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At least 19 recordsLinked to original sources
PubMed2025

SIGEL: a context-aware genomic representation learning framework for spatial genomics analysis.

Spatial transcriptomics (ST) integrates spatial information into genomics, yet methods for generating spatially-informed gene representations are limited and computationally intensive. We present SIGEL, a cost-effective framework that derives gene manifolds from ST data by exploiting spatial genomic context. The resulting SIGEL-generated gene representations (SGRs) are context-aware, biologically meaningful, and robust across samples, making them highly effective for key downstream tasks, including imputing missing genes, detecting spatial expression patterns, identifying disease-related genes and interactions, and improving spatial clustering. Extensive experiments across diverse ST datasets validate SIGEL's effectiveness and highlight its potential in advancing spatial genomics research.

Genomics↗
PubMed2004

Spatial genome organization during T-cell differentiation.

The spatial organization of genomes within the mammalian cell nucleus is non-random. The functional relevance of spatial genome organization might be in influencing gene expression programs as cells undergo changes during development and differentiation. To gain insight into the plasticity of genomes in space and time and to correlate the activity of specific genes with their nuclear position, we systematically analyzed the spatial genome organization in differentiating mouse T-cells. We find significant global reorganization of centromeres, chromosomes and gene loci during the differentiation process. Centromeres were repositioned from a preferentially internal distribution in undifferentiated cells to a preferentially peripheral position in differentiated CD4+ and CD8+ cells. Chromosome 6, containing the differentially expressed T-cell markers CD4 and CD8, underwent differential changes in position depending on whether cells differentiated into CD4+ or CD8+ thymocytes. Similarly, the two marker loci CD4 and CD8 showed distinct behavior in their position relative to the chromosome 6 centromere at various stages of differentiation. Our results demonstrate that significant spatial genome reorganization occurs during differentiation and indicate that the relationship between dynamic genome topology and single gene regulation is highly complex.

Animals↗
PubMed2004

Spatial genome organization.

The linear sequence of genomes exists within the three-dimensional space of the cell nucleus. The spatial arrangement of genes and chromosomes within the interphase nucleus is nonrandom and gives rise to specific patterns. While recent work has begun to describe some of the positioning patterns of chromosomes and gene loci, the structural constraints that are responsible for nonrandom positioning and the relevance of spatial genome organization for genome expression are unclear. Here we discuss potential functional consequences of spatial genome organization and we speculate on the possible molecular mechanisms of how genomes are organized within the space of the mammalian cell nucleus.

Animals↗
PubMed2006

Spatial genome organization in the formation of chromosomal translocations.

Chromosomal translocations and genomic instability are universal hallmarks of tumor cells. While the molecular mechanisms leading to the formation of translocations are rapidly being elucidated, a cell biological understanding of how chromosomes undergo translocations in the context of the cell nucleus in vivo is largely lacking. The recent realization that genomes are non-randomly arranged within the nuclear space has profound consequences for mechanisms of chromosome translocations. We review here the emerging principles of spatial genome organization and discuss the implications of non-random spatial genome organization for the genesis and specificity of cancerous chromosomal translocations.

Cell Nucleus↗
PubMed2026

Emerging Principles in Spatial Functional Genomics.

Spatial transcriptomic and proteomic atlases have enabled mapping of gene programs within intact tissues, but these measurements remain largely descriptive and do not define the mechanisms controlling tissue biology. Pooled CRISPR screening provides scalable causal interrogation of gene function but remains largely confined to dissociated systems that lack spatial context. In vivo spatial functional genomics (SFG) bridges these approaches by integrating genetic perturbations with in situ transcriptomic and proteomic readouts to measure gene function within intact tissue ecosystems. By preserving spatial organization, SFG enables interpretation of perturbations through effects on cell-cell interactions, diffusible signals, multicellular niches, and tissue architecture. Here, we outline key design axes of SFG: perturbation strategy, barcoding strategy, and phenotypic readout. We discuss computational challenges, including spatial autocorrelation, neighborhood dependence, and context-aware null modeling, and highlight how SFG reveals non-cell-autonomous, architecture-dependent mechanisms of gene function, advancing toward predictive models of tissue organization and gene function.

Genomics↗
PubMed2025

Spatial genomics: Mapping the landscape of fibrosis.

Organ fibrosis causes major morbidity and mortality worldwide. Treatments for fibrosis are limited, with organ transplantation being the only cure. Here, we review how various state-of-the-art spatial genomics approaches are being deployed to interrogate fibrosis across multiple organs, providing exciting insights into fibrotic disease pathogenesis. These include the detailed topographical annotation of pathogenic cell populations and states, detection of transcriptomic perturbations in morphologically normal tissue, characterization of fibrotic and homeostatic niches and their cellular constituents, and in situ interrogation of ligand-receptor interactions within these microenvironments. Together, these powerful readouts enable detailed analysis of fibrosis evolution across time and space.

Humans↗
PubMed2026

Optics-free spatial genomics for mapping mammalian brain aging by IRISeq.

Spatial transcriptomics has emerged as a transformative approach for in situ mapping of cellular heterogeneity and interactions, yet existing methods often compromise throughput, cost and tissue coverage. Here we introduce Imaging Reconstruction using Indexed Sequencing (IRISeq): an optics-free, cost-effective platform that leverages spatial interaction mapping by indexed sequencing to profile tissues at adjustable sizes and resolutions (5-50 µm). We applied IRISeq to map gene expression across more than 70 coronal sections from both adult and aged mouse brains, including wild-type and two lymphocyte-deficient models (Rag1 and Prkdc mutants) and generated more than 460,000 spatial transcriptome profiles. Our integrated analysis with 783,264 single-cell transcriptomes revealed region-specific aging signatures that are lymphocyte dependent, notably a downregulation of interferon signaling and inflammation in ventricular regions upon lymphocyte depletion, alongside mutant-specific upregulation of senescence pathways. Furthermore, lymphocyte deficiency was linked to preserved abundance of ependymal cells that line the brain's ventricles and to distinct microglial state dynamics, highlighting a key role for lymphocytes in driving inflammatory processes during brain aging. Overall, IRISeq provides a high-throughput and cost-effective solution for spatially resolved transcriptomic profiling, opening new avenues for elucidating region-specific cellular mechanisms underlying aging and identifying potential therapeutic targets to preserve brain homeostasis.

Animals↗
PubMed2025

Spatial Genomic Approaches to Investigate HOX Genes in Mouse Brain Tissues.

Spatial transcriptomic tools are an upcoming and powerful way to investigate targeted gene expression patterns within tissues. These tools offer the unique advantage of visualizing and understanding gene expression while preserving tissue integrity, thereby maintaining the spatial context of genes. Curio is a robust spatial transcriptomic tool that facilitates high throughput comprehensive spatial gene expression analysis across the entir e transcriptome with high efficiency. Here, we present a bioinformatics protocol for performing whole transcriptome gene expression analysis of mouse brain tissue using Curio. Specifically, we demonstrate using computational techniques to visualize expression patterns of various HOX genes in the mouse brain.

Animals↗
PubMed1999

A view from the genome: spatial control of transcription in sea urchin development.

The process of embryogenesis depends on differential regulation of genes in the spatial components defined by the embryonic cells (blastomeres). Developmental regulation is mediated by complex, hardwired genomic control systems consisting of clusters of multiple target sites at which specific interactions with regionally presented transcription factors occur. In the age of genomics and gene-transfer technology, the sea urchin embryo provides unique opportunities for experimental analysis of these processes. Research on gene regulation in sea urchin embryos in the past year has seen remarkable progress in two large areas: in understanding functional cis-regulatory architecture; and in understanding the mechanism by which the axial coordinates of the egg are transduced into a molecular system for differential gene activation.

Animals↗
PubMed2005

Human archival tissues provide a valuable source for the analysis of spatial genome organization.

Sections from archival formalin-fixed, paraffin wax-embedded human tissues are a valuable source for the study of the nuclear architecture of specific tissue types in terms of the three-dimensional spatial positioning and architecture of chromosome territories and sub-chromosomal domains. Chromosome painting, centromeric, and locus-specific probes were hybridized to tissue microarrays prepared from formalin-fixed paraffin wax-embedded samples of pancreas and breast. The cell nuclei were analyzed using quantitative three-dimensional image microscopy. The results obtained from non-neoplastic pancreatic cells of randomly selected individuals indicated that the radial arrangement of the chromosome 8 territories as well as their shape (roundness) did not significantly differ between the individuals and were in accordance with assumptions of a probabilistic model for computer simulations. There were considerable differences between pancreatic tumor and non-neoplastic cells. In non-neoplastic ductal epithelium of the breast there was a larger, but insignificant, variability in the three-dimensional positioning of the centromere 17 and HER2 domains between individuals. In neoplastic epithelial breast cells, however, the distances between centromere and gene domains were, on average, smaller than in non-neoplastic cells. In conclusion, our results demonstrate the feasibility of studying the genome architecture in archival, formalin-fixed, paraffin wax-embedded human tissues, opening new directions in tumor research and cell classification.

Breast↗
PubMed2006

Genomes as geography: using GIS technology to build interactive genome feature maps.

BACKGROUND: Many commonly used genome browsers display sequence annotations and related attributes as horizontal data tracks that can be toggled on and off according to user preferences. Most genome browsers use only simple keyword searches and limit the display of detailed annotations to one chromosomal region of the genome at a time. We have employed concepts, methodologies, and tools that were developed for the display of geographic data to develop a Genome Spatial Information System (GenoSIS) for displaying genomes spatially, and interacting with genome annotations and related attribute data. In contrast to the paradigm of horizontally stacked data tracks used by most genome browsers, GenoSIS uses the concept of registered spatial layers composed of spatial objects for integrated display of diverse data. In addition to basic keyword searches, GenoSIS supports complex queries, including spatial queries, and dynamically generates genome maps. Our adaptation of the geographic information system (GIS) model in a genome context supports spatial representation of genome features at multiple scales with a versatile and expressive query capability beyond that supported by existing genome browsers. RESULTS: We implemented an interactive genome sequence feature map for the mouse genome in GenoSIS, an application that uses ArcGIS, a commercially available GIS software system. The genome features and their attributes are represented as spatial objects and data layers that can be toggled on and off according to user preferences or displayed selectively in response to user queries. GenoSIS supports the generation of custom genome maps in response to complex queries about genome features based on both their attributes and locations. Our example application of GenoSIS to the mouse genome demonstrates the powerful visualization and query capability of mature GIS technology applied in a novel domain. CONCLUSION: Mapping tools developed specifically for geographic data can be exploited to display, explore and interact with genome data. The approach we describe here is organism independent and is equally useful for linear and circular chromosomes. One of the unique capabilities of GenoSIS compared to existing genome browsers is the capacity to generate genome feature maps dynamically in response to complex attribute and spatial queries.

Animals↗
PubMed2025

Integrating genomic and spatial analyses to describe tuberculosis transmission: a scoping review.

Tuberculosis remains a leading cause of infection-related mortality, and efforts to reduce its incidence have been hindered by an incomplete understanding of local Mycobacterium tuberculosis transmission dynamics. Advances in pathogen sequencing and spatial analysis have created new opportunities to map M tuberculosis transmission patterns more precisely. In this scoping review, we searched for studies combining pathogen genetics and location data to analyse the spatial patterns of M tuberculosis transmission and identified 142 studies published between 1994 and 2024. Secular changes in genetic methods were observed, with genome sequencing approaches largely replacing lower-resolution genotyping methods since 2020. The included studies addressed four primary research questions: how are tuberculosis cases and M tuberculosis transmission clusters geographically distributed; do spatially concentrated M tuberculosis clusters exist, and where are these areas located; when spatial concentration occurs, what host, pathogen, or environmental factors contribute to these patterns; and do identifiable relationships exist between the spatial proximity of tuberculosis cases and the genetic similarity of the M tuberculosis isolates infecting these individuals? Collectively, in this Review, we examined the available study data, evaluated the analytical requirements for addressing these questions, and discussed opportunities and challenges for future research. We found that the integration of spatial and genomic data can inform a detailed understanding of local M tuberculosis transmission patterns, but improved study designs and new analytical methods to address gaps in sampling completeness and to integrate additional movement data are needed to fully realise the potential of these tools.

Humans↗
PubMed2026

Subnuclear genome compartmentalization controls bivalent chromatin activity.

The nuclear genome is spatially organized into a three-dimensional architecture by physical association of large chromosomal domains with subnuclear compartments including the nuclear lamina at the radial periphery and nuclear speckles within the nucleoplasm1-5. However, how higher-order spatial genome architecture regulates human development has been overlooked, and the interplay between chromatin state and subnuclear genome compartmentalization is poorly understood. Here we generate high-resolution maps of genomic interactions with the lamina and speckles in cells of the neurogenic lineage isolated from mid-gestational human cortex, identifying an intimate association between subnuclear genome compartmentalization, chromatin state and transcription. During cortical neurogenesis, subnuclear genome compartmentalization is extensively remodelled, relocating hundreds of neuronal genes from the lamina to speckles, including key neurodevelopmental genes bivalent for trimethylation of histone H3 at Lys27 (H3K27me3) and Lys4 (H3K4me3). At the lamina, bivalent genes have exceptionally low expression, and relocation to speckles enhances resolution of bivalent chromatin to H3K4me3 monovalency and increases transcription more than eightfold. We further demonstrate that proximity to the nuclear periphery-not the presence of H3K27me3-maintains the lowly expressed, poised state of bivalent genes embedded in the lamina. We find that the repressive environment of the lamina is associated with spatial segregation of the transcriptional elongation machinery from the nuclear periphery. Our results establish a paradigm in which knowing the spatial location of a gene is necessary for understanding its epigenomic regulation.

Humans↗
PubMed2026

Spatial clustering and transmission networks of multidrug-resistant tuberculosis in Rwanda: a national retrospective genomic and spatial epidemiological study.

BACKGROUND: Approximately 96% of rifampicin resistance/multidrug-resistant tuberculosis (RR/MDR-TB) cases in Rwanda result from direct transmission rather than acquired resistance. However, the nationwide spatial distribution and transmission dynamics of RR/MDR-TB remain poorly characterised. This study aims to analyse spatial patterns of RR/MDR-TB in Rwanda and explore relationships between spatial proximity and RR/MDR-TB strains' genetic relatedness. METHODS: We conducted a retrospective analysis of 249 confirmed RR-TB cases across Rwanda from 2017 to 2024, using the known geolocations of patients' residences. Spatial and space-time clustering was assessed using Kulldorff's scan statistics. Demographic and socioeconomic determinants were evaluated using multivariable regression. For 201 cases with whole-genome sequencing data, we performed transmission analysis using a 5-SNP threshold to define recent transmission clusters and investigated spatial relationships within genetically related strains. RESULTS: Significant spatial clustering of RR/MDR-TB was identified in 21 sectors, mainly in Nyarugenge, southern Gasabo and western Kicukiro (relative risk: 10.06; p<0.001). Our multivariable analysis showed that population density is positively associated with case notification rates. Molecular analysis revealed 88.5% of cases belonged to genotype clusters defined using a 12-SNP threshold, with 73.6% forming clusters at a strict 5-SNP threshold. Spatial K-function analysis of the six major clusters revealed heterogeneous transmission patterns, characterised by both tightly clustered outbreaks and regional transmission networks that spanned administrative boundaries. Most clusters (5/6) extended beyond Kigali, indicating that transmission networks operate across administrative divides. CONCLUSION: RR/MDR-TB in Rwanda shows significant spatial clustering with transmission occurring through both localised and regional networks. Integrating genomic and spatial data reveals transmission patterns that extend beyond household contacts and administrative boundaries. These findings underscore the need to implement geographically targeted interventions that address community-level transmission to control RR/MDR-TB in Rwanda effectively.

Rwanda↗
PubMed2005

Universal 1/f noise, crossovers of scaling exponents, and chromosome-specific patterns of guanine-cytosine content in DNA sequences of the human genome.

Spatial fluctuations of guanine and cytosine base content (GC%) are studied by spectral analysis for the complete set of human genomic DNA sequences. We find that (i) 1/ f(alpha) decay is universally observed in the power spectra of all 24 chromosomes, and (ii) the exponent alpha approximately 1 extends to about 10(7) bases, one order of magnitude longer than has previously been observed. We further find that (iii) almost all human chromosomes exhibit a crossover from alpha(1) approximately 1 (1/ f (alpha(1))) at lower frequency to alpha(2) <1 (1/ f (alpha(2))) at higher frequency, typically occurring at around 30,000-100,000 bases, while (iv) the crossover in this frequency range is virtually absent in human chromosome 22. In addition to the universal 1/ f(alpha) noise in power spectra, we find (v) several lines of evidence for chromosome-specific correlation structures, including a 500,000 base long oscillation in human chromosome 21. The universal 1/ f(alpha) spectrum in the human genome is further substantiated by a resistance to reduction in variance of guanine and cytosine content when the window size is increased.

Base Composition↗
PubMed2004

Tissue-specific spatial organization of genomes.

BACKGROUND: Genomes are organized in vivo in the form of chromosomes. Each chromosome occupies a distinct nuclear subvolume in the form of a chromosome territory. The spatial positioning of chromosomes within the interphase nucleus is often nonrandom. It is unclear whether the nonrandom spatial arrangement of chromosomes is conserved among tissues or whether spatial genome organization is tissue-specific. RESULTS: Using two-dimensional and three-dimensional fluorescence in situ hybridization we have carried out a systematic analysis of the spatial positioning of a subset of mouse chromosomes in several tissues. We show that chromosomes exhibit tissue-specific organization. Chromosomes are distributed tissue-specifically with respect to their position relative to the center of the nucleus and also relative to each other. Subsets of chromosomes form distinct types of spatial clusters in different tissues and the relative distance between chromosome pairs varies among tissues. Consistent with the notion that nonrandom spatial proximity is functionally relevant in determining the outcome of chromosome translocation events, we find a correlation between tissue-specific spatial proximity and tissue-specific translocation prevalence. CONCLUSIONS: Our results demonstrate that the spatial organization of genomes is tissue-specific and point to a role for tissue-specific spatial genome organization in the formation of recurrent chromosome arrangements among tissues.

Animals↗