3TR is a transdisciplinary consortium made of experts in all areas of medicine, basic sciences and bioinformatics from academic institutions, SMEs, and 8 major pharmaceutical companies, teamed to study a fundamental issue in medicine: the mechanisms of response and non-response to therapies, the major aim of 3TR, both within single disease entities and across diseases, where molecular stratification may identify shared disease taxonomies. The molecular identification of groups of patients to whom a drug will benefit, will allow focusing on those who are drug orphan. Harmonization of data from existing academy or industry-sponsored studies will identify biomarkers to inform a new collection. Specimens of diseased tissues, blood, stools, and other fluids will be obtained in a de novo observational prospective trial with standard of care medication prior, during and after first or second line of treatment. Because the studies will be at different phases of progression, a carrousel model of work was designed for input and output of data to be continuously analysed, and interpreted, to inform those measurements to be undertaken and allow cross-validation of results. The 3TR team will elucidate the role of the microbiome, genetics and regulatory genomic features in disease progression. The working aims of 3TR are: 1) establish a centralized data management platform; 2) perform comprehensive molecular and clinical characterisation of a prospective patient cohort; 3) establish integrated analysis of all data using advanced bioinformatics/statistical and modelling methods; 4) identify sets of predictive biomarkers of response/non-response to therapies; 5) improve the competitiveness of European industry and support development of novel solutions. 3TR will sustain beyond the project end the samples and its knowledge base. 3TR will challenge and revolutionize the conventional single-disease based approach with important implications in future disease treatment.

Lung diseases are a leading cause of death, with increasing incidence and lack of curative interventions. The development of novel therapeutic interventions is hampered by our incomplete knowledge of the cellular complexity of the lung, as evidenced by the recent identification of the CFTR-expressing ionocyte. To overcome this limitation, we urgently need to acquire detailed knowledge of the cells of the lung, their fixed and variable molecular features, their interactions and their organization into macroscopic tissue architecture in health and disease. To achieve this, discovAIR aims to establish the first draft of the Human Lung Cell Atlas. Herein, discovAIR will combine multimodal molecular profiling of lung tissue cells with a detailed spatial mapping of the identified cell states, 3D reconstruction of lung tissue architecture, and in-depth molecular phenotyping of local cellular neighbourhoods. We will develop novel computational approaches to integrate the multilevel data of the spatial and the cellular branches of discovAIR. To identify the molecular phenotypes of cells in disease, discovAIR will include lung tissue from patients with asthma, COPD and IPF in the molecular profiling and spatial mapping effort. Moreover, discovAIR will chart cell state transitions from health to disease in a novel experimental approach, the lung cell perturbation map. The discovAIR results will be shared with the basic, translational and clinical scientific community as well as diagnostic and pharmaceutical industry through and open-access data visualization and exploration platform. For sustainability, this platform will be embedded in the Human Cell Atlas infrastructure. The discovAIR results will facilitate progress in regenerative and precision medicine and identify novel candidates for precision diagnostics and curative interventions in lung disease, thereby contributing to healthy ageing and active living in Europe.

OPTIMA is a multi-stakeholder-led consortium with the vision that each and every patient should have access to the most up-to-date individualised treatments and to innovative therapies. In that perspective, we will design, develop and deliver the first interoperable and GDPR compliant European real-world oncology data and evidence generation platform, along with decision support toolsets for prostate, lung and breast cancer. By designing this platform from the onset based on the needs of the clinicians and patients in an inclusive and sustainable way, OPTIMA aims to strengthen shared decision-making based on innovative data and AI-driven technology and tools. To achieve our vision, we have united the key partners from other data-driven European wide oncology initiatives (PIONEER, EHDEN, HARMONY) in our project along with Europes leading clinicians in the fields of breast, prostate and lung cancer that all have leading roles in medical societies such as ERS, ESMO, and EAU. At the core of the OPTIMA project are the major guideline offices of the three indications, whilst the project is further strengthened by patient advocacy groups, well-known academic partners and 6 SMEs as partners covering the needed expertise to implement OPTIMA successfully. The platform will build on existing open source solutions such as the OMOP-CDM, tranSMART and OHDSI ATLAS whilst developing novel AI models based on federated learning to facilitate knowledge discovery. At the start of the project, we will already have access to datasets covering over 200M people in Europe, along with data from high quality patient cohorts for AI model building. Moreover, the platform will be hosted in-kind on existing infrastructure provided by Helmholtz Institute in Germany. Finally, OPTIMA envisions sustainability of its platform through a value-based approach with various business models for commercial users.