Basic biology as well as applied fields such as agrobiology, biomedicine or biotechnology are undergoing a revolution driven by the realisation that microorganisms impact virtually all biological processes. Microorganisms associated with complex organisms are no longer considered passive passengers but active crews that continuously interact with their host to shape a wide range of biological functions that play a key role in major basic and applied processes. The application of the newest high throughput molecular technologies to address such interplay has given rise to the novel field of hologenomics, which entails the joint analysis of host genomes and microbial metagenomes with the aim of understanding the impact of host-microbiota interactions in basic and applied biological processes. The DN HoloGen has been conceived to lead the development and practical implementation of hologenomics in order to gain a more comprehensive understanding of host-microbiota interactions, and their impact in both basic and applied areas with direct relevance to many of the global societal challenges. We propose to form an unprecedented multidisciplinary and scientifically sound training network by bringing together top researchers with theoretical knowledge on symbiosis biology, microbial ecology, animal evolution, animal production and biomedicine, as well as practical expertise in large- scale (meta)genomics, DNA sequence analysis, metabolomics, computational biology and biological systems modelling. We anticipate that the research results will be (i) of academic relevance through development of new analytical frameworks and understandings of host-microbiome interactions, (ii) of direct relevance to the portfolios of the industrial partners, and (iii) through these portfolios stand to benefit the European Research and Innovation community.

In the EU alone, according to the Orphanet DB (https://pubmed.ncbi.nlm.nih.gov/31527858/), 30 million persons, 3,5-6% of the general population, are affected by one of the 6,172 different rare diseases (RDs) of which 72% are genetic and 70% affect children. The path to diagnosis for people suffering from a RD is burdensome, often severely delayed by a diagnostic odyssey. Lack of timely diagnosis affects disease management, family planning, identification of potential beneficial treatments and / or clinical trials. This unacceptable situation does not meet the concept of equity for EU citizens, and requires rapid, structured, and cost-effective corrective actions. The Screen4Care (S4C) consortium will leverage the genomic and digital advent to develop and pilot genetic NBS and AI-guided symptom recognition algorithms, while accounting for all relevant legal, regulatory and ethical considerations. S4C aims to harmonize the results of existing efforts in a horizon scan, by looking at the totality of the available data resources, diagnostic algorithms, and other initiatives with similar ultimate goals. The genetic NBS will interrogate 1) currently treatable RDs (TREAT-map gene panel), 2) actionable RDs (ACT-map gene panel) in 18.000 new-borns in 3 EU countries (D, It, and Cz). Further, S4C will offer whole genome sequencing (WGS) to early symptomatic babies, tested negatively during panel-based NBS to identify known NBS-escaped RDs and novel genes/phenotypes. S4C will also provide two digital diagnosis support systems for RD on the basis of features and symptom complexes: 1) federated ML- and literature-evidence-based algorithm for continuous and automated screening of EHR and 2) meta symptom checker with virtual clinics for patients and HCP offering the possibility of increased accuracy of diagnosis and ongoing supports. Our ambitious goal is to evaluate the validity of our multi-pronged approach to shorten the time to diagnosis for all patients affect by RDs, improve value-based healthcare resource utilization, and hopefully reduce the suffering of millions of European citizens.

The European Rare Diseases Research Alliance (ERDERA) aims to improve the health and well-being of the 30 million people living with a rare disease in Europe, by making Europe a world leader in Rare Disease (RD) research and innovation, to support concrete health benefits to rare disease patients, through better prevention, diagnosis and treatment. This Partnership will deliver a RD ecosystem that builds on the successes of previous programmes by supporting robust patient need-led research, developing new diagnostic methods and pathways, spearheading the digital transformational change connecting the dots between care, patient data and research, while ensuring strong alignment of strategies in RD research across countries and regions. Structuring goal-oriented public-private collaborations targeted at interventions all along the R&D value chain will ensure that the journey from knowledge to patient impact is expedited, thereby optimising EU innovation potential in RD. To support its ambition and missions ERDERA has been designed as a comprehensive and integrated ecosystem of which structure can be compared to an institute encompassing three main parts: (i) funding, (ii) internal (in house) Clinical Research Network that implements research activities targeting clinical trial readiness of RDs and accelerating diagnosis and translation of research discovery into improved patient care, and (iii) related supporting services (Data, Expertise, Education and Training) as well as an acceleration hub that serve external and internal RD community, all supported by all-embracing coordination and strategy and foundational (inter)national alignment.

Immune-Mediated Inflammatory Diseases (IMIDs) are a group of common autoimmune diseases that include clinically heterogeneous disorders such as rheumatoid arthritis, psoriasis, psoriatic arthritis, Crohn’s disease, ulcerative colitis and systemic lupus erythematosus. Despite their clinical heterogeneity, IMIDs share a significant number of features at the molecular and cellular levels. Recently developed therapies targeting common key molecules of the immune system like anti-TNF agents, have collectively resulted in a significant improvement in the management of IMIDs. Still, the complete control of the chronic inflammatory process is rarely attained, and too many patients experience a poor response, if at all. This inefficacy has become a major economic burden and severely impacts on the wellbeing of many European citizens. The DocTIS projects aims to profoundly change this trend by identifying highly effective combinatorial therapies as well as the group of patients where this response will be optimal. Using the standardized samples from one of the world’s largest biobanks specialized in IMIDs, new molecular data will be generated using advanced high-throughput technologies including single cell RNA-seq. Systems biology methods will be applied to this unique clinical and molecular data to model the response to targeted therapies and predict what drug combinations will act synergistically and on which types of patients. After validation in a preclinical stage, the optimal combinatorial therapy will be tested in a group of patients with a positive biomarker profile. Using a basket trial, a new type of clinical trial design that incorporates molecular marker information, the DocTIS project will provide proof of concept of the utility of combinatorial therapy and personalized medicine for the effective control of disease activity in IMIDs.

HEREDITARY aims to significantly transform the way we approach disease detection, prepare treatment response, and explore medical knowledge by building a robust, interoperable, trustworthy and secure framework that integrates multimodal health data (including genetic data) while ensuring compliance with cross-national privacy-preserving policies. The HEREDITARY framework comprises five interconnected layers, from federated data processing and semantic data integration to visual interaction. By utilizing advanced federated analytics and learning workflows, we aim to identify new risk factors and treatment responses focusing, as exploratory use cases, on neurodegenerative and gut microbiome related disorders. HEREDITARY is harmonizing and linking various sources of clinical, genomic, and environmental data on a large scale. This enables clinicians, researchers, and policymakers to understand these diseases better and develop more effective treatment strategies. HEREDITARY adheres to the citizen science paradigm to ensure that patients and the public have a primary role in guiding scientific and medical research while maintaining full control of their data. Our goal is to change the way we approach healthcare by unlocking insights that were previously impossible to obtain.