The SYSCID consortium aims to develop a systems medicine approach for disease prediction in CID. We will focus on three major CID indications with distinct characteristics, yet a large overlap of their molecular risk map: inflammatory bowel disease, systemic lupus erythematodes and rheumatoid arthritis. We have joined 15 partners from major cohorts and initiatives in Europe (e.g.IHEC, ICGC, TwinsUK and Meta-HIT) to investigate human data sets on three major levels of resolution: whole blood signatures, signatures from purified immune cell types (with a focus on CD14 and CD4/CD8) and selected single cell level analyses. Principle data layers will comprise SNP variome, methylome, transcriptome and gut microbiome. SYSCID employs a dedicated data management infrastructure, strong algorithmic development groups (including an SME for exploitation of innovative software tools for data deconvolution) and will validate results in independent retrospective and prospective clinical cohorts. Using this setup we will focus on three fundamental aims : (i) the identification of shared and unique "core disease signatures” which are associated with the disease state and independent of temporal variation, (ii) the generation of "predictive models of disease outcome"- builds on previous work that pathways/biomarkers for disease outcome are distinct from initial disease risk and may be shared across diseases to guide therapy decisions on an individual patient basis, (iii) "reprogramming disease"- will identify and target temporally stable epigenetic alterations in macrophages and lymphocytes in epigenome editing approaches as biological validation and potential novel therapeutic tool . Thus, SYSCID will foster the development of solid biomarkers and models as stratification in future long-term systems medicine clinical trials but also investigate new causative therapies by editing the epigenome code in specific immune cells, e.g. to alleviate macrophage polarization defects.

The PREFER project will deliver an overview and evaluation of preference elicitation methods to be applied in the entire drug life cycle, i.e. in the early stages of identifying medical needs, in clinical testing, to guide decisions on reimbursement and to make decisions on withdrawal of drugs from the market. A broad array of (combinations of) patient preference methods will be tested prospectively in a large number of case studies. The availability of large patient cohorts will enable to test new methods or deviations from existing methods in a randomized manner, by comparing well-known methods with newer ones. The use of simulation studies will both contribute to smarter design of case studies and to exploring the sensitivity of outcomes of preference studies. Based on discussions with a broad representation of stakeholders e.g. patients, patient organisations, regulatory authorities, HTA bodies and reimbursement agencies, suitable methods will be tested and their contributions to improved decision making will be discussed in recommendations adapted to the needs of all relevant stakeholders. The recommendations from PREFER are expected to lead to changed practices, in that industry will routinely assess whether a preference study would add value at key decision points in the medicinal product life cycle and, if so, implement patient-preference elicitation studies according to the PREFER project recommendations. The PREFER consortium consist of 16 industry partners and 16 academic and SME members including representation from academia, patient organizations, HTA bodies, reimbursement agencies, and project management.

ChromDesign is an innovative and interdisciplinary network of 10 European academic and private institutions that will characterize how 3D chromatin organization affects gene regulation during cellular differentiation and in several human disorders. We will train 13 Early Stage Researchers (ESR), equipping them with the skills, knowledge, expertise, and enthusiasm necessary to develop successful future careers in the biomedical field (in academia or the private sector). Together with European experts in chromatin biology, 3D genomics, and research design, these ESRs will work towards the goal of identifying novel alterations in chromatin topology responsible for cellular malfunctions to: i) develop new diagnostic tools, ii) effectively communicate research results through specific toolkits; and iii) identify novel therapeutic targets with the potential to be exploited as treatments. Alteration of gene regulation occurs naturally during aging and underlies several human diseases. Its better characterization requires a deeper understanding of the spatial organization of the genome. We will investigate how the genome organizes in 3D over time, and how the 3D organization is related to gene regulation in health and disease. We will use and develop technologies in imaging, cell biology, genomics, and computational modelling and will focus on translating our results into clinical applications. ESRs will thereby receive training with state-of-the-art technologies in distinct research areas and in modules with theoretical and hands-on sessions on transferable skills: entrepreneurship, management, communication, and outreach. ChromDesign comprises 6 work packages: WP1–4 address the 4 main areas of chromatin biology and 3D genomics; WP5 applies the knowledge obtained from WPs1–4 into translational research; WP6 develops (with a dedicated ESR) a set of design toolkits for communicating results to scientists, the public, and schools; and WP7 ensures quality training for ESRs.

Counteracting high attrition rates in oncology drug development and providing optimal therapeutic management of cancer patients require preclinical models that properly recapitulate the complexity and diversity of human tumours. Patient-derived tumour xenografts (PDXs), established by transplanting tumour fragments into immunodeficient mice, are being widely embraced by the scientific community as preclinical tools for target and biomarker discovery. The overall goal of EDIReX is to establish a cutting-edge European infrastructure offering Trans-national Access (TA) of PDX resources to academic and industrial cancer researchers, including the distribution of cryopreserved samples to third parties, the structured biobanking of user-developed models, and the performance of efficacy studies. To ensure interoperability in services, TA initiatives will be backed by Networking Activities (NAs); these will be mainly centred around the establishment of standard procedures for PDX quality control, long-term storage and therapeutic mouse trials. NAs will also entail the adoption of shared ethics parameters for animal experimentation, the wide dissemination of services and project results, and the design of plans to ensure sustainability of the infrastructure. User outreach will be maximised by Joint Research Activities through a three-pronged approach: i) the implementation of a public Data Portal for efficient and user-friendly query and visualisation of clinical, molecular and pharmacological annotation of the models; ii) a cross-validation mouse trial to harmonise inter-laboratory procedures, thus improving the quality and reliability of service provision; and iii) the development of exploratory, more advanced PDX-based preclinical platforms, such as orthotopic and humanised models and in vitro PDX-derived cells. Capitalising on all these assets, EDIReX will contribute to structuring the European Research Area and global cooperation of research infrastructures.