Determining the Hierarchical Architecture of the Human Brain Using Subject-Level Clustering of Functional Networks.
Ontology highlight
ABSTRACT:
SUBMITTER: Akiki TJ
PROVIDER: S-EPMC6917755 | biostudies-literature | 2019 Dec
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:A Bayesian model for sparse, hierarchical, inver-covariance estimation is presented, and applied to multi-subject functional connectivity estimation in the human brain. It enables simultaneous inference of the strength of connectivity between brain regions at both subject and population level, and is applicable to fMRI, MEG and EEG data. Two versions of the model can encourage sparse connectivity, either using continuous priors to suppress irrelevant connections, or using an explicit description of the network structure to estimate the connection probability between each pair of regions. A large evaluation of this model, and thirteen methods that represent the state of the art of inverse covariance modelling, is conducted using both simulated and resting-state functional imaging datasets. Our novel Bayesian approach has similar performance to the best extant alternative, Ng et al.'s Sparse Group Gaussian Graphical Model algorithm, which also is based on a hierarchical structure. Using data from the Human Connectome Project, we show that these hierarchical models are able to reduce the measurement error in MEG beta-band functional networks by 10%, producing concomitant increases in estimates of the genetic influence on functional connectivity.
| S-EPMC6565932 | biostudies-literature
Project description:Specialized processing in the brain is performed by multiple groups of brain regions organized as functional modules. Although, in vivo studies of brain functional modules involve multiple functional Magnetic Resonance Imaging (fMRI) scans, the methods used to derive functional modules from functional networks of the brain ignore individual differences in the functional architecture and use incomplete functional connectivity information. To correct this, we propose an Iterative Consensus Spectral Clustering (ICSC) algorithm that detects the most representative modules from individual dense weighted connectivity matrices derived from multiple scans. The ICSC algorithm derives group-level modules from modules of multiple individuals by iteratively minimizing the consensus-cost between the two. We demonstrate that the ICSC algorithm can be used to derive biologically plausible group-level (for multiple subjects) and subject-level (for multiple subject scans) brain modules, using resting-state fMRI scans of 589 subjects from the Human Connectome Project. We employed a multipronged strategy to show the validity of the modularizations obtained from the ICSC algorithm. We show a heterogeneous variability in the modular structure across subjects where modules involved in visual and motor processing were highly stable across subjects. Conversely, we found a lower variability across scans of the same subject. The performance of our algorithm was compared with existing functional brain modularization methods and we show that our method detects group-level modules that are more representative of the modules of multiple individuals. Finally, the experiments on synthetic images quantitatively demonstrate that the ICSC algorithm detects group-level and subject-level modules accurately under varied conditions. Therefore, besides identifying functional modules for a population of subjects, the proposed method can be used for applications in personalized neuroscience. The ICSC implementation is available at https://github.com/SCSE-Biomedical-Computing-Group/ICSC.
| S-EPMC7200822 | biostudies-literature
Project description:Community detection algorithms have been widely used to study the organization of complex networks like the brain. These techniques provide a partition of brain regions (or nodes) into clusters (or communities), where nodes within a community are densely interconnected with one another. In their simplest application, community detection algorithms are agnostic to the presence of community hierarchies: clusters embedded within clusters of other clusters. To address this limitation, we exercise a multi-scale extension of a common community detection technique, and we apply the tool to synthetic graphs and to graphs derived from human neuroimaging data, including structural and functional imaging data. Our multi-scale community detection algorithm links a graph to copies of itself across neighboring topological scales, thereby becoming sensitive to conserved community organization across levels of the hierarchy. We demonstrate that this method is sensitive to topological inhomogeneities of the graph's hierarchy by providing a local measure of community stability and inter-scale reliability across topological scales. We compare the brain's structural and functional network architectures, and we demonstrate that structural graphs display a more prominent hierarchical community organization than functional graphs. Finally, we build an explicitly multimodal multiplex graph that combines both structural and functional connectivity in a single model, and we identify the topological scales where resting state functional connectivity and underlying structural connectivity show similar versus unique hierarchical community architecture. Together, our results demonstrate the advantages of the multi-scale community detection algorithm in studying hierarchical community structure in brain graphs, and they illustrate its utility in modeling multimodal neuroimaging data.
| S-EPMC6508662 | biostudies-literature
Project description:BACKGROUND:Unsupervised clustering represents one of the most widely applied methods in analysis of high-throughput 'omics data. A variety of unsupervised model-based or parametric clustering methods and non-parametric clustering methods have been proposed for RNA-seq count data, most of which perform well for large samples, e.g. N???500. A common issue when analyzing limited samples of RNA-seq count data is that the data follows an over-dispersed distribution, and thus a Negative Binomial likelihood model is often used. Thus, we have developed a Negative Binomial model-based (NBMB) clustering approach for application to RNA-seq studies. RESULTS:We have developed a Negative Binomial Model-Based (NBMB) method to cluster samples using a stochastic version of the expectation-maximization algorithm. A simulation study involving various scenarios was completed to compare the performance of NBMB to Gaussian model-based or Gaussian mixture modeling (GMM). NBMB was also applied for the clustering of two RNA-seq studies; type 2 diabetes study (N?=?96) and TCGA study of ovarian cancer (N?=?295). Simulation results showed that NBMB outperforms GMM applied with different transformations in majority of scenarios with limited sample size. Additionally, we found that NBMB outperformed GMM for small clusters distance regardless of sample size. Increasing total number of genes with fixed proportion of differentially expressed genes does not change the outperformance of NBMB, but improves the overall performance of GMM. Analysis of type 2 diabetes and ovarian cancer tumor data with NBMB found good agreement with the reported disease subtypes and the gene expression patterns. This method is available in an R package on CRAN named NB.MClust. CONCLUSION:Use of Negative Binomial model based clustering is advisable when clustering over dispersed RNA-seq count data.
| S-EPMC6292049 | biostudies-literature
Project description:Human brains perform tasks via complex functional networks consisting of separated brain regions. A popular approach to characterize brain functional networks in fMRI studies is independent component analysis (ICA), which is a powerful method to reconstruct latent source signals from their linear mixtures. In many fMRI studies, an important goal is to investigate how brain functional networks change according to specific clinical and demographic variabilities. Existing ICA methods, however, cannot directly incorporate covariate effects in ICA decomposition. Heuristic post-ICA analysis to address this need can be inaccurate and inefficient. In this paper, we propose a hierarchical covariate-adjusted ICA (hc-ICA) model that provides a formal statistical framework for estimating covariate effects and testing differences between brain functional networks. Our method provides a more reliable and powerful statistical tool for evaluating group differences in brain functional networks while appropriately controlling for potential confounding factors. We present an analytically tractable EM algorithm to obtain maximum likelihood estimates of our model. We also develop a subspace-based approximate EM that runs significantly faster while retaining high accuracy. To test the differences in functional networks, we introduce a voxel-wise approximate inference procedure which eliminates the need of computationally expensive covariance matrix estimation and inversion. We demonstrate the advantages of our methods over the existing method via simulation studies. We apply our method to an fMRI study to investigate differences in brain functional networks associated with post-traumatic stress disorder (PTSD).
| S-EPMC5375118 | biostudies-literature
Project description:Emerging large-scale biobanks pairing genotype data with phenotype data present new opportunities to prioritize shared genetic associations across multiple phenotypes for molecular validation. Past research, by our group and others, has shown gene-level tests of association produce biologically interpretable characterization of the genetic architecture of a given phenotype. Here, we present a new method, Ward clustering to identify Internal Node branch length outliers using Gene Scores (WINGS), for identifying shared genetic architecture among multiple phenotypes. The objective of WINGS is to identify groups of phenotypes, or "clusters," sharing a core set of genes enriched for mutations in cases. We validate WINGS using extensive simulation studies and then combine gene-level association tests with WINGS to identify shared genetic architecture among 81 case-control and seven quantitative phenotypes in 349,468 European-ancestry individuals from the UK Biobank. We identify eight prioritized phenotype clusters and recover multiple published gene-level associations within prioritized clusters.
| S-EPMC7268989 | biostudies-literature
Project description:In this study we illustrate how the functional networks involved in a single task (e.g. the sensory, cognitive and motor components) can be segregated without cognitive subtractions at the second-level. The method used is based on meaningful variability in the patterns of activation between subjects with the assumption that regions belonging to the same network will have comparable variations from subject to subject. fMRI data were collected from thirty nine healthy volunteers who were asked to indicate with a button press if visually presented words were semantically related or not. Voxels were classified according to the similarity in their patterns of between-subject variance using a second-level unsupervised fuzzy clustering algorithm. The results were compared to those identified by cognitive subtractions of multiple conditions tested in the same set of subjects. This illustrated that the second-level clustering approach (on activation for a single task) was able to identify the functional networks observed using cognitive subtractions (e.g. those associated with vision, semantic associations or motor processing). In addition the fuzzy clustering approach revealed other networks that were not dissociated by the cognitive subtraction approach (e.g. those associated with high- and low-level visual processing and oculomotor movements). We discuss the potential applications of our method which include the identification of "hidden" or unpredicted networks as well as the identification of systems level signatures for different subgroupings of clinical and healthy populations.
| S-EPMC2652023 | biostudies-literature
Project description:To spatially cluster resting state-functional magnetic resonance imaging (rs-fMRI) data into potential networks, there are only a few general approaches that determine the number of networks/clusters, despite a wide variety of techniques proposed for clustering. For individual subjects, extraction of a large number of spatially disjoint clusters results in multiple small networks that are spatio-temporally homogeneous but irreproducible across subjects. Alternatively, extraction of a small number of clusters creates spatially large networks that are temporally heterogeneous but spatially reproducible across subjects. We propose a fully automatic, iterative reclustering framework in which a small number of spatially large, heterogeneous networks are initially extracted to maximize spatial reproducibility. Subsequently, the large networks are iteratively subdivided to create spatially reproducible subnetworks until the overall within-network homogeneity does not increase substantially. The proposed approach discovers a rich network hierarchy in the brain while simultaneously optimizing spatial reproducibility of networks across subjects and individual network homogeneity. We also propose a novel metric to measure the connectivity of brain regions, and in a simulation study show that our connectivity metric and framework perform well in the face of low signal to noise and initial segmentation errors. Experimental results generated using real fMRI data show that the proposed metric improves stability of network clusters across subjects, and generates a meaningful pattern for spatially hierarchical structure of the brain.
| S-EPMC6869720 | biostudies-literature
Project description:This study examines the effects of focused-attention meditation on functional brain states in novice meditators. There are a number of feature metrics for functional brain states, such as functional connectivity, graph theoretical metrics, and amplitude of low frequency fluctuation (ALFF). It is necessary to choose appropriate metrics and also to specify the region of interests (ROIs) from a number of brain regions. Here, we use a Tucker3 clustering method, which simultaneously selects the feature vectors (graph theoretical metrics and fractional ALFF) and the ROIs that can discriminate between resting and meditative states based on the characteristics of the given data. In this study, breath-counting meditation, one of the most popular forms of focused-attention meditation, was used and brain activities during resting and meditation states were measured by functional magnetic resonance imaging. The results indicated that the clustering coefficients of the eight brain regions, Frontal Inf Oper L, Occipital Inf R, ParaHippocampal R, Cerebellum 10 R, Cingulum Mid R, Cerebellum Crus1 L, Occipital Inf L, and Paracentral Lobule R increased through the meditation. Our study also provided the framework of data-driven brain functional analysis and confirmed its effectiveness on analyzing neural basis of focused-attention meditation.
| S-EPMC6990115 | biostudies-literature
Project description:Large brain imaging databases contain a wealth of information on brain organization in the populations they target, and on individual variability. While such databases have been used to study group-level features of populations directly, they are currently underutilized as a resource to inform single-subject analysis. Here, we propose leveraging the information contained in large functional magnetic resonance imaging (fMRI) databases by establishing population priors to employ in an empirical Bayesian framework. We focus on estimation of brain networks as source signals in independent component analysis (ICA). We formulate a hierarchical "template" ICA model where source signals-including known population brain networks and subject-specific signals-are represented as latent variables. For estimation, we derive an expectation maximization (EM) algorithm having an explicit solution. However, as this solution is computationally intractable, we also consider an approximate subspace algorithm and a faster two-stage approach. Through extensive simulation studies, we assess performance of both methods and compare with dual regression, a popular but ad-hoc method. The two proposed algorithms have similar performance, and both dramatically outperform dual regression. We also conduct a reliability study utilizing the Human Connectome Project and find that template ICA achieves substantially better performance than dual regression, achieving 75-250% higher intra-subject reliability.
| S-EPMC7556739 | biostudies-literature