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At least 415 records · Page 23Linked to original sources
PubMed2003

Dose-dependent transcriptome changes by metal ores on a human acute lymphoblastic leukemia cell line.

The increased morbidity of childhood leukemia in Fallon, Nevada and Sierra Vista, Arizona has prompted great health concern. The main characteristic that these two towns share is the environmental pollution attributed to metal ore from abandoned mining operations. Consequently, we have investigated the transcriptome effects of metal ores from these endemic areas using a human T-cell acute lymphoblastic leukemia cell line (T-ALL). Metal ore from Fallon significantly increased cell growth after 24, 48 and 72 h of incubation at 1.5 microg/mL concentration, as measured by trypan-blue. Sierra Vista ore significantly increased cell growth with 0.15 and 1.5 microg/mL following 72 h of incubation. From human cDNA microarray, results indicate that in total, eight genes, mostly metallothionein (MT) genes, were up-regulated and 10 genes were down-regulated following treatment of the T-ALL cells with 0.15 and 1.5 microg/mL of metal ores at 72 h, in comparison with untreated cells. Twenty-eight metals of both ores were quantified and their presence may be associated with the cell growth rate and dose-dependent activation of transcriptomes in immature T-cells.

Arizona↗
PubMed2005

Transcriptome and proteome analysis of soleus muscle of hormone-sensitive lipase-null mice.

Hormone-sensitive lipase (HSL), a key enzyme in fatty acid mobilization in adipocytes, has been demonstrated also in skeletal muscle. To gain further insight into the role and importance of HSL in skeletal muscle, a transcriptome analysis of soleus muscle of HSL-null mice was performed. A total of 161 transcripts were found to be differentially expressed. Increased mRNA levels of fructose-1,6-bisphosphatase, fructose-2,6-bisphosphatase, and phosphorylase kinase gamma1A suggest a higher glycogen flux in soleus muscle of HSL-null mice. An observed increase in the utilization of glycogen stores supports this finding. Moreover, an increased amount of intramyocellular lipid droplets, observed by transmission electron microscopy, suggests decreased mobilization of lipid stores in HSL-null mice. To complement the transcriptome data, protein expression analysis was performed. Five spots were found to be differentially expressed: pyruvate dehydrogenase E1alpha, creatine kinase (CK), ankyrin-repeat domain 2, glyceraldehyde-3-phosphate dehydrogenase, and one protein yet to be identified. The increased protein level of CK indicates creatine phosphate degradation to be of increased importance in HSL-null mice. The results of this study suggest that in the absence of HSL, a metabolic switch from reliance on lipid to carbohydrate energy substrates takes place, supporting an important role of HSL in soleus muscle lipid metabolism.

Animals↗
PubMed2003

Composition and dynamics of the Caenorhabditis elegans early embryonic transcriptome.

Temporal profiles of transcript abundance during embryonic development were obtained by whole-genome expression analysis from precisely staged C. elegans embryos. The result is a highly resolved time course that commences with the zygote and extends into mid-gastrulation, spanning the transition from maternal to embryonic control of development and including the presumptive specification of most major cell fates. Transcripts for nearly half (8890) of the predicted open reading frames are detected and expression levels for the majority of them (>70%) change over time. The transcriptome is stable up to the four-cell stage where it begins rapidly changing until the rate of change plateaus before gastrulation. At gastrulation temporal patterns of maternal degradation and embryonic expression intersect indicating a mid-blastula transition from maternal to embryonic control of development. In addition, we find that embryonic genes tend to be expressed transiently on a time scale consistent with developmental decisions being made with each cell cycle. Furthermore, overall rates of synthesis and degradation are matched such that the transcriptome maintains a steady-state frequency distribution. Finally, a versatile analytical platform based on cluster analysis and developmental classification of genes is provided.

Animals↗
PubMed2004

Detection and evaluation of intron retention events in the human transcriptome.

Alternative splicing is a very frequent phenomenon in the human transcriptome. There are four major types of alternative splicing: exon skipping, alternative 3' splice site, alternative 5' splice site, and intron retention. Here we present a large-scale analysis of intron retention in a set of 21,106 known human genes. We observed that 14.8% of these genes showed evidence of at least one intron retention event. Most of the events are located within the untranslated regions (UTRs) of human transcripts. For those retained introns interrupting the coding region, the GC content, codon usage, and the frequency of stop codons suggest that these sequences are under selection for coding potential. Furthermore, 26% of the introns within the coding region participate in the coding of a protein domain. A comparison with mouse shows that at least 22% of all informative examples of retained introns in human are also present in the mouse transcriptome. We discuss that the data we present suggest that a significant fraction of the observed events is not spurious and might reflect biological significance. The analyses also allowed us to generate a reliable set of intron retention events that can be used for the identification of splicing regulatory elements.

Animals↗
PubMed2002

Transcriptome analysis of acetate metabolism in Corynebacterium glutamicum using a newly developed metabolic array.

Following the determination of the whole-genome sequence of Corynebacterium glutamicum, we have developed a DNA array to extensively investigate gene expression and regulation relevant to carbon metabolism. For this purpose, a total of 120 C. glutamicum genes, including those in central metabolism and amino acid biosyntheses, were amplified by PCR and printed onto glass slides. The resulting array, designated a "metabolic array", was used for hybridization with fluorescently labeled cDNA probes generated by reverse transcription from total RNA samples. As the first demonstration of transcriptome analysis in this industrially important microorganism, we applied the metabolic array to study differential transcription profiles between cells grown on glucose and on acetate as the sole carbon source. The changes in gene expression observed for the known acetate-regulated genes (aceA, aceB, pta, and ack) were well consistent with the literature data of northern analyses and enzyme assays, indicating the utility of the metabolic array in transcriptome analysis of C. glutamicum. In addition to the known responses, many previously unrecognized co-regulated genes were identified. For example, several TCA cycle genes, such as gltA, sdhA, sdhB, fumH, and mdh, and the gluconeogenic gene pck were up-regulated in the acetate medium. On the other hand, a few genes involved in glycolysis and the pentose phosphate pathway, as well as many amino acid biosynthetic genes, were down-regulated in acetate. Furthermore, two gap genes, gapA and gapB, were found to be inversely regulated, suggesting the presence of a new regulatory step for carbon metabolism between glycolysis and gluconeogenesis.

Acetates↗
PubMed2003

The transcriptome of the intraerythrocytic developmental cycle of Plasmodium falciparum.

Plasmodium falciparum is the causative agent of the most burdensome form of human malaria, affecting 200-300 million individuals per year worldwide. The recently sequenced genome of P. falciparum revealed over 5,400 genes, of which 60% encode proteins of unknown function. Insights into the biochemical function and regulation of these genes will provide the foundation for future drug and vaccine development efforts toward eradication of this disease. By analyzing the complete asexual intraerythrocytic developmental cycle (IDC) transcriptome of the HB3 strain of P. falciparum, we demonstrate that at least 60% of the genome is transcriptionally active during this stage. Our data demonstrate that this parasite has evolved an extremely specialized mode of transcriptional regulation that produces a continuous cascade of gene expression, beginning with genes corresponding to general cellular processes, such as protein synthesis, and ending with Plasmodium-specific functionalities, such as genes involved in erythrocyte invasion. The data reveal that genes contiguous along the chromosomes are rarely coregulated, while transcription from the plastid genome is highly coregulated and likely polycistronic. Comparative genomic hybridization between HB3 and the reference genome strain (3D7) was used to distinguish between genes not expressed during the IDC and genes not detected because of possible sequence variations. Genomic differences between these strains were found almost exclusively in the highly antigenic subtelomeric regions of chromosomes. The simple cascade of gene regulation that directs the asexual development of P. falciparum is unprecedented in eukaryotic biology. The transcriptome of the IDC resembles a "just-in-time" manufacturing process whereby induction of any given gene occurs once per cycle and only at a time when it is required. These data provide to our knowledge the first comprehensive view of the timing of transcription throughout the intraerythrocytic development of P. falciparum and provide a resource for the identification of new chemotherapeutic and vaccine candidates.

Animals↗
PubMed2006

Pseudo-messenger RNA: phantoms of the transcriptome.

The mammalian transcriptome harbours shadowy entities that resist classification and analysis. In analogy with pseudogenes, we define pseudo-messenger RNA to be RNA molecules that resemble protein-coding mRNA, but cannot encode full-length proteins owing to disruptions of the reading frame. Using a rigorous computational pipeline, which rules out sequencing errors, we identify 10,679 pseudo-messenger RNAs (approximately half of which are transposon-associated) among the 102,801 FANTOM3 mouse cDNAs: just over 10% of the FANTOM3 transcriptome. These comprise not only transcribed pseudogenes, but also disrupted splice variants of otherwise protein-coding genes. Some may encode truncated proteins, only a minority of which appear subject to nonsense-mediated decay. The presence of an excess of transcripts whose only disruptions are opal stop codons suggests that there are more selenoproteins than currently estimated. We also describe compensatory frameshifts, where a segment of the gene has changed frame but remains translatable. In summary, we survey a large class of non-standard but potentially functional transcripts that are likely to encode genetic information and effect biological processes in novel ways. Many of these transcripts do not correspond cleanly to any identifiable object in the genome, implying fundamental limits to the goal of annotating all functional elements at the genome sequence level.

Animals↗
PubMed2002

Yellow pages to the transcriptome.

Transcriptomics has become an important tool for the large-scale analysis of biological processes. This review aims to provide sufficient criteria to make an appropriate choice among the variety of 'closed' systems, represented by DNA microarrays, and 'open' systems like fragment display, tag sequencing and subtractive hybridization, depending on the biological system under investigation. The most important technologies currently available are presented, their strengths and weaknesses are discussed and companies active in the field are listed. The potential of transcriptomics in the pharmaceutical research and development process is highlighted by applications in oncology, research on neurological diseases, and predictive toxicology. Finally, a prognosis for future developments of the technologies is given.

Animals↗
PubMed2006

Transcriptome amplification methods in gene expression profiling.

The increasing use of microarray expression profiling to study the molecular biology of cancer and the cellular physiology of difficult-to-isolate cell types has led to a need for methods that accurately and precisely amplify small quantities of RNA. The purpose of this review is to provide an overview of the existing methods for transcriptome amplification and to define the parameters for comparing different amplification methods. The authors propose a standardized protocol for the assessment and evaluation of amplification methods, focusing on a new whole-transcriptome amplification kit, which amplifies total RNA into cDNA fragments. Reproducibility and reliability of the method were analyzed and discussed using both quantitative real-time PCR and a high-density oligonucleotide microarray platform.

DNA, Complementary↗
PubMed2004

A genomic view of estrogen actions in human breast cancer cells by expression profiling of the hormone-responsive transcriptome.

Estrogen controls key cellular functions of responsive cells including the ability to survive, replicate, communicate and adapt to the extracellular milieu. Changes in the expression of 8400 genes were monitored here by cDNA microarray analysis during the first 32 h of human breast cancer (BC) ZR-75.1 cell stimulation with a mitogenic dose of 17beta-estradiol, a timing which corresponds to completion of a full mitotic cycle in hormone-stimulated cells. Hierarchical clustering of 344 genes whose expression either increases or decreases significantly in response to estrogen reveals that the gene expression program activated by the hormone in these cells shows 8 main patterns of gene activation/inhibition. This newly identified estrogen-responsive transcriptome represents more than a simple cell cycle response, as only a few affected genes belong to the transcriptional program of the cell division cycle of eukaryotes, or showed a similar expression profile in other mitogen-stimulated human cells. Indeed, based on the functions assigned to the products of the genes they control, estrogen appears to affect several key features of BC cells, including their metabolic status, proliferation, survival, differentiation and resistance to stress and chemotherapy, as well as RNA and protein synthesis, maturation and turn-over rates. Interestingly, the estrogen-responsive transcriptome does not appear randomly interspersed in the genome. In chromosome 17, for example, a site particularly rich in genes activated by the hormone, physical association of co-regulated genes in clusters is evident in several instances, suggesting the likely existence of estrogen-responsive domains in the human genome.

Breast Neoplasms↗
PubMed2026

Integrated transcriptome analysis and machine learning to construct a homeostatic model of acetylation for bladder cancer and validate the key gene CES1.

BACKGROUND: Bladder cancer (BLCA) is one of the most common malignant tumors of the urinary system. Protein acetylation (PA) plays a critical role in regulating multiple biological processes (BPs), cellular homeostasis, and cancer-related signaling pathways. This study aimed to construct a homeostatic model of acetylation for BLCA using integrated transcriptome analysis and machine learning and to validate the key gene CES1. METHODS: RNA sequencing (RNA-seq) and clinical data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Acetylation-related differentially expressed genes (DEGs) in BLCA were screened using differential expression analysis (DEA). An acetylation homeostatic model was constructed via univariate, machine learning-based least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses, followed by validation in multiple cohorts. Single-cell RNA-seq analysis was used to explore gene expression patterns in diverse cell types. Enrichment analysis (EA), immune infiltration, and drug sensitivity analysis (DSA) were performed to characterize molecular features of different risk groups. Finally, the biological function of CES1 as the key gene was verified by in vitro knockdown experiments. RESULTS: We established a robust acetylation homeostatic model consisting of five genes, which effectively predicted overall survival (OS) and served as an independent prognostic factor in BLCA. High-risk patients showed significantly poorer prognosis, distinct immune infiltration profiles, and differential drug sensitivity. CES1 was identified and validated as the key gene in this model, which was highly expressed in BLCA and associated with poor prognosis. Knockdown of CES1 markedly suppressed cell proliferation, invasion, and migration, and reduced intracellular coenzyme A (CoA) levels, thereby regulating PA homeostasis. CONCLUSIONS: We developed and validated a novel acetylation homeostatic model for survival stratification and personalized treatment guidance in BLCA, based on integrated transcriptome analysis and machine learning. CES1 is closely associated with intracellular CoA levels and the malignant progression of BLCA. Its potential association with PA homeostasis requires further mechanistic validation, and it may act as a candidate therapeutic biomarker for BLCA.

Bladder cancer (BLCA)↗
PubMed2026

Transcriptome Analysis and Experimental Validation of Palmitoylation- Related Biomarkers in Atherosclerosis.

INTRODUCTION: Protein palmitoylation contributes to membrane localisation, signal transduction, and cell-fate regulation. It is closely associated with lipid metabolic dysfunction, immune inflammation, and vascular remodelling in atherosclerosis (AS). However, key palmitoylation-related transcriptomic markers and their potential causal associations with AS remain incompletely defined. METHODS: The Gene Expression Omnibus (GEO) dataset GSE100927 was used as the training cohort, and GSE43292 was used as an external validation cohort. Differentially expressed genes were identified using limma and intersected with palmitoylation-related genes to obtain palmitoylation-related differentially expressed genes (PRDEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were then performed using clusterProfiler. Two-sample Mendelian randomisation was used to evaluate potential causal relationships between characteristic genes and AS. Feature selection was conducted using random forest and support vector machine recursive feature elimination (SVM-RFE), and the overlapping genes selected by both methods were retained. Receiver operating characteristic (ROC) curves were used to assess diagnostic performance. A five-gene nomogram was constructed, and its clinical utility was evaluated using calibration curves and decision curve analysis (DCA). Gene set variation analysis (GSVA) was applied to compare pathway activity between high- and low-expression groups for each core gene. Single-cell analysis using Seurat and expression-based cell-cell communication analysis using CellChat were conducted with GSE159677, and upstream transcription factors were predicted using NetworkAnalyst. For in vivo validation, an AS model was established in ApoE⁸/⁸ mice fed a high-fat diet, and aortic gene and protein expression were assessed by RT-qPCR and western blotting. RESULTS: In GSE100927, 51 PRDEGs were identified. GO and KEGG enrichment analyses highlighted pathways associated with regulation of monoatomic ion transport, sarcomere and myofibril organisation, and immune inflammation. Mendelian randomisation suggested a potential protective causal association between SLC7A7 and AS. By integrating MR with random forest and SVM-RFE feature selection, we prioritised five core genes: PLCB2, GMIP, NEXN, PLN, and SLC7A7. These genes showed good diagnostic performance in GSE43292. The resulting nomogram was well calibrated and demonstrated stable net benefit in decision curve and clinical impact curve analyses. Single-gene GSVA identified consistently activated pathways across multiple genes, including innate and adaptive immune recognition, calcium signalling and myocardial contraction/cardiomyopathy, extracellular matrix-receptor interaction, cell junction pathways, autophagy-lysosome pathways, and several metabolic programmes. At the single-cell level, PLCB2 and GMIP were predominantly expressed in T cells and macrophages, NEXN and PLN were enriched in vascular smooth muscle cells, and SLC7A7 was mainly expressed in macrophages. CellChat analysis indicated increased signals for immune-related ligand-receptor interactions. In ApoE⁸/⁸ mice fed a high-fat diet, PLCB2, GMIP, and SLC7A7 were upregulated, whereas NEXN and PLN were downregulated; protein-level changes were concordant with the transcriptomic trends. DISCUSSION: These findings indicate that palmitoylation-related dysregulation in AS converges on immune inflammation, calcium signalling/contractile programmes, ECM remodelling, and autophagy-linked metabolism. The five-gene panel is supported by external validation, single-cell localisation to immune and vascular compartments, and concordant results in ApoE⁸/⁸ mice. CONCLUSION: This study identified and validated five palmitoylation-related genes associated with AS. SLC7A7 showed a potential protective causal signal in MR analysis. The enriched pathway patterns linked these genes to immune inflammation, calcium signalling-contraction coupling, ECM remodelling, cell adhesion, and autophagy- associated metabolic reprogramming. The five-gene nomogram showed potential utility for diagnostic classification and decision support, nominating candidate biomarkers and pathway targets for AS molecular subtyping, diagnosis, and mechanistic investigation.

Atherosclerosis (AS)↗
PubMed2006

Transcriptome analyses of human genes and applications for proteome analyses.

By utilizing recently developed full-length cDNA technologies, large-scale cDNA sequencing was carried out by several cDNA projects. Now full-length cDNA resources cover the major part of the protein-coding human genes. Comprehensive analyses of the collected full-length cDNA data revealed not only the complete sequences of thousands of novel gene transcripts but also novel alternatively spliced isoforms of hitherto identified genes. However, it was not as easy as expected to deduce their encoded amino acid sequences based solely on the full-length cDNA sequences. It was neither always the case that the longest open reading frame corresponded to the real protein coding region nor that the first ATG was the translation initiator codon. Also, proteome-wide mass-spectrometry analysis has shown that there is an unexpectedly large population of small proteins, encoded by so-called upstream open reading frames, within the cell. Since sound manual annotations by experts were still indispensable to address these problems, an international meeting to make transcriptome-wide functional annotations of cDNAs was held, namely the H-invitational. In this meeting, functional annotations were made both manually and computationally for most of the pre-existing full-length cDNAs collected from world-wide cDNA projects. The achieved integrated information for each of the cDNAs was published as a database. It was also shown that the full-length cDNA data were useful for identifying alternative splicing variants, exact transcriptional start sites of the mRNAs and the adjacent promoter regions. Rapidly accumulating genome data as well as versatile use of the transcriptome information will shortly lay a firm foundation for proteome-level understanding of human gene networks.

Alternative Splicing↗
PubMed2005

Application of transcriptome analysis to clinical pharmacology studies.

Clinical pharmacology is the investigation of drug effects in humans. This review discusses the basic tenets of clinical pharmacology research, including pharmacokinetic and pharmacodynamic analysis, therapeutic window, and clinical trial design, and the issues that may arise in the application of transcriptome analysis to clinical pharmacology studies. Examples of how transcriptome analysis can be applied to clinical pharmacology research are described, including a model system of endotoxin challenge (in vitro and in vivo), and an example of a cross-over drug study in normal volunteers. Various data display and analysis methods are also illustrated, including principal component analysis, hierarchical cluster analysis, and pathways analysis.

Animals↗
PubMed2005

From traditional biomarkers to transcriptome analysis in drug development.

Traditional biomarkers have played an important role in drug development as well as patient care. A single traditional biomarker or surrogate endpoint is unlikely to either characterize the complete pathophysiology of a complex disease or capture all the therapeutic benefits or potential adverse effects that a drug will have in a diverse patient population. Transciptome analysis, on the other hand, can provide a large-scale survey of gene expression associated with the etiology of a human disease or pharmacological responses to a therapeutic intervention. The quantitative and qualitative readouts can provide increased power to identify novel drug targets or biomarkers indicative of drug safety or efficacy. Transcriptomics has positively impacted drug development and will continue to improve the medicines of the future. Here, we describe the increasingly important roles that traditional biomarkers and transcriptome analysis have played in various phases of drug discovery and development as well as the opportunities and challenges that they present to the pharmaceutical industry.

Biomarkers↗
PubMed2026

Transcriptomic Association Between Poliovirus Receptor (PVR/CD155) and Claudin Signaling Pathways in Colorectal Cancer.

BACKGROUND/AIM: Enterotoxigenic Bacteroides fragilis promotes colorectal carcinogenesis through toxin-mediated cleavage of E-cadherin, a process facilitated by membrane-associated Claudin-4 (CLDN4). Separately, the poliovirus receptor (PVR/CD155) modulates tumor epithelial and immune dynamics. This study explored potential transcriptomic interactions and co-expression frameworks between PVR and claudin signaling pathways in colorectal cancer. MATERIALS AND METHODS: Transcriptomic and proteomic data from the The Cancer Genome Atlas-colon adenocarcinoma cohort (TCGA-COAD) were evaluated. An exploratory E-cadherin Cleavage Index was modeled to capture transcript-protein discordance. To control for tissue composition heterogeneity without mathematical circularity, a de-circularized, non-parametric partial rank residual model adjusted for independent CLDN4 expression was deployed within the stable microsatellite-stable (MSS) sub-cohort (N=473). RESULTS: Multivariable survival models showed no independent associations between overall survival and continuous PVR (p=0.79) or CLDN3 (p=0.56) expression. Robust linear modeling revealed no significant baseline interaction between PVR and CLDN4 regarding the exploratory Cleavage Index (p=0.82). However, de-circularized partial correlation analysis revealed a highly stable, positive co-expression between PVR and CLDN3 (rho=0.2459, p=3.23×10-7). Both epithelial markers retained modest inverse correlations with the infiltrating lymphocytic axis (TIGIT and CD96). CONCLUSION: Baseline PVR expression is coordinated with CLDN3 tissue programs independent of general epithelial cellularity but does not interact with the CLDN4 axis or impact overall survival in an unexposed cohort. Because TCGA lacks virome or active microbial exposure tracking, these findings serve as baseline benchmarks for future context-dependent mechanistic studies.

Bacteroides fragilis toxin↗
PubMed2025

African Swine Fever Virus MGF 360-2L Disrupts Host Antiviral Immunity Based on Transcriptomic Analysis.

Background/Objectives: The African swine fever virus (ASFV) multi-gene family (MGF) 360 proteins play critical roles in immune evasion, replication regulation, and virulence determination. Despite substantial advances in this field, the functional roles of many members within this gene family remain to be fully characterized. Methods: In this study, Transcriptional kinetics analysis indicated that the expression profile of MGF 360-2L was consistent with that of the late marker gene B646L (p72). Transcriptomic profiling identified 13 and 171 differentially expressed genes (DEGs) at 12 and 24 h post-infection (hpi) with ΔMGF 360-2L, respectively. Results: Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated that these DEGs were predominantly enriched in Type I interferon (IFN-I) signaling pathways. It is noteworthy that transcriptome analysis further demonstrates that the absence of MGF 360-2L specifically results in the dysregulation of expression of the replication-essential genes E199L and E301R. These findings indicate that MG F360-2L is essential for maintaining the stable expression of these proteins. Conclusions:MGF 360-2L is a late gene that contributes to the precise regulation of viral protein expression and modulates the host immune response during infection.

African swine fever virus↗