Periodic Reporting for period 2 - OpenRiskNet (OpenRiskNet: Open e-Infrastructure to Support Data Sharing, Knowledge Integration and in silico Analysis and Modelling in Risk Assessment) Reporting period: 2018-06-01 to 2019-11-30 Summary of the context and overall objectives of the project Toxicology and risk assessment are undergoing a paradigm shift, from a phenomenological to a mechanistic discipline based on in vitro and in silico approaches that represent an important alternative to classical animal testing applied to the evaluation of chronic and systemic toxicity risks. Large databases and highly sophisticated methods, algorithms and tools are available for different tasks such as hazard prediction, toxicokinetics, and in vitro-in vivo extrapolations to support this transition. However, since these services are developed independently and provided by different groups world-wide, there is no standardised way to access the data or run modelling workflows.The main objective of the project was to provide an open e-infrastructure making available existing resources and services in an easier-to-use, harmonised and interoperable way to a variety of communities requiring risk assessment, including chemicals, cosmetic ingredients, therapeutic agents and nanomaterials. To achieve this goal, more specific objectives were defined and used continuously throughout the project to guide the developments, prototyping, implementation, showcasing of functionality, dissemination and training and support offerings. The approach taken in OpenRiskNet supports also the overall goal of the targeted communities on the implementation of the 3Rs (Replacement, Reduction and Refinement) principles.OpenRiskNet developed and deployed an integrated, secure, service-driven and sustainable infrastructure for data management, data sharing, processing, analysis, information mining, modelling and simulations. Development and sharing of analysis workflows, visualisation and reporting were also supported. These developments were focused to support communities in the areas of toxicology, risk assessment and chemical, pharmaceutical, cosmetic and nanomaterial product development, including safety-by-design. OpenRiskNet e-infrastructure supports all aspects of these areas by allowing for the integration of all toxicology-related data sources, for the implementation and execution of processing and analysis pipelines and for the execution of modelling workflows for pharmacokinetics or pharmacodynamics. OpenRiskNet activities improved the accessibility, interoperability and standardisation of existing services, interconnected them and developed protocols for their deployment on all relevant hardware settings including aspects of data security. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far The OpenRiskNet infrastructure is based on the concept of virtual (research) environments, comprising IT-infrastructure (e.g. compute, storage, network resources), operating system, middleware, data, and services. Such VEs are means to provide the OpenRiskNet e-infrastructure in a defined way deployable to a large variety of hardware systems ranging from single computer and laptops to large cloud or high-performance computing systems, which can be operated either as public services or in-house for higher data security.OpenRiskNet and its associated partners have integrated state-of-the-art data and software services into the infrastructure highly relevant to predictive toxicology and risk assessment and, in this way, made them easily findable and accessible and combinable.Harmonised APIs and the semantic annotation concepts as implemented in the OpenRiskNet services clearly represent a step beyond the state of the art in data sharing and accessing computational tools and highly improved the interoperability of the services with respect to data exchange and callability from other services and workflows.OpenRiskNet provides the services as containers equipped with standardised and semantically annotated application programming interfaces (APIs) and findable using the OpenRiskNet service catalogue and service registry additionally replicated in the EOSC and eInfraCentral catalogues.Seven case studies were defined and used to test and evaluate the solutions provided by OpenRiskNet to the predictive toxicology and risk assessment community. Each of them addressed a specific area of the risk assessment process where automation is highly desirable. The case study workflows and the services used therein have been deployed, are functionally operational with proven interoperationality and can now be re-used and adopted as modules of risk assessment frameworks.OpenRiskNet was working together with its stakeholders, related projects, communities and infrastructure, as well as pan-European research activities and e-infrastructures to fully collect and address the users requirements and needs, foster adoption as well as align with other major research, innovation and infrastructure activities for optimising mutual benefits. An important activity was represented by the interactions established with the other EU e-infrastructures initiatives (EOSC, ELIXIR and EU Nanosafety Cluster/NanoCommons communities). Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) OpenRiskNet played an important role and has an impact in five main areas: developing an innovation-driven knowledge infrastructure, enabling the access to data and modelling tools, support scientific advancements in risk assessment, community impact and impact of standards and ontologies.The OpenRiskNet knowledge base and systems modelling platform provides users with the necessary tools to develop, curate, analyse and compare systems-level toxicological models for human and animal systems. The focus of the project has been to offer users simple means to instantiate and maintain VEs on cloud-agnostic infrastructures, the standards and middleware to enable and sustain interoperable deployment of data and services and at the same time reducing the technical complexity for performing these deployment operations and adhering to state-of-the-art open standards and technical concepts. OpenRisknet enabled easier access and sharing of integrated approaches in the form of workflows all the way from data collection to reporting opens up new opportunities by advancing our knowledge of the relationship between toxicity, architecture, function and risk. The OpenRiskNet infrastructure is optimally suited to support the scientific advancements in risk assessment, as demonstrated in the case studies by providing a platform and solid foundation for toxicology and risk assessment based on a refined theory of Heterogeneous Evidence including effects, interactions, kinetics, scales, dynamics and uncertainty implemented into our practical framework.Our community impact activities were targeting into two directions: to strengthen the interdisciplinary community of practice focusing on data and in silico aspects of predictive toxicology and chemical/nanomaterial risk assessment and to establish toxicology as one of the important communities in the pan-European e-infrastructure landscape by collaborating with the major infrastructure activities like EOSC and providing services on these platforms.OpenRiskNet data resources and software services are aligned with the activities of international projects leading the development of open standards for predictive toxicology resources like the EU NanoSafety Cluster, OpenTox, NanoCommons and the US Nano Working Group and at a larger scale with ELIXIR and EOSC. The exchange with these groups ensures that OpenRiskNet reuses standards wherever possible and that OpenRiskNet also contributes to standards by putting forward project results to the most suitable international bodies. OpenRiskNet logo OpenRiskNet case studies diagram OpenRiskNet concept
