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At least 1,513 records · Page 84Linked to original sources
PubMed2005

Identifying genes with differential expression in gemcitabine-resistant pancreatic cancer cells using comprehensive transcriptome analysis.

Pancreatic cancer is often unresectable at diagnosis, and chemotherapy using gemcitabine is now the standard treatment for advanced pancreatic cancer. However, acquired resistance to gemcitabine resulting in therapeutic failure is often encountered. Therefore, we sought to identify genes that determine gemcitabine resistance by evaluating the relationship between gene expression profiles and gemcitabine sensitivity to provide molecular targets for overcoming gemcitabine resistance. First, the gemcitabine concentration needed for 50% growth inhibition was examined in six pancreatic cancer cell lines. By exposing MIA PaCa-2 cells to long-term gemcitabine, we established gemcitabine-resistant cells. The gene expression profiles of the six pancreatic cancer cell lines and gemcitabine-resistant cells were determined using cDNA microarray analysis. By comparing the results, 30 genes were identified as differentially expressed genes correlated with gemcitabine sensitivity. Differentially expressed genes in the parental cell lines were also examined, and six overlapping genes were identified as genes correlated with gemcitabine sensitivity in both assays. Of these genes, the down-regulated expression of TNFSF6 protein, also known as Fas ligand, was confirmed in the gemcitabine-resistant cell line. These results should provide therapeutic molecular targets for overcoming gemcitabine resistance.

Antimetabolites, Antineoplastic↗
PubMed2004

Monitoring of stress responses.

New developments in the RNA analysis techniques now enable a comprehensive view on the bacterial physiology under bioprocess conditions. The DNA-chip technology allows a genome wide transcriptional profiling of bacterial cells, whose genome sequence is available. Although the analyses of microbial bioprocesses have still been somewhat limited to date, this technique has already been successfully applied in different laboratories for the investigation of stress responses of selected industrially relevant bacterial hosts. Transcriptome analyses in combination with high resolution two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and mass spectrometry have been extensively applied for the description of general and specific stress and starvation responses of Escherichia coli and Bacillus subtilis. The consideration of bacterial stress and starvation responses is of crucial importance for the successful establishment of an industrial large scale bioprocess. Stress genes can be used as marker genes in order to monitor the fitness of industrial bacterial hosts during fermentation processes. This chapter gives an overview of current RNA analysis techniques. The bacterial stress and starvation responses, which are of potential importance for industrial microbial bioprocesses are summarised.

Adaptation, Physiological↗
PubMed2007

Serial analysis of gene expression in sugarcane (Saccharum spp.) leaves revealed alternative C4 metabolism and putative antisense transcripts.

Sugarcane (Saccharum spp.) is a highly efficient biomass and sugar producing crop. Leaf reactions have been considered as potential rate-limiting step for sucrose accumulation in sugarcane stalks. To characterize the sugarcane leaf transcriptome, field-grown mature leaves from cultivar "SP80-3280" were analyzed using Serial Analysis of Gene Expression (SAGE). From 480 sequenced clones, 9,482 valid tags were extracted, with 5,227 unique sequences, from which 3,659 (70%) matched at least a sugarcane assembled sequence (SAS) with putative function; while 872 tags (16.7%) matched SAS with unknown function; 523 (10%) matched SAS without a putative annotation; and only 173 (3.3%) did not match any sugarcane ESTs. Based on gene ontology (GO), photosystem (PS) I reaction center was identified as the most frequent gene product location, followed by the remaining sites of PS I, PS II and thylakoid complexes. For metabolic processes, photosynthesis light harvesting complexes; carbon fixation; and chlorophyll biosynthesis were the most enriched GO-terms. Considering the alternative photosynthetic C(4) cycles, tag frequencies related to phosphoenolpyruvate carboxykinase (PEPCK) and aspartate aminotransferase compared to those for NADP(+)-malic enzyme (NADP-ME) and NADP-malate dehydrogenase, suggested that PEPCK-type decarboxylation appeared to predominate over NADP-ME in mature leaves, although both may occur, opposite to currently assumed in sugarcane. From the unique tag set, 894 tags (17.1%) were assigned as potentially derived from antisense transcripts, while 73 tags (1.4%) were assigned to more than one SAS, suggesting the occurrence of alternative processing. The occurrence of antisense was validated by quantitative reverse transcription amplification. Sugarcane leaf transcriptome provided new insights for functional studies associated with sucrose synthesis and accumulation.

Carbohydrate Metabolism↗
PubMed2002

Laser capture microdissection of Plasmodium falciparum liver stages for mRNA analysis.

Plasmodium falciparum liver-stages are important targets for vaccine-induced protective immune responses and prophylactic treatment against malaria. Little is known of the gene expression profile of malaria parasites during their development inside hepatocytes. The sequencing of the P. falciparum genome and the development of DNA microarray technology give new opportunities to identify genes expressed during the development of Plasmodium. However, transcriptome analysis cannot currently be applied to the hepatic stages, due to difficulties in obtaining sufficient amounts of parasite material that lie among the large excess of host cell RNA. Here, we describe the isolation of liver-stages by a modified laser capture microdissection approach applied to human hepatocyte cultures infected with P. falciparum. RT-PCR amplification of several P. falciparum transcripts demonstrated the high quality of the RNA recovered after microdissection. This approach should enable analyses of P. falciparum transcriptome during its hepatic development and substantially assist the identification of new therapeutic and vaccine targets.

Animals↗
PubMed2024

Species-wide quantitative transcriptomes and proteomes reveal distinct genetic control of gene expression variation in yeast.

Gene expression varies between individuals and corresponds to a key step linking genotypes to phenotypes. However, our knowledge regarding the species-wide genetic control of protein abundance, including its dependency on transcript levels, is very limited. Here, we have determined quantitative proteomes of a large population of 942 diverse natural Saccharomyces cerevisiae yeast isolates. We found that mRNA and protein abundances are weakly correlated at the population gene level. While the protein coexpression network recapitulates major biological functions, differential expression patterns reveal proteomic signatures related to specific populations. Comprehensive genetic association analyses highlight that genetic variants associated with variation in protein (pQTL) and transcript (eQTL) levels poorly overlap (3%). Our results demonstrate that transcriptome and proteome are governed by distinct genetic bases, likely explained by protein turnover. It also highlights the importance of integrating these different levels of gene expression to better understand the genotype-phenotype relationship.

Saccharomyces cerevisiae↗
PubMed2005

Interactome-transcriptome analysis reveals the high centrality of genes differentially expressed in lung cancer tissues.

MOTIVATION: Global protein interaction network (interactome) analysis provides an effective way to understand the relationships between genes. Through this approach, it was demonstrated that the essential genes in yeast tend to be highly connected as well as connected to other highly connected genes. This is in contrast to the genes that are not essential, which share neither of these properties. Using a similar interactome-transcriptome approach, the topological features in the interactome of differentially expressed genes in lung squamous cancer tissues are assessed. RESULTS: This analysis reveals that the genes that are differentially elevated, as obtained from the microarray gene profiling data, in cancer are well connected, whereas the suppressed genes and randomly selected ones are less so. These results support the notion that a topological analysis of cancer genes using protein interaction data will allow the placement of the list of genes, often of the disparate nature, into the global, systematic context of the cell. The result of this type of analysis may provide the rationale for therapeutic targets in cancer treatment.

Algorithms↗
PubMed2001

Human mast cell transcriptome project.

After draft reading of the human genome sequence, systemic analysis of the transcriptome (the whole transcripts present in a cell) is progressing especially in commonly available cell types. Until recently, human mast cells were not commonly available. We have succeeded to generate a substantial number of human mast cells from umbilical cord blood and from adult peripheral blood progenitors. Then, we have examined messenger RNA selectively transcribed in these mast cells using high-density oligonucleotide probe arrays. Many unexpected but important transcripts were selectively expressed in human mast cells. We discuss the results obtained from transcriptome screening by introducing our data regarding mast-cell-specific genes.

Blood Cells↗
PubMed2006

Functional validation of the anaplastic lymphoma kinase signature identifies CEBPB and BCL2A1 as critical target genes.

Anaplastic large cell lymphomas (ALCLs) represent a subset of lymphomas in which the anaplastic lymphoma kinase (ALK) gene is frequently fused to the nucleophosmin (NPM) gene. We previously demonstrated that the constitutive phosphorylation of ALK chimeric proteins is sufficient to induce cellular transformation in vitro and in vivo and that ALK activity is strictly required for the survival of ALK-positive ALCL cells. To elucidate the signaling pathways required for ALK-mediated transformation and tumor maintenance, we analyzed the transcriptomes of multiple ALK-positive ALCL cell lines, abrogating their ALK-mediated signaling by inducible ALK RNA interference (RNAi) or with potent and cell-permeable ALK inhibitors. Transcripts derived from the gene expression profiling (GEP) analysis uncovered a reproducible signature, which included a novel group of ALK-regulated genes. Functional RNAi screening on a set of these ALK transcriptional targets revealed that the transcription factor C/EBPbeta and the antiapoptotic protein BCL2A1 are absolutely necessary to induce cell transformation and/or to sustain the growth and survival of ALK-positive ALCL cells. Thus, we proved that an experimentally controlled and functionally validated GEP analysis represents a powerful tool to identify novel pathogenetic networks and validate biologically suitable target genes for therapeutic interventions.

Anaplastic Lymphoma Kinase↗
PubMed2004

MiCoViTo: a tool for gene-centric comparison and visualization of yeast transcriptome states.

BACKGROUND: Information obtained by DNA microarray technology gives a rough snapshot of the transcriptome state, i.e., the expression level of all the genes expressed in a cell population at any given time. One of the challenging questions raised by the tremendous amount of microarray data is to identify groups of co-regulated genes and to understand their role in cell functions. RESULTS: MiCoViTo (Microarray Comparison Visualization Tool) is a set of biologists' tools for exploring, comparing and visualizing changes in the yeast transcriptome by a gene-centric approach. A relational database includes data linked to genome expression and graphical output makes it easy to visualize clusters of co-expressed genes in the context of available biological information. To this aim, upload of personal data is possible and microarray data from fifty publications dedicated to S. cerevisiae are provided on-line. A web interface guides the biologist during the usage of this tool and is freely accessible at http://www.transcriptome.ens.fr/micovito/. CONCLUSIONS: MiCoViTo offers an easy-to-read picture of local transcriptional changes connected to current biological knowledge. This should help biologists to mine yeast microarray data and better understand the underlying biology. We plan to add functional annotations from other organisms. That would allow inter-species comparison of transcriptomes via orthology tables.

Cluster Analysis↗
PubMed2026

Optimized Hot Phenol-Based RNA Extraction from Mycobacteria: A Robust Approach for Reliable Gene Expression Analysis.

Mycobacterium tuberculosis (Mtb) remains a major global health threat, underscoring the need for reliable transcriptomic studies to understand its biology and drug resistance mechanisms. Such analyses depend on obtaining high-quality, high-yield RNA. Although several RNA extraction methods are available, many require expensive reagents, large culture volumes, or specialized equipment, limiting their suitability for large-scale studies, particularly in resource-constrained settings. Here, an optimized Hot Phenol based RNA extraction method specifically tailored for mycobacteria is presented. The method uses minimal culture volume and commonly available reagents to consistently yield high-quality RNA suitable for high-throughput transcriptomic applications. RNA quantity and integrity were assessed by gel electrophoresis and RNA integrity analysis (RIN), and its suitability for downstream applications was confirmed by qPCR and Qubit 4. To benchmark the performance of the optimized method, a parallel RNA extraction using TRIzol and RNeasy under identical experimental conditions was carried out, including the same Mycobacterium species, culture volume, growth phase (logarithmic and stationary), and lysis conditions. This allowed a direct comparison of yield, quality, feasibility, and cost. The optimized Hot Phenol method demonstrated comparable or improved RNA yield and quality while significantly reducing reagent cost and dependence on specialized equipment. Owing to its efficiency, reproducibility, and affordability, this protocol provides a practical alternative for large-scale gene expression and transcriptomic studies in Mtb and other mycobacterial species.

RNA, Bacterial↗
PubMed2006

Comprehensive transcriptional profiling of NaCl-stressed Arabidopsis roots reveals novel classes of responsive genes.

BACKGROUND: Roots are an attractive system for genomic and post-genomic studies of NaCl responses, due to their primary importance to agriculture, and because of their relative structural and biochemical simplicity. Excellent genomic resources have been established for the study of Arabidopsis roots, however, a comprehensive microarray analysis of the root transcriptome following NaCl exposure is required to further understand plant responses to abiotic stress and facilitate future, systems-based analyses of the underlying regulatory networks. RESULTS: We used microarrays of 70-mer oligonucleotide probes representing 23,686 Arabidopsis genes to identify root transcripts that changed in relative abundance following 6 h, 24 h, or 48 h of hydroponic exposure to 150 mM NaCl. Enrichment analysis identified groups of structurally or functionally related genes whose members were statistically over-represented among up- or down-regulated transcripts. Our results are consistent with generally observed stress response themes, and highlight potentially important roles for underappreciated gene families, including: several groups of transporters (e.g. MATE, LeOPT1-like); signalling molecules (e.g. PERK kinases, MLO-like receptors), carbohydrate active enzymes (e.g. XTH18), transcription factors (e.g. members of ZIM, WRKY, NAC), and other proteins (e.g. 4CL-like, COMT-like, LOB-Class 1). We verified the NaCl-inducible expression of selected transcription factors and other genes by qRT-PCR. CONCLUSION: Microarray profiling of NaCl-treated Arabidopsis roots revealed dynamic changes in transcript abundance for at least 20% of the genome, including hundreds of transcription factors, kinases/phosphatases, hormone-related genes, and effectors of homeostasis, all of which highlight the complexity of this stress response. Our identification of these transcriptional responses, and groups of evolutionarily related genes with either similar or divergent transcriptional responses to stress, will facilitate mapping of regulatory networks and extend our ability to improve salt tolerance in plants.

Arabidopsis↗
PubMed2006

Evaluating the comparability of gene expression in blood and brain.

The availability of an accessible tissue whose gene expression profile is similar to more inaccessible CNS tissues has the potential to advance research in neuropsychiatric disorders. We conducted secondary data analysis of transcriptional profiling of 79 human tissues for 33,698 genes using the Affymetrix U133A microarray augmented with a custom microarray (Affymetrix GNF1H), which were produced by the Genomics Institute of the Novartis Research Foundation (http://symatlas.gnf.org). Our analyses suggested that: (a) on a transcriptome level, whole blood shares significant gene expression similarities with multiple CNS tissues; (b) the median non-parametric correlation between transcripts present in both whole blood and CNS was around 0.5; (c) this correlation of 0.5 was intermediate relative to all tissues in the Novartis data set--less than for the maximum achievable value of 0.85, less than a set of immune tissues (0.64), comparable to a heterogeneous set of somatic tissues (0.57) but greater than muscle (0.48) and peripheral nervous system tissues (0.36); (d) about half of a set of candidate genes relevant to schizophrenia were expressed in both whole blood and prefrontal cortex; and (e) the expression levels of many classes of biologically relevant processes were not significantly different between whole blood and prefrontal cortex. These analyses suggest that gene expression in whole blood is neither perfectly correlated and useful nor perfectly uncorrelated and useless with gene expression in multiple brain tissues. This suggests that the cautious and thoughtful use of peripheral gene expression may be a useful surrogate for gene expression in the CNS when it has been determined that the relevant gene is expressed in both.

Brain↗
PubMed2006

Molecular profiling of CD34+ cells in idiopathic myelofibrosis identifies a set of disease-associated genes and reveals the clinical significance of Wilms' tumor gene 1 (WT1).

This study was aimed at the characterization of a gene expression signature of the pluripotent hematopoietic CD34(+) stem cell in idiopathic myelofibrosis (IM), which would eventually provide novel pathogenetic insights and/or diagnostic/prognostic information. Aberrantly regulated genes were revealed by transcriptome comparative microarray analysis of normal and IM CD34(+) cells; selected genes were also assayed in granulocytes. One-hundred seventy four differentially expressed genes were identified and in part validated by quantitative polymerase chain reaction. Altered gene expression was corroborated by the detection of abnormally high CD9 or CD164, and low CXCR4, membrane protein expression in IM CD34(+) cells. According to class prediction analysis, a set of eight genes (CD9, GAS2, DLK1, CDH1, WT1, NFE2, HMGA2, and CXCR4) properly recognized IM from normal CD34(+) cells. These genes were aberrantly regulated also in IM granulocytes that could be reliably differentiated from control polycythemia vera and essential thrombocythemia granulocytes in 100% and 81% of cases, respectively. Abnormal expression of HMGA2 and CXCR4 in IM granulocytes was dependent on the presence and the mutational status of JAK2(V617F) mutation. The expression levels of both CD9 and DLK1 were associated with the platelet count, whereas higher WT1 expression levels identified IM patients with more active disease, as revealed by elevated CD34(+) cell count and higher severity score. In conclusion, molecular profiling of IM CD34(+) cells uncovered a limited number of genes with altered expression that, beyond their putative role in disease pathogenesis, are associated with patients' clinical characteristics and may have potential prognostic application.

Algorithms↗
PubMed2004

Global gene expression profile of nasopharyngeal carcinoma by laser capture microdissection and complementary DNA microarrays.

A number of genetic and epigenetic changes underlying the development of nasopharyngeal carcinomas have recently been identified. However, there is still limited information on the nature of the genes and gene products whose aberrant expression and activity promote the malignant conversion of nasopharyngeal epithelium. Here, we have performed a genome-wide transcriptome analysis by probing cDNA microarrays with fluorescent-labeled amplified RNA derived from laser capture microdissected cells procured from normal nasopharyngeal epithelium and areas of metaplasia-dysplasia and carcinoma from EBV-associated nasopharyngeal carcinomas. This approach enabled the identification of genes differentially expressed in each cell population, as well as numerous genes whose expression can help explain the aggressive clinical nature of this tumor type. For example, genes indicating cell cycle aberrations (cyclin D2, cyclin B1, activator of S-phase kinase, and the cell cycle checkpoint kinase, CHK1) and invasive-metastatic potential (matrix metalloproteinase 11, v-Ral, and integrin beta(4)) were highly expressed in tumor cells. In contrast, genes underexpressed in tumors included genes involved in apoptosis (B-cell CLL/lymphoma 6, secretory leukocyte protease inhibitor, and calpastatin), cell structure (keratin 7 and carcinoembryonic antigen-related cell adhesion molecule 6), and putative tumor suppressor genes (H-Ras-like suppressor 3, retinoic acid receptor responder 1, and growth arrested specific 8) among others. Gene expression patterns also suggested alterations in the Wnt/beta-catenin and transforming growth factor beta pathways in nasopharyngeal carcinoma. Thus, expression profiles indicate that aberrant expression of growth, survival, and invasion-promoting genes may contribute to the molecular pathogenesis of nasopharyngeal carcinoma. Ultimately, this approach may facilitate the identification of clinical useful markers of disease progression and novel potential therapeutic targets for nasopharyngeal carcinoma.

Carcinoma↗
PubMed2006

Challenges in the stratification of breast tumors for tailored therapies.

Studying the molecular stratification of breast carcinoma is a real challenge considering the extreme heterogeneity of these tumors. Many patients are now treated following recommendation established at several NIH and St Gallen consensus conferences. However a significant fraction of these breast cancer patients do not need adjuvant chemotherapies while other patients receive inefficacious therapies. High density gene expression arrays have been designed to attempt to establish expression profiles that could be used as prognostic indicators or as predictive markers for response to treatment. This review is intended to discuss the potential value of these new indicators, but also the current weaknesses of these new genomic and bioinformatic approaches. The combined analysis of transcriptomic and genomic alteration data from relatively large numbers of well annotated tumor specimens may offer an opportunity to overcome the current difficulties in validating recently published non overlapping gene lists as prognostic or therapeutic indicators. There is also hope for identifying and deciphering signal transduction pathways driving tumor progression with newly developed algorithms and semi quantitative parameters obtained in simplified in vitro or in vivo models for specific transduction pathways.

Animals↗
PubMed2004

ESTs, cDNA microarrays, and gene expression profiling: tools for dissecting plant physiology and development.

Gene expression profiling holds tremendous promise for dissecting the regulatory mechanisms and transcriptional networks that underlie biological processes. Here we provide details of approaches used by others and ourselves for gene expression profiling in plants with emphasis on cDNA microarrays and discussion of both experimental design and downstream analysis. We focus on methods and techniques emphasizing fabrication of cDNA microarrays, fluorescent labeling, cDNA hybridization, experimental design, and data processing. We include specific examples that demonstrate how this technology can be used to further our understanding of plant physiology and development (specifically fruit development and ripening) and for comparative genomics by comparing transcriptome activity in tomato and pepper fruit.

DNA, Complementary↗
PubMed2003

Profiling ethylene-regulated gene expression in Arabidopsis thaliana by microarray analysis.

Ethylene-regulated gene expression in leaves of Arabidopsis thaliana was investigated with an expressed sequence tag-based microarray containing about 6000 unique genes. Comparing expression profiles of the ethylene-insensitive mutant etr1-1, the ethylene-constitutive mutant ctr1-1, ethylene-treated wild-type and untreated wild-type plants identified ca. 7% of the investigated genes as ethylene-regulated. Exogenous ethylene treatment and ctr1-1 had similar changes in gene expression, but differences were noted. Ethylene-regulated genes involved in its own biosynthesis and signal transduction pathway were identified. A large number of transcription factors and some putative signaling components were highly regulated by ethylene. Chloroplast structural protein and photosynthetic genes were generally down-regulated. Ethylene appeared to regulate other primary metabolic genes. Plant defense and PR protein genes were differentially regulated, with some genes within this class highly up-regulated. Other ethylene-regulated genes identified were known sugar-, auxin-, wounding- and jasmonic acid-related genes, suggesting the existence of coordinated interactions between ethylene and other hormonal and defense signaling pathways. Although hundreds of potentially important transcriptome changes were identified, the functions of many ethylene-regulated genes remain unknown.

Arabidopsis↗
PubMed2026

Machine learning identifies ac4C-related prognostic signature and TUBA1C as therapeutic target in COAD.

To explore the role of N4-acetylcytidine (ac4C)-related genes (acRGs) in colon adenocarcinoma (COAD) and identify reliable prognostic biomarkers and potential therapeutic targets. Multi-source transcriptomic datasets (TCGA-COAD, GSE39582, GSE17536) and single-cell RNA-seq data were analyzed. Ten machine learning algorithms were integrated to construct an acRG-based prognostic signature (acRGBS). Immune microenvironment (TME) and genomic profiling were performed, with in vitro functional experiments validating TUBA1C's role. acRGBS, comprising four hub genes (SARAF, CDC42SE2, TSPYL2, TUBA1C), effectively stratified COAD patients into high- and low-risk groups with distinct survival outcomes and was an independent prognostic factor. High-risk patients exhibited increased genomic instability and immunosuppressive TME, while low-risk patients had favorable immunotherapy response. TUBA1C was overexpressed in COAD cells, and its knockdown inhibited proliferation/migration and induced apoptosis. The acRGBS is a robust prognostic tool for COAD, and TUBA1C serves as a candidate therapeutic target, providing new insights for personalized COAD management.

Humans↗