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Results for “Comparative transcriptomics”

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PubMed2005

Circulating transcriptome reveals markers of atherosclerosis.

Circulating monocytes mediate inflammation in atherosclerosis and may serve as easily accessible reporters of disease. To search for markers of atherosclerosis, we compared the in vivo transcriptomes of monocytes purified from patients undergoing carotid endarterectomy and normal subjects by using the serial analysis of gene expression technique. We selected a subset of differentially expressed monocyte-specific genes and confirmed their expression levels. The Finkel-Biskis-Jinkins osteosarcoma (FOS) gene was significantly increased in patients, and the highest levels of FOS associated with patients who had previously undergone coronary revascularization. The correlation between coronary revascularization and FOS was higher than that compared with the cardiac risk marker high sensitivity C-reactive protein. In vitro inhibition of FOS using small interfering RNA and 3-hydroxy-3-methyl-glutaryl CoA reductase inhibitor simvastatin (statin) affected monocyte activation and suggested an important role in pathogenesis. Given the prominent role of FOS in inflammation and calcification, its association with atherosclerosis severity has clear pathophysiologic bases as well as clinical implications as a marker. Our results suggest that analysis of gene expression in circulating cells may provide biological and clinical insights into human atherosclerosis, and that this type of approach may be applicable for studying other types of diseases.

Arteriosclerosis↗

PubMed2005

Comparative genomics of nematodes.

Recent transcriptome and genome projects have dramatically expanded the biological data available across the phylum Nematoda. Here we summarize analyses of these sequences, which have revealed multiple unexpected results. Despite a uniform body plan, nematodes are more diverse at the molecular level than was previously recognized, with many species- and group-specific novel genes. In the genus Caenorhabditis, changes in chromosome arrangement, particularly local inversions, are also rapid, with breakpoints occurring at 50-fold the rate in vertebrates. Tylenchid plant parasitic nematode genomes contain several genes closely related to genes in bacteria, implicating horizontal gene transfer events in the origins of plant parasitism. Functional genomics techniques are also moving from Caenorhabditis elegans to application throughout the phylum. Soon, eight more draft nematode genome sequences will be available. This unique resource will underpin both molecular understanding of these most abundant metazoan organisms and aid in the examination of the dynamics of genome evolution in animals.

Animals↗

PubMed2026

Integrated transcriptomic and metabolomic analyses reveal key regulators associated with lipid metabolic differences between subcutaneous and visceral adipose tissues in sheep.

The location of fat deposition has a significant impact on meat quality and body health, and different adipose tissues exhibit significant differences in lipid metabolism and immune regulation. This study aimed to systematically compare the phenotypic characteristics, transcriptome, and metabolome of subcutaneous adipose tissue (SAT) and two types of visceral adipose tissue (VAT) in sheep, in order to reveal the metabolic differences between SAT and VAT and their potential regulatory mechanisms. The results showed that compared with VAT, SAT had stronger triglyceride deposition ability and obvious cellular hypertrophy. Through integrative analysis, 15 key lipid metabolism genes and 12 differential metabolites were identified. Among them, ACACA, FASN, ELOVL6, SCD, as well as metabolites palmitic acid and glycerol-3-phosphate, may play a central role in SAT lipid synthesis and storage; whereas IGFBP2, ADRB3, LTA4H, and metabolites arachidonic acid and leukotriene B4 may be involved in the lipolysis regulation and inflammatory response of VAT. These findings may provide deeper insights into the regulatory mechanisms of fat deposition in sheep.

Animals↗

PubMed2024

Single-tissue proteomics in Caenorhabditis elegans reveals proteins resident in intestinal lysosome-related organelles.

The nematode intestine is the primary site for nutrient uptake and storage as well as the synthesis of biomolecules; lysosome-related organelles known as gut granules are important for many of these functions. Aspects of intestine biology are not well understood, including the export of the nutrients it imports and the molecules it synthesizes, as well as the complete functions and protein content of the gut granules. Here, we report a mass spectrometry (MS)-based proteomic analysis of the intestine of the Caenorhabditis elegans and of its gut granules. Overall, we identified approximately 5,000 proteins each in the intestine and the gonad and showed that most of these proteins can be detected in samples extracted from a single worm, suggesting the feasibility of individual-level genetic analysis using proteomes. Comparing proteomes and published transcriptomes of the intestine and the gonad, we identified proteins that appear to be synthesized in the intestine and then transferred to the gonad. To identify gut granule proteins, we compared the proteome of individual intestines deficient in gut granules to the wild type. The identified gut granule proteome includes proteins known to be exclusively localized to the granules and additional putative gut granule proteins. We selected two of these putative gut granule proteins for validation via immunohistochemistry, and our successful confirmation of both suggests that our strategy was effective in identifying the gut granule proteome. Our results demonstrate the practicability of single-tissue MS-based proteomic analysis in small organisms and in its future utility.

Animals↗

PubMed2001

What we could do now: molecular pathology of bladder cancer.

There is much information on the genetic alterations that contribute to the development of bladder cancer. Because it is hypothesised that the genotype of the cancer cell plays a major role in determining phenotype, this genetic information should impact on clinical practice. To date however, this has not happened. Some of the alterations identified in bladder cancer have clear associations with outcome-for example, mutational inactivation of the cell cycle regulator proteins p53 and the retinoblastoma protein (Rb). However, as single markers, these events have insufficient predictive power to be applied in the management of individual patients. The use of panels of markers is a potential solution to this problem. Examples of suitable panels include those genes/proteins with known impact on specific cell cycle checkpoints or with impact on cellular phenotypes, such as immortalisation, invasion, or metastasis. To evaluate such marker panels, large tumour series will be needed-for example, archival samples from completed clinical trials. The use of these valuable resources will require coordination of sample provision. This might involve central collection and distribution of tissue blocks, sections, or tissue arrays and the provision of patient follow up information to laboratories participating in a study. With the availability of microarray technologies, including cDNA and comparative genomic hybridisation arrays, the transcriptome and genome of transitional cell carcinomas of different phenotypes can be compared and will undoubtedly provide a wealth of information with potential diagnostic and prognostic uses. Although these studies can be initiated using small local tissue collections, high quality collection of fresh tissues from new clinical trials will be crucial for proper evaluation of associations with clinical outcome. Funding for molecular pathological studies to date has been poor. To begin to translate molecular information from the laboratory to the clinic and to make maximum use of valuable urological patient resources in the UK, adequate funding and scientific energy are required. Whereas the latter is not in doubt, present funding for this type of translational research is inadequate.

Carcinoma, Transitional Cell↗

PubMed2025

The extracellular vesicle transcriptome provides tissue-specific functional genomic annotation relevant to disease susceptibility in obesity.

We characterized circulating extracellular vesicles (EVs) in obese and lean humans, identifying transcriptional cargo differentially expressed in obesity (277 unique genes; false discovery rate < 10%). Since circulating EVs may have broad origin, we compared this obesity EV transcriptome with expression from human visceral-adipose-tissue-derived EVs from freshly collected and cultured biopsies from the same obese individuals, observing high concordance. Using a comprehensive set of adipose-specific epigenomic and chromatin conformation assays, we found that the differentially expressed transcripts from the EVs were those regulated in adipose by body mass index-associated SNPs (p < 5 × 10-8) from a large-scale genome-wide association study (GWAS). Using a phenome-wide association study of the regulatory SNPs for the EV-derived transcripts, we identified a substantial enrichment for inflammatory phenotypes, including type 2 diabetes. Collectively, these findings represent the convergence of the GWAS (genetics), epigenomics (transcript regulation), and EV (liquid biopsy) fields, enabling powerful future genomic studies of complex diseases.

Humans↗

PubMed2005

Global transcriptome analysis of the C57BL/6J mouse testis by SAGE: evidence for nonrandom gene order.

BACKGROUND: We generated the gene expression profile of the total testis from the adult C57BL/6J male mice using serial analysis of gene expression (SAGE). Two high-quality SAGE libraries containing a total of 76 854 tags were constructed. An extensive bioinformatic analysis and comparison of SAGE transcriptomes of the total testis, testicular somatic cells and other mouse tissues was performed and the theory of male-biased gene accumulation on the X chromosome was tested. RESULTS: We sorted out 829 genes predominantly expressed from the germinal part and 944 genes from the somatic part of the testis. The genes preferentially and specifically expressed in total testis and testicular somatic cells were identified by comparing the testis SAGE transcriptomes to the available transcriptomes of seven non-testis tissues. We uncovered chromosomal clusters of adjacent genes with preferential expression in total testis and testicular somatic cells by a genome-wide search and found that the clusters encompassed a significantly higher number of genes than expected by chance. We observed a significant 3.2-fold enrichment of the proportion of X-linked genes specific for testicular somatic cells, while the proportions of X-linked genes specific for total testis and for other tissues were comparable. In contrast to the tissue-specific genes, an under-representation of X-linked genes in the total testis transcriptome but not in the transcriptomes of testicular somatic cells and other tissues was detected. CONCLUSION: Our results provide new evidence in favor of the theory of male-biased genes accumulation on the X chromosome in testicular somatic cells and indicate the opposite action of the meiotic X-inactivation in testicular germ cells.

Animals↗

PubMed2026

Integrated metabolomic, transcriptomic, and proteomic analyses reveal changes in the non-volatile metabolite profile of LED light-withered oolong tea.

LED light withering is a crucial method for overcoming weather limitations and enhancing the quality of oolong tea. To elucidate the underlying molecular mechanisms, this study simulated solar spectra using multiwavelength LED light and compared the resulting metabolic, transcriptomic, and proteomic profiles during the enzymatic-catalysis process (ECP) in oolong tea processing. Results indicated that LED light withering altered gene expression and protein regulation of secondary metabolism, particularly in the flavonoid biosynthesis pathway. These shifts encompassed key quality-related compounds, including flavonoids (quercetin-3-O-rhamnoside, dihydroquercetin), amino acids (L-asparagine, L-histidine), guanosine 5'-monophosphate (GMP), and carbohydrates. Furthermore, LED light withering accelerated tea leaf water loss, influenced gene expression involved in photosynthetic cellular components (chloroplasts, thylakoids), increased ascorbate peroxidase regulation under stress, and subsequently modulated energy metabolism and signal transduction in tea leaves. This study offers molecular theoretical framework for the controlled light-withering of oolong tea under bad weather and the associated improvements in its quality.

Camellia sinensis↗

PubMed2026

Endurance training attenuates acute exercise-induced monocyte transcriptomic responses in adolescents: sex-specific molecular adaptations.

Circulating monocytes contribute to atherogenesis and vascular dysfunction. Although clinical cardiovascular disease presents in adulthood, its biological origins often begin in youth and differ substantially between females and males. Twelve males and nine females (13-17 yr) completed an acute exercise protocol consisting of 10, 2-min cycling bouts at 70% of maximal work rate interspersed with 1-min rest intervals, performed before and after an 8-wk supervised endurance training intervention with brief supplementary strength work (60 min/session, 3 sessions/wk). Blood was collected before and immediately after each exercise challenge. Peripheral blood monocytes were isolated, and whole transcriptome RNA sequencing (RNA-seq) was performed. Before training, acute exercise induced a markedly greater monocyte transcriptomic response in females compared with males [5,135 vs. 567 differentially expressed transcripts, false discovery rate (FDR) < 0.1]. Pathway analyses identified vascular function-related pathways in males, whereas females showed enrichment of pathways related to adipose tissue cross talk and oxidative metabolism. Following training, the acute transcriptomic response was markedly attenuated in both sexes (165 transcripts in males and 94 in females, FDR < 0.1), representing an ∼98% reduction in females and a ∼70% reduction in males relative to pre-training responses. These findings reveal sex-specific monocyte responses to acute exercise in youth and suggest that endurance exercise alters immune transcriptional responsiveness in pathways relevant to vascular and cardiovascular health.NEW & NOTEWORTHY Acute exercise induced a markedly greater monocyte transcriptomic response in female adolescents than in males. Females showed activation of pathways related to adipose tissue signaling and oxidative metabolism, whereas males exhibited vascular-function pathways. Following exercise training, the monocyte transcriptomic response to acute exercise was substantially attenuated in both sexes. These findings identify sex-specific immune transcriptional responses to exercise during adolescence with potential implications for cardiovascular health.

Humans↗

PubMed2025

Functional characterization of the MED12 p.Arg1138Trp variant in females: implications for neural development and disease mechanism.

BACKGROUND: Seven female individuals with multiple congenital anomalies, developmental delay and/or intellectual disability have been found to have a genetic variant of uncertain significance in the mediator complex subunit 12 gene (MED12 c.3412C>T, p.Arg1138Trp). The functional consequence of this genetic variant in disease is undetermined, and insight into disease mechanism is required. METHODS: We identified a de novo MED12 p.Arg1138Trp variant in a female patient and compared disease phenotypes with six female individuals identified in the literature. To investigate affected biological pathways, we derived two induced pluripotent stem cell (iPSC) lines from the patient: one expressing wildtype MED12 and the other expressing the MED12 p.Arg1138Trp variant. We performed neural disease modelling, transcriptomics and protein analysis, comparing healthy and variant cells. RESULTS: When comparing the two cell lines, we identified altered gene expression in neural cells expressing the variant, including genes regulating RNA polymerase II activity, transcription, pre-mRNA processing, and neural development. We also noted a decrease in MED12L expression. Pathway analysis indicated temporal delays in axon development, forebrain differentiation, and neural cell specification with significant upregulation of pre-ribosome complex gene pathways. CONCLUSION: In a human neural model, expression of MED12 p.Arg1138Trp altered neural cell development and dysregulated the pre-ribosome complex providing functional evidence of disease aetiology and mechanism in MED12-related disorders.

Humans↗

PubMed2005

In vivo transcriptome of Plasmodium falciparum reveals overexpression of transcripts that encode surface proteins.

Infections with the human parasite Plasmodium falciparum continue to present a great challenge to global health. Fundamental questions regarding the molecular basis of virulence and immune evasion in P. falciparum have been only partially answered. Because of the parasite's intracellular location and complex life cycle, standard genetic approaches to the study of the pathogenesis of malaria have been limited. The present study presents a novel approach to the identification of the biological processes involved in host-pathogen interactions, one that is based on the analysis of in vivo P. falciparum transcripts. We demonstrate that a sufficient quantity of P. falciparum RNA transcripts can be derived from a small blood sample from infected patients for whole-genome microarray analysis. Overall, excellent correlation was observed between the transcriptomes derived from in vivo samples and in vitro samples with ring-stage P. falciparum 3D7 reference strain. However, gene families that encode surface proteins are overexpressed in vivo. Moreover, this analysis has identified a new family of hypothetical genes that may encode surface variant antigens. Comparative studies of the transcriptomes derived from in vivo samples and in vitro 3D7 samples may identify important strategies used by the pathogen for survival in the human host and highlight, for vaccine development, new candidate antigens that were not previously identified through the use of in vitro cultures.

Adaptation, Physiological↗

PubMed2005

Analysis of the Macaca mulatta transcriptome and the sequence divergence between Macaca and human.

We report the initial sequencing and comparative analysis of the Macaca mulatta transcriptome. Cloned sequences from 11 tissues, nine animals, and three species (M. mulatta, M. fascicularis, and M. nemestrina) were sampled, resulting in the generation of 48,642 sequence reads. These data represent an initial sampling of the putative rhesus orthologs for 6,216 human genes. Mean nucleotide diversity within M. mulatta and sequence divergence among M. fascicularis, M. nemestrina, and M. mulatta are also reported.

Animals↗

PubMed2025

Host-Associated Genetic Differentiation in the Face of Ongoing Gene Flow: Ecological Speciation in a Pathogenic Parasite of Freshwater Fish.

Adaptive evolution in response to varying environments, leading to population divergence, is among the most intriguing processes of speciation. However, the extent to which these adaptive processes effectively drive population divergence amidst ongoing gene flow remains controversial. Our study addresses this by analyzing population genetic structure, gene flow, and genomic divergence between lineages of a tapeworm parasite (Ligula intestinalis) isolated from sympatric fish hosts. This parasite, which must overcome host immunological defenses for successful infection, significantly impacts host health. Utilizing genome-wide Single Nucleotide Polymorphisms (SNPs) and transcriptome data, we investigated whether host species impose distinct selection pressures on parasite populations. Genetic clustering analyses revealed clear divergence, with parasites from bream (Abramis brama) forming a distinct genetic cluster separate from those infecting roach (Rutilus rutilus), rudd (Scardinius erythrophthalmus), and bleak (Alburnus alburnus). Demographic modeling indicated isolation with continuous gene flow as the most plausible scenario for this divergence. Selection analyses identified 896 SNPs under selection, displaying low to moderate nucleotide diversity and genetic divergence compared with neutral loci. Transcriptome profiling supported these findings, revealing distinct gene expression profiles between parasite populations. Examination of selected SNPs and differentially expressed genes identified candidate genes linked to immune evasion mechanisms, potentially driving ecological speciation. This research highlights the interplay of host specificity, population demography, and disruptive selection in ecological speciation. By dissecting genomic factors, our study improves the understanding of mechanisms facilitating population divergence despite ongoing gene flow.

Animals↗

PubMed2002

The dynamics of the Saccharomyces carlsbergensis brewing yeast transcriptome during a production-scale lager beer fermentation.

The transcriptome of a lager brewing yeast (Saccharomyces carlsbergensis, syn. of S. pastorianus), was analysed at 12 different time points spanning a production-scale lager beer fermentation. Generally, the average expression rapidly increased and had a maximum value on day 2, then decreased as the sugar got consumed. Especially genes involved in protein and lipid biosynthesis or glycolysis were highly expressed during the beginning of the fermentation. Similarities as well as significant differences in expression profiles could be observed when comparing to a previous transcriptome analysis of a laboratory yeast grown in YPD. The regional distribution of various expression levels on the chromosomes appeared to be random or near-random and no reduction in expression near telomeres was observed.

Beer↗

PubMed2004

Plasticity of mouse renal collecting duct in response to potassium depletion.

Plasticity of mouse renal collecting duct in response to potassium depletion.--Renal collecting ducts are the main sites for regulation of whole body potassium balance. Changes in dietary intake of potassium induce pleiotropic adaptations of collecting duct cells, which include alterations of ion and water transport properties along with an hypertrophic response. To study the pleiotropic adaptation of the outer medullary collecting duct (OMCD) to dietary potassium depletion, we combined functional studies of renal function (ion, water, and acid/base handling), analysis of OMCD hypertrophy (electron microscopy) and hyperplasia (PCNA labeling), and large scale analysis of gene expression (transcriptome analysis). The transcriptome of OMCD was compared in mice fed either a normal or a potassium-depleted diet for 3 days using serial analysis of gene expression (SAGE) adapted for downsized extracts. SAGE is based on the generation of transcript-specific tag libraries. Approximately 20,000 tags corresponding to 10,000 different molecular species were sequenced in each library. Among the 186 tags differentially expressed (P < 0.05) between the two libraries, 120 were overexpressed and 66 were downregulated. The SAGE expression profile obtained in the control library was representative of different functional classes of proteins and of the two cell types (principal and alpha-intercalated cells) constituting the OMCD. Combined with gene expression analysis, results of functional and morphological studies allowed us to identify candidate genes for distinct physiological processes modified by potassium depletion: sodium, potassium, and water handling, hyperplasia and hypertrophy. Finally, comparison of mouse and human OMCD transcriptomes allowed us to address the question of the relevance of the mouse as a model for human physiology and pathophysiology.

Acid-Base Equilibrium↗

PubMed2005

Circadian profiling of the transcriptome in immortalized rat SCN cells.

Endogenous oscillations in gene expression are a prevalent feature of the circadian clock in the mammalian suprachiasmatic nucleus (SCN) and similar timekeeping systems in other organisms. To determine whether immortalized cells derived from the rat SCN (SCN2.2) retain these intrinsic rhythm-generating properties, oscillatory behavior of the SCN2.2 transcriptome was analyzed and compared with that found in the rat SCN in vivo using rat U34A Affymetrix GeneChips. In SCN2.2 cells, 116 unique genes and 46 ESTs or genes of unknown function exhibited circadian fluctuations with a 1.5-fold or greater difference in their mRNA abundance for two cycles. Many (35%) of these rhythmically regulated genes in SCN2.2 cells also exhibited circadian profiles of mRNA expression in the rat SCN in vivo. Functional analyses and cartography indicate that a diverse set of cellular pathways are strategically regulated by the circadian clock in SCN2.2 cells and that the largest categories of rhythmic genes are those involved in cellular and systems-level communication or in metabolic processes like cellular respiration, fatty acid recycling, and steroid synthesis. Because many of the same genes or nodes within these functional categories were rhythmically expressed in both SCN2.2 cells and the rat SCN, the circadian regulation of these pathways may be important in modulating input to or output from the SCN clock mechanism. In summary, global expression and circadian regulation of the SCN2.2 transcriptome retain many SCN-like properties, suggesting that genes displaying rhythmic profiles in both experimental models may be integral to their function as both circadian oscillators and pacemakers.

Animals↗

PubMed2006

Differential disruption of cell cycle pathways in small cell and non-small cell lung cancer.

Lung cancer is the leading cause of cancer-related mortality in the world, with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) comprising the two major cell types. Although these cell types can be distinguished readily at the histological level, knowledge of their underlying molecular differences is very limited. In this study, we compared 14 SCLC cell lines against 27 NSCLC cell lines using an integrated array comparative genomic hybridisation and gene expression profiling approach to identify subtype-specific disruptions. Using stringent criteria, we have identified 159 of the genes that are responsible for the different biology of these cell types. Sorting of these genes by their biological functions revealed the differential disruption of key components involved in cell cycle pathways. Our novel comparative combined genome and transcriptome analysis not only identified differentially altered genes, but also revealed that certain shared pathways are preferentially disrupted at different steps in these cell types. Small cell lung cancer exhibited increased expression of MRP5, activation of Wnt pathway inhibitors, and upregulation of p38 MAPK activating genes, while NSCLC showed downregulation of CDKN2A, and upregulation of MAPK9 and EGFR. This information suggests that cell cycle upregulation in SCLC and NSCLC occurs through drastically different mechanisms, highlighting the need for differential molecular target selection in the treatment of these cancers.

Carcinoma, Non-Small-Cell Lung↗

PubMed2006

Molecular dynamics of the Shewanella oneidensis response to chromate stress.

Temporal genomic profiling and whole-cell proteomic analyses were performed to characterize the dynamic molecular response of the metal-reducing bacterium Shewanella oneidensis MR-1 to an acute chromate shock. The complex dynamics of cellular processes demand the integration of methodologies that describe biological systems at the levels of regulation, gene and protein expression, and metabolite production. Genomic microarray analysis of the transcriptome dynamics of midexponential phase cells subjected to 1 mm potassium chromate (K(2)CrO(4)) at exposure time intervals of 5, 30, 60, and 90 min revealed 910 genes that were differentially expressed at one or more time points. Strongly induced genes included those encoding components of a TonB1 iron transport system (tonB1-exbB1-exbD1), hemin ATP-binding cassette transporters (hmuTUV), TonB-dependent receptors as well as sulfate transporters (cysP, cysW-2, and cysA-2), and enzymes involved in assimilative sulfur metabolism (cysC, cysN, cysD, cysH, cysI, and cysJ). Transcript levels for genes with annotated functions in DNA repair (lexA, recX, recA, recN, dinP, and umuD), cellular detoxification (so1756, so3585, and so3586), and two-component signal transduction systems (so2426) were also significantly up-regulated (p < 0.05) in Cr(VI)-exposed cells relative to untreated cells. By contrast, genes with functions linked to energy metabolism, particularly electron transport (e.g. so0902-03-04, mtrA, omcA, and omcB), showed dramatic temporal alterations in expression with the majority exhibiting repression. Differential proteomics based on multidimensional HPLC-MS/MS was used to complement the transcriptome data, resulting in comparable induction and repression patterns for a subset of corresponding proteins. In total, expression of 2,370 proteins were confidently verified with 624 (26%) of these annotated as hypothetical or conserved hypothetical proteins. The initial response of S. oneidensis to chromate shock appears to require a combination of different regulatory networks that involve genes with annotated functions in oxidative stress protection, detoxification, protein stress protection, iron and sulfur acquisition, and SOS-controlled DNA repair mechanisms.

Anion Transport Proteins↗