Deliverable 2.16: Design of neurodegenerative use cases

This report presents the definition of the Neurodegenerative Use Cases that constitute the core of HEREDITARY.

Neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and other related disorders, are complex and challenging to treat due to their multifaceted pathophysiology. The current approach to neurodegenerative diseases focuses on symptom-based classification, which often fails to capture the underlying biological heterogeneity. There is therefore a pressing need for innovative approaches that leverage advanced data integration and analytics to uncover deeper insights into these diseases.

HEREDITARY aims to address these challenges by integrating multimodal data, and particularly combining genetic, clinical, biomarker and imaging data to provide a comprehensive understanding of neurodegenerative diseases.

The tasks presented in this deliverable will employ the multimodal data framework in a research setting, aiming to refine prediction and patient classification in neurodegenerative disorders and uncover novel disease-related biomarkers and etiological mechanisms. The development of a multimodal data framework will enhance predictive analysis and patient classification, Improving the discovery of novel diseaserelated biomarkers or etiological mechanisms.

HEREDITARY will integrate diverse data types from different centres using a federated learning infrastructure. This approach allows for secure, large-scale data analysis without compromising patient privacy by implementing privacy-preserving federated analytics. The effectiveness of the HEREDITARY framework within the realm of neurodegenerative diseases will be assessed primarily in two use cases designed to (a) advance the understanding of ALS by identifying endophenotypes through the integration of comprehensive data modalities and (b) detect biologically informed clusters within neurodegenerative diseases. These two use cases will integrate with three additional clinical applications of HEREDITARY, which will be the focus of future tasks. These additional use cases will concentrate on the early detection of Parkinson's disease using multimodal data and exploring the gut-brain axis in health and disease. Together, these five use cases will demonstrate the broad applicability and effectiveness of the HEREDITARY framework.

The outcomes of the Neurodegenerative Use Cases of HEREDITARY will improve our understanding of neurodegenerative disorders. This approach will pave the way for improved patient classification and the development of effective treatment strategies, uncovering deeper insights into the underlying mechanisms of these diseases and ultimately leading to more targeted and personalized interventions.