Medical Informatics Platform (MIP): A Pilot Study Across Clinical Italian Cohorts

Introduction: With the shift of research focus to personalized medicine in Alzheimer's Dementia (AD), there is an urgent need for tools that are capable of quantifying a patient's risk using diagnostic biomarkers. The Medical Informatics Platform (MIP) is a distributed e-infrastructure federating large amounts of data coupled with machine-learning (ML) algorithms and statistical models to define the biological signature of the disease. The present study assessed (i) the accuracy of two ML algorithms, i.e., supervised Gradient Boosting (GB) and semi-unsupervised 3C strategy (Categorize, Cluster, Classify—CCC) implemented in the MIP and (ii) their contribution over the standard diagnostic workup. / Methods: We examined individuals coming from the MIP installed across 3 Italian memory clinics, including subjects with Normal Cognition (CN, n = 432), Mild Cognitive Impairment (MCI, n = 456), and AD (n = 451). The GB classifier was applied to best discriminate the three diagnostic classes in 1,339 subjects, and the CCC strategy was used to refine the classical disease categories. Four dementia experts provided their diagnostic confidence (DC) of MCI conversion on an independent cohort of 38 patients. DC was based on clinical, neuropsychological, CSF, and structural MRI information and again with addition of the outcome from the MIP tools. / Results: The GB algorithm provided a classification accuracy of 85% in a nested 10-fold cross-validation for CN vs. MCI vs. AD discrimination. Accuracy increased to 95% in the holdout validation, with the omission of each Italian clinical cohort out in turn. CCC identified five homogeneous clusters of subjects and 36 biomarkers that represented the disease fingerprint. In the DC assessment, CCC defined six clusters in the MCI population used to train the algorithm and 29 biomarkers to improve patients staging. GB and CCC showed a significant impact, evaluated as +5.99% of increment on physicians' DC. The influence of MIP on DC was rated from “slight” to “significant” in 80% of the cases. / Discussion: GB provided fair results in classification of CN, MCI, and AD. CCC identified homogeneous and promising classes of subjects via its semi-unsupervised approach. We measured the effect of the MIP on the physician's DC. Our results pave the way for the establishment of a new paradigm for ML discrimination of patients who will or will not convert to AD, a clinical priority for neurology

Trust and Transparency in Artificial Intelligence. Ethics & Society Opinion. European Commission

The Ethics and Society Subproject has developed this Opinion in order to clarify lessons the Human Brain Project (HBP) can draw from the current discussion of artificial intelligence, in particular the social and ethical aspects of AI, and outline areas where it could usefully contribute. The EU and numerous other bodies are promoting and implementing a wide range of policies aimed to ensure that AI is beneficial - that it serves society. The HBP as a leading project bringing together neuroscience and ICT is in an excellent position to contribute to and to benefit from these discussions. This Opinion therefore highlights some key aspects of the discussion, shows its relevance to the HBP and develops a list of six recommendations

Just-in-time Analytics Over Heterogeneous Data and Hardware

Industry and academia are continuously becoming more data-driven and data-intensive, relying on the analysis of a wide variety of datasets to gain insights. At the same time, data variety increases continuously across multiple axes. First, data comes in multiple formats, such as the binary tabular data of a DBMS, raw textual files, and domain-specific formats. Second, different datasets follow different data models, such as the relational and the hierarchical one. Data location also varies: Some datasets reside in a central "data lake", whereas others lie in remote data sources. In addition, users execute widely different analysis tasks over all these data types. Finally, the process of gathering and integrating diverse datasets introduces several inconsistencies and redundancies in the data, such as duplicate entries for the same real-world concept. In summary, heterogeneity significantly affects the way data analysis is performed. In this thesis, we aim for data virtualization: Abstracting data out of its original form and manipulating it regardless of the way it is stored or structured, without a performance penalty. To achieve data virtualization, we design and implement systems that i) mask heterogeneity through the use of heterogeneity-aware, high-level building blocks and ii) offer fast responses through on-demand adaptation techniques. Regarding the high-level building blocks, we use a query language and algebra to handle multiple collection types, such as relations and hierarchies, express transformations between these collection types, as well as express complex data cleaning tasks over them. In addition, we design a location-aware compiler and optimizer that masks away the complexity of accessing multiple remote data sources. Regarding on-demand adaptation, we present a design to produce a new system per query. The design uses customization mechanisms that trigger runtime code generation to mimic the system most appropriate to answer a query fast: Query operators are thus created based on the query workload and the underlying data models; the data access layer is created based on the underlying data formats. In addition, we exploit emerging hardware by customizing the system implementation based on the available heterogeneous processors â CPUs and GPGPUs. We thus pair each workload with its ideal processor type. The end result is a just-in-time database system that is specific to the query, data, workload, and hardware instance. This thesis redesigns the data management stack to natively cater for data heterogeneity and exploit hardware heterogeneity. Instead of centralizing all relevant datasets, converting them to a single representation, and loading them in a monolithic, static, suboptimal system, our design embraces heterogeneity. Overall, our design decouples the type of performed analysis from the original data layout; users can perform their analysis across data stores, data models, and data formats, but at the same time experience the performance offered by a custom system that has been built on demand to serve their specific use case

Towards the Identification of Disease Signatures

The identification of biological signatures of diseases will enable the development of new biologically grounded classifications of brain diseases, leading to a new systematic understanding of their causes, and new diagnostic tools. In this paper we present the challenges and steps taken towards the identification of disease signatures, through the Medical Informatics Platform of the Human Brain Project, that will expedite diagnosis and lead to more accurate prognosis and objective diagnosis