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Results for “Transcriptomic analysis”

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PubMed2002

Density of points clustering, application to transcriptomic data analysis.

With the increasing amount of data produced by high-throughput technologies in many fields of science, clustering has become an integral step in exploratory data analysis in order to group similar elements into classes. However, many clustering algorithms can only work properly if aided by human expertise. For example, one parameter which is crucial and often manually set is the number of clusters present in the analyzed set. We present a novel stopping rule to find the optimal number of clusters based on the comparison of the density of points inside the clusters and between them. The method is evaluated on synthetic as well as on real transcriptomic data and compared with two current methods. Finally, we illustrate its usefulness in the analysis of the expression profiles of promyelocytic cells before and after treatment with all-trans retinoic acid. Simultaneous clustering for gene regulation and absolute initial expression levels allowed the identification of numerous genes associated with signal transduction revealing the complexity of retinoic acid signaling.

Algorithms↗

PubMed2025

Epstein-Barr Virus-Associated Gastric Cancer: A Histopathologic Study With Comprehensive Molecular Profiling.

A subset of gastric cancers (GCs) is linked to Epstein-Barr virus (EBV) infection. This study aims to characterize the histopathological and molecular features of EBV-associated GCs (EBVaGCs), focusing on predictive biomarkers and genomic and transcriptomic analysis. A total of 35 primary EBVaGCs were considered. The presence of EBV was confirmed with in situ hybridization. Immunohistochemical analyses for HER2, PD-L1, claudin 18.2, and mismatch repair proteins were performed. Genomic and transcriptomic profiles were assessed using AmoyDx Master Panel, which can identify single-nucleotide variants, InDels, and copy number variations on 571 hot genes, as well as microsatellite status, tumor molecular burden, and homologous recombination deficiency at the DNA level; however, at the RNA level, it identifies rearrangements/fusions in 45 genes and also quantifies the expression of 2396 cancer-related transcripts. The following histotypes were identified: carcinoma with lymphoid stroma (CLS; 69%), tubular (20%), and mixed (11%). Most cases were associated with atrophic gastritis (71%), and only 11% with dysplasia. The vast majority (94%) of EBVaGCs expressed EBV-encoded RNA in all tumor cells. Mismatch repair deficiency and HER2 overexpression were each observed in 6% of cases, whereas all tumors had a PD-L1-combined positive score ≥10. Sixty-six percent of cases showed moderate/strong claudin 18.2 expression in ≥75% of cancer cells. The most frequently altered genes were PIK3CA (41%) and ARID1A (17%). Transcriptomic analysis revealed substantial differential gene expression between EBVaGCs and EBV-negative controls, with upregulation of genes involved in antigen presentation, natural killer cell-mediated cytotoxicity, and cytokine-cytokine receptor interaction in EBVaGCs. Within EBVaGC, CLS showed higher expression of immune-related transcripts and higher PD-L1 expression than other histotypes. This study establishes EBVaGC as a distinct molecular class, with a distinctive profile of genomic alterations and expression of predictive biomarkers, and also with a unique immune microenvironment with enhanced cytotoxic activity. The findings highlight EBV's role in early tumor development and EBVaG-CLS as a distinct subgroup within EBVaGC, characterized by unique morphologic features and a pronounced immune activation profile.

Humans↗

PubMed2004

Global regulation of erythroid gene expression by transcription factor GATA-1.

Transcription factor GATA-1 is required for erythropoiesis, yet its full actions are unknown. We performed transcriptome analysis of G1E-ER4 cells, a GATA-1-null erythroblast line that undergoes synchronous erythroid maturation when GATA-1 activity is restored. We interrogated more than 9000 transcripts at 6 time points representing the transition from late burst forming unit-erythroid (BFU-E) to basophilic erythroblast stages. Our findings illuminate several new aspects of GATA-1 function. First, the large number of genes responding quickly to restoration of GATA-1 extends the repertoire of its potential targets. Second, many transcripts were rapidly down-regulated, highlighting the importance of GATA-1 in gene repression. Third, up-regulation of some known GATA-1 targets was delayed, suggesting that auxiliary factors are required. For example, induction of the direct GATA-1 target gene beta major globin was late and, surprisingly, required new protein synthesis. In contrast, the gene encoding Fog1, which cooperates with GATA-1 in beta globin transcription, was rapidly induced independently of protein synthesis. Guided by bioinformatic analysis, we demonstrated that selected regions of the Fog1 gene exhibit enhancer activity and in vivo occupancy by GATA-1. These findings define a regulatory loop for beta globin expression and, more generally, demonstrate how transcriptome analysis can be used to generate testable hypotheses regarding transcriptional networks.

Animals↗

PubMed2004

A combination of proteomics, principal component analysis and transcriptomics is a powerful tool for the identification of biomarkers for macrophage maturation in the U937 cell line.

The monocyte-like human histiocytic lymphoma cell line U937 can be induced by phorbol 12-myristate 13-acetate (PMA) to undergo differentiation into a macrophage-like phenotype. We have used two-dimensional gel electrophoresis (2-DE), oligonucleotide microarrays and principal component analysis (PCA) to characterize the U937 cell line as a model system for the differentiation of monocytes into macrophages. A total of 226 differentially expressed proteins were found, of which 41 were selected by PCA for identification using matrix-assisted laser desorption/ionization tandem mass spectrometry. Based on the PCA results, three marker proteins were selected for confirmation of differential expression using Western blot and quantitative real time-PCR. The selected marker proteins were: gamma interferon inducible lysosomal thiol reductase, cathepsin D and adipocyte-fatty acid binding protein. All three proved to be good differentiation markers for macrophage maturation of U937 cells as well as peripheral blood-derived macrophages. The transcriptomics data revealed a large number of additional putative differentiation markers in U937 macrophages, many of which are known to be expressed in peripheral blood-derived macrophages. These include osteospontin, matrix metalloproteinase 9, and HC-gp39. Our results show that the characteristics of U937 macrophages resemble those of inflammatory (exudate) macrophages, exemplified by the down-regulation of 5' nucleotidase and the up-regulation of leucine aminopeptidase mRNAs. In conclusion, using the powerful combination of transcriptomics, 2-DE and PCA, our results show that U937 cells differentiated by PMA treatment are an excellent model system for monocyte derived macrophage generation from blood.

Cell Differentiation↗

PubMed2002

Functional transcriptomes: comparative analysis of biological pathways and processes in eukaryotes to infer genetic networks among transcripts.

Microarray technology enables us to monitor large changes in transcripts at any given time. The compilation of these data makes possible the comparison of such gene expression data on a genome-wide scale. As comparisons of genome sequence data yield new biological insights, comparative analyses of transcriptome data also promise new discoveries regarding metabolic pathways and cellular processes. The coordinated expression of genes shows that these genes physically interact with each other or are part of the same cascade. We have produced one of the largest expression profiles of adult mice and developmental tissues. These data, as well as the data on yeast from previous reports, were used to see whether coordinated expression (with high correlation coefficient) is closely coupled to the actual cascade on the pathway map.

Animals↗

PubMed2026

Targeting the Fatty Acid Binding Protein 5-Specificity Protein 1 Axis Restores Enzalutamide Sensitivity by Suppressing Androgen Receptor/Androgen Receptor Splice Variant 7 Signaling: Implications for Prostate Cancer Therapy.

BACKGROUND: Castration-resistant prostate cancer (CRPC) remains a major clinical challenge driven by persistent androgen receptor (AR) signaling and constitutively active splice variants such as androgen receptor splice variant 7 (AR-V7), which confer resistance to therapies including enzalutamide. Although metabolic reprogramming contributes to disease progression, the integration of metabolic and transcriptional regulators sustaining therapeutic resistance remains incompletely understood. METHODS: We integrated clinical transcriptomic analysis of The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) cohort with mechanistic and functional validation in 22RV1 CRPC cells to investigate the role of the fatty acid binding protein 5-specificity protein 1 (FABP5-Sp1) regulatory axis. RESULTS: Transcriptomic analysis revealed that FABP5 is significantly upregulated in prostate tumors compared with normal tissue and increases with higher Gleason score. In contrast, AR and Sp1 exhibited heterogeneous expression patterns. Mechanistically, genetic ablation of FABP5 markedly reduced AR-V7 expression and restored sensitivity to enzalutamide, leading to suppression of AR signaling. Conversely, FABP5 overexpression increased Sp1 protein levels. Pharmacological inhibition of Sp1 using mithramycin A resulted in coordinated downregulation of FABP5, AR, and AR-V7, along with suppression of peroxisome proliferator-activated receptor gamma (PPARγ) signaling and downstream vascular endothelial growth factor A (VEGFA) expression. Functionally, Sp1 inhibition significantly reduced anchorage-independent growth and invasion. CONCLUSION: These findings define a FABP5-Sp1-AR/AR-V7 transcriptional-metabolic axis driving enzalutamide resistance in CRPC. Targeting FABP5 restores therapeutic sensitivity and represents a promising biomarker and therapeutic strategy in advanced prostate cancer.

AR-V7↗

PubMed2026

Integrative analysis of transcriptome and DNA methylome dynamics during caudal fin regeneration in silver pomfret (Pampus argenteus).

Caudal fin regeneration in teleost fish is a complex, multi-stage process involving coordinated molecular and cellular changes. While the role of epigenetic regulation particularly DNA methylation has been studied in model freshwater species such as zebrafish, its contribution to regeneration in marine teleosts remains largely unexplored. In this study, we integrated transcriptomic and DNA methylomic data to characterize the temporal dynamics of gene expression and methylation during caudal fin regeneration in the silver pomfret (Pampus argenteus). Using RNA-sequencing and reduced representation bisulfite sequencing (RRBS) at three biologically critical time points 1, 3, and 7 days post-amputation (dpa), we characterized the spatiotemporal molecular landscape of caudal fin regeneration. These time points capture the key transitional phases of wound healing and inflammation (1 dpa), blastema formation and progenitor proliferation (3 dpa), and regenerative outgrowth with tissue remodeling (7 dpa), enabling robust detection of the major molecular programs underlying epimorphic regeneration. Concurrently, CG-methylome analysis identified thousands of dynamically changing differentially methylated regions (DMRs). A strong global inverse correlation was observed between promoter methylation and gene expression. Integrative analysis pinpointed key regeneration genes (fgf20a, msxb, sox9b) whose expression was associated with dynamic methylation changes in their promoters or gene bodies. We conclude that DNA methylation is a dynamic and key regulatory layer that acts in concert with transcriptional reprogramming to coordinate tissue regeneration, providing new insights into the epigenetic mechanisms underlying complex regenerative processes in teleosts.

Animals↗

PubMed2004

Smc01944, a secreted peroxidase induced by oxidative stresses in Sinorhizobium meliloti 1021.

Sequencing of the Sinorhizobium meliloti strain 1021 genome led to the detection of 6204 open reading frames, 41 % of which have no hypothetical function. To help annotate this genome, a transcriptome analysis was carried out with a dedicated microarray consisting of 146 genes belonging to three different classes: (i) no hypothetical function; (ii) potentially involved in oxidative stress responses; (iii) known to participate in oxidative stress responses (e.g. catalase and superoxide dismutase genes). This transcriptome analysis, together with biological experiments and in silico investigations, identified new genes induced by exogenous H(2)O(2). The smc01944 gene was the most strongly induced: quantitative PCR showed that the amount of smc01944 mRNA increased 50-fold following the addition of 10 mM H(2)O(2), whereas the amount of katA mRNA (encoding a catalase) only increased 10-fold. Smc01944 is a non-haem chloroperoxidase (Cpo). The only member of this family to have been so far characterized is encoded by prxC of Pseudomonas fluorescens. Unexpectedly, the NH(2)-terminus of Smc01944 includes a signal peptide and Smc01944 is secreted into the supernatant. Interestingly, smc01944 is preceded by smc01945, encoding an OhrR-like regulator (MarR family). Thus, Smc01944 is the first exported Cpo encoded by a gene possibly regulated by an OhrR regulator. It was also shown that smc01944 is induced by t-butyl and cumene hydroperoxides but only slightly by menadione. The study of Smc01944 described in this work showed that the oxidative stress response of S. meliloti seems to differ from that of other bacteria characterized to date.

Amino Acid Sequence↗

PubMed2005

Application of Affymetrix array and Massively Parallel Signature Sequencing for identification of genes involved in prostate cancer progression.

BACKGROUND: Affymetrix GeneChip Array and Massively Parallel Signature Sequencing (MPSS) are two high throughput methodologies used to profile transcriptomes. Each method has certain strengths and weaknesses; however, no comparison has been made between the data derived from Affymetrix arrays and MPSS. In this study, two lineage-related prostate cancer cell lines, LNCaP and C4-2, were used for transcriptome analysis with the aim of identifying genes associated with prostate cancer progression. METHODS: Affymetrix GeneChip array and MPSS analyses were performed. Data was analyzed with GeneSpring 6.2 and in-house perl scripts. Expression array results were verified with RT-PCR. RESULTS: Comparison of the data revealed that both technologies detected genes the other did not. In LNCaP, 3,180 genes were only detected by Affymetrix and 1,169 genes were only detected by MPSS. Similarly, in C4-2, 4,121 genes were only detected by Affymetrix and 1,014 genes were only detected by MPSS. Analysis of the combined transcriptomes identified 66 genes unique to LNCaP cells and 33 genes unique to C4-2 cells. Expression analysis of these genes in prostate cancer specimens showed CA1 to be highly expressed in bone metastasis but not expressed in primary tumor and EPHA7 to be expressed in normal prostate and primary tumor but not bone metastasis. CONCLUSION: Our data indicates that transcriptome profiling with a single methodology will not fully assess the expression of all genes in a cell line. A combination of transcription profiling technologies such as DNA array and MPSS provides a more robust means to assess the expression profile of an RNA sample. Finally, genes that were differentially expressed in cell lines were also differentially expressed in primary prostate cancer and its metastases.

Cell Line, Tumor↗

PubMed2026

Transcriptomic Changes Associated with Electroacupuncture in a DMCAO Model of Delayed Cognitive Impairment.

INTRODUCTION: Delayed Cognitive Impairment (DCIS) occurs in approximately 31% to 77% of individuals following stroke. Clinical findings have indicated that electroacupuncture may alleviate post-stroke DCIS. However, insights derived from animal models remain limited. The present study utilized a Distal Middle Cerebral Artery Occlusion (DMCAO) mouse model to investigate the potential mechanisms of electroacupuncture through hippocampal transcriptomic analysis. MATERIALS AND METHODS: Adult male BALB/c mice were subjected to DMCAO and received electroacupuncture treatment. High-throughput RNA sequencing of hippocampal tissue was performed to identify Differentially Expressed Genes (DEGs). Enrichment analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, hierarchical clustering, and Protein-Protein Interaction (PPI) network analysis, were performed to elucidate potential biological mechanisms. RESULTS: The DMCAO model exhibited features consistent with DCIS. Electroacupuncture treatment was associated with improved cognitive performance and enhanced hippocampal neuroplasticity. A total of 116 DEGs were identified in the DMCAO group compared with the sham group, while 69 DEGs were identified in the DMCAO + electroacupuncture group compared with the untreated DMCAO group. DISCUSSION: GO enrichment analysis indicated that electroacupuncture modulated biological processes related to nerve fibers, axonal development, neuronal regulation, cellular processes, and cardiovascular protection. KEGG pathway analysis indicated involvement in pathways associated with neuronal recovery and axonal function. The PPI network comprised 28 nodes and 33 interactions, with hub genes such as Gna13, Hipk2, and Stambp playing key roles. Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) results were consistent with RNA sequencing findings. CONCLUSION: Electroacupuncture improved DCIS in the DMCAO mouse model. Transcriptomic analysis of the hippocampus provided preliminary evidence of the potential mechanisms underlying the therapeutic effects of electroacupuncture treatment following ischemic stroke.

Animals↗

PubMed2004

Directed evolution of pyruvate decarboxylase-negative Saccharomyces cerevisiae, yielding a C2-independent, glucose-tolerant, and pyruvate-hyperproducing yeast.

The absence of alcoholic fermentation makes pyruvate decarboxylase-negative (Pdc(-)) strains of Saccharomyces cerevisiae an interesting platform for further metabolic engineering of central metabolism. However, Pdc(-) S. cerevisiae strains have two growth defects: (i) growth on synthetic medium in glucose-limited chemostat cultures requires the addition of small amounts of ethanol or acetate and (ii) even in the presence of a C(2) compound, these strains cannot grow in batch cultures on synthetic medium with glucose. We used two subsequent phenotypic selection strategies to obtain a Pdc(-) strain without these growth defects. An acetate-independent Pdc(-) mutant was obtained via (otherwise) glucose-limited chemostat cultivation by progressively lowering the acetate content in the feed. Transcriptome analysis did not reveal the mechanisms behind the C(2) independence. Further selection for glucose tolerance in shake flasks resulted in a Pdc(-) S. cerevisiae mutant (TAM) that could grow in batch cultures ( micro (max) = 0.20 h(-1)) on synthetic medium, with glucose as the sole carbon source. Although the exact molecular mechanisms underlying the glucose-tolerant phenotype were not resolved, transcriptome analysis of the TAM strain revealed increased transcript levels of many glucose-repressible genes relative to the isogenic wild type in nitrogen-limited chemostat cultures with excess glucose. In pH-controlled aerobic batch cultures, the TAM strain produced large amounts of pyruvate. By repeated glucose feeding, a pyruvate concentration of 135 g liter(-1) was obtained, with a specific pyruvate production rate of 6 to 7 mmol g of biomass(-1) h(-1) during the exponential-growth phase and an overall yield of 0.54 g of pyruvate g of glucose(-1).

Culture Media↗

PubMed2006

Regulation of uptake hydrogenase and effects of hydrogen utilization on gene expression in Rhodopseudomonas palustris.

Rhodopseudomonas palustris is a purple, facultatively phototrophic bacterium that uses hydrogen gas as an electron donor for carbon dioxide fixation during photoautotrophic growth or for ammonia synthesis during nitrogen fixation. It also uses hydrogen as an electron supplement to enable the complete assimilation of oxidized carbon compounds, such as malate, into cell material during photoheterotrophic growth. The R. palustris genome predicts a membrane-bound nickel-iron uptake hydrogenase and several regulatory proteins to control hydrogenase synthesis. There is also a novel sensor kinase gene (RPA0981) directly adjacent to the hydrogenase gene cluster. Here we show that the R. palustris regulatory sensor hydrogenase HupUV acts in conjunction with the sensor kinase-response regulator protein pair HoxJ-HoxA to activate hydrogenase expression in response to hydrogen gas. Transcriptome analysis indicated that the HupUV-HoxJA regulatory system also controls the expression of genes encoding a predicted dicarboxylic acid transport system, a putative formate transporter, and a glutamine synthetase. RPA0981 had a small effect in repressing hydrogenase synthesis. We also determined that the two-component system RegS-RegR repressed expression of the uptake hydrogenase, probably in response to changes in intracellular redox status. Transcriptome analysis indicated that about 30 genes were differentially expressed in R. palustris cells that utilized hydrogen when growing photoheterotrophically on malate under nitrogen-fixing conditions compared to a mutant strain that lacked uptake hydrogenase. From this it appears that the recycling of reductant in the form of hydrogen does not have extensive nonspecific effects on gene expression in R. palustris.

Bacterial Proteins↗

PubMed2005

Combined global localization analysis and transcriptome data identify genes that are directly coregulated by Adr1 and Cat8.

In Saccharomyces cerevisiae, glucose depletion causes a profound alteration in metabolism, mediated in part by global transcriptional changes. Many of the transcription factors that regulate these changes act combinatorially. We have analyzed combinatorial regulation by Adr1 and Cat8, two transcription factors that act during glucose depletion, by combining genome-wide expression and genome-wide binding data. We identified 32 genes that are directly activated by Adr1, 28 genes that are directly activated by Cat8, and 14 genes that are directly regulated by both. Our analysis also uncovered promoters that Adr1 binds but does not regulate and promoters that are indirectly regulated by Cat8, stressing the advantage of combining global expression and global localization analysis to find directly regulated targets. At most of the coregulated promoters, the in vivo binding of one factor is independent of the other, but Adr1 is required for optimal Cat8 binding at two promoters with a poor match to the Cat8 binding consensus. In addition, Cat8 is required for Adr1 binding at promoters where Adr1 is not required for transcription. These data provide a comprehensive analysis of the direct, indirect, and combinatorial requirements for these two global transcription factors.

Chromatin Immunoprecipitation↗

PubMed2004

Expression of cardiac myosin-binding protein-C (cMyBP-C) in Drosophila as a model for the study of human cardiomyopathies.

Mutations in the MYBPC3 gene encoding human cardiac myosin-binding protein-C (cMyBP-C) are associated with familial hypertrophic cardiomyopathy (FHC), but the molecular mechanisms involved are not fully understood. In addition, development of FHC is sensitive to genetic background, and the search for candidate modifier genes is crucial with a view to proposing diagnosis and exploring new therapies. We used Drosophila as the model to investigate the in vivo consequences of human cMyBP-C mutations. We first produced transgenic flies that specifically express human wild-type or two C-terminal truncated cMyBP-Cs in indirect flight muscles (IFM), a tissue particularly amenable to genetic and molecular analyses. First, incorporation of human cMyBP-C into the IFM led to sarcomeric structural abnormalities and to a flightless phenotype aggravated by age and human gene dosage. Second, transcriptome analysis of transgenic IFM using nylon microarrays showed the remodelling of a transcriptional program involving 97 out of 3570 Drosophila genes. Among them, the Calmodulin gene encoding a key component of muscle contraction, found up-regulated in transgenic IFM, was evaluated as a potential modifier gene. Calmodulin mutant alleles rescued the flightless phenotype, and therefore behave as dominant suppressors of the flightless phenotype suggesting that Calmodulin might be a modifier gene in the context of human FHC. In conclusion, we suggest that the combination of heterologous transgenesis and transcriptome analysis in Drosophila could be of great value as a way to glean insights into the molecular mechanisms underlying FHC and to propose potential candidate modifier genes.

Animals↗

PubMed2026

Transcriptomic Insights into Acupuncture Mechanisms in Protecting Ovarian Function in Mice with Premature Ovarian Insufficiency.

OBJECTIVE: To explore the molecular mechanisms underlying the protective effect of acupuncture on ovarian function in mice with cyclophosphamide-induced premature ovarian insufficiency (POI) via transcriptomic analysis. METHODS: Twenty female C57BL/6 mice were divided into 4 groups: control, model, acupuncture, and non-meridian/non-acupoint (NOMA). POI was induced in the model, acupuncture, and non-meridian/non-acupoint groups via cyclophosphamide injection. The acupuncture group received acupuncture at Guanyuan (CV 4), bilateral Guilai (ST 29), and Sanyinjiao (SP 6) for 3 weeks. After the intervention, ovarian tissue weight and ovarian coefficient were calculated, serum levels of key reproductive hormones including follicle-stimulating hormone (FSH), luteinizing hormone (LH) and anti-Müllerian hormone (AMH) were detected, and ovarian histopathological changes were observed to evaluate ovarian function. Transcriptome sequencing was performed to identify differentially expressed genes (DEGs), followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to explore key functional terms and signaling pathways. Western blot was finally applied to validate the expression of core proteins related to mitochondrial function, endoplasmic reticulum stress and inflammatory pathways. RESULTS: The model group showed reduced ovarian weight and elevated FSH levels. The acupuncture group exhibited significantly higher ovarian weight and coefficient, lower FSH levels, and increased E2 and AMH levels compared to the model group (all P<0.01). Transcriptomic analysis revealed 4,021 DEGs between groups. GO and KEGG analyses revealed that these DEGs were mainly involved in oocyte development, steroid hormone synthesis, and pathways related to mitochondrial function, endoplasmic reticulum stress, and inflammatory signaling. Western blot analysis showed that acupuncture partially restored mitochondrial function markers cytochrome c oxidase subunit IV and NADH dehydrogenase 1 beta subcomplex subunit 8 and reduced endoplasmic reticulum stress markers (glucose-regulated protein 78 and Calnexin, P<0.01). It also downregulated pro-inflammatory proteins (IL-17R, IL-17A, NF-κB p65, p-NF-κB p65, ERK1/2, and p-ERK1/2) and upregulated proteins related to metabolic homeostasis (peroxisome proliferator-activated receptor γ, receptor-interacting protein 140, nicotinamide phosphoribosyltransferase, and sirtuin 1, P<0.01). CONCLUSION: Acupuncture effectively alleviates cyclophosphamide-induced POI in mice, improves ovarian function and follicular quality by regulating cellular functions and inflammatory pathways, suggesting a novel therapeutic approach for POI.

acupuncture↗

PubMed2002

Analysis of transcriptomes of human malaria parasite Plasmodium falciparum using full-length enriched library: identification of novel genes and diverse transcription start sites of messenger RNAs.

Now that the sequencing of the complete genome of the human malaria parasite Plasmodium falciparum is now underway, importance of analyses of complementary DNAs (cDNAs) is looming up. We constructed a full-length-enriched cDNA library from erythrocytic stage P. falciparum using the 'oligo-capping' method (Nucleic Acids Res. 29 (2001) 70). In this report we describe the novel genes identified using this library and detailed characterization of transcriptional start site of knob-associated histidine rich protein gene. Contrary to the previous report we conclude all the transcripts of plasmodium genes have diverse start sites. Sequence comparisons between the cDNAs and the complete sequences of chromosomes 2 identified three novel genes that had been missed by computational predictions. Moreover, analysis of transcriptional start sites revealed that the average length of the 5' untranslated region was 346 nt, which is much longer than that in humans. The transcriptional start sites of all the genes studied were far more diverse than those of human genes. These observations may reflect unique mechanism(s) of gene expression in this organism, which has an extremely AT-rich genome.

5' Untranslated Regions↗

PubMed2006

A leuC mutation leading to increased L-lysine production and rel-independent global expression changes in Corynebacterium glutamicum.

We previously found by transcriptome analysis that global induction of amino acid biosynthetic genes occurs in a classically derived industrial L-lysine producer, Corynebacterium glutamicum B-6. Based on this stringent-like transcriptional profile in strain B-6, we analyzed the relevant mutations from among those identified in the genome of the strain, with special attention to the genes that are involved in amino acid biosynthesis and metabolism. Among these mutations, a Gly-456-->Asp mutation in the 3-isopropylmalate dehydratase large subunit gene (leuC) was defined as a useful mutation. Introduction of the leuC mutation into a defined L-lysine producer, AHD-2 (hom59 and lysC311), by allelic replacement led to the phenotype of a partial requirement for L-leucine and approximately 14% increased L-lysine production. Transcriptome analysis revealed that many amino acid biosynthetic genes, including lysC-asd operon, were significantly upregulated in the leuC mutant in a rel-independent manner.

Corynebacterium glutamicum↗

PubMed2005

Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia.

Understanding the complexity and dynamics of cancer cells in response to effective therapy requires hypothesis-driven, quantitative, and high-throughput measurement of genes and proteins at both spatial and temporal levels. This study was designed to gain insights into molecular networks underlying the clinical synergy between retinoic acid (RA) and arsenic trioxide (ATO) in acute promyelocytic leukemia (APL), which results in a high-quality disease-free survival in most patients after consolidation with conventional chemotherapy. We have applied an approach integrating cDNA microarray, 2D gel electrophoresis with MS, and methods of computational biology to study the effects on APL cell line NB4 treated with RA, ATO, and the combination of the two agents and collected in a time series. Numerous features were revealed that indicated the coordinated regulation of molecular networks from various aspects of granulocytic differentiation and apoptosis at the transcriptome and proteome levels. These features include an array of transcription factors and cofactors, activation of calcium signaling, stimulation of the IFN pathway, activation of the proteasome system, degradation of the PML-RARalpha oncoprotein, restoration of the nuclear body, cell-cycle arrest, and gain of apoptotic potential. Hence, this investigation has provided not only a detailed understanding of the combined therapeutic effects of RA/ATO in APL but also a road map to approach hematopoietic malignancies at the systems level.

Antineoplastic Agents↗