Slide-tags enables spatial single-nucleus sequencing
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The spatial coupling and its influencing mechanism between rural human-habitat heritage and key rural tourism villages in China
Exploring the influencing factors and its influencing mechanism of the spatial coupling between rural human-habitat heritage (RHH) and key rural tourism villages (RTV) at county scale from the perspective of space can expand the theoretical research on the spatial coupling mechanism between RHH and RTV, and further provide theoretical reference and data support for the coordinated development and high-quality development of RHH and RTV in China. At the same time, previous studies have failed to systematically analyze the influencing factors and influencing mechanisms of the spatial coupling between RHH and RTV at the county scale, which restricted decision makers from formulating coordinated development measures between RHH and RTV at the macro level. In this study, bivariate spatial autocorrelation model and spatial coupling coordination model were used to quantitatively analyze the spatial coupling level between RHH and RTV at the county scale in China. Then, the linear regression (OLS) model, geographically weighted regression (GWR) model, and optimal parameter GeoDetector (OPGD) model were integrated to systematically analyze the linear influencing, spatial heterogeneity effect and interactive effect of natural environment and socioeconomic factors on the spatial coupling level between RHH and RTV in China, and explore the interactive influencing mechanism. The results show that the spatial coupling level of RHH and RTV in China show a significant east-west differentiation. There were 2024, 473, 293, 55 and 6 areas of severe, moderate, mild, basic and moderate coordination between RHH and RTV, respectively. Among them, severe and moderate discoordination areas are mainly distributed in Northeast China, arid and semi-arid areas in Western China, plateau areas in Southwest China, densely populated urban agglomerations and plains agricultural areas in the Middle East China. Mild discoordination areas and basic and moderate coordination areas are mainly located in transition zones in mountainous and plain areas, economically developed mountainous and hilly counties along the southeastern coast, and coastal tourist cities. Economic and population factors are the fundamental factors that affect the spatial coupling between RHH and RTV. Rural tourism facilities and rural public service facilities are important external driving forces for the coupling development of RHH and RTV, and Sociocultural environment factors are the important internal driving forces. Different surface forms, different climate conditions and different ecological environment conditions can form different natural textures and spatial organizations. Suitable climate conditions, sufficient water sources and ecological environment conditions can form more suitable rural settlement construction conditions and production and living conditions, and ultimately affect the protection and activation of rural human settlement heritage and the development and layout of key tourist villages. The spatial coupling relationship between RHH and RTV is the result of the complex interaction between the natural directivity law caused by natural environmental factors and the humanistic directivity law caused by human social and economic activities.
Spotiphy enables single-cell spatial whole transcriptomics across an entire section
Spatial transcriptomics (ST) has advanced our understanding of tissue regionalization by enabling the visualization of gene expression within whole-tissue sections, but current approaches remain plagued by the challenge of achieving single-cell resolution without sacrificing whole-genome coverage. Here we present Spotiphy (spot imager with pseudo-single-cell-resolution histology), a computational toolkit that transforms sequencing-based ST data into single-cell-resolved whole-transcriptome images. Spotiphy delivers the most precise cellular proportions in extensive benchmarking evaluations. Spotiphy-derived inferred single-cell profiles reveal astrocyte and disease-associated microglia regional specifications in Alzheimer’s disease and healthy mouse brains. Spotiphy identifies multiple spatial domains and alterations in tumor–tumor microenvironment interactions in human breast ST data. Spotiphy bridges the information gap and enables visualization of cell localization and transcriptomic profiles throughout entire sections, offering highly informative outputs and an innovative spatial analysis pipeline for exploring complex biological systems.
Rapid brain tumor classification from sparse epigenomic data
Although the intraoperative molecular diagnosis of the approximately 100 known brain tumor entities described to date has been a goal of neuropathology for the past decade, achieving this within a clinically relevant timeframe of under 1 h after biopsy collection remains elusive. Advances in third-generation sequencing have brought this goal closer, but established machine learning techniques rely on computationally intensive methods, making them impractical for live diagnostic workflows in clinical applications. Here we present MethyLYZR, a naive Bayesian framework enabling fully tractable, live classification of cancer epigenomes. For evaluation, we used nanopore sequencing to classify over 200 brain tumor samples, including 10 sequenced in a clinical setting next to the operating room, achieving highly accurate results within 15 min of sequencing. MethyLYZR can be run in parallel with an ongoing nanopore experiment with negligible computational overhead. Therefore, the only limiting factors for even faster time to results are DNA extraction time and the nanopore sequencer’s maximum parallel throughput. Although more evidence from prospective studies is needed, our study suggests the potential applicability of MethyLYZR for live molecular classification of nervous system malignancies using nanopore sequencing not only for the neurosurgical intraoperative use case but also for other oncologic indications and the classification of tumors from cell-free DNA in liquid biopsies.
Rapid 3D imaging at cellular resolution for digital cytopathology with a multi-camera array scanner (MCAS)
Optical microscopy has long been the standard method for diagnosis in cytopathology. Whole slide scanners can image and digitize large sample areas automatically, but are slow, expensive and therefore not widely available. Clinical diagnosis of cytology specimens is especially challenging since these samples are both spread over large areas and thick, which requires 3D capture. Here, we introduce a new parallelized microscope for scanning thick specimens across extremely wide fields-of-view (54 × 72 mm2) at 1.2 and 0.6 μm resolutions, accompanied by machine learning software to rapidly assess these 16 gigapixel scans. This Multi-Camera Array Scanner (MCAS) comprises 48 micro-cameras closely arranged to simultaneously image different areas. By capturing 624 megapixels per snapshot, the MCAS is significantly faster than most conventional whole-slide scanners. We used this system to digitize entire cytology samples (scanning three entire slides in 3D in just several minutes) and demonstrate two machine learning techniques to assist pathologists: first, an adenocarcinoma detection model in lung specimens (0.73 recall); second, a slide-level classification model of lung smears (0.969 AUC).
Spatially resolved transcriptomics and graph-based deep learning improve accuracy of routine CNS tumor diagnostics
The diagnostic landscape of brain tumors integrates comprehensive molecular markers alongside traditional histopathological evaluation. DNA methylation and next-generation sequencing (NGS) have become a cornerstone in central nervous system (CNS) tumor classification. A limiting requirement for NGS and methylation profiling is sufficient DNA quality and quantity, which restrict its feasibility. Here we demonstrate NePSTA (neuropathology spatial transcriptomic analysis) for comprehensive morphological and molecular neuropathological diagnostics from single 5-µm tissue sections. NePSTA uses spatial transcriptomics with graph neural networks for automated histological and molecular evaluations. Trained and evaluated across 130 participants with CNS malignancies and healthy donors across four medical centers, NePSTA predicts tissue histology and methylation-based subclasses with high accuracy. We demonstrate the ability to reconstruct immunohistochemistry and genotype profiling on tissue with minimal requirements, inadequate for conventional molecular diagnostics, demonstrating the potential to enhance tumor subtype identification with implications for fast and precise diagnostic workup.
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