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Many real-world networks contain rich textual information in the edges, such as email networks where an edge between two nodes is an email exchange. Other examples include co-author networks and social media networks. The useful textual information carried in the edges is often discarded in most network analyses, resulting in an incomplete view of the relationships between nodes. In this work, we propose to represent the text document between each pair of nodes as a vector counting the appearances of keywords extracted from the corpus, and introduce a new and flexible preferential latent space network model that can offer direct insights on how contents of the textual exchanges modulate the relationships between nodes. We establish identifiability conditions for the proposed model and tackle model estimation with a computationally efficient projected gradient descent algorithm. We further derive the non-asymptotic error bound of the estimator from each step of the algorithm. The efficacy of our proposed method is demonstrated through simulations and an analysis of the Enron email network., Comment: 30 pages

Dynamic networks have been increasingly used to characterize brain connectivity that varies during resting and task states. In such characterizations, a connectivity network is typically measured at each time point for a subject over a common set of nodes representing brain regions, together with rich subject-level information. A common approach to analyzing such data is an edge-based method that models the connectivity between each pair of nodes separately. However, such approach may have limited performance when the noise level is high and the number of subjects is limited, as it does not take advantage of the inherent network structure. To better understand if and how the subject-level covariates affect the dynamic brain connectivity, we introduce a semi-parametric dynamic network response regression that relates a dynamic brain connectivity network to a vector of subject-level covariates. A key advantage of our method is to exploit the structure of dynamic imaging coefficients in the form of high-order tensors. We develop an efficient estimation algorithm and evaluate the efficacy of our approach through simulation studies. Finally, we present our results on the analysis of a task-related study on social cognition in the Human Connectome Project, where we identify known sex-specific effects on brain connectivity that cannot be inferred using alternative methods.

There is a growing interest in cell-type-specific analysis from bulk samples with a mixture of different cell types. A critical first step in such analyses is the accurate estimation of cell-type proportions in a bulk sample. Although many methods have been proposed recently, quantifying the uncertainties associated with the estimated cell-type proportions has not been well studied. Lack of consideration of these uncertainties can lead to missed or false findings in downstream analyses. In this article, we introduce a flexible statistical deconvolution framework that allows a general and subject-specific covariance of bulk gene expressions. Under this framework, we propose a decorrelated constrained least squares method called DECALS that estimates cell-type proportions as well as the sampling distribution of the estimates. Simulation studies demonstrate that DECALS can accurately quantify the uncertainties in the estimated proportions whereas other methods fail. Applying DECALS to analyze bulk gene expression data of post mortem brain samples from the ROSMAP and GTEx projects, we show that taking into account the uncertainties in the estimated cell-type proportions can lead to more accurate identifications of cell-type-specific differentially expressed genes and transcripts between different subject groups, such as between Alzheimer's disease patients and controls and between males and females.

We consider the problem of jointly modeling and clustering populations of tensors by introducing a high-dimensional tensor mixture model with heterogeneous covariances. To effectively tackle the high dimensionality of tensor objects, we employ plausible dimension reduction assumptions that exploit the intrinsic structures of tensors such as low-rankness in the mean and separability in the covariance. In estimation, we develop an efficient high-dimensional expectation-conditional-maximization (HECM) algorithm that breaks the intractable optimization in the M-step into a sequence of much simpler conditional optimization problems, each of which is convex, admits regularization and has closed-form updating formulas. Our theoretical analysis is challenged by both the non-convexity in the EM-type estimation and having access to only the solutions of conditional maximizations in the M-step, leading to the notion of dual non-convexity. We demonstrate that the proposed HECM algorithm, with an appropriate initialization, converges geometrically to a neighborhood that is within statistical precision of the true parameter. The efficacy of our proposed method is demonstrated through comparative numerical experiments and an application to a medical study, where our proposal achieves an improved clustering accuracy over existing benchmarking methods.

Functional connectivity (FC) has been widely used to study brain network interactions underlying the emerging cognition and behavior of an individual. FC is usually defined as the correlation or partial correlation between brain regions. Although FC is proved to be a good starting point to understand the brain organization, it fails to tell the causal relationship or the direction of interactions. Many directed acyclic graph (DAG) based methods were applied to study the directed interactions using functional magnetic resonance imaging (fMRI) data but the performance was severely limited by the small sample size and high dimensionality, hindering its applications. To overcome the obstacles, we propose a score based joint directed acyclic graph model to estimate the directed FC in fMRI data. Instead of using a combinatorial optimization framework, the structure of DAG is characterized with an algebra equation and further regularized with sparsity and group similarity terms. The simulation results have demonstrated the improved accuracy of the proposed model in detecting causality as compared to other existing methods. In our case-control study of the MIND Clinical Imaging Consortium (MCIC) data, we have successfully identified decreased functional integration, disrupted hub structures and characteristic edges (CtEs) in schizophrenia (SZ) patients. Further comparison between the results from directed FC and undirected FC illustrated the their different emphasis on selected features. We speculate that combining the features from undirected graphical model and directed graphical model might be a promising way to do FC analysis.

Resting-state functional magnetic resonance imaging (rs-fMRI)-derived functional connectivity patterns have been extensively utilized to delineate global functional organization of the human brain in health, development, and neuropsychiatric disorders. In this paper, we investigate how functional connectivity in males and females differs in an age prediction framework. We first estimate functional connectivity between regions-of-interest (ROIs) using distance correlation instead of Pearson's correlation. Distance correlation, as a multivariate statistical method, explores spatial relations of voxel-wise time courses within individual ROIs and measures both linear and nonlinear dependence, capturing more complex information of between-ROI interactions. Then, a novel non-convex multi-task learning (NC-MTL) model is proposed to study age-related gender differences in functional connectivity, where age prediction for each gender group is viewed as one task. Specifically, in the proposed NC-MTL model, we introduce a composite regularizer with a combination of non-convex $\ell_{2,1-2}$ and $\ell_{1-2}$ regularization terms for selecting both common and task-specific features. Finally, we validate the proposed NC-MTL model along with distance correlation based functional connectivity on rs-fMRI of the Philadelphia Neurodevelopmental Cohort for predicting ages of both genders. The experimental results demonstrate that the proposed NC-MTL model outperforms other competing MTL models in age prediction, as well as characterizing developmental gender differences in functional connectivity patterns.

The dynamic characteristics of functional network connectivity have been widely acknowledged and studied. Both shared and unique information has been shown to be present in the connectomes. However, very little has been known about whether and how this common pattern can predict the individual variability of the brain, i.e. "brain fingerprinting", which attempts to reliably identify a particular individual from a pool of subjects. In this paper, we propose to enhance the individual uniqueness based on an autoencoder network. More specifically, we rely on the hypothesis that the common neural activities shared across individuals may lessen individual discrimination. By reducing contributions from shared activities, inter-subject variability can be enhanced. Results show that that refined connectomes utilizing an autoencoder with sparse dictionary learning can successfully distinguish one individual from the remaining participants with reasonably high accuracy (up to 99:5% for the rest-rest pair). Furthermore, high-level cognitive behavior (e.g., fluid intelligence, executive function, and language comprehension) can also be better predicted using refined functional connectivity profiles. As expected, the high-order association cortices contributed more to both individual discrimination and behavior prediction. The proposed approach provides a promising way to enhance and leverage the individualized characteristics of brain networks.

Emotion perception is essential to affective and cognitive development which involves distributed brain circuits. The ability of emotion identification begins in infancy and continues to develop throughout childhood and adolescence. Understanding the development of brain's emotion circuitry may help us explain the emotional changes observed during adolescence. Our previous study delineated the trajectory of brain functional connectivity (FC) from late childhood to early adulthood during emotion identification tasks. In this work, we endeavour to deepen our understanding from association to causation. We proposed a Bayesian incorporated linear non-Gaussian acyclic model (BiLiNGAM), which incorporated our previous association model into the prior estimation pipeline. In particular, it can jointly estimate multiple directed acyclic graphs (DAGs) for multiple age groups at different developmental stages. Simulation results indicated more stable and accurate performance over various settings, especially when the sample size was small (high-dimensional cases). We then applied to the analysis of real data from the Philadelphia Neurodevelopmental Cohort (PNC). This included 855 individuals aged 8-22 years who were divided into five different adolescent stages. Our network analysis revealed the development of emotion-related intra- and inter- modular connectivity and pinpointed several emotion-related hubs. We further categorized the hubs into two types: in-hubs and out-hubs, as the center of receiving and distributing information. Several unique developmental hub structures and group-specific patterns were also discovered. Our findings help provide a causal understanding of emotion development in the human brain.

Functional connectivity (FC) has become a primary means of understanding brain functions by identifying brain network interactions and, ultimately, how those interactions produce cognitions. A popular definition of FC is by statistical associations between measured brain regions. However, this could be problematic since the associations can only provide spatial connections but not causal interactions among regions of interests. Hence, it is necessary to study their causal relationship. Directed acyclic graph (DAG) models have been applied in recent FC studies but often encountered problems such as limited sample sizes and large number of variables (namely high-dimensional problems), which lead to both computational difficulty and convergence issues. As a result, the use of DAG models is problematic, where the identification of DAG models in general is nondeterministic polynomial time hard (NP-hard). To this end, we propose a $\psi$-learning incorporated linear non-Gaussian acyclic model ($\psi$-LiNGAM). We use the association model ($\psi$-learning) to facilitate causal inferences and the model works well especially for high-dimensional cases. Our simulation results demonstrate that the proposed method is more robust and accurate than several existing ones in detecting graph structure and direction. We then applied it to the resting state fMRI (rsfMRI) data obtained from the publicly available Philadelphia Neurodevelopmental Cohort (PNC) to study the cognitive variance, which includes 855 individuals aged 8-22 years. Therein, we have identified three types of hub structure: the in-hub, out-hub and sum-hub, which correspond to the centers of receiving, sending and relaying information, respectively. We also detected 16 most important pairs of causal flows. Several of the results have been verified to be biologically significant.

Multimodal fusion benefits disease diagnosis by providing a more comprehensive perspective. Developing algorithms is challenging due to data heterogeneity and the complex within- and between-modality associations. Deep-network-based data-fusion models have been developed to capture the complex associations and the performance in diagnosis has been improved accordingly. Moving beyond diagnosis prediction, evaluation of disease mechanisms is critically important for biomedical research. Deep-network-based data-fusion models, however, are difficult to interpret, bringing about difficulties for studying biological mechanisms. In this work, we develop an interpretable multimodal fusion model, namely gCAM-CCL, which can perform automated diagnosis and result interpretation simultaneously. The gCAM-CCL model can generate interpretable activation maps, which quantify pixel-level contributions of the input features. This is achieved by combining intermediate feature maps using gradient-based weights. Moreover, the estimated activation maps are class-specific, and the captured cross-data associations are interest/label related, which further facilitates class-specific analysis and biological mechanism analysis. We validate the gCAM-CCL model on a brain imaging-genetic study, and show gCAM-CCL's performed well for both classification and mechanism analysis. Mechanism analysis suggests that during task-fMRI scans, several object recognition related regions of interests (ROIs) are first activated and then several downstream encoding ROIs get involved. Results also suggest that the higher cognition performing group may have stronger neurotransmission signaling while the lower cognition performing group may have problem in brain/neuron development, resulting from genetic variations.

Learning the latent network structure from large scale multivariate point process data is an important task in a wide range of scientific and business applications. For instance, we might wish to estimate the neuronal functional connectivity network based on spiking times recorded from a collection of neurons. To characterize the complex processes underlying the observed data, we propose a new and flexible class of nonstationary Hawkes processes that allow both excitatory and inhibitory effects. We estimate the latent network structure using an efficient sparse least squares estimation approach. Using a thinning representation, we establish concentration inequalities for the first and second order statistics of the proposed Hawkes process. Such theoretical results enable us to establish the non-asymptotic error bound and the selection consistency of the estimated parameters. Furthermore, we describe a least squares loss based statistic for testing if the background intensity is constant in time. We demonstrate the efficacy of our proposed method through simulation studies and an application to a neuron spike train data set.

Modeling event patterns is a central task in a wide range of disciplines. In applications such as studying human activity patterns, events often arrive clustered with sporadic and long periods of inactivity. Such heterogeneity in event patterns poses challenges for existing point process models. In this article, we propose a new class of clustered point processes that alternate between active and inactive states. The proposed model is flexible, highly interpretable, and can provide useful insights into event patterns. A composite likelihood approach and a composite EM estimation procedure are developed for efficient and numerically stable parameter estimation. We study both the computational and statistical properties of the estimator including convergence, consistency, and asymptotic normality. The proposed method is applied to Donald Trump's Twitter data to investigate if and how his behaviors evolved before, during, and after the presidential campaign. Additionally, we analyze large-scale social media data from Sina Weibo and identify interesting groups of users with distinct behaviors.