Spoke 1 will contribute to the conduction of many activities and its impact will be multidisciplinary thanks to the harmonic integration of different professional expertise. From the technological point of view, the mapping of relevant clinical databases available for different conditions, their integration in a single platform to feed AI algorithms, and the contribution for creating a virtual replica of some clinical conditions in a digital twin represent a model that can be further extended and reproduced at different scales and for several clinical conditions. Not only data integration requires data characteristics allowing interoperability that is essential for several computational applications, but also simulations performed with digital twins will inform biological experiments guided by the relevant clinical queries developed by spoke 1 for the 5 diseases that have been selected. The integration of digital and biological models will be used for recursive experiments that will be instrumental to clarify the patho-physiological mechanisms explaining clinical outcomes of diseases investigated by spoke 1. This approach will be extremely important to create new knowledge useful for diagnosis, prevention, risk-group stratification and treatment outcome of patients affected by one of the 5 selected diseases. The management of CNS tumors, metastatic colon-rectal carcinoma, liver cancer, type 1 diabetes, and multiple sclerosis still has a number of unmet needs that, if addressed, can help improve the quality of care of these patients and their clinical outcomes.