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Towards enduring mouse resources and services advancing research into human health and disease

Periodic Reporting for period 3 - INFRAFRONTIER2020 (Towards enduring mouse resources and services advancing research into human health and disease)

Reporting period: 2020-01-01 to 2021-12-31

INFRAFRONTIER is the European Research Infrastructure for the generation, phenotyping, archiving and distribution of model mammalian genomes. The INFRAFRONTIER Research Infrastructure provides access to first-class tools and data for biomedical research, and thereby contributes to improving the understanding of gene function in human health and disease using the mouse model. The overall objective of the INFRAFRONTIER2020 project is to evolve INFRAFRONTIER towards a sustained and excellent operation. Further objectives are improving data management and fostering innovation potential. All project coordination, outreach, operations, data management, and service objectives are aligned with the EC Research Infrastructures Work Program, its call objectives, and expected impacts.
INFRAFRONTIER2020 (I2020) concluded the third and final project phase on 31st December (60 months). During this time, I2020 achieved tremendous success in driving forward the sustainability of the INFRAFRONTIER consortium. This was achieved by:

1. Advancing towards a stable legal framework to establish the ERIC legal status (Objective 1)

2. Raising awareness of the INFRAFRONTIER consortium in the global research community with continuous communication activities including promoting and organising world-class research conferences – INFRAFRONTIER Conferences (Objective 2)

3. Adapting and addressing user demands via state-of-the-art transnational access calls and distribution of CRISPR-Cas9 generated mouse strains (Objective 3)

4. Showcasing best practices and improving reproducibility by promoting and establishing common quality management activities in the consortium (Objective 4)

5. Reengineering and revitalising the IT backbone of the INFRAFRONTIER database to increase efficiency, improve user experience and streamline data exchange (Objective 5)

6. Implementing a service and resource provision strategy that focusses specific disease areas and research topics (Objective 6)

With the end of the final period, the following results were achieved, disseminated, and exploited:

Thirteen transnational access calls were successfully conducted. These calls supported 63 user projects totalling 1,2 million € in funding. When possible, the results of the TA calls like novel mouse strains or phenotyping data were made available to research community via EMMA or mouse phenotyping databases. In addition, the results from these TA calls have contributed to peer-reviewed publications.

The EMMA distribution license for CRISPR-Cas9-generated mouse lines was a very important I2020 achievement that was greatly exploited to meet the high user demands for novel mouse strains generated via CRISPR-Cas9 gene editing. After lengthy negotiations and discussions, the distribution of these strains was started in August 2021.

The INFRAFRONTIER Operations Handbook and the peer-reviewed publication on common INFRAFRONTIER Quality Principles in systemic phenotyping contributed heavily to common quality INFRAFRONTIER management activities. The Operations Handbook provides an overview of main operational procedures at the INFRAFRONTIER GmbH needed to achieve the GmbH’s operational objective – the management and coordination of the INFRAFRONTIER Research Infrastructure (RI). This document is exploited as a guide to implement a Quality Management System at the INFRAFRONTIER GmbH. The peer-review publication on the other hand is exploited to inform mouse phenotyping standards in the biomedical research community.

The largest I2020 communication and dissemination activities were the annual INFRAFRONTIER Stakeholder Conferences (later renamed to INFRAFRONTIER Conferences, for recognisable branding, easy recognition and reduced ambiguity). These events were attended by around 200 participants every year with focussed topics like rare diseases, cancer research, brain research, genomic big data etc., and engaged new stakeholders like the rare disease community, population geneticists and the Cancer Mission Board.

The INFRAFRONTIER central database system is the core IT backbone of INFRAFRONTIER and EMMA services. Owing to its importance in many INFRAFRONTIER resources and services, the reengineering of this database was a heavily exploited I2020 result. The database reengineering efforts have greatly contributed to quality-of-life improvements for new and current EMMA users and streamlined data exchange with IMPC mouse production and phenotyping activities. Like database reengineering, the annotation and curation of mouse data improved the exploitability of EMMA mouse data by FAIRifying and displaying validated mouse models of disease prominently on the INFRAFRONTER portal according to major disease categories.
A significant impact of INFRAFRONTIER2020 was boosting the long-term sustainability of the INFRAFRONTIER RI. Nearly all the project results have an impact in this space with the key ones being the significant progress towards the ERIC legal entity, the INFRAFRONTIER business plan, implementation of a quality management system, database reengineering and pilot transnational access calls.

Achieving operational excellence of the INFRAFRONTIER RI is another significant impact of I2020. The focus on promoting quality and standardised approaches via I2020 INFRAFRONTIER Quality Management activities greatly benefits animal welfare and helps ensure highest levels of experimental data in terms of reproducibility and quality.

I2020 also strengthened the role of ERA in the distribution, archiving and phenotyping of mouse models by developing a vast network of 29 leading research institutions in 15 member states. More than 8500 mouse strains are available in the European Mouse Mutant Archive (EMMA) accessible on INFRAFRONTIER web portal (www.infrafrontier.eu) via this network. The web portal also provides access to state-of-the-art mouse resources and services that includes dedicated mouse resources on rare diseases, cancer, and COVID-19.

The partnerships between funders, research infrastructures and user communities were reinforced in I2020 by the engagement of relevant stakeholders like the Cancer Mission Board, European Brain Project, EBRAINS, EJP-RD, EurOPDX, Euro-BioImaging etc. in various I2020 communication and dissemination events and activities. In particular, the INFRAFRONTIER stakeholder conferences, jointly organised with the global IMPC effort, continuous supported engagement with international consortia and organisations, and promoted the role and visibility of the EU. Moreover, a memorandum of understanding signed with EurOPDX formalised the partnership with INFRAFRONTIER and another with ELIXIR is underway.

Another significant impact in today’s world of big data and data science is the FAIRification (findable, accessible, interoperable and reusable) of data. In this direction, INFRAFRONTIER mouse model data is listed as a FAIR resource on EJP-RD’s virtual platform (https://resourcemap.ejprarediseases.org). Moreover, the curated INFRAFRONTIER-EMMA database and its specific dataset of strains for COVID-19 research have been reviewed and selected as FAIR resources by the reference FAIRSharing Consortium (fairsharing.org/10.25504/FAIRsharing.g2fjt2; fairsharing.org/collection/RDACovid19WG).
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