Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “transcriptomic profiling”

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 1,315 records · Page 73Linked to original sources
PubMed2006

hUPF2 silencing identifies physiologic substrates of mammalian nonsense-mediated mRNA decay.

Nonsense-mediated mRNA decay (NMD) is a conserved eukaryotic surveillance pathway that selectively degrades aberrant mRNAs with premature termination codons (PTCs). Although a small number of cases exist in mammals, where NMD controls levels of physiologic PTC transcripts, it is still unclear whether the engagement of NMD in posttranscriptional control of gene expression is a more prevalent phenomenon. To identify physiologic NMD substrates and to study how NMD silencing affects the overall dynamics of a cell, we stably down-regulated hUPF2, the human homolog of the yeast NMD factor UPF2, by RNA interference. As expected, hUPF2-silenced HeLa cells were impaired in their ability to recognize ectopically expressed aberrant PTC transcripts. Surprisingly, hUPF2 silencing did not affect cell growth and viability but clearly diminished phosphorylation of hUPF1, suggesting a role of hUPF2 in modulating NMD activity through phosphorylation of hUPF1. Genome-wide DNA microarray expression profiling identified 37 novel up-regulated and 57 down-regulated transcripts in hUPF2-silenced cells. About 60% of the up-regulated mRNAs carry typical NMD motifs. Hence, NMD is important not only for maintaining the transcriptome integrity by removing nonfunctional and aberrant PTC-bearing transcripts but also for posttranscriptional control of selected physiologic transcripts with NMD features.

Base Sequence↗
PubMed2026

Integrated multi-omics analysis of fluoroquinolone tolerance mechanisms induced by enrofloxacin in Pasteurella multocida.

BACKGROUND: The global prevalence of multidrug-resistant bacteria has been rising at an alarming rate, posing a serious threat to both human and animal health. However, the mechanisms by which bacteria acquire antibiotic tolerance and subsequently develop resistance remain incompletely understood. METHODS: In this study, Pasteurella multocida, a common pathogen in the animal husbandry industry, was exposed to enrofloxacin, and genome resequencing, transcriptomic, and metabolomic analyses were performed to elucidate the adaptive mechanisms of P. multocida under fluoroquinolone-induced stress. RESULTS: Compared with the wild-type strain, the enrofloxacin-tolerant strain exhibited an extended lag phase, a prolonged logarithmic phase, reduced sensitivity to polymyxin B, reduced biofilm formation, and an elongated cellular morphology. Multi-omics analysis revealed a deletion in the dusB gene of the tolerant strain, resulting in a truncated non-functional protein. The deletion of dusB enhanced tolerance by prolonging the lag phase and reducing the growth rate. Moreover, the expression of genes in the CAMP pathway was up-regulated, and deletion of cpxR further promoted tolerance by modulating ribosome-associated genes. Integrated transcriptomic and metabolomic analyses indicated activation of the tricarboxylic acid (TCA) cycle during tolerance development. CONCLUSION: This study identified dusB and cpxR as key genes mediating enrofloxacin tolerance in P. multocida, elucidated the association between the antibiotic tolerance, growth, and gene expression, and may provide potential targets for future strategies aimed at limiting tolerance-associated resistance development.

Enrofloxacin↗
PubMed2006

Decoding the fine-scale structure of a breast cancer genome and transcriptome.

A comprehensive understanding of cancer is predicated upon knowledge of the structure of malignant genomes underlying its many variant forms and the molecular mechanisms giving rise to them. It is well established that solid tumor genomes accumulate a large number of genome rearrangements during tumorigenesis. End Sequence Profiling (ESP) maps and clones genome breakpoints associated with all types of genome rearrangements elucidating the structural organization of tumor genomes. Here we extend the ESP methodology in several directions using the breast cancer cell line MCF-7. First, targeted ESP is applied to multiple amplified loci, revealing a complex process of rearrangement and co-amplification in these regions reminiscent of breakage/fusion/bridge cycles. Second, genome breakpoints identified by ESP are confirmed using a combination of DNA sequencing and PCR. Third, in vitro functional studies assign biological function to a rearranged tumor BAC clone, demonstrating that it encodes anti-apoptotic activity. Finally, ESP is extended to the transcriptome identifying four novel fusion transcripts and providing evidence that expression of fusion genes may be common in tumors. These results demonstrate the distinct advantages of ESP including: (1) the ability to detect all types of rearrangements and copy number changes; (2) straightforward integration of ESP data with the annotated genome sequence; (3) immortalization of the genome; (4) ability to generate tumor-specific reagents for in vitro and in vivo functional studies. Given these properties, ESP could play an important role in a tumor genome project.

Breast Neoplasms↗
PubMed2004

Analysis of regulatory networks in Pseudomonas aeruginosa by genomewide transcriptional profiling.

Transcriptional profiling using DNA microarrays has proved to be a valuable tool for dissecting bacterial adaptation to various environments, including human hosts. Analysis of genomes and transcriptomes of Pseudomonas aeruginosa shows that this bacterium possesses and expresses a core set of genes, including virulence factors, which allow it to thrive in a range of environments. Transcriptional regulators previously thought to control single virulence traits are now shown to regulate complex global signaling networks. Microarray-based research has led to the discovery of upstream regulators and downstream components of these pathways, as well as probed the response to antibiotics, environmental stresses and other bacteria. Independent studies have highlighted the role of media composition, the makeup of the physical environment and experimental methods in the outcome of microarray analyses. A compilation of all the published data clearly shows transcriptional regulation of genes in all functional classes. Under conditions examined to date, slightly more than a quarter of the genome is regulated, suggesting that P. aeruginosa may use much of its genome for conditions unexplored in the laboratory.

Animals↗
PubMed2004

Molecular basis for catecholaminergic neuron diversity.

Catecholaminergic neurons control diverse cognitive, motor, and endocrine functions and are associated with multiple psychiatric and neurodegenerative disorders. We present global gene-expression profiles that define the four major classes of dopaminergic (DA) and noradrenergic neurons in the brain. Hypothalamic DA neurons and noradrenergic neurons in the locus coeruleus display distinct group-specific signatures of transporters, channels, transcription, plasticity, axon-guidance, and survival factors. In contrast, the transcriptomes of midbrain DA neurons of the substantia nigra and the ventral tegmental area are closely related with <1% of differentially expressed genes. Transcripts implicated in neural plasticity and survival are enriched in ventral tegmental area neurons, consistent with their role in schizophrenia and addiction and their decreased vulnerability in Parkinson's disease. The molecular profiles presented provide a basis for understanding the common and population-specific properties of catecholaminergic neurons and will facilitate the development of selective drugs.

Animals↗
PubMed2004

A technical trick for studying proteomics in parallel to transcriptomics in symbiotic root-fungus interactions.

We have developed a protocol in which proteins and mRNA can be analyzed from single root samples. This experimental design was validated in arbuscular mycorrhiza by comparing the proteins profiles obtained with those from a classical protein extraction process. It is a step forward to make simultaneous proteome and transcriptiome profiling possible.

Electrophoresis, Gel, Two-Dimensional↗
PubMed2003

Relevance network between chemosensitivity and transcriptome in human hepatoma cells.

Generally, hepatoma is not a chemosensitive tumor, and the mechanism of resistance to anticancer drugs is not fully elucidated. We aimed to comprehensively evaluate the relationship between chemosensitivity and gene expression profile in human hepatoma cells, by using microarray analysis, and analyze the data by constructing relevance networks. In eight hepatoma cell lines (HLE, HLF, Huh7, Hep3B, PLC/PRF/5, SK-Hep1, Huh6, and HepG2), the baseline expression levels of 2300 genes were measured by cDNA microarray. The concentrations of eight anticancer drugs (nimustine, mitomycin C, cisplatin, carboplatin, doxorubicin, epirubicin, mitoxantrone, and 5-fluorouracil) needed for 50% growth inhibition were examined and used as a measure of chemosensitivity. These data were combined and comprehensive pair-wise correlations between gene expression levels and the 50% growth inhibition values were calculated. Significant correlations with significance were used to construct networks of similarity. Fifty-two relations, including 42 genes, were selected. Among them, nearly 20% were various types of transporters, and most of them negatively correlated with chemosensitivity. Transporter associated with antigen processing 1 was associated with resistance to mitoxantrone, consistent with previous reports. Other transporters were not reported previously to associate with chemosensitivity. Resistance to doxorubicin and its analogue, epirubicin, were positively correlated with topoisomerase II beta expression, whereas it negatively correlated with expression of carboxypeptidases A3 and Z. Response to nimustine was associated with expression of superoxide dismutase 2. Relevance networks identified several negative correlations between gene expression and resistance, which were missed by hierarchical clustering. Our results suggested the necessity of systematically evaluating the transporting systems that may play a major role in resistance in hepatoma. This may provide useful information to modify anticancer drug action in hepatoma.

Antineoplastic Agents↗
PubMed2026

Transcriptomic and proteomic signatures following AS03-adjuvanted Influenza A/H7N9 vaccine.

INTRODUCTION: Vaccines targeting avian influenza virus A/H7N9 are poorly immunogenic. While the immune responses can be improved with oil-in-water emulsion adjuvants such as Adjuvant System 03 (AS03), the cellular mechanisms underpinning the adjuvant effect are incompletely characterized and poorly understood. METHODS: We enrolled 30 healthy adult participants and used RNA sequencing and quantitative proteomics to characterize the response to two doses of the influenza A/H7N9 vaccine, with and without AS03, in six immune cell types. These responses were compared to those seen after administration of an unadjuvanted seasonal in uenza A/H3N2 variant vaccine to identify signatures unique to adjuvanted influenza vaccines and correlated with later antibody responses. Transcriptomic and proteomic analyses revealed that. RESULTS: AS03-adjuvanted vaccine was associated with upregulation of immune pathways in innate immune cells within 24h following vaccination for phagocytosis, antigen presentation and processing, inflammasome activation, NK-cell mediated cytotoxicity, IgA production, and interferon-response pathways. Moreover, while major histocompatibility complex (MHC I and II) upregulation was observed across multiple immune cell types, MHCII gene transcription was also increased in the neutrophil compartment, generating the hypothesis that neutrophils may play a more important role in antigen presentation than previously understood. DISCUSSION: Taken together, these data provide a more complete mechanistic understanding of oil-in-water adjuvants and their role in enhancing the immune response for pandemic influenza preparedness. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT02921997?term=NCT02921997&viewType, idientifier NCT02921997.

Adult↗
PubMed2025

Deciphering Pseudoendocrine Sarcoma: A Clinicopathological, Molecular, and Epigenetic Study Suggesting Biological Links With Solid Pseudopapillary Neoplasm of the Pancreas.

Pseudoendocrine sarcoma (PS) is a recently described neoplasm of uncertain differentiation, characterized by recurrent CTNNB1 mutations, frequent paravertebral location, and a neuroendocrine-like histomorphology. In this study, we report the clinicopathologic, immunohistochemical, transcriptomic, and epigenetic findings of 12 PS cases. The tumors affected 7 men and 5 women with a median age of 66 years and were located in the paraspinal/paravertebral region (n = 11) and the thigh (n = 1). Median tumor size was 82 mm (range, 32-170 mm). Histologically, the tumors comprised sheets and nests of epithelioid-to-ovoid cells with uniform nuclei and speckled chromatin, frequently associated with extracellular hyaline globules and fibrovascular cords/septa. Uncommon findings included microcalcifications, myxoid stroma, pseudopapillary, pseudoglandular, microcystic or corded architecture, and lumen and rosette-like structures. Necrosis was absent, and mitotic activity was low. On immunohistochemistry, the tumors showed aberrant nuclear staining for beta-catenin (8/8) and expression of CD56 (7/7), S100 (8/8), desmin (2/6), and androgen receptor (1/4). Pankeratin (AE1/AE3), progesterone receptor, synaptophysin, chromogranin, and INSM1 were negative. All tested cases harbored CTNNB1 mutations. Using a customized cohort, methylation profiling revealed that PS formed a common cluster with solid pseudopapillary neoplasm of the pancreas (SPNP), distinct from all methylation classes from the Heidelberg sarcoma classifier and a subset of paragangliomas. Transcriptomic analysis showed that PS formed an independent cluster from a control group of tumors (including SPNP). Differential gene expression analysis showed enrichment in genes of the Wnt signaling pathway (HALLMARK gene sets) and biological processes related to sensory perception, among others (gene ontology - biological process [GO-BP]). Additionally, upregulated genes were related to various fetal cell types from the cell type signature data set (MSigDB), particularly of neuronal and epithelial lineage. Immunohistochemical assessment of potential markers identified through gene expression analysis revealed focal-to-diffuse expression of GLUT1 (6/6) and focal/multifocal expression of Brachyury (4/9) and HuD (3/7). Follow-up information, available for 10 cases (median duration of 18 months; range, 7-69 months), showed local recurrences and metastatic spread in 2 patients each. Evidence of response to radiotherapy was documented in one tumor. Altogether, this study expands knowledge on PS and suggests biological links with SPNP, including a potential shared cell of origin.

Humans↗
PubMed2002

SAGE identification of gene transcripts with profiles unique to pluripotent mouse R1 embryonic stem cells.

The identification of signals that regulate pluripotentiality and self-renewal is fundamental to the understanding of stem cell biology. To quantify the functionally active genome of pluripotent R1 embryonic stem (ES) cells, we used the method of serial analysis of gene expression (SAGE) to sequence a total of 140,313 SAGE tags. Of 44,569 unique transcripts, 9% matched known genes in the nonredundant GenBank database, whereas >35% of the unique tags did not match any known mouse sequence. Comparisons of relatively abundant (> or = 20) tags in the ES cell SAGE catalog with publicly available SAGE data sets identified 16 transcripts with an abundance profile unique to pluripotent R1 ES cells. We confirmed 12 by RT-PCR including those encoding KLF2, a transcription factor; galanin, a hypothalamic neurohormone; BAX, a proapoptotic signaling factor; and CDK4 and PAL31, cell cycle progression associated proteins. The data from this study provide a starting point for detailed transcriptome analyses of stem cells.

Animals↗
PubMed2006

Connexin43 and the brain transcriptome of newborn mice.

Our previously reported cDNA array datasets from neonatal wild-type and Cx43-/- (approved gene symbol Gja1) mouse brains were further analyzed to identify underlying interlinkages in the brain transcriptome. The analysis revealed that no gene cohort sharing either primary function or chromosomal location was significantly altered (up-and down-regulation were roughly balanced) in Cx43-/- brains, but each cohort exhibited significant perturbation of transcript abundance proportions and reduced expression variability and coordination. By comparing pairwise expression correlations of all genes with one another in wild-type brains, we found genes exhibiting remarkable similarity or opposition to the coordination profile (set of synergistically, antagonistically, and independently expressed partners) of Cx43, one of the most similar being pannexin1, a vertebrate homolog of invertebrate gap junction proteins. This study indicates striking redundancy of expression controls over functional pathways and suggests that certain genes may play roles similar to or opposite that of Cx43 in organizing the brain transcriptome.

Animals↗
PubMed2026

Genome-Wide Identification of the PAL Gene Family in Idesia polycarpa and Transcriptomic Responses to Botryosphaeria dothidea Infection.

Idesia polycarpa is a woody oil tree threatened by stem canker caused by Botryosphaeria dothidea, yet the organization and infection-responsive behavior of its phenylalanine ammonia-lyase (PAL) gene family remain poorly understood. Here, we identified five IpPAL genes and characterized their phylogenetic relationships, conserved features, duplication patterns, promoter cis-elements, and infection-associated expression profiles. Segmental and tandem duplication contributed to IpPAL family evolution, and all duplicated pairs showed Ka/Ks ratios below 1, consistent with purifying selection. RNA sequencing (RNA-seq) of contrasting Chengdu and Zhangjiajie provenances revealed distinct temporal responses. In Chengdu, IpPAL2-IpPAL4 were significantly upregulated at 24 h after inoculation, whereas all five genes were upregulated at 96 h. In Zhangjiajie, all five IpPAL genes were significantly upregulated at 24 h, while IpPAL2-IpPAL5 remained upregulated at 96 h. No IpPAL gene met the differential-expression criteria between provenances under mock conditions or at 24 h; at 96 h, IpPAL1 and IpPAL3 were lower and IpPAL5 was higher in Zhangjiajie than in Chengdu. Scanning electron microscopy (SEM) provided complementary qualitative evidence of provenance-associated tissue responses. These findings demonstrate time- and gene-specific IpPAL responses to B. dothidea and identify candidate genes for further functional analysis.

Ascomycota↗
PubMed2026

Integrated Multi-omics Profiling of 2,4-dinitrochlorobenzene (DNCB)-induced Atopic Dermatitis in Mice Reveals a Coordinated Network of Barrier Dysfunction, Immune Activation, and Metabolic Reprogramming.

Atopic dermatitis (AD) is caused by a combination of epidermal barrier defect and immune imbalance. However, the molecular networks between these structural abnormalities and metabolic variations are unclear. This study aim of this research was to examine the concurrent molecular alterations in skin barrier damage and metabolic disorders in an AD-like mouse model by a multi-omics strategy. A 2,4-dinitrochlorobenzene (DNCB)-induced AD-like mouse model was established and the skin tissues were examined through the combination of transcriptomic, quantitative proteomic, and metabolomic analyses. Cross-omics correlation and network analyses were performed to identify consistently abnormal molecular pathways and crucial regulatory molecules. DNCB treatment caused severe epidermal hyperplasia, and prominent infiltration of CD3&#x207a; T cells, F4/80&#x207a; macrophages, and mast cells. Transcriptomic and proteomic analysis indicated significant disruption in keratinocyte differentiation, extracellular matrix organization, and cornified envelope formation pathways. Combined analysis detected 171 molecules which were simultaneously altered at both mRNA and protein levels, and network analysis identified FLG2 and KRT6B as central barrier-related molecules. Pathway enrichment analysis consistently showed the participation of AMPK and PPAR signaling pathways. Metabolomic analysis also revealed coordinated changes in lipid and amino acid metabolism which were closely associated with cornified envelope-associated genes and collagen-modifying enzymes. These findings indicate a close relationship between barrier, immune and metabolic regulation in DNCB-induced dermatitis and provide a multi-omics resource for future mechanistic studies of atopic skin inflammation.

Animals↗
PubMed2026

Morphological changes and transcriptomic insights into skeletal development of embryos and larvae of the sea urchin Strongylocentrotus intermedius.

To explore morphological features and molecular dynamics underlying skeletogenesis in the sea urchin Strongylocentrotus intermedius, we conducted combined morphological observation and comparative transcriptome analyses across representative embryonic and larval developmental stages. Morphological results showed that triradiate spicules first emerged at the gastrula stage. The 8-arm pluteus stage was identified as a key phase for skeletal remodeling, during which new three-radiate crystals transformed into complex stereoscopic ossicles including tube feet, spines and test plates. Transcriptomic data indicated that most differentially expressed genes (DEGs) were downregulated from the blastula to gastrula. The altered expression of basal metabolic genes and extracellular matrix genes including Colp2&#x3b1; and calm may be correlated with the linear mineralization of early spicules, which potentially reflects an energy adjustment pattern in developing larvae. During the transition from 6-arm to 8-arm pluteus, expression changes of calmodulin-like, Colp2&#x3b1; and SISin18G001660 suggest potential associations with regional calcium deposition and modifications of skeletal matrix properties. This work systematically characterizes morphological traits and transcriptional dynamics of skeletogenesis in S. intermedius. Its early spiculogenesis follows the conserved developmental pattern of echinoderms, while massive formation of stereoscopic ossicles occurs at the 8-arm pluteus stage. Stage-specific transcriptional changes across key larval skeletogenic stages are uncovered, offering transcriptomic resources for functional verification of skeletal regulatory genes.

Animals↗
PubMed2006

Mass spectrometric analysis of N- and O-glycosylation of tissues and cells.

Mass spectrometry has been at the forefront of glycobiological analysis for more than two decades. Recent advances in technology, coupled with increased global appreciation of the importance of the glycome in solving biological problems, have laid the foundations for an unprecedented increase in output. Under the auspices of major international consortia, significant progress is being made towards the development of integrated databases of specific cell and tissue N- and O-glycan profiles. Tools for the automation of both sample handling and data analysis are enabling a more concerted approach to glycan structural analysis. When combined with complementary transcriptomics and bioinformatics analyses, these tools will facilitate a new systems glycobiology approach to research.

Animals↗
PubMed2025

Integrated histopathology, spatial and single cell transcriptomics resolve cellular drivers of early and late alveolar damage in COVID-19.

The most common cause of death due to COVID-19 remains respiratory failure. Yet, our understanding of the precise cellular and molecular changes underlying lung alveolar damage is limited. Here, we integrate single cell transcriptomic data of COVID-19&#xa0;and donor lung&#xa0;tissue with spatial transcriptomic data stratifying histopathological stages of diffuse alveolar damage. We identify changes in cellular composition across progressive damage, including waves of molecularly distinct macrophages and depletion of epithelial and endothelial populations. Predicted markers of pathological states identify immunoregulatory signatures, including IFN-alpha and metallothionein signatures in early damage, and fibrosis-related collagens in late damage. Furthermore, we predict a fibrinolytic shutdown via endothelial upregulation of SERPINE1/PAI-1. Cell-cell interaction analysis revealed macrophage-derived SPP1/osteopontin signalling as a key regulator during early steps of alveolar damage. These results provide a comprehensive, spatially resolved atlas of alveolar damage progression in COVID-19, highlighting the cellular mechanisms underlying pro-inflammatory and pro-fibrotic pathways in severe disease.

COVID-19↗
PubMed2025

The offonome reveals on and off states of gene expression near the detection limit of RNA-seq.

RNA-seq, widely used for gene expression profiling, provides nucleotide level genome coverage and summary gene expression values. Generally, low-expressed genes are ignored due to their unfavorable signal-to-noise ratio, however, these genes may offer crucial information, such as detecting rare cells in bulk tissues. In this study, we applied an approach that transforms the expression levels of low-expressed genes into a robust dichotomized on/off state by leveraging similarities in transcript coverage shape. Applied to three human cancer cohorts from the Cancer Genome Atlas (TCGA), chosen based on tissue morphology and anatomic site, we identified genes, the "offonome" near the detection limit, consistently or occasionally off across samples. Genes in the offonome spectrum proved useful for supervised and unsupervised applications, including characterizing oncogenic pathways, and identifying rare populations of cells in bulk tissue. Interrogating the offonome is relevant to bulk tumor analyses like TCGA, potentially expediting gene investigation in low-input situations like single cell RNA-seq.

Humans↗