| 1. |
- Bhhatarai, Barun, et al.
(författare)
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CADASTER QSPR Models for Predictions of Melting and Boiling Points of Perfluorinated Chemicals
- 2011
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Ingår i: Molecular Informatics. - : John Wiley & Sons. - 1868-1751 .- 1868-1743. ; 30:2-3, s. 189-204
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Tidskriftsartikel (refereegranskat)abstract
- Quantitative structure property relationship (QSPR) studies on per- and polyfluorinated chemicals (PFCs) on melting point (MP) and boiling point (BP) are presented. The training and prediction chemicals used for developing and validating the models were selected from Syracuse PhysProp database and literatures. The available experimental data sets were split in two different ways: a) random selection on response value, and b) structural similarity verified by self-organizing-map (SOM), in order to propose reliable predictive models, developed only on the training sets and externally verified on the prediction sets. Individual linear and non-linear approaches based models developed by different CADASTER partners on 0D-2D Dragon descriptors, E-state descriptors and fragment based descriptors as well as consensus model and their predictions are presented. In addition, the predictive performance of the developed models was verified on a blind external validation set (EV-set) prepared using PERFORCE database on 15 MP and 25 BP data respectively. This database contains only long chain perfluoro-alkylated chemicals, particularly monitored by regulatory agencies like US-EPA and EU-REACH. QSPR models with internal and external validation on two different external prediction/validation sets and study of applicability-domain highlighting the robustness and high accuracy of the models are discussed. Finally, MPs for additional 303 PFCs and BPs for 271 PFCs were predicted for which experimental measurements are unknown.
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| 2. |
- Brandmaier, Stefan, et al.
(författare)
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The QSPR-THESAURUS : The Online Platform of the CADASTER Project
- 2014
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Ingår i: ATLA (Alternatives to Laboratory Animals). - : SAGE Publications. - 0261-1929. ; 42:1, s. 13-24
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the CADASTER project (CAse Studies on the Development and Application of in Silico Techniques for Environmental Hazard and Risk Assessment) was to exemplify REACH-related hazard assessments for four classes of chemical compound, namely, polybrominated diphenylethers, per and polyfluorinated compounds, (benzo)triazoles, and musks and fragrances. The QSPR-THESAURUS website (http: / /qspr-thesaurus.eu) was established as the project's online platform to upload, store, apply, and also create, models within the project. We overview the main features of the website, such as model upload, experimental design and hazard assessment to support risk assessment, and integration with other web tools, all of which are essential parts of the QSPR-THESAURUS.
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| 3. |
- Cassani, Stefano, et al.
(författare)
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Evaluation of CADASTER QSAR Models for the Aquatic Toxicity of (Benzo)triazoles and Prioritisation by Consensus Prediction
- 2013
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Ingår i: ATLA (Alternatives to Laboratory Animals). - : SAGE Publications. - 0261-1929. ; 41:1, s. 49-64
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Tidskriftsartikel (refereegranskat)abstract
- QSAR regression models of the toxicity of triazoles and benzotriazoles ([B] TAZs) to an alga (Pseudokirchneriella subcapitata), Daphnia magna and a fish (Onchorhynchus mykiss), were developed by five partners in the FP7-EU Project, CADASTER. The models were developed by different methods - Ordinary Least Squares (OLS), Partial Least Squares (PLS), Bayesian regularised regression and Associative Neural Network (ASNN) - by using various molecular descriptors (DRAGON, PaDEL-Descriptor and QSPR-THESAURUS web). In addition, different procedures were used for variable selection, validation and applicability domain inspection. The predictions of the models developed, as well as those obtained in a consensus approach by averaging the data predicted from each model, were compared with the results of experimental tests that were performed by two CADASTER partners. The individual and consensus models were able to correctly predict the toxicity classes of the chemicals tested in the CADASTER project, confirming the utility of the QSAR approach. The models were also used for the prediction of aquatic toxicity of over 300 (B)TAZs, many of which are included in the REACH pre-registration list, and were without experimental data. This highlights the importance of QSAR models for the screening and prioritisation of untested chemicals, in order to reduce and focus experimental testing.
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| 4. |
- Hardy, Barry, et al.
(författare)
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Toxicology Ontology Perspectives
- 2012
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Ingår i: ALTEX. Alternatives zu Tierexperimenten. - 0946-7785. ; 29:2, s. 139-156
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Tidskriftsartikel (refereegranskat)abstract
- The field of predictive toxicology requires the development of open, public, computable, standardized toxicology vocabularies and ontologies to support the applications required by in silico, in vitro, and in vivo toxicology methods and related analysis and reporting activities. In this article we review ontology developments based on a set of perspectives showing how ontologies are being used in predictive toxicology initiatives and applications. Perspectives on resources and initiatives reviewed include OpenTox, eTOX, Pistoia Alliance, ToxWiz, Virtual Liver, EU-ADR, BEL, ToxML, and Bioclipse. We also review existing ontology developments in neighboring fields that can contribute to establishing an ontological framework for predictive toxicology. A significant set of resources is already available to provide a foundation for an ontological framework for 21st century mechanistic-based toxicology research. Ontologies such as ToxWiz provide a basis for application to toxicology investigations, whereas other ontologies under development in the biological, chemical, and biomedical communities could be incorporated in an extended future framework. OpenTox has provided a semantic web framework for the implementation of such ontologies into software applications and linked data resources. Bioclipse developers have shown the benefit of interoperability obtained through ontology by being able to link their workbench application with remote OpenTox web services. Although these developments are promising, an increased international coordination of efforts is greatly needed to develop a more unified, standardized, and open toxicology ontology framework.
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| 5. |
- Harry, Barry, et al.
(författare)
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Food for thought... : A toxicology ontology roadmap
- 2012
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Ingår i: ALTEX. Alternatives zu Tierexperimenten. - 0946-7785. ; 29:2, s. 129-137
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Tidskriftsartikel (refereegranskat)abstract
- Foreign substances can have a dramatic and unpredictable adverse effect on human health. In the development of new therapeutic agents, it is essential that the potential adverse effects of all candidates be identified as early as possible. The field of predictive toxicology strives to profile the potential for adverse effects of novel chemical substances before they occur, both with traditional in vivo experimental approaches and increasingly through the development of in vitro and computational methods which can supplement and reduce the need for animal testing. To be maximally effective, the field needs access to the largest possible knowledge base of previous toxicology findings, and such results need to be made available in such a fashion so as to be interoperable, comparable, and compatible with standard toolkits. This necessitates the development of open, public, computable, and standardized toxicology vocabularies and ontologies so as to support the applications required by in silico, in vitro, and in vivo toxicology methods and related analysis and reporting activities. Such ontology development will support data management, model building, integrated analysis, validation and reporting, including regulatory reporting and alternative testing submission requirements as required by guidelines such as the REACH legislation, leading to new scientific advances in a mechanistically-based predictive toxicology. Numerous existing ontology and standards initiatives can contribute to the creation of a toxicology ontology supporting the needs of predictive toxicology and risk assessment. Additionally, new ontologies are needed to satisfy practical use cases and scenarios where gaps currently exist. Developing and integrating these resources will require a well-coordinated and sustained effort across numerous stakeholders engaged in a public-private partnership. In this communication, we set out a roadmap for the development of an integrated toxicology ontology, harnessing existing resources where applicable. We describe the stakeholders’ requirements analysis from the academic and industry perspectives, timelines, and expected benefits of this initiative, with a view to engagement with the wider community.
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| 6. |
- O'Boyle, Noel, et al.
(författare)
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Open Data, Open Source and Open Standards in chemistry : The Blue Obelisk five years on
- 2011
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Ingår i: Journal of Cheminformatics. - : BioMed Central. - 1758-2946. ; 3, s. 37-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Blue Obelisk movement was established in 2005 as a response to the lack of Open Data,Open Standards and Open Source (ODOSOS) in chemistry. It aims to make it easier to carry out chemistryresearch by promoting interoperability between chemistry software, encouraging cooperation between OpenSource developers, and developing community resources and Open Standards. Results: This contribution looks back on the work carried out by the Blue Obelisk in the past 5 years and surveysprogress and remaining challenges in the areas of Open Data, Open Standards, and Open Source in chemistry. Conclusions: We show that the Blue Obelisk has been very successful in bringing together researchers anddevelopers with common interests in ODOSOS, leading to development of many useful resources freely availableto the chemistry community
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| 7. |
- Willighagen, Egon, et al.
(författare)
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Computational toxicology using the OpenTox application programming interface and Bioclipse
- 2011
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Ingår i: BMC Research Notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 4:1, s. 487-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Toxicity is a complex phenomenon involving the potential adverse effect on a range of biological functions. Predicting toxicity involves using a combination of experimental data (endpoints) and computational methods to generate a set of predictive models. Such models rely strongly on being able to integrate information from many sources. The required integration of biological and chemical information sources requires, however, a common language to express our knowledge ontologically, and interoperating services to build reliable predictive toxicology applications. Findings: This article describes progress in extending the integrative bio- and cheminformatics platform Bioclipse to interoperate with OpenTox, a semantic web framework which supports open data exchange and toxicology model building. The Bioclipse workbench environment enables functionality from OpenTox web services and easy access to OpenTox resources for evaluating toxicity properties of query molecules. Relevant cases and interfaces based on ten neurotoxins are described to demonstrate the capabilities provided to the user. The integration takes advantage of semantic web technologies, thereby providing an open and simplifying communication standard. Additionally, the use of ontologies ensures proper interoperation and reliable integration of toxicity information from both experimental and computational sources. Conclusions: A novel computational toxicity assessment platform was generated from integration of two open science platforms related to toxicology: Bioclipse, that combines a rich scriptable and graphical workbench environment for integration of diverse sets of information sources, and OpenTox, a platform for interoperable toxicology data and computational services. The combination provides improved reliability and operability for handling large data sets by the use of the Open Standards from the OpenTox Application Programming Interface. This enables simultaneous access to a variety of distributed predictive toxicology databases, and algorithm and model resources, taking advantage of the Bioclipse workbench handling the technical layers.
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