Accessibility Maps Research Articles

Deciphering the generation of heterogeneity in esophageal squamous cell carcinoma metastasis via single-cell multiomics analysis

BackgroundChromatin accessibility plays a crucial role in mediating transcriptional dysregulation and heterogeneity in Esophageal Squamous Cell Carcinoma (ESCC). Examining the chromatin accessibility of ESCC at single-cell level is imperative to understand how it activates oncogenes and contributes to the onset and metastasis of ESCC.MethodsWe performed single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) on cancerous and adjacent noncancerous tissues from four ESCC patients who were pathological staged as T1a, T2b, T3b, or T4a, to investigate whether regulatory elements are pivotal in instigating cellular heterogeneity during ESCC metastasis. In conjunction, we integrated these data with 55 scRNA-seq datasets, ChIP-seq or CUT&Tag sequencing data, Hi-C sequencing data, bulk RNA-seq data, and bulk ATAC-seq data from ESCC cell lines to dissect the mechanisms underlying the heterogeneity of ESCC and tumor microenvironment (TME).ResultsOur study identified enhancer-specific activation within epithelial cells orchestrated by the three-dimensional structure of chromatin that regulates SERPINH1 transcription, and promotes the epithelial-mesenchymal transition (EMT) and metastasis of ESCC. Additionally, chromatin element activation facilitated the expression of TNFSF4 in CD8 + exhausted T cells, thereby activating Tregs. Furthermore, we observed that chromatin accessibility promoted the differentiation of tumor-associated macrophages (TAMs) and cancer associated fibroblasts (CAFs).ConclusionsIn summary, utilizing multiomics analyses, we have revealed chromatin accessibility maps and illuminated the intricate molecular mechanisms that underlie cellular heterogeneity during ESCC metastasis, offering valuable insights to further advance research on tumor progression and deterioration.

MapReader: a framework for learning a visual language model for map analysis

Intelligent map analysis is an important yet challenging topic. Recently, the development of large models, especially Visual Language Models (VLMs), has shown potential for intelligent image analysis. However, these models are primarily trained on natural images, which have intrinsic differences from maps. Consequently, there remains a gap in applying existing general-domain VLMs to map analysis. To address this issue, we propose a framework for developing a specialized VLM, called MapReader. To achieve this goal, a comprehensive data resource is collected using a strategy that combines self-instruct with expert refinement, including training data (MapTrain: 2,000 pairs of maps and descriptions) and evaluation data (MapEval: 250 maps and 500 map-related questions). Based on the training data, MapReader is fine-tuned on top of a general-domain VLM to learn to understand and describe map contents. The evaluation results on MapEval suggest that: (1) MapReader can accept map inputs and generate detailed descriptions of core geographic information, and it also possesses visual question-answering capabilities, showing potential for application in various map analysis scenarios, such as accessible map reading and robotic map usage; (2) The proposed data collection strategy is effective, and the collected dataset can serve as a benchmark to promote further map analysis research.

Common and specific gene regulatory programs in zebrafish caudal fin regeneration at single-cell resolution.

Following amputation, zebrafish regenerate their injured caudal fin through lineage-restricted reprogramming. Although previous studies have charted various genetic and epigenetic dimensions of this process, the intricate gene regulatory programs shared by, or unique to, different regenerating cell types remain underinvestigated. Here, we mapped the regulatory landscape of fin regeneration by applying paired snRNA-seq and snATAC-seq on uninjured and regenerating fins. This map delineates the regulatory dynamics of predominant cell populations at multiple stages of regeneration. We observe a marked increase in the accessibility of chromatin regions associated with regenerative and developmental processes at 1 dpa, followed by a gradual closure across major cell types at later stages. This pattern is distinct from that of transcriptomic dynamics, which is characterized by several waves of gene upregulation and downregulation. We identified and in vivo validated cell-type-specific and position-specific regeneration-responsive enhancers and constructed regulatory networks by cell type and stage. Our single-cell resolution transcriptomic and chromatin accessibility map across regenerative stages provides new insights into regeneration regulatory mechanisms and serves as a valuable resource for the community.

Differences in Perspectives between Facility Managers and Crowd Workers in Accessibility Mapping

Differences in Perspectives between Facility Managers and Crowd Workers in Accessibility Mapping

Integrating Single-Cell RNA-Seq and ATAC-Seq Analysis Reveals Uterine Cell Heterogeneity and Regulatory Networks Linked to Pimpled Eggs in Chickens.

Pimpled eggs have defective shells, which severely impacts hatching rates and transportation safety. In this study, we constructed single-cell resolution transcriptomic and chromatin accessibility maps from uterine tissues of chickens using single-cell RNA sequencing (scRNA-seq) and single-cell ATAC sequencing (scATAC-seq). We identified 11 major cell types and characterized their marker genes, along with specific transcription factors (TFs) that determine cell fate. CellChat analysis showed that fibroblasts had the most extensive intercellular communication network and that the chickens laying pimpled eggs had amplified immune-related signaling pathways. Differential expression and enrichment analyses indicated that inflammation in pimpled egg-laying chickens may lead to disruptions in their circadian rhythm and changes in the expression of ion transport-related genes, which negatively impacts eggshell quality. We then integrated TF analysis to construct a regulatory network involving TF-target gene-Gene Ontology associations related to pimpled eggs. We found that the transcription factors ATF3, ATF4, JUN, and FOS regulate uterine activities upstream, while the downregulation of ion pumps and genes associated with metal ion binding directly promotes the formation of pimpled eggs. Finally, by integrating the results of scRNA-seq and scATAC-seq, we identified a rare cell type-ionocytes. Our study constructed single-cell resolution transcriptomic and chromatin accessibility maps of chicken uterine tissue and explored the molecular regulatory mechanisms underlying pimpled egg formation. Our findings provide deeper insights into the structure and function of the chicken uterus, as well as the molecular mechanisms of eggshell formation.

Impact of disease-associated chromatin accessibility QTLs across immune cell types and contexts.

Only a third of immune-associated loci from genome-wide association studies (GWAS) colocalize with expression quantitative trait loci (eQTLs). To learn about causal genes and mechanisms at the remaining loci, we created a unified single-cell chromatin accessibility (scATAC-seq) map in peripheral blood comprising a total of 282,424 cells from 48 individuals. Clustering and topic modeling of scATAC data identified discrete cell-types and continuous cell states, which helped reveal disease-relevant cellular contexts, and allowed mapping of genetic effects on chromatin accessibility across these contexts. We identified 37,390 chromatin accessibility QTLs (caQTL) at 10% FDR across eight cell groups and observed extensive sharing of caQTLs across immune cell contexts, finding that fewer than 20% of caQTLs are specific to a single cell type. Notably, caQTLs colocalized with ∼50% more GWAS loci compared to eQTLs, helping to nominate putative causal genes for many unexplained loci. However, most GWAS-caQTL colocalizations had no detectable downstream regulatory effects on gene expression levels in the same cell type. We find evidence that the higher rates of colocalization between caQTLs and GWAS signals reflect missing disease-relevant cellular contexts among existing eQTL studies. Thus, there remains a pressing need for identifying disease-causing cellular contexts and for mapping gene regulatory variation in these cells.

Detailed mapping of chromatin accessibility and transcriptome of the healthy breast.

Detailed mapping of chromatin accessibility and transcriptome of the healthy breast.

RWD56 Artificial Intelligence-Powered Identification, Access, and Utility Mapping of Real-World Data Sources for Alzheimer's Disease in Asia Pacific

RWD56 Artificial Intelligence-Powered Identification, Access, and Utility Mapping of Real-World Data Sources for Alzheimer's Disease in Asia Pacific

Single-nucleus chromatin accessibility and transcriptomic map of breast tissues of women of diverse genetic ancestry.

Single-nucleus analysis allows robust cell-type classification and helps to establish relationships between chromatin accessibility and cell-type-specific gene expression. Here, using samples from 92 women of several genetic ancestries, we developed a comprehensive chromatin accessibility and gene expression atlas of the breast tissue. Integrated analysis revealed ten distinct cell types, including three major epithelial subtypes (luminal hormone sensing, luminal adaptive secretory precursor (LASP) and basal-myoepithelial), two endothelial and adipocyte subtypes, fibroblasts, T cells, and macrophages. In addition to the known cell identity genes FOXA1 (luminal hormone sensing), EHF and ELF5 (LASP), TP63 and KRT14 (basal-myoepithelial), epithelial subtypes displayed several uncharacterized markers and inferred gene regulatory networks. By integrating breast epithelial cell gene expression signatures with spatial transcriptomics, we identified gene expression and signaling differences between lobular and ductal epithelial cells and age-associated changes in signaling networks. LASP cells and fibroblasts showed genetic ancestry-dependent variability. An estrogen receptor-positive subpopulation of LASP cells with alveolar progenitor cell state was enriched in women of Indigenous American ancestry. Fibroblasts from breast tissues of women of African and European ancestry clustered differently, with accompanying gene expression differences. Collectively, these data provide a vital resource for further exploring genetic ancestry-dependent variability in healthy breast biology.

RWD140 Artificial Intelligence-Powered Identification, Access, and Utility Mapping of Real-World Data Sources for Alzheimer's Disease in Europe

RWD140 Artificial Intelligence-Powered Identification, Access, and Utility Mapping of Real-World Data Sources for Alzheimer's Disease in Europe

DEBEcoMod: A dynamic energy budget R tool to predict life-history traits of marine organisms across time and space

DEBEcoMod is an open-source R script designed to apply Dynamic Energy Budget (DEB) theory to predict life-history traits of marine organisms under various environmental and anthropogenic stressors. It presents a novel approach to overcoming the computational and scale limitations of previous DEB applications, enabling the generation of spatially explicit outputs. DEBEcoMod is intended to predict traits such as maximum size, reproductive output, and life-history traits across different temporal and spatial scales. It utilises parameters from the AddMyPet database for various species and environmental time series to simulate the past, present, and future performance of organisms. The tool also includes a module for spatio-temporal representation, producing clear and accessible maps for stakeholders. The document highlights DEBEcoMod's application in invasion biology, marine spatial planning, integrated multi-trophic aquaculture, and marine ecology, drawing on published examples of spatial applications to demonstrate its versatility and potential in ecological research and adaptive management. Furthermore, the code has been cross-validated with the official DEBtool to ensure its accuracy and reliability. DEBEcoMod is available for download on GitHub, enhancing its accessibility and utility for a wide range of ecological and conservation applications.

The single-molecule accessibility landscape of newly replicated mammalian chromatin.

We present replication-aware single-molecule accessibility mapping (RASAM), a method to nondestructively measure replication status and protein-DNA interactions on chromatin genome-wide. Using RASAM, we uncover a genome-wide state of single-molecule "hyperaccessibility" post-replication that resolves over several hours. Combining RASAM with cellular models for rapid protein degradation, we demonstrate that histone chaperone CAF-1 reduces nascent chromatin accessibility by filling single-molecular "gaps" and generating closely spaced dinucleosomes on replicated DNA. At cis-regulatory elements, we observe unique modes by which nascent chromatin hyperaccessibility resolves: at CCCTC-binding factor (CTCF)-binding sites, CTCF and nucleosomes compete, reducing CTCF occupancy and motif accessibility post-replication; at active transcription start sites, high chromatin accessibility is maintained, implying rapid re-establishment of nucleosome-free regions. Our study introduces a new paradigm for studying replicated chromatin fiber organization. More broadly, we uncover a unique organization of newly replicated chromatin that must be reset by active processes, providing a substrate for epigenetic reprogramming.

National-scale 1-km maps of hospital travel time and hospital accessibility in China

Ensuring equitable access to health services is crucial for public welfare and social equity, and is a key objective of the United Nations’ Sustainable Development Goals (SDGs). However, existing datasets often define hospital accessibility using travel time to hospitals in geographic dimension only, without considering the supply (hospital capacity) and demand (population distribution) dynamics. To overcome this limitation, we developed and validated a national-scale 1 km map of both hospital travel time and hospital accessibility in China. We used the Gaussian two-step floating catchment area (Ga2SFCA) model to calculate hospital accessibility, incorporating hospital capacity and service population. Various file types and statistical indicators are provided, making the dataset highly accessible for non-specialists. The dataset fills the gap in publicly available nationwide hospital accessibility data for China and can serve as a critical tool in optimizing resource allocation and developing targeted strategies to improve healthcare equity.

Experience-Sharing to Support Inclusive Travel for Blind and Partially Sighted People

This research aimed to understand the challenges blind and partially sighted people experience in tourism and the travel information they need to plan their travel experiences effectively. To this end, we designed a mixed-methods study consisting of semi-structured interviews and co-design workshops, which were conducted to identify the needs of BPS people and the barriers experienced due to a lack of access to such information. The findings provide insights into the information-seeking process and highlight the role of experience sharing in cultivating a sense of agency, contribution, and interdependence. This study also contributes an accessible tourism ecosystem map based on our findings to highlight the different sources of travel information and their potential role in supporting inclusive travel for BPS people. The findings have implications for research and tourism service design and serve as a tool to motivate research on technologies to support inclusive leisure travel for BPS people and to inform the design of inclusive tourism services.

Single-cell transcriptome and chromatin accessibility mapping of upper lip and primary palate fusion.

Cleft lip and/or primary palate (CL/P) represent a prevalent congenital malformation, the aetiology of which is highly intricate. Although it is generally accepted that the condition arises from failed fusion between the upper lip and primary palate, the precise mechanism underlying this fusion process remains enigmatic. In this study, we utilized transposase-accessible chromatin sequencing (scATAC-seq) and single-cell RNA sequencing (scRNA-seq) to interrogate lambdoidal junction tissue derived from C57BL/6J mouse embryos at critical stages of embryogenesis (10.5, 11.5 and 12.5 embryonic days). We successfully identified distinct subgroups of mesenchymal and ectodermal cells involved in the fusion process and characterized their unique transcriptional profiles. Furthermore, we conducted cell differentiation trajectory analysis, revealing a dynamic repertoire of genes that are sequentially activated or repressed during pseudotime, facilitating the transition of relevant cell types. Additionally, we employed scATAC data to identify key genes associated with the fusion process and demonstrated differential chromatin accessibility across major cell types. Finally, we constructed a dynamic intercellular communication network and predicted upstream transcriptional regulators of critical genes involved in important signalling pathways. Our findings provide a valuable resource for future studies on upper lip and primary palate development, as well as congenital defects.

Single-nucleus multiomics reveals the gene-regulatory networks underlying sex determination of murine primordial germ cells.

Accurate specification of female and male germ cells during embryonic development is critical for sexual reproduction. Primordial germ cells (PGCs) are the bipotential precursors of mature gametes that commit to an oogenic or spermatogenic fate in response to sex-determining cues from the fetal gonad. The critical processes required for PGCs to integrate and respond to signals from the somatic environment in gonads are not understood. In this study, we developed the first single-nucleus multiomics map of chromatin accessibility and gene expression during murine PGC development in both XX and XY embryos. Profiling of cell-type specific transcriptomes and regions of open chromatin from the same cell captured the molecular signatures and gene networks underlying PGC sex determination. Joint RNA and ATAC data for single PGCs resolved previously unreported PGC subpopulations and cataloged a multimodal reference atlas of differentiating PGC clusters. We discovered that regulatory element accessibility precedes gene expression during PGC development, suggesting that changes in chromatin accessibility may prime PGC lineage commitment prior to differentiation. Similarly, we found that sexual dimorphism in chromatin accessibility and gene expression increased temporally in PGCs. Combining single-nucleus sequencing data, we computationally mapped the cohort of transcription factors that regulate the expression of sexually dimorphic genes in PGCs. For example, the gene regulatory networks of XX PGCs are enriched for the transcription factors, TFAP2c, TCFL5, GATA2, MGA, NR6A1, TBX4, and ZFX. Sex-specific enrichment of the forkhead-box and POU6 families of transcription factors was also observed in XY PGCs. Finally, we determined the temporal expression patterns of WNT, BMP, and RA signaling during PGC sex determination, and our discovery analyses identified potentially new cell communication pathways between supporting cells and PGCs. Our results illustrate the diversity of factors involved in programming PGCs towards a sex-specific fate.

Variation of Soil Erosion Estimates when Using Different Maps of Arable Land of the Belgorod Region

Current medium- and small-scale estimates of soil erosion in Russia are very few. At the same time, a favorable situation has now developed for assessing the rates and volumes of soil erosion losses. Erosion models have been developed that are adapted to available digital elevation models, various farmland masks and climate databases have been created. The paper studies the accuracy of erosion estimates using various maps of arable land. Two maps are public (ESA WC, GLCLU), the third is the official Ministry of Agriculture (MA) of the Russian Federation, the fourth map is an author’s reference map of Alekseevsky district. It has been established that the map of the MA gives the most average arable land areas among the first three maps. Public access maps showed maximum and minimum estimates of arable land area. Comparison with the standard showed that the accuracy of the map of the MA does not exceed 90%, the remaining maps – 84 and 83%. The area of arable land in the Belgorod region varies slightly (from 1,445 to 1,586 thousand hectares); so the region is favorable for erosion modelling. Deviations from the average rates of soil erosion calculated using different maps of arable land in the region as a whole amounted to 7%, and in some areas reached 27%. Thus, today assessments of soil erosion at the regional level can be carried out with an error of at least 10–15% only as a result of the uncertainty in mapping the boundaries of arable land. In the Russia as a whole, data on the area of arable land varies significantly, from 80 to 132 million hectares. Consequently, the use of existing maps of arable land can lead to significant uncertainties in soil erosion estimates averaged at the level of districts and above.

Integrating Active and Passive Remote Sensing Data for Forest Age Estimation in Shangri-La City, China

The accurate mapping of age structure and access to spatially explicit information are essential to optimal planning and policy-making for forest ecosystems, including forest management and sustainable economic development. Specifically, surveying and mapping the age structure of forests is crucial for calculating the carbon sequestration capacity of forest ecosystems. However, spatial heterogeneity and limited accessibility make forest age mapping in mountainous areas challenging. Here, we present a new workflow using ICESat-2 LiDAR data integrated with multisource remote sensing imagery to estimate forest age in Shangri-La, China. Two methods—a climate-driven exponential model and a random forest algorithm—are compared to infer the age structure of the five dominant species in Shangri-La. The climate-driven model, with an R2 of 0.67 and an RMSE of 12.79 years, outperforms the random forest model. The derived wall-to-wall forest age map at 30 m resolution reveals that nearly all forests in Shangri-La are mature or overmature, especially among the high-elevation species Abies fabri (Mast.) Craib and Picea asperata Mast., compared with Pinus yunnanensis Franch., Quercus aquifolioides Rehd. and E.H. Wils. and Pinus densata Mast., where the age structure is more evenly distributed across different elevation ranges. Younger forests are frequently found around human settlements and along the Jinsha River valley, whereas older forests are located in remote and high-elevation areas that are less disturbed. The combined use of active and passive remote sensing data has resulted in substantial improvements in the spatial detail and accuracy of wall-to-wall age mapping, which is expected to be a cost-effective approach for supporting forest management and carbon accounting in this important ecological region. The method developed here can be scaled to other mountain areas both to understand the age patterns and structure of mountain forests and to provide critical information for forestation, reforestation and carbon accounting in surface-to-high mountain areas, which are increasingly crucial for climate mitigation.

Context-aware single-cell multiomics approach identifies cell-type-specific lung cancer susceptibility genes

Genome-wide association studies (GWAS) identified over fifty loci associated with lung cancer risk. However, underlying mechanisms and target genes are largely unknown, as most risk-associated variants might regulate gene expression in a context-specific manner. Here, we generate a barcode-shared transcriptome and chromatin accessibility map of 117,911 human lung cells from age/sex-matched ever- and never-smokers to profile context-specific gene regulation. Identified candidate cis-regulatory elements (cCREs) are largely cell type-specific, with 37% detected in one cell type. Colocalization of lung cancer candidate causal variants (CCVs) with these cCREs combined with transcription factor footprinting prioritize the variants for 68% of the GWAS loci. CCV-colocalization and trait relevance score indicate that epithelial and immune cell categories, including rare cell types, contribute to lung cancer susceptibility the most. A multi-level cCRE-gene linking system identifies candidate susceptibility genes from 57% of the loci, where most loci display cell-category-specific target genes, suggesting context-specific susceptibility gene function.

Urban traffic incident management, using network analysis to improve the evacuation time to healthcare facilities

The city of Biskra is ranked the second city in Algeria with the highest traffic accident rate. There are multiple causes of accidents that derive from the diversity of traffic. In addition, its geographical location as a crossroads between the northeast and the south of Algeria is a major factor. Biskra is also considered a commercial and industrial city that receives daily large flows of travellers and merchandise. Traffic accidents are a complex problems that is dealt with in several approaches. In this research, from a geographical point of view, we will contribute to improve the trajectory of intervention and evacuation. Therefore, this research paper aims to create a geodatabase including the road network with associated entities to carry out spatiotemporal analyses and evaluate the service area of health facilities in terms of the nearest path. This paper uses GIS tools for evacuation to the public hospital employing a Network Analyst. This study may serve as a decision-making aid for the local authorities of this city in terms of evacuation and intervention in the event of a road accident. It provides real-time information on the location of the accident and the nearest path along with an estimated time. The outputs of these analyses can determine a map of accessibility, which allows for training in order to improve the real-time evacuation. As a result, this approach will lead to the reduction of evacuation time by less than 10 minutes, and thus leading to a decrease in the number of fatalities.