvia Lapennab, Andrew Worthb
a) Ideaconsult Ltd, 4 A. Kanchev str., Sofia 1000, Bulgaria, [email protected] b) European Commission, Joint Research Centre, Via E. Fermi 2749, 21027 Ispra, Italy
References [1] Patlewicz G, Jeliazkova N, Safford RJ, Worth AP, Aleksiev B. (2008) An evaluation of the implementation of the Cramer classification scheme in the Toxtree software. SAR QSAR Environ Res. ;19(5-6):495-524.
[2] Jeliazkova N., Jeliazkov V. AMBIT RESTful web services: an implementation of the OpenTox application programming interface, Journal of Cheminformatics 2011, 3:18, doi:10.1186/1758-2946-3-18.
[3] OpenTox D3.4 Report on Final Database http://opentox.org/data/documents/development/opentoxreports/opentoxreportd34
• Toxtree is a flexible and user-friendly open-source application [1]. • Places chemicals into categories and predicts various kinds of toxic effect,
mostly by applying structural alerts, arranged in a decision tree fashion. • Available at http://toxtree.sourceforge.net • Initially commissioned by the European Commission’s Joint Research Centre. • The first version (v. 1.0) was released in 2005. It implemented the
Cramer structural rules for estimating the threshold of toxicological concern. • More than 10 major releases since 2005. • Input: SDF, MOL, SMILES, XLS, CSV, CML, structure diagram editor (since v. 1.0),
InChI, chemical names (since 2.2.0), chemical identifier lookup via remote OpenTox web service (since 2.5.0).
• The latest version Toxtree 2.5.1 includes 15 prediction modules:
A 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.
• Cramer rules & Cramer rules with extensions • Verhaar scheme • Modified Verhaar scheme for predicting toxicity mode of action • Skin irritation (BfR rules) and Eye irritation (BfR rules) • Benigni / Bossa rule base for mutagenicity and carcinogenicity • START biodegradation and persistence • Structural alerts for identification of Michael acceptors; • Structural alerts for skin sensitization • Kroes Threshold of Toxicological Concern Decision tree • SMARTCyp - Cytochrome P450-Mediated Drug Metabolism and
metabolites prediction; • Structural alerts for the in vivo micronucleus assay in rodents (ISSMIC) • Structural alerts for Functional Group Identification (ISSFUNC) • Structural alerts for protein binding
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Toxtree usage map
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• Designed with flexible capabilities for future extensions.
• Provides a core platform, implementing the user interface and common functionalities as input and output, and standardized Java interfaces for the prediction modules.
• 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.
• You could develop the next toxicity prediction module!
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 http://toxpredict.org .
Frequently Asked Questions: http://toxtree.sourceforge.net/faq.html#K2 Q: How to run Toxtree predictions from (Java) code and embed Toxtree into my software? A1: Java standalone example • Toxtree and CDK dependencies are available via Apache Maven
repository. Example code available. A2: REST web service - via OpenTox API http://opentox.org/dev/apis/api-1.2 • Toxtree modules are available as OpenTox REST API web services. The
example assumes your dataset is uploaded to an OpenTox dataset service. The dataset service accepts common chemical data formats for upload via HTTP POST calls.
Chemical structures and data from various sources have been imported into the Ambit database [2,3] and made available via the OpenTox REST API interface. Toxtree modules are available as OpenTox API compliant models.
Application to publicly available datasets
Plant Protection Products ECHA Preregistration list
Cramer rules
Structural alerts for the in vivo micronucleus assay in rodents START biodegradation
Structural alerts for acyl transfer agents
Verhaar scheme for toxicity mode of action Cramer rules
Structural alerts for acyl transfer agents
Verhaar scheme for toxicity mode of action