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Nonnegative matrix factorization (NMF) provides a lower rank approximation of a matrix by a product of two nonnegative factors. NMF has been shown to produce clustering results that are often superior to those by other methods such as K-means. In this paper, we provide further interpretation of NMF as a clustering method and study an extended formulation for graph clustering called Symmetric NMF (SymNMF). In contrast to NMF that takes a data matrix as an input, SymNMF takes a nonnegative similarity matrix as an input, and a symmetric nonnegative lower rank approximation is computed. We show that SymNMF is related to spectral clustering, justify SymNMF as a general graph clustering method, and discuss the strengths and shortcomings of SymNMF and spectral clustering. We propose two optimization algorithms for SymNMF and discuss their convergence properties and computational efficiencies. Our experiments on document clustering, image clustering, and image segmentation support SymNMF as a graph clustering method that captures latent linear and nonlinear relationships in the data.

Here, we introduce the 3D Genome Browser, http://3dgenome.org , which allows users to conveniently explore both their own and over 300 publicly available chromatin interaction data of different types. We design a new binary data format for Hi-C data that reduces the file size by at least a magnitude and allows users to visualize chromatin interactions over millions of base pairs within seconds. Our browser provides multiple methods linking distal cis -regulatory elements with their potential target genes. Users can seamlessly integrate thousands of other omics data to gain a comprehensive view of both regulatory landscape and 3D genome structure.

Single cell ATAC-seq (scATAC-seq) experimental designs have become increasingly complex, with multiple factors that might affect chromatin accessibility, including genotype, cell type, tissue of origin, sample location, batch, etc., whose compound effects are difficult to test by existing methods. In addition, current scATAC-seq data present statistical difficulties due to their sparsity and variations in individual sequence capture. To address these problems, we present a zero-adjusted statistical model, Probability model of Accessible Chromatin of Single cells (PACS), that allows complex hypothesis testing of accessibility-modulating factors while accounting for sparse and incomplete data. For differential accessibility analysis, PACS controls the false positive rate and achieves a 17% to 122% higher power on average than existing tools. We demonstrate the effectiveness of PACS through several analysis tasks, including supervised cell type annotation, compound hypothesis testing, batch effect correction, and spatiotemporal modeling. We apply PACS to datasets from various tissues and show its ability to reveal previously undiscovered insights in scATAC-seq data. scATAC-seq data pose statistical challenges due to sparsity and cell-specific sequence capture. Here, the authors present PACS, a zero-adjusted statistical model that enables complex hypothesis testing of accessibility-modulating factors while addressing sparse and incomplete data.

Amid growing demands for heritage conservation and precision urban governance, this study proposes a multimodal framework to analyze tourist perception and behavior in Macau’s Historic Centre. We integrate geotagged social media images and text, ultra-wideband (UWB) pedestrian trajectories, and a LiDAR-derived 3D digital twin to examine the interplay among spatial configuration, movement, and affect. Visual content in tourist photos is classified with You Only Look Once (YOLOv8), and sentiment polarity in Weibo posts is estimated with a fine-tuned Bidirectional Encoder Representations from Transformers (BERT) model. UWB data provide fine-grained trajectories, and all modalities are georeferenced within the digital twin. Results indicate that iconic landmarks concentrate visual attention, pedestrian density, and positive sentiment, whereas peripheral sites show lower footfall yet strong emotional resonance. We further identify three coupling typologies that differentiate tourist experiences across spatial contexts. The study advances multimodal research on historic urban centers by delivering a reproducible framework that aligns image, text, and trajectory data to extract microscale patterns. Theoretically, it elucidates how spatial configuration, movement intensity, and affective expression co-produce experiential quality. Using Macau’s Historic Centre as an empirical testbed, the findings inform heritage revitalization, wayfinding, and crowd-management strategies.

Carbonate strata are widely distributed in China, which can be found in more than 30 provinces and cities, covering about 1/3 of the country’s territorial area. Affected by different geological and climatic conditions, carbonate strata in China geographically present different karst landscapes and groundwater resources. Specifically, northern China is dominated by large karst springs, while southern China is characterized by underground rivers. By determining the distribution range of carbonate strata in China, this paper pointed out the locations of large karst springs in the north and underground rivers in the south, analyzed the distribution characteristics of carbonate rocks in the north and south, the degree of karst development as well as their geological and climate genesis, and discussed the differences between karsts in northern and southern China in terms of occurrence forms of karst water and groundwater systems.

In view of the realistic environment of the cold chain logistics development in Guangzhou, this paper aims at analyzing the present pre-cooling equipment of the cold chain logistics in Guangzhou, the lack of cold storage facilities, the incomplete cold chain structure, the lagging of the development of the third-party cold chain logistics industry, the lack of trace ability of the products, the information tracking mechanism and the deficiency of the standard specifications of the cold chain, the shortage of cold chain professionals etc., and the countermeasures are put forward from three aspects: strengthening the policy support for the overall planning of the cold chain logistics; strengthening the construction and improvement of the cold chain logistics system and the platform and the main body; and developing the Guangzhou cold chain logistics industry in various modes.

Background Computational variant effect predictors offer a scalable and increasingly reliable means of interpreting human genetic variation, but concerns of circularity and bias have limited previous methods for evaluating and comparing predictors. Population-level cohorts of genotyped and phenotyped participants that have not been used in predictor training can facilitate an unbiased benchmarking of available methods. Using a curated set of human gene-trait associations with a reported rare-variant burden association, we evaluate the correlations of 24 computational variant effect predictors with associated human traits in the UK Biobank and All of Us cohorts. Results AlphaMissense outperformed all other predictors in inferring human traits based on rare missense variants in UK Biobank and All of Us participants. The overall rankings of computational variant effect predictors in these two cohorts showed a significant positive correlation. Conclusion We describe a method to assess computational variant effect predictors that sidesteps the limitations of previous evaluations. This approach is generalizable to future predictors and could continue to inform predictor choice for personal and clinical genetics.

Urban waterfront renewal, especially public space improvement, is important for regaining waterfront space vitality. However, existing studies constrained by sparse and hard-to-access data are hard to explore how changes in spatial elements during waterfront renewal would affect space vitality. Waterfront space vitality comprises social vitality represented by public behaviors and economic vitality represented by urban functional facilities. Taking the Maozhou River renewal project in China as an example, we collect spatial elements and vitality on corresponding periods in 2018 and 2020 (before and after the renewal construction) and use multiple linear regression models to assess the relationships. We find that the functional diversity (e.g., commercial and cultural facilities) and design quality (e.g., path density and the shoreline’s proximity to the water) are the two most influential spatial elements affecting space vitality during waterfront renewal. Overall, the use of two-time datasets has generated strong evidence for measuring waterfront revitalization.

NADPH oxidase 2 (NOX2) is a major subtype of NOX and is responsible for the generation of reactive oxygen species (ROS) in brain tissues. MicroRNAs (miRNAs/miRs) are important epigenetic regulators of NOX2. The present study aimed to identify the role of NOX2 miRNA-targets in ischemic stroke (IS). A rat cerebral ischemia/reperfusion (CI/R) injury model and a SH-SY5Y cell hypoxia/reoxygenation (H/R) model were used to simulate IS. Gene expression levels, ROS production and apoptosis in tissue or cells were determined, and bioinformatic analysis was conducted for target prediction of miRNA. In vitro experiments, including function-gain and luciferase activity assays, were also performed to assess the roles of miRNAs. The results indicated that NOX2 was significantly increased in brain tissues subjected to I/R and in SH-SY5Y cells subjected to H/R, while the expression of miR-532-3p (putative target of NOX2) was significantly decreased in brain tissues and plasma. Overexpression of miR-532-3p significantly suppressed NOX2 expression and ROS generation in SH-SY5Y cells subjected to H/R, as well as reduced the relative luciferase activity of cells transfected with a reporter gene plasmid. Collectively, these data indicated that miR-532-3p may be a target of NOX2 and a biomarker for CI/R injury. Thus, the present study may provide a novel target for drug development and IS therapy.