Human brain is a complex system composed of many components that interact with each other. A well-designed computational model, usually in the format of partial differential equations (PDEs), is vital to understand the working mechanisms that can explain dynamic and self-organized behaviors. However, the model formulation and parameters are often tuned empirically based on the predefined domain-specific knowledge, which lags behind the emerging paradigm of discovering novel mechanisms from the unprecedented amount of spatiotemporal data. To address this limitation, we sought to link the power of deep neural networks and physics principles of complex systems, which allows us to design explainable deep models for uncovering the mechanistic role of how human brain (the most sophisticated complex system) maintains controllable functions while interacting with external stimulations. In the spirit of optimal control, we present a unified framework to design an explainable deep model that describes the dynamic behaviors of underlying neurobiological processes, allowing us to understand the latent control mechanism at a system level. We have uncovered the pathophysiological mechanism of Alzheimer's disease to the extent of controllability of disease progression, where the dissected system-level understanding enables higher prediction accuracy for disease progression and better explainability for disease etiology than conventional (black box) deep models.

Graphs are ubiquitous in various domains, such as social networks and biological systems. Despite the great successes of graph neural networks (GNNs) in modeling and analyzing complex graph data, the inductive bias of locality assumption, which involves exchanging information only within neighboring connected nodes, restricts GNNs in capturing long-range dependencies and global patterns in graphs. Inspired by the classic Brachistochrone problem, we seek how to devise a new inductive bias for cutting-edge graph application and present a general framework through the lens of variational analysis. The backbone of our framework is a two-way mapping between the discrete GNN model and continuous diffusion functional, which allows us to design application-specific objective function in the continuous domain and engineer discrete deep model with mathematical guarantees. First, we address over-smoothing in current GNNs. Specifically, our inference reveals that the existing layer-by-layer models of graph embedding learning are equivalent to a ${\ell _2}$-norm integral functional of graph gradients, which is the underlying cause of the over-smoothing problem. Similar to edge-preserving filters in image denoising, we introduce the total variation (TV) to promote alignment of the graph diffusion pattern with the global information present in community topologies. On top of this, we devise a new selective mechanism for inductive bias that can be easily integrated into existing GNNs and effectively address the trade-off between model depth and over-smoothing. Second, we devise a novel generative adversarial network (GAN) to predict the spreading flows in the graph through a neural transport equation. To avoid the potential issue of vanishing flows, we tailor the objective function to minimize the transportation within each community while maximizing the inter-community flows. Our new GNN models achieve state-of-the-art (SOTA) performance on graph learning benchmarks such as Cora, Citeseer, and Pubmed.

Human brain is a complex yet economically organized system, where a small portion of critical hub regions support the majority of brain functions. The identification of common hub nodes in a population of networks is often simplified as a voting procedure on the set of identified hub nodes across individual brain networks, which ignores the intrinsic data geometry and partially lacks the reproducible findings in neuroscience. Hence, we propose a first-ever group-wise hub identification method to identify hub nodes that are common across a population of individual brain networks. Specifically, the backbone of our method is to learn common graph embedding that can represent the majority of local topological profiles. By requiring orthogonality among the graph embedding vectors, each graph embedding as a data element is residing on the Grassmannian manifold. We present a novel Grassmannian manifold optimization scheme that allows us to find the common graph embeddings, which not only identify the most reliable hub nodes in each network but also yield a population-based common hub node map. Results of the accuracy and replicability on both synthetic and real network data show that the proposed manifold learning approach outperforms all hub identification methods employed in this evaluation.

BACKGROUND: Recent advances in tissue clearing techniques, combined with high-speed image acquisition through light sheet microscopy, enable rapid three-dimensional (3D) imaging of biological specimens, such as whole mouse brains, in a matter of hours. Quantitative analysis of such 3D images can help us understand how changes in brain structure lead to differences in behavior or cognition, but distinguishing densely packed features of interest, such as nuclei, from background can be challenging. Recent deep learning-based nuclear segmentation algorithms show great promise for automated segmentation, but require large numbers of accurate manually labeled nuclei as training data. RESULTS: We present Segmentor, an open-source tool for reliable, efficient, and user-friendly manual annotation and refinement of objects (e.g., nuclei) within 3D light sheet microscopy images. Segmentor employs a hybrid 2D-3D approach for visualizing and segmenting objects and contains features for automatic region splitting, designed specifically for streamlining the process of 3D segmentation of nuclei. We show that editing simultaneously in 2D and 3D using Segmentor significantly decreases time spent on manual annotations without affecting accuracy as compared to editing the same set of images with only 2D capabilities. CONCLUSIONS: Segmentor is a tool for increased efficiency of manual annotation and refinement of 3D objects that can be used to train deep learning segmentation algorithms, and is available at https://www.nucleininja.org/ and https://github.com/RENCI/Segmentor .

With the popularity of multimedia applications and social networks, various multimedia data (i.e., texts, images, and videos) on the internet have shown exponential growth [1, 5, 6]. By regarding the storage cost and the computation efficiency, it is becoming more and more popular for data owners to employ cloud services [2, 3]. However, the data owners afraid of cloud services to reveal their private information, such as location and financial status. Moreover, the data analysis (such as feature extraction, retrieval, model construction, etc.) may easily leak important private information [4, 7]. For example, recent study in machine learning have demonstrated that sensitive data can be recovered from models. In this case, both cybersecurity and knowledge discovery are extremely important for analyzing big data. This special issue collects some recent studies on current machine learning techniques as well as privacy-preserving data analysis. In [9], Wen et al. proposed a new clustering method considering both the local structure and the global structure for conducting nonlinear clustering. Specifically, the proposed method learns a robust spectral representation of the original data in the kernel space, and then introduces both the technique of feature selection and the method of adaptive graph learning into the proposed model. Furthermore, the proposed model utilizes low-rank constraint to make the adaptive graph to achieve the purpose of one-step clustering.

Hyper-graph techniques have been widely investigated in computer vision and medical imaging applications, showing superior performance for modeling complex subject-wise relationships and sufficient flexibility to deal with missing data from multi-modal neuroimaging data. Existing hyper-graph methods, however, are inadequate for two reasons. First, representations are generated only from the observed imaging data, a process that is completely independent of the subsequent data label inference/ classification step. Thus, hyper-graph results constructed in this way may not be consistent with phenotype data such as clinical labels or scores. More critically, it might generate sub-optimal predictions in relation to clinical labels/scores. Second, current hyper-graph inference methods rely on two sequential steps: 1) building the hyper-graph for each individual modality and then predicted latent labels for new subjects upon each constructed hyper-graph and 2) a voting procedure to incorporate inference results across different hyper-graphs. This approach, however, is limited by failing to consider the complex and complementary relationships of multi-modal imaging data with respect to hyper-graph inference procedure. To address these two issues, we propose a novel dynamic hyper-graph inference method supported by a semi-supervised framework. Our method iteratively estimates and adjusts the hyper-graph structures from multi-modal imaging data until consistency between the learned hyper-graph and the observed clinical labels and scores is achieved. This hyper-graph inference framework also eases the integration process of classification (identifying individuals having neurodegenerative disease) and regression (predicting the clinical scores) within the same framework. The experimental results on identifying mild cognition impairment (MCI) subjects and the fine grained recognition of MCI progression stages show improved performance using our proposed hyper-graph inference method compared with conventional methods.

In this paper, we propose a general framework for performance improvement of the current state-of-the-art registration algorithms in terms of both accuracy and computation time. The key concept involves rapid prediction of a deformation field for registration initialization, which is achieved by a statistical correlation model learned between image appearances and deformation fields. This allows us to immediately bring a template image as close as possible to a subject image that we need to register. The task of the registration algorithm is hence reduced to estimating small deformation between the subject image and the initially warped template image, i.e., the intermediate template (IT). Specifically, to obtain a good subject-specific initial deformation, support vector regression is utilized to determine the correlation between image appearances and their respective deformation fields. When registering a new subject onto the template, an initial deformation field is first predicted based on the subject's image appearance for generating an IT. With the IT, only the residual deformation needs to be estimated, presenting much less challenge to the existing registration algorithms. Our learning-based framework affords two important advantages: 1) by requiring only the estimation of the residual deformation between the IT and the subject image, the computation time can be greatly reduced; 2) by leveraging good deformation initialization, local minima giving suboptimal solution could be avoided. Our framework has been extensively evaluated using medical images from different sources, and the results indicate that, on top of accuracy improvement, significant registration speedup can be achieved, as compared with the case where no prediction of initial deformation is performed.