Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “spatial genomics”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 451 records · Page 25Linked to original sources
PubMed2006

Transcriptional regulatory elements in the human genome.

The faithful execution of biological processes requires a precise and carefully orchestrated set of steps that depend on the proper spatial and temporal expression of genes. Here we review the various classes of transcriptional regulatory elements (core promoters, proximal promoters, distal enhancers, silencers, insulators/boundary elements, and locus control regions) and the molecular machinery (general transcription factors, activators, and coactivators) that interacts with the regulatory elements to mediate precisely controlled patterns of gene expression. The biological importance of transcriptional regulation is highlighted by examples of how alterations in these transcriptional components can lead to disease. Finally, we discuss the methods currently used to identify transcriptional regulatory elements, and the ability of these methods to be scaled up for the purpose of annotating the entire human genome.

Gene Expression Regulation↗
PubMed2006

Intratumor genomic heterogeneity in breast cancer with clonal divergence between primary carcinomas and lymph node metastases.

Conflicting theories of epithelial carcinogenesis disagree on the clonal composition of primary tumors and on the time at which metastases occur. In order to study the spatial distribution of disparate clonal populations within breast carcinomas and the extent of the genetic relationship between primary tumors and regional metastases, we have analyzed by comparative genomic hybridization 122 tissue samples from altogether 60 breast cancer patients, including 34 tumor samples obtained from different quadrants of 9 breast carcinomas, as well as paired primary-metastatic samples from 12 patients. The median intratumor genetic heterogeneity score (HS) was 17.4% and unsupervised hierarchical clustering analysis comparing the genetic features to those of an independent series of 41 breast carcinomas confirmed intratumor clonal divergence in a high proportion of cases. The median HS between paired primary breast tumors and lymph node metastases was 33.3%, but the number of genomic imbalances did not differ significantly. Clustering analysis confirmed extensive clonal divergence between primary carcinomas and lymph node metastases in several cases. In the independent series of 41 breast carcinomas, the number of genomic imbalances in primary tumors was significantly higher in patients presenting lymph node metastases (median = 15.5) than in the group with no evidence of disease spreading at diagnosis (median = 5.0). We conclude that primary breast carcinomas may be composed of several genetically heterogeneous and spatially separated cell populations and that paired primary breast tumors and lymph node metastases often present divergent clonal evolution, indicating that metastases may occur relatively early during breast carcinogenesis.

Alleles↗
PubMed1999

Statistical properties of open reading frames in complete genome sequences.

Some statistical properties of open reading frames in all currently available complete genome sequences are analyzed (seventeen prokatyotic genomes, and 16 chromosome sequences from the yeast genome). The size distribution of open reading frames is characterized by various techniques, such as quantile tables, QQ-plots, rank-size plots (Zipf's plots), and spatial densities. The issue of the influence of CG% on the size distribution is addressed. When yeast chromosomes are compared with archaeal and eubacterial genomes, they tend to have more long open reading frames. There is little or no evidence to reject the null hypothesis that open reading frames on six different reading frames and two strands distribute similarly. A topic of current interest, the base composition asymmetry in open reading frames between the two strands, is studied using regression analysis. The base composition asymmetry at three codon positions is analyzed separately. It was shown in these genome sequences that the first codon position is G- and A-rich (i.e. purine-rich); there is a co-existence of A- and T-rich branches at the second codon position; and the third codon position is weakly T-rich.

Base Sequence↗
PubMed1997

Spatial distribution of collagen type I mRNA in Paracentrotus lividus eggs and embryos.

We have identified the presence of type I collagen (COLL1alpha) mRNA in Paracentrotus lividus unfertilized egg, indicating a maternal origin of this mRNA. By in situ whole mount hybridization the spatial distribution of COLL1alpha mRNA in egg and embryo at different developmental stages was established. Moreover, the presence of COLL1alpha gene in Paracentrotus lividus genome was analyzed by Southern blot experiments. The localization pattern indicates that the maternal mRNA is placed in the fertilized egg in a fixed position, relative to the embryonic axes. Furthermore, the embryonic expression is spatially restricted during development, suggesting involvement in sea urchin embryo cell specification events. The presence of two bands in Southern blot hybridization may indicate that two genes specific for COLL1alpha are present in the sea urchin genome.

Animals↗
PubMed2003

Large-scale adaptive hitchhiking upon high recombination in Drosophila simulans.

Natural selection is expected to leave a characteristic footprint on neighboring nucleotide variation through the effects of genetic linkage. The size of the region affected is proportional to the strength of selection and greatly reduced with the recombinational distance from the selected site. Thus, the genomic footprint of selection is generally believed to be restricted to a small DNA stretch in normal and highly recombining regions. Here, we study the effect of selection on linked polymorphism (hitchhiking effect) by surveying nucleotide variation across a highly recombining approximately 88-kb genomic fragment in an African population of Drosophila simulans. We find a core region of up to 38 kb with a major haplotype at intermediate frequency. The extended haplotype structure that gradually vanishes until disappearing is unusual for a highly recombining region. Both the presence in the structured genomic domain of a single major haplotype depleted of variability and the detected spatial pattern of variation along the approximately 88-kb fragment are incompatible with neutral predictions in a panmictic population. A major role of demographic effects could also be discarded. The observed pattern of variation clearly provides evidence that directional selection has acted recently on this region, sweeping out variation around a strongly adaptive mutation. Our findings suggest a major role of positive selection in shaping DNA variability even in highly recombining regions.

Adaptation, Biological↗
PubMed1996

Structure of the gene encoding the sea urchin blastula protease 10 (BP10), a member of the astacin family of Zn2+-metalloproteases.

Blastula protease 10 (BP10), a metalloprotease of the astacin family, is secreted at the blastula stage by the sea urchin embryo. The BP10 gene shows a precise temporal and spatial regulation during embryogenesis. It has been cloned from a sea urchin lambda genomic library and the transcription unit has been entirely sequenced. It spans 6kb and contains seven exons (2.8 kb) and six introns (3.2 kb). Sequence comparison and phylogeny analysis show that BP10 belongs to a sub-family of molecular proteins which all play a role during development. In the two cases where the exon/intron organization of the gene is known (BP10 and tolloid), the modular structure of the protein is not reflected at the gene level, which indicates that this sub-family probably did not evolve by exon shuffling.

Amino Acid Sequence↗
PubMed2026

Spatial Integration of Protein and Chromosomal States Reveals Early Copy-Number Changes and Genotype-Associated Immune Neighborhoods in Serous Ovarian Cancer Evolution.

UNLABELLED: Detecting chromosomal copy-number alterations together with protein-defined cell states in intact tissue is critical for understanding early clonal evolution and microenvironmental interactions in cancer. We developed ORION-FISH, which integrates high-plex tissue imaging with a morphology-preserving DNA fluorescence in situ hybridization (DNA-FISH) workflow and single-cell registration, yielding measurements concordant with clinical FISH. In high-grade serous ovarian carcinoma (HGSOC), ORION-FISH recapitulated known chromosomal changes while revealing subclonal heterogeneity missed by targeted sequencing. Applied to serous tubal intraepithelial carcinomas, precursors of HGSOC, ORION-FISH identified intermixed epithelial cells with MYC or CCNE1 copy-number gains, as well as concurrent alterations associated with distinct immune microenvironments. In addition, epithelial cells with MYC and CCNE1 copy-number gains were detected in morphologically normal fallopian tube epithelium, along with rare MDM4 increases across epithelial lineages. Together, ORION-FISH provides a framework linking chromosomal copy-number states to protein-defined phenotypes within preserved tissue architecture, enabling context-aware interrogation of early copy-number diversification at single-cell resolution. SIGNIFICANCE: We introduce ORION-FISH, a spatially resolved workflow integrating multiplexed protein imaging with DNA-FISH to map genomic alterations within intact tissues. Applying this approach to ovarian cancer precursors reveals early copy-number diversification and associations with the local immune context, providing a foundation for studying how genomic and microenvironmental states coevolve during tumor initiation.

Female↗
PubMed2006

Linking cDNA-AFLP-based gene expression patterns and ESTs.

Massive amounts of DNA sequence data, generated from expressed sequence tag (EST) and genome sequencing projects, require efficient methods to link sequence databases with temporal and spatial expression profiles. To meet this need, we have developed a powerful computer program (GenEST), which links cDNA sequence data (including EST sequences) with transcript profiles revealed by cDNA-amplified fragment length polymorphism (AFLP). cDNA-AFLP is a highly reproducible differential display method based on restriction enzyme digests and selective amplification under high stringency conditions. GenEST predicts the sizes of virtual transcript derived fragments (TDFs) from cDNA sequences digested in silico. The resulting virtual TDFs could be traced back among the thousands of TDFs displayed on cDNA-AFLP gels. As a consequence, cDNA sequence databases can be screened very efficiently to identify genes with relevant expression profiles. Vice versa, using the restriction enzyme recognition sites, the primer extensions and the estimated TDF size as identifiers, the DNA sequence(s) corresponding to a TDF with an interesting expression pattern can be identified.

Automation↗
PubMed2026

A voyage of reprogrammable metabolic bioengineering reshapes plant defense: from editing tools to synthetic systems.

Metabolic bioengineering has emerged as a transformative approach for reshaping plant defense by targeting intrinsic biosynthetic pathways to enhance immunity in modern agriculture. Moving beyond proof-of-concept metabolomics to broad-spectrum programmable pathway engineering addresses gaps in plant rational design and optimizes resilience in response to diverse environmental cues. This review aims to comprehensively highlight the transition of innovative approaches to phenolics, alkaloids, flavonoids, terpenoids, and benzoxazinoids, inferring adaptive reprogramming that mediates the growth-defense balance and functions as molecular sentinels in plants. Furthermore, decoding the volatile metabolome reveals a dynamic signaling interface that influences defense responses and stress-induced plant-microbe interactions, with the shikimate, jasmonate, and salicylate pathways functioning as central hubs for microbial deterrence and priming immune memory. Recent developments in multi-scalar genome-editing strategies, including CRISPR-driven combinatorial edits, enzyme orthogonalization, fluxomics, and spatially resolved multi-omics, reconfigure central and specialized metabolic fluxes toward improved defense function and regulation. Additionally, emerging tools, such as WUSCHEL2 and BABY BOOM transcriptional modules, and artificial engineering strategies integrating deep learning model-driven predictions facilitate rapid development of synthetic genetic circuits and support a predictive engineering of plants. Moreover, Mass spectrometry imaging (MSI) in spatial metabolomics enables to obtain structures and locations of unidentified endogenous metabolites within cells and tissues. Overall, this review emphasizes a diverse array of primary and secondary metabolites, spanning molecular concepts to recent advances in plant immune mechanisms. It also illustrates new frontiers in programmable metabolic engineering that accelerate the understanding of plant-microbe-metabolite cross-talks, offering strategies to improve plant resistance and advance sustainable agricultural solutions.

metabolic bioengineering↗
PubMed2002

A bi-recursive neural network architecture for the prediction of protein coarse contact maps.

Prediction of contact maps may be seen as a strategic step towards the solution of fundamental open problems in structural genomics. In this paper we focus on coarse grained maps that describe the spatial neighborhood relation between secondary structure elements (helices, strands, and coils) of a protein. We introduce a new machine learning approach for scoring candidate contact maps. The method combines a specialized noncausal recursive connectionist architecture and a heuristic graph search algorithm. The network is trained using candidate graphs generated during search. We show how the process of selecting and generating training examples is important for tuning the precision of the predictor.

Algorithms↗
PubMed2002

Genomics and the tree physiologist.

During the last decade, a strong case has been made for viewing trees as model systems in plant biology. More recently, forest biologists have argued for the sequencing of the genome of a forest tree. Now, the United States Department of Energy has announced plans for sequencing the genome of the Populus trichocarpa clone, "Nisqually-1." Thus, forest biology is poised to enter an exciting period of scientific discovery. Embracing new technology and new research paradigms, however, is never easy. It is, therefore, timely to ask how tree physiologists will take advantage of the Populus genome data. We contend that the most attractive opportunities will arise through genome-wide research designed to: (1). examine the differences between trees and herbaceous annuals; (2). explore questions relating to the temporal and spatial scales that characterize the life histories and growth of trees; and (3). investigate cause-and-effect relationships that are intractable to conventional research methodologies. To highlight the potential applications of genomics in tree physiology, we briefly discuss each of these approaches.

Genome, Plant↗
PubMed2006

From functional genomics to functional immunomics: new challenges, old problems, big rewards.

The development of DNA microarray technology a decade ago led to the establishment of functional genomics as one of the most active and successful scientific disciplines today. With the ongoing development of immunomic microarray technology-a spatially addressable, large-scale technology for measurement of specific immunological response-the new challenge of functional immunomics is emerging, which bears similarities to but is also significantly different from functional genomics. Immunonic data has been successfully used to identify biological markers involved in autoimmune diseases, allergies, viral infections such as human immunodeficiency virus (HIV), influenza, diabetes, and responses to cancer vaccines. This review intends to provide a coherent vision of this nascent scientific field, and speculate on future research directions. We discuss at some length issues such as epitope prediction, immunomic microarray technology and its applications, and computation and statistical challenges related to functional immunomics. Based on the recent discovery of regulation mechanisms in T cell responses, we envision the use of immunomic microarrays as a tool for advances in systems biology of cellular immune responses, by means of immunomic regulatory network models.

Biotechnology↗
PubMed1994

Structure of the human annexin VI gene.

We report the structure of the human annexin VI gene and compare the intron-exon organization with the known structures of the human annexin I and II genes. The gene is approximately 60 kbp long and contains 26 exons. Consistent with the published annexin VI cDNA sequence, the genomic sequence at the 3' end does not contain a canonical polyadenylation signal. The genomic sequence upstream of the transcription start site contains TATAA and CAAT motifs. The spatial organization of the exons does not reveal any obvious similarities between the two halves of the annexin VI gene. Comparison of the intron-exon boundary positions of the annexin VI gene with those of annexins I and II reveals that within the repeated domains the break points are perfectly conserved except for exon 8, which is one codon smaller in annexin II. The corresponding point in the second half of annexin VI is represented by two exons, exons 20 and 21. The latter exon is alternatively spliced, giving rise to two annexin VI isoforms that differ with respect to a 6-amino acid insertion at the start of repeat 7.

Alternative Splicing↗
PubMed2000

Spatial expression of Hox cluster genes in the ontogeny of a sea urchin.

The Hox cluster of the sea urchin Strongylocentrous purpuratus contains ten genes in a 500 kb span of the genome. Only two of these genes are expressed during embryogenesis, while all of eight genes tested are expressed during development of the adult body plan in the larval stage. We report the spatial expression during larval development of the five 'posterior' genes of the cluster: SpHox7, SpHox8, SpHox9/10, SpHox11/13a and SpHox11/13b. The five genes exhibit a dynamic, largely mesodermal program of expression. Only SpHox7 displays extensive expression within the pentameral rudiment itself. A spatially sequential and colinear arrangement of expression domains is found in the somatocoels, the paired posterior mesodermal structures that will become the adult perivisceral coeloms. No such sequential expression pattern is observed in endodermal, epidermal or neural tissues of either the larva or the presumptive juvenile sea urchin. The spatial expression patterns of the Hox genes illuminate the evolutionary process by which the pentameral echinoderm body plan emerged from a bilateral ancestor.

Animals↗
PubMed2005

Nano-sizing of specific gene domains in intact human cell nuclei by spatially modulated illumination light microscopy.

Although light microscopy and three-dimensional image analysis have made considerable progress during the last decade, it is still challenging to analyze the genome nano-architecture of specific gene domains in three-dimensional cell nuclei by fluorescence microscopy. Here, we present for the first time chromatin compaction measurements in human lymphocyte cell nuclei for three different, specific gene domains using a novel light microscopic approach called Spatially Modulated Illumination microscopy. Gene domains for p53, p58, and c-myc were labeled by fluorescence in situ hybridization and the sizes of the fluorescence in situ hybridization "spots" were measured. The mean diameters of the gene domains were determined to 103 nm (c-myc), 119 nm (p53), and 123 nm (p58) and did not correlate to the genomic, labeled sequence length. Assuming a spherical domain shape, these values would correspond to volumes of 5.7 x 10(-4) microm(3) (c-myc), 8.9 x 10(-4) microm(3) (p53), and 9.7 x 10(-4) microm(3) (p58). These volumes are approximately 2 orders of magnitude smaller than the diffraction limited illumination or observation volume, respectively, in a confocal laser scanning microscope using a high numerical aperture objective lens. By comparison of the labeled sequence length to the domain size, compaction ratios were estimated to 1:129 (p53), 1:235 (p58), and 1:396 (c-myc). The measurements demonstrate the advantage of the SMI technique for the analysis of gene domain nano-architecture in cell nuclei. The data indicate that chromatin compaction is subjected to a large variability which may be due to different states of genetic activity or reflect the cell cycle state.

Biophysical Phenomena↗
PubMed1995

Tightly regulated, developmentally specific expression of the first open reading frame from LINE-1 during mouse embryogenesis.

LINE-1 (L1) has achieved its status as a middle repetitive DNA family in mammalian genomes by duplicative transposition. Although transposition may occur in any cell type, expression and transposition of a full-length functional element in the germ line are necessary for evolutionarily significant propagation of L1. An immunohistochemical analysis of adult mouse ovaries and mouse postimplantation embryos revealed expression of L1 open reading frame 1 in the germ line as well as in steroidogenic tissues. These results demonstrate that L1 expression is controlled by a tightly regulated temporal and spatial program of events during development and imply that multiple loci of L1 in the mouse genome are active for expression.

Animals↗
PubMed1996

Organization of the mouse cardiac natriuretic peptide locus encoding BNP and ANP.

The genes encoding the mouse atrial natriuretic peptide and B-type natriuretic peptide were previously shown to be physically linked on mouse chromosome 4 (Steinhelper ME, 1993, Structure, expression, and genomic mapping of the mouse natriuretic peptide type-B gene. Circ Res 72: 984-992). In the present study the spatial relationship and orientation of the mouse atrial natriuretic peptide and B-type natriuretic peptide transcription units were identified and a physical map of the mouse cardiac natriuretic peptide locus was obtained. To this end, genomic clones encoding atrial natriuretic peptide and B-type natriuretic peptide were isolated from a mouse genomic library in bacteriophage P1. Three independent clones encoding atrial natriuretic peptide were isolated and two of these also encode B-type natriuretic peptide. Both transcripts were shown to arise from the same DNA strand, with B-type natriuretic peptide encoded approximately 15 kb 5'-of atrial natriuretic peptide based on field inversion gel electrophoresis of fragments amplified with specific oligonucleotides. This finding was confirmed by isolation of subclones comprising the entire locus and by blot hybridization analysis of mouse genomic DNA. The results show that the genes encoding the two natriuretic peptides expressed predominantly in mammalian cardiac myocytes are organized in tandem on mouse chromosome 4. This information provides a physical framework for investigating mechanisms that regulate transcription of the cardiac natriuretic peptide locus.

Animals↗
PubMed2002

Spatial organization of active and inactive genes and noncoding DNA within chromosome territories.

The position of genes within the nucleus has been correlated with their transcriptional activity. The interchromosome domain model of nuclear organization suggests that genes preferentially locate at the surface of chromosome territories. Conversely, high resolution analysis of chromatin fibers suggests that chromosome territories do not present accessibility barriers to transcription machinery. To clarify the relationship between the organization of chromosome territories and gene expression, we have used fluorescence in situ hybridization to analyze the spatial organization of a contiguous approximately 1 Mb stretch of the Wilms' tumor, aniridia, genitourinary anomalies, mental retardation syndrome region of the human genome and the syntenic region in the mouse. These regions contain constitutively expressed genes, genes with tissue-restricted patterns of expression, and substantial regions of intergenic DNA. We find that there is a spatial organization within territories that is conserved between mouse and humans: certain sequences do preferentially locate at the periphery of the chromosome territories in both species. However, we do not detect genes necessarily at the periphery of chromosome territories or at the surface of subchromosomal domains. Intraterritory organization is not different among cell types that express different combinations of the genes under study. Our data demonstrate that transcription of both ubiquitous and tissue-restricted genes is not confined to the periphery of chromosome territories, suggesting that the basal transcription machinery and transcription factors can readily gain access to the chromosome interior.

Animals↗