In silico assessment of nanoparticle toxicity powered by the Enalos Cloud Platform: Integrating automated machine learning and synthetic data for enhanced nanosafety evaluation.

The rapid advance of nanotechnology has led to the development and widespread application of nanomaterials, raising concerns regarding their potential adverse effects on human health and the environment. Traditional (experimental) methods for assessing the nanoparticles (NPs) safety are time-consuming, expensive, and resource-intensive, and raise ethical concerns due to their reliance on animals. To address these challenges, we propose an in silico workflow that serves as an alternative or complementary approach to conventional hazard and risk assessment strategies, which incorporates state-of-the-art computational methodologies. In this study we present an automated machine learning (autoML) scheme that employs dose-response toxicity data for silver (Ag), titanium dioxide (TiO2), and copper oxide (CuO) NPs. This model is further enriched with atomistic descriptors to capture the NPs' underlying structural properties. To overcome the issue of limited data availability, synthetic data generation techniques are used. These techniques help in broadening the dataset, thus improving the representation of different NP classes. A key aspect of this approach is a novel three-step applicability domain method (which includes the development of a local similarity approach) that enhances user confidence in the results by evaluating the prediction's reliability. We anticipate that this approach will significantly expedite the nanosafety assessment process enabling regulation to keep pace with innovation, and will provide valuable insights for the design and development of safe and sustainable NPs. The ML model developed in this study is made available to the scientific community as an easy-to-use web-service through the Enalos Cloud Platform (www.enaloscloud.novamechanics.com/sabydoma/safenanoscope/), facilitating broader access and collaborative advancements in nanosafety.

Testing ethical impact assessment for nano risk governance.

Risk governance of nanomaterials and nanotechnologies is traditionally mainly limited to risk assessment, risk management and life cycle assessment. Recent approaches have experimented with widening the scope and including economic, social, and ethical aspects. This paper reports on tests and stakeholder feedback on the use of ethical impact assessment guidelines and tools adapting CEN Workshop Agreement part 2 CWA 17145-2:2017 (E)) to support risk governance of nanomaterials, in the RiskGONE project.

Nanotechnology and artificial intelligence to enable sustainable and precision agriculture.

Climate change, increasing populations, competing demands on land for production of biofuels and declining soil quality are challenging global food security. Finding sustainable solutions requires bold new approaches and integration of knowledge from diverse fields, such as materials science and informatics. The convergence of precision agriculture, in which farmers respond in real time to changes in crop growth with nanotechnology and artificial intelligence, offers exciting opportunities for sustainable food production. Coupling existing models for nutrient cycling and crop productivity with nanoinformatics approaches to optimize targeting, uptake, delivery, nutrient capture and long-term impacts on soil microbial communities will enable design of nanoscale agrochemicals that combine optimal safety and functionality profiles.

Manually curated transcriptomics data collection for toxicogenomic assessment of engineered nanomaterials.

Toxicogenomics (TGx) approaches are increasingly applied to gain insight into the possible toxicity mechanisms of engineered nanomaterials (ENMs). Omics data can be valuable to elucidate the mechanism of action of chemicals and to develop predictive models in toxicology. While vast amounts of transcriptomics data from ENM exposures have already been accumulated, a unified, easily accessible and reusable collection of transcriptomics data for ENMs is currently lacking. In an attempt to improve the FAIRness of already existing transcriptomics data for ENMs, we curated a collection of homogenized transcriptomics data from human, mouse and rat ENM exposures in vitro and in vivo including the physicochemical characteristics of the ENMs used in each study.

Editorial for the Special Issue From Nanoinformatics to Nanomaterials Risk Assessment and Governance.

Ensuring the safe and responsible use of nanotechnologies and nanoscale materials is imperative to maximize consumer confidence and drive commercialization of nano-enabled products that underpin innovation and advances in every industrial sector [...].

NanoSolveIT Project: Driving nanoinformatics research to develop innovative and integrated tools for in silico nanosafety assessment.

Nanotechnology has enabled the discovery of a multitude of novel materials exhibiting unique physicochemical (PChem) properties compared to their bulk analogues. These properties have led to a rapidly increasing range of commercial applications; this, however, may come at a cost, if an association to long-term health and environmental risks is discovered or even just perceived. Many nanomaterials (NMs) have not yet had their potential adverse biological effects fully assessed, due to costs and time constraints associated with the experimental assessment, frequently involving animals. Here, the available NM libraries are analyzed for their suitability for integration with novel nanoinformatics approaches and for the development of NM specific Integrated Approaches to Testing and Assessment (IATA) for human and environmental risk assessment, all within the NanoSolveIT cloud-platform. These established and well-characterized NM libraries (e.g. NanoMILE, NanoSolutions, NANoREG, NanoFASE, caLIBRAte, NanoTEST and the Nanomaterial Registry (>2000 NMs)) contain physicochemical characterization data as well as data for several relevant biological endpoints, assessed in part using harmonized Organisation for Economic Co-operation and Development (OECD) methods and test guidelines. Integration of such extensive NM information sources with the latest nanoinformatics methods will allow NanoSolveIT to model the relationships between NM structure (morphology), properties and their adverse effects and to predict the effects of other NMs for which less data is available. The project specifically addresses the needs of regulatory agencies and industry to effectively and rapidly evaluate the exposure, NM hazard and risk from nanomaterials and nano-enabled products, enabling implementation of computational 'safe-by-design' approaches to facilitate NM commercialization.

Transcriptomics in Toxicogenomics, Part III: Data Modelling for Risk Assessment.

Transcriptomics data are relevant to address a number of challenges in Toxicogenomics (TGx). After careful planning of exposure conditions and data preprocessing, the TGx data can be used in predictive toxicology, where more advanced modelling techniques are applied. The large volume of molecular profiles produced by omics-based technologies allows the development and application of artificial intelligence (AI) methods in TGx. Indeed, the publicly available omics datasets are constantly increasing together with a plethora of different methods that are made available to facilitate their analysis, interpretation and the generation of accurate and stable predictive models. In this review, we present the state-of-the-art of data modelling applied to transcriptomics data in TGx. We show how the benchmark dose (BMD) analysis can be applied to TGx data. We review read across and adverse outcome pathways (AOP) modelling methodologies. We discuss how network-based approaches can be successfully employed to clarify the mechanism of action (MOA) or specific biomarkers of exposure. We also describe the main AI methodologies applied to TGx data to create predictive classification and regression models and we address current challenges. Finally, we present a short description of deep learning (DL) and data integration methodologies applied in these contexts. Modelling of TGx data represents a valuable tool for more accurate chemical safety assessment. This review is the third part of a three-article series on Transcriptomics in Toxicogenomics.

MouseTox: An online toxicity assessment tool for small molecules through Enalos Cloud platform.

Advances in the drug discovery research substantially depend on in silico methods and techniques that capitalize on experimental data to enable the accurate property/activity assessment by employing a variety of computational techniques. These in silico tools can significantly reduce expensive and time consuming experimental procedures required and are strongly recommended to avoid animal testing, especially as far as toxicity evaluation and risk assessment is concerned. In this context, in the present work we aim to develop a predictive model for the cytotoxic effects of a wide range of compounds based solely on calculated molecular descriptors that account for their topological, geometric and structural characteristics. The developed model was fully validated and was released online via Enalos Cloud platform accessible through http://enalos.insilicotox.com/MouseTox/. This ready-to-use web service offers, through a user-friendly interface, free access to the model results and therefore can act as a toxicity prediction tool for the risk assessment of novel compounds, without any special requirements or prior programming skills.

A Risk Assessment Tool for the Virtual Screening of Metal Oxide Nanoparticles through Enalos InSilicoNano Platform.

The increasing use of Nanoparticles (NPs) in a wide range of applications has led to a rising concern on the possible toxicological effects that this use may have on human health and the environment. Since experimental toxicity evaluation for the different types of NPs already available, is often expensive and time consuming, several computational approaches are proposed for the risk assessment of NPs. In this work, we have developed a predictive classification model for the toxicological assessment of iron oxide NPs with different core, coating and surface modification based on a number of different properties including size, relaxivities, zeta potential and type of coating. The model was fully validated based on several validation measurements and was released online via Enalos InSilicoNano Platform (http://enalos.insilicotox.com/QNAR_IronOxide_Toxicity/). The developed web service gives the interested user the opportunity to insert the indicated properties and get a toxicity prediction accompanied by an indication of its reliability based on the domain of applicability. This newly introduced web service complements our previously reported efforts to extract important information from available datasets and develop user friendly applications for the toxicity assessment of NPs.