Section: Partnerships and Cooperations

European Initiatives

• Project acronym: EuroPOND

• Project title: Data-driven models for Progression Of Neurological Disease

• Duration: Jan 2016 - Dec 2019

• Amount: 6M€

• Coordinator: Daniel Alexander

• Other partners: University College London (UK), EMC Rotterdam (The Netherlands), VUMC (The Netherlands), Fate Bene Fratelli (Italy), Carol Besta Institute (Italy), Université de Genève (Switzerland), Icometrix (Belgium)

• Abstract: EuroPOND will develop a data-driven statistical and computational modeling framework for neurological disease progression. This will enable major advances in differential and personalized diagnosis, prognosis, monitoring, and treatment and care decisions, positioning Europe as world leaders in one of the biggest societal challenges of 21st century healthcare. The inherent complexity of neurological disease, the overlap of symptoms and pathologies, and the high comorbidity rate suggests a systems medicine approach, which matches the specific challenge of this call. We take a uniquely holistic approach that, in the spirit of systems medicine, integrates a variety of clinical and biomedical research data including risk factors, biomarkers, and interactions. Our consortium has a multidisciplinary balance of essential expertise in mathematical/statistical/computational modelling; clinical, biomedical and epidemiological expertise; and access to a diverse range of datasets for sporadic and well-phenotyped disease types.The project will devise and implement, as open-source software tools, advanced statistical and computational techniques for reconstructing long-term temporal evolution of disease markers from cross-sectional or short-term longitudinal data. We will apply the techniques to generate new and uniquely detailed pictures of a range of important diseases. This will support the development of new evidence-based treatments in Europe through deeper disease understanding, better patient stratification for clinical trials, and improved accuracy of diagnosis and prognosis. For example, Alzheimer’s disease alone costs European citizens around €200B every year in care and loss of productivity. No disease modifying treatments are yet available. Clinical trials repeatedly fail because disease heterogeneity prevents bulk response. Our models enable fine stratification into phenotypes enabling more focussed analysis to identify subgroups that respond to putative treatments.

• Project acronym: HBP

• Project title: Human Brain Project

• Sub-project: SP8 - Medical Informatics Platform

• Duration: 2016-

• Abstract: The Human Brain Project (HBP) is a European Commission Future and Emerging Technologies Flagship. The HBP aims to put in place a cutting-edge, ICT-based scientific Research Infrastructure for brain research, cognitive neuroscience and brain-inspired computing. The Project promotes collaboration across the globe, and is committed to driving forward European industry. Our team is involved in the Subproject SP8 (Medical Informatics Platform). The Medical Informatics Platform (MIP) is an innovative data management system that gives researchers the means to access and analyse large amounts of anonymized clinical neuroscience data. Within that framework, we will develop and implement a method to construct disease progression models from longitudinal biomarkers. The method will use statistical learning techniques to infer a long-term disease progression model from multiple short term data from a series of individuals. The model will account for variability in age at disease onset, pace of disease progression and trajectories of biomarkers changes across individuals in the observed population.

• Project acronym: LEASP

• Project title: Learning Spatiotemporal Patterns in Longitudinal Image Data Sets of the Aging Brain

• Duration: 2016-2021

• Abstract: Time-series of multimodal medical images offer a unique opportunity to track anatomical and functional alterations of the brain in aging individuals. A collection of such time series for several individuals forms a longitudinal data set, each data being a rich iconic-geometric representation of the brain anatomy and function. These data are already extraordinary complex and variable across individuals. Taking the temporal component into account further adds difficulty, in that each individual follows a different trajectory of changes, and at a different pace. Furthermore, a disease is here a progressive departure from an otherwise normal scenario of aging, so that one could not think of normal and pathologic brain aging as distinct categories, as in the standard case-control paradigm.

  Bio-statisticians lack a suitable methodological framework to exhibit from these data the typical trajectories and dynamics of brain alterations, and the effects of a disease on these trajectories, thus limiting the investigation of essential clinical questions. To change this situation, we propose to construct virtual dynamical models of brain aging by learning typical spatiotemporal patterns of alterations propagation from longitudinal iconic-geometric data sets.

  By including concepts of the Riemannian geometry into Bayesian mixed effect models, the project will introduce general principles to average complex individual trajectories of iconic-geometric changes and align the pace at which these trajectories are followed. It will estimate a set of elementary spatiotemporal patterns, which combine to yield a personal aging scenario for each individual. Disease-specific patterns will be detected with an increasing likelihood.

  This new generation of statistical and computational tools will unveil clusters of patients sharing similar lesion propagation profiles, paving the way to design more specific treatments, and care patients when treatments have the highest chance of success.