Functional connectivity analysis of cerebellum using spatially constrained spectral clustering

The human cerebellum contains almost 50% of the neurons in the brain, although its volume does not exceed 10% of the total brain volume. The goal of this study is to derive the functional network of the cerebellum during the resting-state and then compare the ensuing group networks between males and females. Toward this direction, a spatially constrained version of the classic spectral clustering algorithm is proposed and then compared against conventional spectral graph theory approaches, such as spectral clustering, and N-cut, on synthetic data as well as on resting-state fMRI data obtained from the Human Connectome Project (HCP). The extracted atlas was combined with the anatomical atlas of the cerebellum resulting in a functional atlas with 46 regions of interest. As a final step, a gender-based network analysis of the cerebellum was performed using the data-driven atlas along with the concept of the minimum spanning trees. The simulation analysis results confirm the dominance of the spatially constrained spectral clustering approach in discriminating activation patterns under noisy conditions. The network analysis results reveal statistically significant differences in the optimal tree organization between males and females. In addition, the dominance of the left VI lobule in both genders supports the results reported in a previous study of ours. To our knowledge, the extracted atlas comprises the first resting-state atlas of the cerebellum based on HCP data

FCLAB:An EEGLAB module for performing functional connectivity analysis on single-subject EEG data

Functional connectivity (FC) analysis constitutes a fundamental neuroscientific approach that has been extensively used for the investigation of brain's connectivity and activation patterns. To that end, several software tools have been developed. This paper presents FCLAB, the only EEGLAB-based plugin, which is able to work with EEG signals in order to estimate and visualize brain functional connectivity networks based on a variety of similarity measures as well as run a complete graph analysis procedure followed by a detailed visualization of the ensuing local and global measures distribution. FCLAB entails optimization procedures for the implementation of the connectivity structures and is the result of long-term research in EEG functional connectivity. The computed functional connectivity measures have been carefully selected to reflect the state-of-art in the field. Future work focuses on extending the platform for multi-subject analysis in order to enable the implementation of statistical analysis tools

A machine learning-based risk stratification model for ventricular tachycardia and heart failure in hypertrophic cardiomyopathy

Background: Machine learning (ML) and artificial intelligence are emerging as important components of precision medicine that enhance diagnosis and risk stratification. Risk stratification tools for hypertrophic cardiomyopathy (HCM) exist, but they are based on traditional statistical methods. The aim was to develop a novel machine learning risk stratification tool for the prediction of 5-year risk in HCM. The goal was to determine if its predictive accuracy is higher than the accuracy of the state-of-the-art tools. Method: Data from a total of 2302 patients were used. The data were comprised of demographic characteristics, genetic data, clinical investigations, medications, and disease-related events. Four classification models were applied to model the risk level, and their decisions were explained using the SHAP (SHapley Additive exPlanations) method. Unwanted cardiac events were defined as sustained ventricular tachycardia occurrence (VT), heart failure (HF), ICD activation, sudden cardiac death (SCD), cardiac death, and all-cause death. Results: The proposed machine learning approach outperformed the similar existing risk-stratification models for SCD, cardiac death, and all-cause death risk-stratification: it achieved higher AUC by 17%, 9%, and 1%, respectively. The boosted trees achieved the best performing AUC of 0.82. The resulting model most accurately predicts VT, HF, and ICD with AUCs of 0.90, 0.88, and 0.87, respectively. Conclusions: The proposed risk-stratification model demonstrates high accuracy in predicting events in patients with hypertrophic cardiomyopathy. The use of a machine-learning risk stratification model may improve patient management, clinical practice, and outcomes in general

Resting-State Functional Connectivity and Network Analysis of Cerebellum with Respect to Crystallized IQ and Gender

During the last years, it has been established that the prefrontal and posterior parietal brain lobes, which are mostly related to intelligence, have many connections to cerebellum. However, there is a limited research investigating cerebellum's relationship with cognitive processes. In this study, the network of cerebellum was analyzed in order to investigate its overall organization in individuals with low and high crystallized Intelligence Quotient (IQ). Functional magnetic resonance imaging (fMRI) data were selected from 136 subjects in resting-state from the Human Connectome Project (HCP) database and were further separated into two IQ groups composed of 69 low-IQ and 67 high-IQ subjects. Cerebellum was parcellated into 28 lobules/ROIs (per subject) using a standard cerebellum anatomical atlas. Thereafter, correlation matrices were constructed by computing Pearson's correlation coefficients between the average BOLD time-series for each pair of ROIs inside the cerebellum. By computing conventional graph metrics, small-world network properties were verified using the weighted clustering coefficient and the characteristic path length for estimating the trade-off between segregation and integration. In addition, a connectivity metric was computed for extracting the average cost per network. The concept of the Minimum Spanning Tree (MST) was adopted and implemented in order to avoid methodological biases in graph comparisons and retain only the strongest connections per network. Subsequently, six global and three local metrics were calculated in order to retrieve useful features concerning the characteristics of each MST. Moreover, the local metrics of degree and betweenness centrality were used to detect hubs, i.e., nodes with high importance. The computed set of metrics gave rise to extensive statistical analysis in order to examine differences between low and high-IQ groups, as well as between all possible gender-based group combinations. Our results reveal that both male and female networks have small-world properties with differences in females (especially in higher IQ females) indicative of higher neural efficiency in cerebellum. There is a trend toward the same direction in men, but without significant differences. Finally, three lobules showed maximum correlation with the median response time in low-IQ individuals, implying that there is an increased effort dedicated locally by this population in cognitive tasks

Addressing the clinical unmet needs in primary Sjögren's Syndrome through the sharing, harmonization and federated analysis of 21 European cohorts

For many decades, the clinical unmet needs of primary Sjögren's Syndrome (pSS) have been left unresolved due to the rareness of the disease and the complexity of the underlying pathogenic mechanisms, including the pSS-associated lymphomagenesis process. Here, we present the HarmonicSS cloud-computing exemplar which offers beyond the state-of-the-art data analytics services to address the pSS clinical unmet needs, including the development of lymphoma classification models and the identification of biomarkers for lymphomagenesis. The users of the platform have been able to successfully interlink, curate, and harmonize 21 regional, national, and international European cohorts of 7,551 pSS patients with respect to the ethical and legal issues for data sharing. Federated AI algorithms were trained across the harmonized databases, with reduced execution time complexity, yielding robust lymphoma classification models with 85% accuracy, 81.25% sensitivity, 85.4% specificity along with 5 biomarkers for lymphoma development. To our knowledge, this is the first GDPR compliant platform that provides federated AI services to address the pSS clinical unmet needs. © 2022 The Author(s

Towards a European Health Research and Innovation Cloud (HRIC)

The European Union (EU) initiative on the Digital Transformation of Health and Care (Digicare) aims to provide the conditions necessary for building a secure, flexible, and decentralized digital health infrastructure. Creating a European Health Research and Innovation Cloud (HRIC) within this environment should enable data sharing and analysis for health research across the EU, in compliance with data protection legislation while preserving the full trust of the participants. Such a HRIC should learn from and build on existing data infrastructures, integrate best practices, and focus on the concrete needs of the community in terms of technologies, governance, management, regulation, and ethics requirements. Here, we describe the vision and expected benefits of digital data sharing in health research activities and present a roadmap that fosters the opportunities while answering the challenges of implementing a HRIC. For this, we put forward five specific recommendations and action points to ensure that a European HRIC: i) is built on established standards and guidelines, providing cloud technologies through an open and decentralized infrastructure; ii) is developed and certified to the highest standards of interoperability and data security that can be trusted by all stakeholders; iii) is supported by a robust ethical and legal framework that is compliant with the EU General Data Protection Regulation (GDPR); iv) establishes a proper environment for the training of new generations of data and medical scientists; and v) stimulates research and innovation in transnational collaborations through public and private initiatives and partnerships funded by the EU through Horizon 2020 and Horizon Europe

An explainable machine learning-driven proposal of pulmonary fibrosis biomarkers

Pulmonary fibrosing diseases are in the very epicenter of biomedical research both due to their increasing prevalence and their association with SARS-CoV-2 infections. Research of idiopathic pulmonary fibrosis, the most lethal among the interstitial lung diseases, is in need for new biomarkers and potential disease targets, a goal that could be accelerated using machine learning techniques. In this study, we have used Shapley values to explain the decisions made by an ensemble learning model trained to classify samples to an either pulmonary fibrosis or steady state based on the expression values of deregulated genes. This process resulted in a full and a laconic set of features capable of separating phenotypes to an at least equal degree as previously published marker sets. Indicatively, a maximum increase of 6% in specificity and 5% in Mathew’s correlation coefficient was achieved. Evaluation with an additional independent dataset showed our feature set having a greater generalization potential than the rest. Ultimately, the proposed gene lists are expected not only to serve as new sets of diagnostic marker elements, but also as a target pool for future research initiatives

3D clustering of gene expression data from systemic autoinflammatory diseases using self-organizing maps (Clust3D)

Background and objective: Systemic autoinflammatory diseases (SAIDs) are characterized by widespread inflammation, but for most of them there is a lack of specific biomarkers for accurate diagnosis. Although a number of machine learning algorithms have been used to analyze SAID datasets, aiding in the discovery of novel biomarkers, there is a growing recognition of the importance of SAID timeseries clustering, as it can capture the temporal dynamics of gene expression patterns. Methodology: This paper proposes a novel clustering methodology to efficiently associate three-dimensional data. The algorithm utilizes competitive learning to create a self-organizing neural network and adjust neuron positions in time-dependent and high dimensional feature space in order to assign them as clustering centers. The quantitative evaluation of the clustering was based on well-known clustering indices. Furthermore, a differential expression analysis and classification pipeline was employed to assess the capability of the proposed methodology to extract more accurate pathway-specific genes from its clusters. For that, a comparative analysis was also conducted against a heuristic timeseries clustering method. Results: The proposed methodology achieved better overall clustering indices scores and classification metrics using genes derived from its clusters. Notable cases include a threefold increase in the Calinski-Harabasz clustering index, a twofold improvement in the Davies–Bouldin clustering index and a ∼60% increase in the classification specificity score. Conclusion: A novel clustering methodology was developed and applied on several gene expression timeseries datasets from systemic autoinflammatory diseases, and its ability to efficiently produce well separated clusters compared to existing heuristic methods was demonstrated

Table6_Resting-State Functional Connectivity and Network Analysis of Cerebellum with Respect to IQ and Gender.DOCX

<p>During the last years, it has been established that the prefrontal and posterior parietal brain lobes, which are mostly related to intelligence, have many connections to cerebellum. However, there is a limited research investigating cerebellum's relationship with cognitive processes. In this study, the network of cerebellum was analyzed in order to investigate its overall organization in individuals with low and high fluid Intelligence Quotient (IQ). Functional magnetic resonance imaging (fMRI) data were selected from 136 subjects in resting-state from the Human Connectome Project (HCP) database and were further separated into two IQ groups composed of 69 low-IQ and 67 high-IQ subjects. Cerebellum was parcellated into 28 lobules/ROIs (per subject) using a standard cerebellum anatomical atlas. Thereafter, correlation matrices were constructed by computing Pearson's correlation coefficients between the average BOLD time-series for each pair of ROIs inside the cerebellum. By computing conventional graph metrics, small-world network properties were verified using the weighted clustering coefficient and the characteristic path length for estimating the trade-off between segregation and integration. In addition, a connectivity metric was computed for extracting the average cost per network. The concept of the Minimum Spanning Tree (MST) was adopted and implemented in order to avoid methodological biases in graph comparisons and retain only the strongest connections per network. Subsequently, six global and three local metrics were calculated in order to retrieve useful features concerning the characteristics of each MST. Moreover, the local metrics of degree and betweenness centrality were used to detect hubs, i.e., nodes with high importance. The computed set of metrics gave rise to extensive statistical analysis in order to examine differences between low and high-IQ groups, as well as between all possible gender-based group combinations. Our results reveal that both male and female networks have small-world properties with differences in females (especially in higher IQ females) indicative of higher neural efficiency in cerebellum. There is a trend toward the same direction in men, but without significant differences. Finally, three lobules showed maximum correlation with the median response time in low-IQ individuals, implying that there is an increased effort dedicated locally by this population in cognitive tasks.</p