COSYN integrates outstanding European academic and three large Pharma to exploit genomic findings for intellectual disability (ID), autism, and schizophrenia. We capitalise on comorbidity, from clinic to cells and synapses, and have access to large existing samples. We focus on rare genetic variants of strong effect in patients with clinical comorbidity. Our aims are: (1) Understand comorbidity by comparing symptom and syndrome overlap with novel neurobiological criteria; (2) Elucidate mechanisms of comorbidity using neurobiology for the major genomic clue of synaptic dysfunction to unravel the cellular mechanisms of comorbidity; (3) Generate novel neuronal cell models by using advanced technologies to make neurons from carefully selected patients, and use genome editing to create or correct genetic variants. Multiple advanced neuroscience platforms are in place to evaluate an extensive set of molecular and cellular parameters, and to identify alterations in synaptic biology characteristic of ID, autism, and schizophrenia. These cellular models will, with Pharma partners, be up-scaled to provide “industry-standard” cellular assays for compound screening; (4) Refine diagnostic tools, use novel genomic and cellular features to improve disease classification and discriminate specific patient subtypes; and (5) Case studies in precision medicine: with Pharma partners, identify patients with a genetic change whose consequences can be reproducibly ameliorated in vitro by an approved medication. Recommend to the patient and clinician a double-blinded, N-of-one crossover case study to evaluate the clinical utility of a medication precisely indicated for that person. COSYN is an integrated, state-of-art, bench-to-bedside programme focused on personalised therapeutics. COSYN is a crucial next step in “decoding” the genetic findings via intensive focus on the clinical and molecular comorbidities of ID, autism, and schizophrenia.

The CoMPaSS-NMD project creates novel and universal tools for the diagnostic stratification of patients suffering from Hereditary NeuroMuscular Diseases (HNMDs) aiming at personalised treatments. HNMDs often occurs in young people, causing long-term disability and early death; these conditions bring lack of participation, need for permanent assistance and may require long-term institutionalisation. Multidimensional HNMD data - clinical, genetic, histopathological and MRI will be provided by third-level clinical centers in Italy, France, Germany, Finland and the United Kingdom as part of the European Reference Network for Rare Neurological Diseases. Computational tools for high-dimensional clustering will be applied in an unsupervised learning approach using the internal structure of data to define groups of similar patients. Classification model averaging and integration techniques for federated learning-inspired model building and novel HNMD-specific descriptors of histopathological images will be implemented. The adoption of this multidimensional view has the potential to increment the diagnostic rate of HNMDs by 30% and foster effective actions by European national health systems. As main project outcome, the CoMPaSS-NMD Atlas Platform will be a cost-effective AI-based application providing precise clinical characterization and diagnosis, with data remaining publicly available for anyone in the research and health community to use. The project will deliver Recommendations and Guidelines for stratification-based patient management to offer superior standard-of-care for diagnosis and prognosis and assist in planning clinical trials. It will follow a user-centred, co-design methodology with a strong stakeholder engagement and networking with other project consortia. The project engages partners with clinical, biotechnological, ICT, AI, ethical and legal, communication and exploitation competences: 6 clinical/academic centres, 1 academic, 4 industrial partners.