Hierarchical network analysis of co-occurring bioentities in literature.

Biomedical databases grow by more than a thousand new publications every day. The large volume of biomedical literature that is being published at an unprecedented rate hinders the discovery of relevant knowledge from keywords of interest to gather new insights and form hypotheses. A text-mining tool, PubTator, helps to automatically annotate bioentities, such as species, chemicals, genes, and diseases, from PubMed abstracts and full-text articles. However, the manual re-organization and analysis of bioentities is a non-trivial and highly time-consuming task. ChexMix was designed to extract the unique identifiers of bioentities from query results. Herein, ChexMix was used to construct a taxonomic tree with allied species among Korean native plants and to extract the medical subject headings unique identifier of the bioentities, which co-occurred with the keywords in the same literature. ChexMix discovered the allied species related to a keyword of interest and experimentally proved its usefulness for multi-species analysis.

Cluster Analysis of Medicinal Plants and Targets Based on Multipartite Network.

Network-based methods for the analysis of drug-target interactions have gained attention and rely on the paradigm that a single drug can act on multiple targets rather than a single target. In this study, we have presented a novel approach to analyze the interactions between the chemicals in the medicinal plants and multiple targets based on the complex multipartite network of the medicinal plants, multi-chemicals, and multiple targets. The multipartite network was constructed via the conjunction of two relationships: chemicals in plants and the biological actions of those chemicals on the targets. In doing so, we introduced an index of the efficacy of chemicals in a plant on a protein target of interest, called target potency score (TPS). We showed that the analysis can identify specific chemical profiles from each group of plants, which can then be employed for discovering new alternative therapeutic agents. Furthermore, specific clusters of plants and chemicals acting on specific targets were retrieved using TPS that suggested potential drug candidates with high probability of clinical success. We expect that this approach may open a way to predict the biological functions of multi-chemicals and multi-plants on the targets of interest and enable repositioning of the plants and chemicals.

Dynamic functional connectivity analysis based on time-varying partial correlation with a copula-DCC-GARCH model.

We suggest a time-varying partial correlation as a statistical measure of dynamic functional connectivity (dFC) in the human brain. Traditional statistical models often assume specific distributions on the measured data such as the Gaussian distribution, which prohibits their application to neuroimaging data analysis. First, we use the copula-based dynamic conditional correlation (DCC), which does not rely on a specific distribution assumption, for estimating time-varying correlation between regions-of-interest (ROIs) of the human brain. Then, we suggest a time-varying partial correlation based on the Gaussian copula-DCC-GARCH model as an effective method for measuring dFC in the human brain. A recursive algorithm is explained for computation of the time-varying partial correlation. Numerical simulation results demonstrate effectiveness of the partial correlation-based methods against pairwise correlation-based methods. In addition, a two-step procedure is described for the inference of sparse dFC structure using functional magnetic resonance imaging (fMRI) data. We illustrate the proposed method by analyzing an fMRI data set of human participants watching a Pixar animated movie. Based on twelve a priori selected brain regions in the cortex, we demonstrate that the proposed method is effective for inferring sparse dFC network structures and robust to noise distribution and a preprocessing step of fMRI data.

Dynamic functional connectivity analysis of functional MRI based on copula time-varying correlation.

BACKGROUND: Recent studies showed that functional connectivity (FC) in the human brain is not static but can dynamically change across time within time scales of seconds to minutes. NEW METHOD: This study introduces a new statistical method called the copula time-varying correlation for dynamic functional connectivity (dFC) analysis from functional magnetic resonance imaging (fMRI) data. RESULTS: Compared to other state-of-the-art statistical measures of dynamic correlation such as the dynamic conditional correlation (DCC), the proposed method can be effectively applied to data having asymmetric or non-normal distributions. COMPARISON WITH EXISTING METHODS: Numerical simulations were conducted under various kinds of time-varying correlations and distributions, and it was demonstrated that the proposed method was superior to the DCC-based method for asymmetric and non-normal distributions. CONCLUSIONS: FMRI data of 138 human participants watching a Pixar animated movie were analyzed by the proposed method based on five a priori selected brain regions in the cortex. Based on statistical group analysis results, it was discovered that (1) the correlation between the left temporoparietal junction (LTPJ) and the primary visual cortex (V1) and the correlation between the dorsal posterior cingulate cortex (dPCC) and V1 were significantly higher for older age groups (5yo-Adult) more often than for younger age groups (3yo-4yo), and (2) the right temporoparietal junction (RTPJ), LTPJ, and dPCC were significantly correlated in all age groups at most of the scanning time periods.

Directional dependence between major cities in China based on copula regression on air pollution measurements.

Air pollution is well-known as a major risk to public health, causing various diseases including pulmonary and cardiovascular diseases. As social concern increases, the amount of air pollution data is increasing rapidly. The purpose of this study is to statistically characterize dependence between major cities in China based on a measure of directional dependence estimated from PM2.5 measurements. As a measure of the directional dependence, we propose the so-called copula directional dependence (CDD) using beta regression models. An advantage of the CDD is that it does not rely on strict assumptions of specific probability distributions or linearity. We used hourly PM2.5 measurement data collected at four major cities in China: Beijing, Chengdu, Guangzhou, and Shanghai, from 2013 to 2017. After accounting for autocorrelation in the PM2.5 time series via nonlinear autoregressive models, CDDs between the four cities were estimated to produce directed network structures of statistical dependence. In addition, a statistical method was proposed to test the directionality of dependence between each pair of cities. From the PM2.5 data, we could discover that Chengdu and Guangzhou are the most closely related cities and that the directionality between them has changed once during 2013 to 2017, which implies a major economic or environmental change in these Chinese regions.

Copula directional dependence for inference and statistical analysis of whole-brain connectivity from fMRI data.

INTRODUCTION: Inferring connectivity between brain regions has been raising a lot of attention in recent decades. Copula directional dependence (CDD) is a statistical measure of directed connectivity, which does not require strict assumptions on probability distributions and linearity. METHODS: In this work, CDDs between pairs of local brain areas were estimated based on the fMRI responses of human participants watching a Pixar animation movie. A directed connectivity map of fourteen predefined local areas was obtained for each participant, where the network structure was determined by the strengths of the CDDs. A resampling technique was further applied to determine the statistical significance of the connectivity directions in the networks. In order to demonstrate the effectiveness of the suggested method using CDDs, statistical group analysis was conducted based on graph theoretic measures of the inferred directed networks and CDD intensities. When the 129 fMRI participants were grouped by their age (3-5 year-old, 7-12 year-old, adult) and gender (F, M), nonparametric two-way analysis of variance (ANOVA) results could identify which cortical regions and connectivity structures correlated with the two physiological factors. RESULTS: Especially, we could identify that (a) graph centrality measures of the frontal eye fields (FEF), the inferior temporal gyrus (ITG), and the temporopolar area (TP) were significantly affected by aging, (b) CDD intensities between FEF and the primary motor cortex (M1) and between ITG and TP were highly significantly affected by aging, and (c) CDDs between M1 and the anterior prefrontal cortex (aPFC) were highly significantly affected by gender. SOFTWARE: The R source code for fMRI data preprocessing, estimation of directional dependences, network visualization, and statistical analyses are available at https://github.com/namgillee/CDDforFMRI.

An improvement on local FDR analysis applied to functional MRI data.

BACKGROUND: Discovering effective connectivity between brain regions gained a lot of attention recently. A vector autoregressive model is a simple and flexible approach for exploratory structural modeling where the involvement of a large number of brain regions is crucial to avoid confounding. The non-zero coefficients of the VAR model are interpreted as actual effective connectivity between brain regions. Thus methods for a higher correct discovery rate are crucial for neuroscience. NEW METHOD: We propose an improved version of the FDR analysis procedure which would be more suitable to fMRI data. The estimates of the VAR coefficients are often not symmetric about 0 with non-zero modes. In this case, we suggest to estimate the null distribution of the estimates which is assumed symmetric about 0 in two steps: use one side of the estimates and then both sides under some condition. RESULTS: A theoretical argument is provided for the proposed procedure with a theorem and two types of experiments are made. In a simulation experiment, we show via ROC curves improvement over previous methods. We apply the proposed method to analyze real fMRI data with results interpreted in the language of cognitive neuroscience. COMPARISON WITH EXISTING METHOD(S): The proposed method outperforms the standard method in the simulation experiment with a VAR model of dimension up to 100 over a wide range of sample sizes. The improvement is made in the context of the true positive rate and performance consistency. CONCLUSIONS: The proposed method is more appropriate for analyzing fMRI data with VAR models when the estimates of the VAR coefficients are not symmetric about 0 and have non-zero modes.