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 649 records · Page 36Linked to original sources
PubMed2026

Friends or foes: Unraveling the tsetse fly-Spiroplasma symbiosis.

Tsetse flies (Glossina spp.) transmit African trypanosomes, the causative agents of human African and African animal trypanosomiases (HAT and AAT, respectively). These neglected tropical diseases impose significant public health and economic burdens across sub-Saharan Africa. Trypanosome transmission by tsetse flies is influenced by multiple factors, including host genetic background, ecological factors, and interactions with heritable microbial endosymbionts. Spiroplasma glossinidia has recently emerged as an important modulator of tsetse reproductive fitness and vector competence, making it a potential target for symbiont-based vector control strategies. In this review, we summarize the current knowledge of the tsetse-Spiroplasma symbiosis. We detail Spiroplasma's spatial and temporal infection dynamics in laboratory-reared and natural populations. Additionally, we highlight key aspects of the bacterium's genomics, phylogenetics, and physiological interactions with its tsetse host, including influences on host gene expression reproductive physiology, and vector competence. Finally, we discuss how the tsetse-Spiroplasma symbiosis could be harnessed to develop innovative, biological-based vector control and trypanosome transmission-blocking strategies, and we identify critical gaps that must be addressed to translate these findings into effective disease control interventions.

Animals↗
PubMed1983

Expression of the yeast CYC genes and CYC1/GalK fusion genes on yeast plasmids.

We have presented the results of our studies of the expression of the CYC genes from plasmids. All our data indicate that the levels of expression and the regulation of expression are very similar for the plasmid-borne genes and the chromosomal genes when care is taken to construct the appropriate plasmids. The usefulness of these plasmids has been demonstrated: mutations affecting regulatory sites adjacent to genes of interest have been constructed [such as the Xho I deletion and inversion in the YCpCYC1(2.4) plasmid] and selected [as in the case of the IS1 insertion into the YCpCYC7(2) plasmid], and these mutations have led us to some tentative conclusions about the location and nature of the regulatory sites of these genes. Furthermore, transformation with plasmids containing modified genes or fusions has permitted isolation of genomic regulatory mutants, as in the selection of lac+ suppressors of the lac- CYC1 1/x inversion carried on the YCpCYC1(2.4) 1/x plasmid. Although we cannot rule out the possibility that use of plasmids might cause us to miss a class of regulatory effects that can be propagated only along a chromosomal structure, we believe that the regulatory effects that we do observe can be more quickly and completely defined by working with plasmids. If any regulatory effects occur only on chromosomes, they can be studied more easily once the basic regulatory phenomena have been analyzed. The regulatory regions of the CYC1, CYC7, and TR2 genes that we have crudely mapped so far all exert their effects 100-300 bp away from the putative transcriptional starting sites. How the information in these regions is transmitted along the DNA is an intriguing question. We are engaged in a mutational analysis of these sites to locate them more precisely, to map second-site mutations that moderate the effects of the original mutations, to obtain genomic mutations that define the genes whose products interact with these sites, and to test combinations of genomic and plasmid mutations to define the sites with which regulatory elements interact. This approach should aid our understanding of the spatial relationships between yeast regulatory sites and transcriptional signals. Ultimately, obtaining mutations in regulatory genes, such as the mutations described here for the anaerobic regulation of TR2, will allow the cloning of these genes by complementation. This will lead to the isolation of the protein encoded and ultimately to an approach to the molecular mechanism of regulation through study of protein-DNA interactions.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1987

Molecular evolution and nucleotide sequences of the maize plastid genes for the alpha subunit of CF1 (atpA) and the proteolipid subunit of CF0 (atpH).

The nucleotide sequences of the maize plastid genes for the alpha subunit of CF1 (atpA) and the proteolipid subunit of CF0 (atpH) are presented. The evolution of these genes among higher plants is characterized by a transition mutation bias of about 2:1 and by rates of synonymous and nonsynonymous substitution which are much lower than similar rates for genes from other sources. This is consistent with the notion that the plastid genome is evolving conservatively in primary sequence. Yet, the mode and tempo of sequence evolution of these and other plastid-encoded coupling factor genes are not the same. In particular, higher rates of nonsynonymous substitution in atpE (the gene for the epsilon subunit of CF1) and higher rates of synonymous substitution in atpH in the dicot vs. monocot lineages of higher plants indicate that these sequences are likely subject to different evolutionary constraints in these two lineages. The 5'- and 3'-transcribed flanking regions of atpA and atpH from maize, wheat and tobacco are conserved in size, but contain few putative regulatory elements which are conserved either in their spatial arrangement or sequence complexity. However, these regions likely contain variable numbers of "species-specific" regulatory elements. The present studies thus suggest that the plastid genome is not a passive participant in an evolutionary process governed by a more rapidly changing, readily adaptive, nuclear compartment, but that novel strategies for the coordinate expression of genes in the plastid genome may arise through rapid evolution of the flanking sequences of these genes.

Amino Acid Sequence↗
PubMed2006

Evolution of Arabidopsis microRNA families through duplication events.

Recently there has been a great interest in the identification of microRNAs and their targets as well as understanding the spatial and temporal regulation of microRNA genes. To understand how microRNA genes evolve, we looked at several rapidly evolving families in Arabidopsis thaliana, and found that they arose from a process of genome-wide duplication, tandem duplication, and segmental duplication followed by dispersal and diversification, similar to the processes that drive the evolution of protein gene families. Using multiple expression data sets to examine the transcription patterns of different members of the microRNA families, we find the sequence diversification of duplicated microRNA genes to be accompanied by a change in spatial and temporal expression patterns, suggesting that duplicated copies acquire new functionality as they evolve.

Arabidopsis↗
PubMed1999

Segmental genomic replacement in embryonic stem cells by double lox targeting.

We have applied Cre-mediated double lox recombination to embryonic stem (ES) cells to facilitate repeated knock-ins at a target locus, thus helping to assure correct temporal and spatial transgene expression in mice. Using homologous recombination, we inserted a double lox cassette a few nucleo-tides before the authentic ATG start of MHL-1, the gene coding for the major subunit of the asialoglycoprotein receptor. The cassette carries a marker gene bounded by heterospecific lox sites that cannot recombine with each other, but which can undergo recombination with like sites on an incoming double lox targeting vector. Cre-mediated replacement of the lox-delimited genomic segment at MHL-1 with targeting DNA occurs at a frequency three times that of random DNA integration and is sufficiently robust that correctly targeted ES colonies can be identified by PCR screening without relying on any drug selection procedure. Moreover, double lox recombination at the MHL-1 locus is not dependent on the presence or absence of a transcriptionally active promoter at the genomic target. The strategy and vectors described here are generally applicable to designing double lox targeted knock-ins at any locus in ES cells and should prove useful in more precise molecular engineering of the mouse genome.

3T3 Cells↗
PubMed2026

Genomic insights into local adaptation of indigenous chickens.

Indigenous chickens are an essential part of biodiversity and a vital protein resource to humans, yet global warming and environmental changes pose serious threats to their survival and productivity. Therefore, assessing population adaptive capacity under shifting environments is crucial for breeding resilient animals, and guiding conservation strategies. Here, we integrated ecological and whole-genome resequencing data from 1 022 chickens from 44 Chinese indigenous populations to reveal genomic signatures of local adaptation. From 87 agroclimatic variables, we identified eight dominant environmental factors including solar radiation, precipitation, diurnal temperature range, and five landcover variables (cropland areas, water areas, trees coverage, bare ground and shrubs coverage) that shape ecological niches of indigenous chickens. Landscape and comparative genomics analyses revealed both known and novel candidate genes, such as UNC80, PTPRO, NCOR2, CSF2RB, NXT2 and PALLD for the solar radiation, precipitation, diurnal temperature range, cropland areas, trees coverage and bare ground, respectively. Particularly, adaptive non-coding variants harbored in these genes exhibited spatial allelic changes across populations and acted as regulatory elements via chromatin accessibility and DNA methylation, influencing adaptation in a tissue-specific manner. Our findings underscore the rich genetic diversity of Chinese indigenous chickens and provide new insights into genomic mechanisms of local adaptation, offering valuable references for domestic animal breeding, conservation, and climate resilience.

Animals↗
PubMed2026

Multi-omics and experimental validation identify RAPGEF2 as a protective prognostic biomarker in clear cell renal cell carcinoma.

Kidney Renal Clear Cell Carcinoma (KIRC) is characterized by marked molecular heterogeneity and metabolic reprogramming, underscoring the need for reliable biomarkers for prognostic assessment and individualized treatment. RAPGEF2, a guanine nucleotide exchange factor has been implicated in cell adhesion and differentiation, but its role in KIRC remains unclear. In this study, we systematically evaluated the expression pattern, prognostic significance, genomic associations, biological function, and therapeutic relevance of RAPGEF2 in KIRC through integrated multi-omics analyses and experimental validation. Pan-cancer single-cell and Spatial transcriptomic analysis revealed heterogeneous RAPGEF2 expression across tumor types, with a relatively prominent signal in KIRC, where RAPGEF2 was mainly enriched in endothelial cells. Survival analyses in the TCGA-KIRC showed that high RAPGEF2 expression was significantly associated with favorable overall survival, disease-specific survival, and progression-free interval, and these findings were validated in independent ICGC_RECA-EU and E-MTAB-1980 cohorts. Multivariate Cox regression further confirmed RAPGEF2 as an independent protective prognostic factor. Immunohistochemistry in a tissue microarray cohort demonstrated that higher RAPGEF2 protein expression was associated with improved overall survival. Genomic analyses showed that low RAPGEF2 expression was related to higher mutational burden. Functional assays demonstrated that RAPGEF2 knockdown promoted KIRC progression. Enrichment analyses indicated that RAPGEF2 may be associated with metabolic pathway remodeling, while immunotherapy cohort analyses suggested its potential association with therapeutic benefit. Collectively, RAPGEF2 is identified as a protective prognostic biomarker and potential functional regulator in KIRC.

Biomarker↗
PubMed2006

Advanced computing for systems biology.

Systems biology is based on computational modelling and simulation of large networks of interacting components. Models may be intended to capture processes, mechanisms, components and interactions at different levels of fidelity. Input data are often large and geographically disperse, and may require the computation to be moved to the data, not vice versa. In addition, complex system-level problems require collaboration across institutions and disciplines. Grid computing can offer robust, scaleable solutions for distributed data, compute and expertise. We illustrate some of the range of computational and data requirements in systems biology with three case studies: one requiring large computation but small data (orthologue mapping in comparative genomics), a second involving complex terabyte data (the Visible Cell project) and a third that is both computationally and data-intensive (simulations at multiple temporal and spatial scales). Authentication, authorisation and audit systems are currently not well scalable and may present bottlenecks for distributed collaboration particularly where outcomes may be commercialised. Challenges remain in providing lightweight standards to facilitate the penetration of robust, scalable grid-type computing into diverse user communities to meet the evolving demands of systems biology.

Animals↗
PubMed2003

Genetic mapping of variation in spatial learning in the mouse.

Inbred strains of mice are known to differ in their performance in the Morris water maze task, a test of spatial discrimination and place navigation in rodents, but the genetic basis of individual variation in spatial learning is unknown. We have mapped genetic effects that contribute to the difference between two strains, DBA/2 and C57BL6/J, using an F2 intercross and methods to detect quantitative trait loci (QTL). We found two QTL, one on chromosome 4 and one on chromosome 12, that influence behavior in the probe trial of the water maze (genome-wide significance p = 0.017 and 0.015, respectively). By including tests of avoidance conditioning and behavior in a novel environment, we show that the QTL on chromosomes 4 and 12 specifically influence variation in spatial learning. QTL that influence differences in fearful behavior (on chromosomes 1, 3, 7, 15, and 19) operate while mice are trained in the water maze apparatus.

Animals↗
PubMed2004

Recombination drives the evolution of GC-content in the human genome.

Unraveling the evolutionary forces responsible for variations of neutral substitution patterns among taxa or along genomes is a major issue in the identification of functional sequence features. Mammalian genomes show large-scale regional variations of GC-content (the isochores), but the substitution processes at the origin of this structure are poorly understood. We have analyzed the pattern of neutral substitutions in 14.3 Mb of primate noncoding regions. We show that the GC-content toward which sequences are evolving is strongly correlated (r(2) = 0.61, P </= 2 10(-16)) with the rate of crossovers (notably in females). This demonstrates that recombination drives the evolution of base composition in human (probably via the process of biased gene conversion). The present substitution patterns are very different from what they had been in the past, resulting in a major modification of the isochore structure of our genome. This non-equilibrium situation suggests that changes of recombination rates occur relatively frequently during evolution, possibly as a consequence of karyotype rearrangements. These results have important implications for understanding the spatial and temporal variations of substitution processes in a broad range of sexual organisms, and for detecting the hallmarks of natural selection in DNA sequences.

Animals↗
PubMedDate not supplied

[The patterns in the molecular biology of the adenoviruses (the results of a 20-year study at the Institute of Microbiology and Virology of the National Academy of Sciences of Ukraine)].

Scientific data of the highest importance and priority concerning regularities of structural and functional organization of proteins of adenoviruses capsids and peculiarities of expression of the virus genome are as follows: New antigen determinants of hexon and adenovirus fiber have been discovered, their different nature (conformational or linear) and different orientation, depending on the spatial organization of proteins, have been proved; localization of some epitopes has been determined with the help of synthesised antigen-active peptides, imitating them. Some regularities of structural and functional organization of adenovirus hexon have been determined on the basis of comparative analysis of antigenic specificity and primary structure of proteins being apart in taxonomic respect. The conception of immunoactivation (infectivity neutralization) of adenoviruses has been developed, and a mathematical model of this process has been first proposed, which determines the impact of antibodies to several antigenic determinants of hexon and fiber as well as interferon and complement. The unknown peculiarities of the adenovirus genome expression were studied in the dynamics of productive infection or under the effect of modified nucleosides, proteolysis inhibitors and those of different nature promising for chemotherapy of adenovirus infection. Lymphotropicity of adenoviruses was established and a model of the mixed infection of lymphocytes with adenoviruses, HIV, and Epstein-Barr virus of the herpes virus family was proposed for the first time. It was determined that the mutual interference of viruses was developed at the process of a single or successive infection and this was important to understand AIDS immunopathogenesis. Data presented substantiate the ways of creation of modern efficient preparations for diagnosis, prophylaxis and chemotherapy of adenovirus infection.

Adenoviridae Infections↗
PubMed2026

Spatial concordance metrics and related risk factors of brain-peripheral barrier axes: unveiling distinct concordance patterns for mental and neurological axes.

Numerous studies have documented bidirectional interactions between the central nervous system and barrier organs (skin, gut, and lung). While genome-wide association studies have revealed shared genetic factors across brain-peripheral barrier axes, investigating these connections from an environmental perspective in large populations remains difficult. Using data from the Global Burden of Disease (GBD) 2023, I extracted annual incidence rates for 56 diseases related to brain-peripheral barrier axes and exposure rates for the 70 most detailed risk factors across 204 countries and territories. By categorizing regional incidence rates into four quartiles for each disease, I pinpointed regions with concordance of these axes and constructed a spatial atlas of disease concordance within the brain-peripheral barrier axis from a macro-epidemiologic view. Subsequently, I calculated global spatial concordance percentages for each axis, which allowed the comparatively assessment of concordance patterns across different axes, specific diseases, and their variations over time, across the lifespan, and by gender. Finally, I applied machine learning models and Shapley additive explanations to identify risk factors related to the spatial concordance of each axis. From 1990 to 2023, the overall trend for most brain-peripheral barrier axis pairs remained stable. Spatial concordance patterns showed dynamic fluctuations across the lifespan, followed by a convergence toward stability in older age. Several risk factors are related to most brain-peripheral barrier axes. Notably, the mental and neurological axes exhibited distinct concordance patterns. Compared with neurological axes, concordance within mental axes showed a broader and more dispersed geographic distribution, with greater variation across sexes and over time. Furthermore, concordance percentages of mental and neurological axes exhibited opposing age-related trends, contrasting disease spectra for peripheral conditions, and inverse relationships with alcohol and sodium consumption. Those divergences suggest distinct mechanisms underlying the brain-peripheral barrier axes in mental and neurological diseases. Related risk factors offer population-based hypotheses for further investigation in individual-level studies.

Humans↗
PubMed1994

Using interval logic for order assembly.

Temporal logic, in particular, interval logic has been used to represent genome maps and to assist genome map constructions. However, interval logic itself appears to be limited in its expressive power because genome mapping requires various information such as partial order, distance and local orientation. In this paper, we first propose an integrated formalism based on a spatial-temporal logic where the concepts of metric information, local orientation and uncertainty are merged. Then, we present and discuss a deductive and object-oriented data model based on this formalism for a genetic deductive database, and the inference rules required. The formalism supports the maintenance of coarser knowledge of unordered, partially ordered and completely ordered genetic data in a relational hierarchy. We believe that this integrated formalism also provides a formal basis for designing a declarative query language.

Animals↗
PubMed2005

Fast and systematic genome-wide discovery of conserved regulatory elements using a non-alignment based approach.

We describe a powerful new approach for discovering globally conserved regulatory elements between two genomes. The method is fast, simple and comprehensive, without requiring alignments. Its application to pairs of yeasts, worms, flies and mammals yields a large number of known and novel putative regulatory elements. Many of these are validated by independent biological observations, have spatial and/or orientation biases, are co-conserved with other elements and show surprising conservation across large phylogenetic distances.

Animals↗
PubMed2004

Enhancer detection and gene trapping as tools for functional genomics in plants.

Although more than 25,000 genes of Arabidopsis thaliana have been sequenced and mapped, adequate expression or functional information is available for less than 15% of them. In the case of Oryza sativa (rice), about half of more than 55,000 predicted genes have been assigned to a vague functional category on the basis of their sequence, but fewer than 100 have been ascribed a precise, verified function after the identification of a mutant phenotype caused by the molecular disruption of the corresponding gene. Enhancer detection and gene trapping represent insertional mutagenesis strategies that report random expression of many genes and often generate loss-of-function mutations. Several trapping vectors have been designed in a limited number of species, and large-scale enhancer detection and gene trap screens that aim to generate a wide range of spatially and temporally restricted expression patterns have been initiated in both Arabidopsis and rice. These strategies are proving to be essential to the functional annotation of completely sequenced genomes, enabling the analysis of gene function in the context of the entire plant life cycle and substantially expanding our understanding of plant growth and development.

Arabidopsis↗
PubMed2001

Roles for genomic imprinting and the zygotic genome in placental development.

The placenta contains several types of feto-maternal interfaces where zygote-derived cells interact with maternal cells or maternal blood for the promotion of fetal growth and viability. The genetic factors regulating the interactions between different cell types within feto-maternal interfaces and the relative contributions of the maternal and zygotic genomes are poorly understood. Genomic imprinting, the epigenetic process responsible for parental origin-dependent functional differences between homologous chromosomes, has been proposed to contribute to these events. Previous studies showed that mouse conceptuses with an absence of imprinted differences between the two copies of chromosome 12 (upon paternal inheritance of both copies) die late in gestation and have a variety of defects, including placentomegaly. Here we examined the role of chromosome 12 imprinting in these placentae in more detail. We show that the spatial interactions between different cell types within feto-maternal interfaces are defective and identify abnormal behaviors in both zygote-derived and maternal cells that are attributed to the genome of the zygote but not the mother. These include compromised invasion of the maternal decidualized endometrium and the central maternal artery situated within it by zygote-derived trophoblast, abnormalities in the wall of the central maternal artery, and defects within the zygote-derived cellular layer of the labyrinth, which is in direct contact with maternal blood. These findings demonstrate multiple roles for chromosome 12 imprinting in the placenta that have not previously been associated with imprinting effects. They provide insights into the function of imprinting in placental development and have evolutionary and clinical implications.

Animals↗
PubMed2002

Molecular targets in cellular response to ionizing radiation and implications in space radiation protection.

DNA repair systems and cell cycle checkpoints closely co-operate in the attempt of maintaining the genomic integrity of cells damaged by ionizing radiation. DNA double-strand breaks (DSB) are considered as the most biologically important radiation-induced damage. Their spatial distribution and association with other types of damage depend on radiation quality. It is believed these features affect damage reparability, thus explaining the higher efficiency for cellular effects of densely ionizing radiation with respect to gamma-rays. DSB repair systems identified in mammalian cells are homologous recombination (HR), single-strand annealing (SSA) and non-homologous end-joining (NHEJ). Some enzymes may participate in more than one of these repair systems. DNA damage also triggers biochemical signals activating checkpoints responsible for delay in cell cycle progression that allows more time for repair. Those at G1/S and S phases prevent replication of damaged DNA and those at G2/M phase prevent segregation of changed chromosomes. Individuals with lack or alterations of genes involved in DNA DSB repair and cell cycle checkpoints exhibit syndromes characterized by genome instability and predisposition to cancer. Information reviewed in this paper on the basic mechanisms of cellular response to ionizing radiation indicates their importance for a number of issues relevant to protection of astronauts from space radiation.

Animals↗
PubMed1997

Structural characterization of the mouse Hfh4 gene, a developmentally regulated forkhead family member.

Hepatocyte nuclear factor-3/forkhead homologue 4 (HFH-4) is a forkhead/winged-helix transcription factor family member that has a unique temporal and spatial pattern of gene expression in the developing and adult lung, choroid plexus, testis, and oviduct. To characterize HFH-4 further, mouse genomic clones were isolated and analyzed. The Hfh4 gene is encoded on a 5.5-kb region located on the distal end of mouse chromosome 11 and consists of two exons and one intron. Unlike most forkhead genes, the DNA binding domain is divided between two exons, and the intron position corresponds precisely to the site of gene translocations involving two known human forkhead homologues. Multiple putative transcription start sites are identified in a G+C-rich sequence that does not contain TATA or CAAT boxes. Within 2.1 kb of 5' flanking sequence are three identical E boxes and multiple putative transcription factor binding sites. Transfection of plasmids containing Hfh4 5' flanking sequence linked to a reporter gene results in promoter activity in lung epithelial cells but not in epithelial-like fibrosarcoma cells, suggesting that this 5' flanking sequence can function as a promoter with the proper cell-type specificity.

Amino Acid Sequence↗