Periodic Reporting for period 3 - IPAD-MD (Research Infrastructures for Phenotyping, Archiving and Distribution of Mouse Disease Models - Promoting International Cooperation and User Engagement to Enhance Biomedical Innovation) Reporting period: 2018-06-01 to 2019-11-30 Summary of the context and overall objectives of the project Mouse disease models have proven to be a key resource for biomedical research to tackle the global health challenges. Europe has a leading position in developing concepts and interoperable standards for mouse disease model resources and data that have been adopted globally. INFRAFRONTIER is the pan-European research infrastructure for the systemic phenotyping, archiving and distribution of mammalian models, serving a global user community. The International Mouse Phenotyping Consortium (IMPC) is a global initiative to support biomedical research and provide the basis for the development of novel disease treatments by building a comprehensive functional catalogue of the mammalian genome by generating and systemically phenotyping knockout mouse strains for the approx. 20.000 protein-coding genes, and INFRAFRONTIER is a major contributor to this initiative.The IPAD-MD project addresses global cooperation and coordination between the pan- European INFRAFRONTIER Research Infrastructure and complementary research infrastructures in America, Asia and Australia, contributing to the global effort of the IMPC, and with complementary research infrastructures and users in Africa.The main activity of IPAD-MD is the organisation of international thematic workshops, bringing together key stakeholders from INFRAFRONTIER, the IMPC, the biomedical research community, industry, funders and policy and patient organisations to achieve three major objectives:1. Strengthen the coordination between the global research infrastructures to facilitate global global interoperability of large-scale resources and services for mammalian disease models;2. Engage key international stakeholders to ensure their input on the global large-scale resources for the use of mammalian models in biomedical research;3. Develop a global approach to the innovation of these resources and services. 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 IPAD-MD project promoted cooperation and coordination between the pan-European INFRAFRONTIER Research Infrastructure and complementary research infrastructures in America, Asia and Australia and contributed to the global effort of the International Mouse Phenotyping Consortium (IMPC).In the first reporting period, IPAD-MD WP2 organised the Kick-Off Meeting (Munich, July 2015), the INFRAFRONTIER Industry and Innovation Workshop and five IPAD-MD expert group meetings. In the second reporting period, WP2 organised the second stakeholder meeting and one IPAD-MD expert group meeting, and also started the preparation of two IPAD-MD expert group meetings. In the final reporting period, WP2 organised two Stakeholder Workshops, six Expert Group Meetings and a Final Workshop.IPAD-MD WP6 implemented the Standards and Technology (S&T) Expert Group and organised four S&T Expert Group Meetings plus an additional meeting. These meetings were based on 1) metabolic and behavioural phenotyping (Seoul, September 2015), and cryopreservation and mouse line distribution (Monterotondo, November 2915), 2) genome editing and phenotyping (Strasbourg, April 2016), 3) forward genetics panel discussion (Rio Grande (PR), November 2018), 4) epigenetics workshop for INFRAFRONTIER stakeholders and epigenetics community and 5) analysis of IMPC clinical blood chemistry parameters.IPAD-MD WP7 implemented the Data and Resources (D&R) Expert Group and organised six D&R Expert Group Meetings on 1) obtaining user feedback and expert input on the User Experience of the INFRAFRONTIER and IMPC web portal, 2) improving curation and annotation tooling for rare disease mouse models, 3) instructing the INFRAFRONTIER and IPAD-MD members about the latest CRISPR based features in iMits (International Micro-Injection Tracking System) 4) application of machine learning and deep learning algorithms on mouse phenotyping data, 5) sustainability of mouse informatics resources and 6) rare diseases data integration between mouse model and clinical data. WP3 surveyed strategic research agendas at the European and global level. First, the current and emerging research priorities were queried from the INFRAFRONTIER and IMPC partners. The research priorities identified were then used for an analysis of the existent strategic research agendas of ERA-Nets, Joint-Programming Initiatives, Public-Private Partnerships such as the Innovative Medicines Initiative (IMI) and other research programmes involving ministries and funding agencies in their strategic planning. WP4 has carried out a survey of user requirements and application scenarios that involved the analysis of the INFRAFRONTIER database to characterise the academic and non-academic user community of INFRAFRONTIER, as well as the analysis of user feedback survey that was sent out to users of INFRAFRONTIER and the IMPC. A report was compiled from the survey summarised the IPAD-MD activities that shaped INFRAFRONTIER’s scientific strategy aligning with the needs of important user communities as well as with the research agendas of key science policy stakeholders on the national, European and international level. In line with the IPAD-MD 'cross-cutting theme - Outreach to Africa', WP4 entered into discussions with African partners on a more formal collaboration with INFRAFRONTIER. This theme further developed in the second and third reporting periods with significant capacity building activities and valuable exchange of expertise among INFRAFRONTIER members and the afore-mentioned African partners. A notable outcome of this work is University of Cape Town’s ‘Letter of Intent’ to join the INFRAFRONTIER / EMMA Consortium and become the first African EMMA node.WP5 mapped patient organisations (Task 1) and identified potential links and interactions with them. This survey was reconsidered and re-evaluated because of their preferential interest in regulatory processes than in preclinical research. This was followed up with a summary report on engagement with stakeholders.WP8 participated in the IPAD-MD meetings to ensure that the cross-cutting topic of 'Animal Welfare' was part of the agenda and the discussions. A report was compiled that included all the animal welfare principles applied by INFRAFRONTIER and IMPC during IPAD-MD. 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) The potential impacts are:•addressing societal challenges with a global dimension by improving the quality and global accessibility of high-quality resources and services that enable the biomedical research community to tackle the global health challenges•developing cooperation with key international partners for research infrastructures by strengthening the global cooperation between the INFRAFRONTIER Research Infrastructure and complementary RIs around the world•supporting progress towards the development of global research infrastructures by the development of common quality standards, standard operation procedures and common standards for data interoperability and data annotation •contributing to the development of a competitive high-performance ERA in the global research environment by strengthening the role of Europe in the global effort to functionally annotate the mammalian genome and supporting the implementation process of innovate technologies imbedded in a global strategy for interoperability and global resource sharing•contributing to capacity building and research infrastructures human capital development in targeted/relevant regions (Africa) by engaging specialised outreach to complementary RIs and user communities The three main topics of IPAD-MD
