Collaborative development of predictive toxicology applications

Abstract

OpenTox provides an interoperable, standards-based Framework for the support of predictive toxicology data management, algorithms, modelling, validation and reporting. It is relevant to satisfying the chemical safety assessment requirements of the REACH legislation as it supports access to experimental data, (Quantitative) Structure-Activity Relationship models, and toxicological information through an integrating platform that adheres to regulatory requirements and OECD validation principles. Initial research defined the essential components of the Framework including the approach to data access, schema and management, use of controlled vocabularies and ontologies, architecture, web service and communications protocols, and selection and integration of algorithms for predictive modelling. OpenTox provides end-user oriented tools to non-computational specialists, risk assessors, and toxicological experts in addition to Application Programming Interfaces (APIs) for developers of new applications. OpenTox actively supports public standards for data representation, interfaces, vocabularies and ontologies, Open Source approaches to core platform components, and community-based collaboration approaches, so as to progress system interoperability goals.The OpenTox Framework includes APIs and services for compounds, datasets, features, algorithms, models, ontologies, tasks, validation, and reporting which may be combined into multiple applications satisfying a variety of different user needs. OpenTox applications are based on a set of distributed, interoperable OpenTox API-compliant REST web services. The OpenTox approach to ontology allows for efficient mapping of complementary data coming from different datasets into a unifying structure having a shared terminology and representation.Two initial OpenTox applications are presented as an illustration of the potential impact of OpenTox for high-quality and consistent structure-activity relationship modelling of REACH-relevant endpoints: ToxPredict which predicts and reports on toxicities for endpoints for an input chemical structure, and ToxCreate which builds and validates a predictive toxicity model based on an input toxicology dataset. Because of the extensible nature of the standardised Framework design, barriers of interoperability between applications and content are removed, as the user may combine data, models and validation from multiple sources in a dependable and time-effective way.

The ToxBank Data Warehouse: Supporting the Replacement of In Vivo Repeated Dose Systemic Toxicity Testing

“…In developing infrastructure, such as the data warehouse, the project is taking advantage of existing open standards, particularly the OpenTox project. [16,17,[27][28][29][30][31] OpenTox developed a standard framework for interoperable predictive toxicology support. [27] It makes extensive use of REpresentational State Transfer (REST)-based web services [32] for interaction with different geographically distributed services necessary to support predictive toxicology data management, algorithms, modeling, validation, and reporting.…”

“…This design is expected to facilitate adding new services of any kind, for example supporting different data types. ToxBank adopts the OpenTox framework design, [27][28][29][30][31] based on the following technological choices (i) the REpresentational State Transfer (REST) [32] software architecture style allowing platform and programming language independence and facilitating the implementation of new data and processing components; (ii) a formally defined common information model, based on the W3C Resource Description Framework (RDF) [45] and communication through well-defined interfaces ensuring interoperability of the web components; (iii) authentication and authorization, allowing defining access policies of REST resources, based on OpenAM; [46] (iv) 4store (http://4store.org) triple store as a backend for the investigation service. The protocol services use MySQL relational database as a backend.…”

“…RDF is the W3C proposed technology to link data on web pages, small resources or large databases, in a unified way. These Linked Resource or Semantic Web approaches are being adopted by the international life sciences community, such as the Health Care & Life Science interest group, [48] and EU projects such as OpenTox [27][28][29][30][31] and Open PHACTS. [49] The standards support many different applications; by adopting them we ensure that ToxBank will be fully interoperable with many other life science projects.…”

Mobile applications driven by Open PHACTS semantic web technology

“…This semantic approach to data integration has been pioneered by other research efforts in the biomedical domain (Belleau et al, 2008;Chen et al, 2010;Hardy et al, 2010;Hassanzadeh et al, 2009) The platform provides a semantically integrated view of the data by exploiting an identity mapping service (IMS) to construct appropriate responses based on the contextual aspects of each query. For instance, will users differentiate to the same level of granularity?…”

Ensuring confidence in predictions: A scheme to assess the scientific validity of in silico models

“…Outside of the eTOX project, the possibility exists for modellers to upload models onto publically accessible online resources, such as QsarDB (http://www.qsardb.org/) [27] or OpenTox (http://www.opentox.org/) [31]. In addition to the actual models, these resources are also able to store modelling datasets, model documentation, model predictions, etc.…”