Dataset Information

Bayesian modeling of dependence in brain connectivity data.

ABSTRACT: Brain connectivity studies often refer to brain areas as graph nodes and connections between nodes as edges, and aim to identify neuropsychiatric phenotype-related connectivity patterns. When performing group-level brain connectivity alternation analyses, it is critical to model the dependence structure between multivariate connectivity edges to achieve accurate and efficient estimates of model parameters. However, specifying and estimating dependencies between connectivity edges presents formidable challenges because (i) the dimensionality of parameters in the covariance matrix is high (of the order of the fourth power of the number of nodes); (ii) the covariance between a pair of edges involves four nodes with spatial location information; and (iii) the dependence structure between edges can be related to unknown network topological structures. Existing methods for large covariance/precision matrix regularization and spatial closeness-based dependence structure specification/estimation models may not fully address the complexity and challenges. We develop a new Bayesian nonparametric model that unifies information from brain network areas (nodes), connectivity (edges), and covariance between edges by constructing the function of covariance matrix based on the underlying network topological structure. We perform parameter estimation using an efficient Markov chain Monte Carlo algorithm. We apply our method to resting-state functional magnetic resonance imaging data from 60 subjects of a schizophrenia study and simulated data to demonstrate the performance of our method.

SUBMITTER: Chen S

PROVIDER: S-EPMC7868047 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Bayesian modeling of dependence in brain connectivity data.

Chen Shuo S Xing Yishi Y Kang Jian J Kochunov Peter P Hong L Elliot LE

Biostatistics (Oxford, England) 20200401 2

Brain connectivity studies often refer to brain areas as graph nodes and connections between nodes as edges, and aim to identify neuropsychiatric phenotype-related connectivity patterns. When performing group-level brain connectivity alternation analyses, it is critical to model the dependence structure between multivariate connectivity edges to achieve accurate and efficient estimates of model parameters. However, specifying and estimating dependencies between connectivity edges presents formid ...[more]

PMID: 30203093

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Project description:BackgroundStable Isotope Resolved Metabolomics (SIRM) is a new biological approach that uses stable isotope tracers such as uniformly [Formula: see text]-enriched glucose ([Formula: see text]-Glc) to trace metabolic pathways or networks at the atomic level in complex biological systems. Non-steady-state kinetic modeling based on SIRM data uses sets of simultaneous ordinary differential equations (ODEs) to quantitatively characterize the dynamic behavior of metabolic networks. It has been increasingly used to understand the regulation of normal metabolism and dysregulation in the development of diseases. However, fitting a kinetic model is challenging because there are usually multiple sets of parameter values that fit the data equally well, especially for large-scale kinetic models. In addition, there is a lack of statistically rigorous methods to compare kinetic model parameters between different experimental groups.ResultsWe propose a new Bayesian statistical framework to enhance parameter estimation and hypothesis testing for non-steady-state kinetic modeling of SIRM data. For estimating kinetic model parameters, we leverage the prior distribution not only to allow incorporation of experts' knowledge but also to provide robust parameter estimation. We also introduce a shrinkage approach for borrowing information across the ensemble of metabolites to stably estimate the variance of an individual isotopomer. In addition, we use a component-wise adaptive Metropolis algorithm with delayed rejection to perform efficient Monte Carlo sampling of the posterior distribution over high-dimensional parameter space. For comparing kinetic model parameters between experimental groups, we propose a new reparameterization method that converts the complex hypothesis testing problem into a more tractable parameter estimation problem. We also propose an inference procedure based on credible interval and credible value. Our method is freely available for academic use at https://github.com/xuzhang0131/MCMCFlux .ConclusionsOur new Bayesian framework provides robust estimation of kinetic model parameters and enables rigorous comparison of model parameters between experimental groups. Simulation studies and application to a lung cancer study demonstrate that our framework performs well for non-steady-state kinetic modeling of SIRM data.

Dataset Information

Bayesian modeling of dependence in brain connectivity data.

Publications

Bayesian modeling of dependence in brain connectivity data.

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