Summary Background: The NanoSafety Cluster, a cluster of projects funded by the European Commision, identified the need for a computational infrastructure for toxicological data management of engineered nanomaterials (ENMs). Ontologies, open standards, and interoperable designs were envisioned to empower a harmonized approach to European research in nanotechnology. This setting provides a number of opportunities and challenges in the representation of nanomaterials data and the integration of ENM information originating from diverse systems. Within this cluster, eNanoMapper works towards supporting the collaborative safety assessment for ENMs by creating a modular and extensible infrastructure for data sharing, data analysis, and building computational toxicology models for ENMs. Results: The eNanoMapper database solution builds on the previous experience of the consortium partners in supporting diverse data through flexible data storage, open source components and web services. We have recently described the design of the eNanoMapper prototype database along with a summary of challenges in the representation of ENM data and an extensive review of existing nano-related data models, databases, and nanomaterials-related entries in chemical and toxicogenomic databases. This paper continues with a focus on the database functionality exposed through its application programming interface (API), and its use in visualisation and modelling. Considering the preferred community practice of using spreadsheet templates, we developed a configurable spreadsheet parser facilitating user friendly data preparation and data upload. We further present a web application able to retrieve the experimental data via the API and analyze it with multiple data preprocessing and machine learning algorithms. Conclusion: We demonstrate how the eNanoMapper database is used to import and publish online ENM and assay data from several data sources, how the “representational state transfer” (REST) API enables building user friendly interfaces and graphical summaries of the data, and how these resources facilitate the modelling of reproducible quantitative structure–activity relationships for nanomaterials (NanoQSAR).

Engineered nanomaterials (ENMs) are being developed to meet specific application needs in diverse domains across the engineering and biomedical sciences (e.g. drug delivery). However, accompanying the exciting proliferation of novel nanomaterials is a challenging race to understand and predict their possibly detrimental effects on human health and the environment. The eNanoMapper project (www.enanomapper.net) is creating a pan-European computational infrastructure for toxicological data management for ENMs, based on semantic web standards and ontologies. Here, we describe the development of the eNanoMapper ontology based on adopting and extending existing ontologies of relevance for the nanosafety domain. The resulting eNanoMapper ontology is available at http://purl.enanomapper.net/onto/enanomapper.owl. We aim to make the re-use of external ontology content seamless and thus we have developed a library to automate the extraction of subsets of ontology content and the assembly of the subsets into an integrated whole. The library is available (open source) at http://github.com/enanomapper/slimmer/. Finally, we give a comprehensive survey of the domain content and identify gap areas. ENM safety is at the boundary between engineering and the life sciences, and at the boundary between molecular granularity and bulk granularity. This creates challenges for the definition of key entities in the domain, which we also discuss.

BackgroundPredictive regression models can be created with many different modelling approaches. Choices need to be made for data set splitting, cross-validation methods, specific regression parameters and best model criteria, as they all affect the accuracy and efficiency of the produced predictive models, and therefore, raising model reproducibility and comparison issues. Cheminformatics and bioinformatics are extensively using predictive modelling and exhibit a need for standardization of these methodologies in order to assist model selection and speed up the process of predictive model development. A tool accessible to all users, irrespectively of their statistical knowledge, would be valuable if it tests several simple and complex regression models and validation schemes, produce unified reports, and offer the option to be integrated into more extensive studies. Additionally, such methodology should be implemented as a free programming package, in order to be continuously adapted and redistributed by others.ResultsWe propose an integrated framework for creating multiple regression models, called RRegrs. The tool offers the option of ten simple and complex regression methods combined with repeated 10-fold and leave-one-out cross-validation. Methods include Multiple Linear regression, Generalized Linear Model with Stepwise Feature Selection, Partial Least Squares regression, Lasso regression, and Support Vector Machines Recursive Feature Elimination. The new framework is an automated fully validated procedure which produces standardized reports to quickly oversee the impact of choices in modelling algorithms and assess the model and cross-validation results. The methodology was implemented as an open source R package, available at https://www.github.com/enanomapper/RRegrs, by reusing and extending on the caret package.ConclusionThe universality of the new methodology is demonstrated using five standard data sets from different scientific fields. Its efficiency in cheminformatics and QSAR modelling is shown with three use cases: proteomics data for surface-modified gold nanoparticles, nano-metal oxides descriptor data, and molecular descriptors for acute aquatic toxicity data. The results show that for all data sets RRegrs reports models with equal or better performance for both training and test sets than those reported in the original publications. Its good performance as well as its adaptability in terms of parameter optimization could make RRegrs a popular framework to assist the initial exploration of predictive models, and with that, the design of more comprehensive in silico screening applications.Graphical abstractRRegrs is a computer-aided model selection framework for R multiple regression models; this is a fully validated procedure with application to QSAR modelling

Increasing amounts of systems toxicology data, including omics results, are becoming publically available and accessible in databases. Data-driven and informatics-tool supported pipeline schemas for fitting such data into Adverse Outcome Pathway (AOP) descriptions could potentially aid the development of nonanimal-based hazard and risk assessment methods. We devised a 6-step workflow that integrated diverse types of toxicology data into a novel AOP scheme for pulmonary fibrosis. Mining of literature references and diverse data sources covering previous pathway descriptions and molecular results were coupled in a stepwise manner with informatics tools applications that enabled gene linkage and pathway identification in molecular interaction maps. Ultimately, a network of functional elements coupled 64 pulmonary fibrosis-associated genes into a novel, open-source AOP-linked molecular pathway, now available for commenting and improvements in WikiPathways (WP3624). Applying in silico-based knowledge extraction and modeling, the pipeline enabled screening and fusion of many different complex data types, including the integration of omics results. Overall, the taken, stepwise approach should be generally useful to construct novel AOP descriptions as well as to enrich developing AOP descriptions in progress.