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Results for “comparative transcriptomics”

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PubMed2006

Differential gene expression in egg cells and zygotes suggests that the transcriptome is restructed before the first zygotic division in tobacco.

We applied suppression subtractive hybridization and mirror orientation selection to compare gene expression profiles of isolated Nicotiana tabacum cv SR1 zygotes and egg cells. Our results revealed that many differentially expressed genes in zygotes were transcribed de novo after fertilization. Some of these genes are critical to zygote polarity and pattern formation during early embryogenesis. This suggests that the transcriptome is restructed in zygote and that the maternal-to-zygotic transition happens before the first zygotic division, which is much earlier in higher plants than in animals. The expressed sequence tags used in this study provide a valuable resource for future research on fertilization and early embryogenesis.

Body Patterning↗

PubMed2026

Targeting USP22 reprograms the tumor microenvironment and sensitizes KRAS/p53-driven lung cancer to anti-PD-1 immunotherapy.

RATIONALE: Ubiquitin-specific peptidase 22 (USP22), a deubiquitinase and component of the "Death-from-Cancer" 11-gene signature, is overexpressed in multiple malignancies and linked to recurrence, therapy resistance, and poor prognosis. Its role in KRAS/p53-driven lung cancer and the response to immune checkpoint inhibitors (ICIs) remains poorly defined. Here, we investigated USP22 as a potential therapeutic target in KRAS/p53-driven lung cancer. METHODS: A conditional Usp22 knockout (Usp22-KO) was generated in the KRASG12D; p53-/- (KP) mouse model. Cancer progression was monitored by micro-computed tomography (micro-CT). Multiplex immunofluorescence (mIF), RNA sequencing, and spatial transcriptomics profiled cancer and tumor microenvironment (TME) changes. Responses to anti-PD-1/PD-L1 therapies were compared between KP and Usp22-KO KP (KPU-) lung cancers. RESULTS: USP22 was highly expressed in early-stage KRAS/p53-driven mouse lung cancers and strongly correlated with proliferation marker Ki67. Usp22 deletion suppressed cancer growth, prolonged survival, and promoted cancer differentiation. Spatial transcriptomics and mIF revealed reduced CD206+ M2 macrophages, myeloid-derived suppressor cells (MDSCs), TGF-β1, and angiogenesis, along with increased functional CD8+ T cells. Mechanistically, USP22 regulated gene expression and protein stability, reducing c-Myc, PD-L1, TGF-β1, and SPARC upon Usp22 loss. Compared with KP cancer, KPU- and SPARC-knockdown KP cancers showed reduced macrophage chemotaxis and impaired basal- and TGF-β1-induced M2 polarization of RAW264.7 cells, suggesting that TGF-β1 and SPARC downregulation partially contributes to decreased M2 macrophage infiltration in KPU- cancers. Notably, Usp22 loss enhanced the efficacy of anti-PD-L1 and anti-PD-1 therapies in orthotopic and subcutaneous KP lung cancer models, respectively. USP22 and SPARC expression were also strongly correlated in human lung cancers. CONCLUSIONS: USP22 promotes progression and immune evasion in KRAS/p53-driven lung cancer. Targeting USP22 reprograms the TME, suppresses oncogenic signaling, and sensitizes tumors to ICI, establishing USP22 as a promising therapeutic target.

Animals↗

PubMed2004

The genomics of malaria infection.

Malaria research is now dominated by information flowing from the genome sequencing projects and the associated transcriptome- and proteome-mapping projects. As more species are sequenced, comparative and phylogenetic comparisons are improving the quality of gene finding, and are providing various approaches to the identification of genes important to parasite biology and the pathogenesis of disease. We are still in the early days of exploiting these data in a systematic way and the sheer volume of data presents daunting challenges. This article reviews the progress in using this genomic information and discusses opportunities for other approaches.

Animals↗

PubMed2002

Transcript abundance in yeast varies over six orders of magnitude.

In the current era of functional genomics, it is remarkable that the intracellular range of transcript abundance is largely unknown. For the yeast Saccharomyces cerevisiae, hybridization-based complexity analysis and SAGE analysis showed that the majority of yeast mRNAs are present at one or fewer copies per cell; however, neither method provides an accurate estimate of the full range of low abundance transcripts. Here we examine the range of intracellular transcript abundance in yeast using kinetically monitored, reverse transcriptase-initiated PCR (kRT-PCR). Steady-state transcript levels encoded by all 65 genes on the left arm of chromosome III and 185 transcription factor genes are quantitated. Abundant transcripts encoded by glycolytic genes, previously quantitated by kRT-PCR, are present at a few hundred copies per cell whereas genes encoding physiologically important transcription factors are expressed at levels as low as one-thousandth transcript per cell. Of the genes assessed, only the silent mating type loci, HML and HMR, are transcriptionally silent. The results show that transcript abundance in yeast varies over six orders of magnitude. Finally, kRT-PCR, cDNA microarray, and high density oligonucleotide array assays are compared for their ability to detect and quantitate the complete yeast transcriptome.

Genes, Fungal↗

PubMed2005

ESTviewer: a web interface for visualizing mouse, rat, cattle, pig and chicken conserved ESTs in human genes and human alternatively spliced variants.

ESTviewer is a web application for interactively visualizing human gene structures, with emphasis on mammalian and avian expressed sequence tags (ESTs) that are conserved in the human genome and alternatively spliced (AS) variants. AS variants from the UCSC, Vega and PSEP annotations are presented in this application for comparison. EST data from six species, human, mouse, rat, cattle, pig and chicken, are mapped to the human genome to show cross-species EST conservation in annotated exonic and intronic regions. Cross-species EST conservation is evolutionarily and functionally important because it represents the effects of selection pressure on genic regions and transcriptome over evolutionary time. Emphatically, ESTviewer provides a convenient tool to compare highly conserved non-human ESTs and human AS variants. The application takes human gene accession Ids or coordinates of genomic sequences as inputs and presents annotated gene structures and their AS variants. In addition, the lengths and percentages of human genic regions covered by ESTs are displayed to show the level of EST coverage of different species. The percentages of the UCSC, Vega and PSEP annotated exons covered by ESTs of the six studied species are also displayed in the interface.

Animals↗

PubMed2006

Global gene expression in Escherichia coli K-12 during short-term and long-term adaptation to glucose-limited continuous culture conditions.

Microarray technology was used to study the cellular events that take place at the transcription level during short-term (physiological) and long-term (genetic) adaptation of the faecal indicator bacterium Escherichia coli K-12 to slow growth under limited nutrient supply. Short-term and long-term adaptation were assessed by comparing the mRNA levels isolated after 40 or 500 h of glucose-limited continuous culture at a dilution rate of 0.3 h(-1) with those from batch culture with glucose excess. A large number of genes encoding periplasmic binding proteins were upregulated, indicating that the cells are prepared for high-affinity uptake of all types of carbon sources during glucose-limited growth in continuous culture. All the genes belonging to the maltose (mal/lamB) and galactose (mgl/gal) operons were upregulated. A similar transcription pattern was observed for long-term cultures except that the expression factors were lower than in the short-term adaptation. The patterns of upregulation were confirmed by real-time RT-PCR. A switch from a fully operational citric acid cycle to the PEP-glyoxylate cycle was clearly observed in cells grown in glucose-limited continuous culture when compared to batch-grown cells and this was confirmed by transcriptome analysis. This transcriptome analysis confirms and extends the observations from previous proteome and catabolome studies in the authors' laboratory.

Adaptation, Physiological↗

PubMed2005

Gene expression profile changes between melanoma metastases and their daughter cell lines: implication for vaccination protocols.

Vaccination protocols based on autologous tumor material often require in vitro culturing of tumor cells to obtain enough cellular material for the production of the vaccine. Cancer cells and particularily melanoma cells are known for their genomic instability. Therefore, it can be assumed that melanoma cells acquire genomic changes and thereby changes in the transcriptome during in vitro culturing. This may lead to a shift of epitopes expressed on the tumor cells. We analyzed the transcriptome of in vitro cultured melanoma cells prepared from melanoma metastases. Comparing the gene expression changes between the tumors and their offspring cell lines, we demonstrate that with increasing passage numbers, gene expression changes increase drastically.

Cancer Vaccines↗

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

Mechanisms by which carbamoylated high-density lipoprotein (C-HDL) promotes calcific aortic valve disease and exploration of potential targeted therapies.

Calcific aortic valve disease (CAVD) is a progressive fibrocalcific illness for which no effective pharmaceutical treatment exists. This study investigated whether carbamoylated high-density lipoprotein (C-HDL), a defective type of HDL that can develop during inflammation, contributes to CAVD progression and the involved molecular pathways. Male ApoE-/- mice were divided into three groups: CAVD model, cyanate-treated, and inhibitor, and analyzed after 12 weeks. C57BL/6 mice on a regular diet served as blank controls. Serum paraoxonase-1 (PON1), aortic valve calcification, cluster of differentiation 31 (CD31), phosphorylated nuclear factor kappa B p65 (p-p65), NOTCH receptor 1 (NOTCH1), and runt-related transcription factor 2 (RUNX2) were evaluated. In parallel, using RNA sequencing (RNA-seq), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, protein-protein interaction (PPI) network analysis, and quantitative real-time polymerase chain reaction. Cyanate treatment reduced serum PON1 levels, increased von Kossa-positive calcium deposition, and raised CD31, p-p65, NOTCH1, and RUNX2 levels compared with the model group, but Gly partially corrected these effects. Transcriptomic research identified 270 C-HDL-associated differentially expressed genes (DEGs) enriched in pathways associated with inflammatory signaling and NF-κB activity. Five potential hub genes (BIRC6, PIK3R1, ATM, IFIH1, and DDX58) were discovered and verified using qRT-PCR. These data show that C-HDL may accelerate CAVD by disrupting valve endothelial homeostasis and stimulating inflammatory signaling, and they identify potential molecular targets for future functional validation.

bioinformatics↗

PubMed2005

Representation and high-quality annotation of the Physcomitrella patens transcriptome demonstrates a high proportion of proteins involved in metabolism in mosses.

To gain insight into the transcriptome of the well-used plant model system Physcomitrella patens, several EST sequencing projects have been undertaken. We have clustered, assembled, and annotated all publicly available EST and CDS sequences in order to represent the transcriptome of this non-seed plant. Here, we present our fully annotated knowledge resource for the Physcomitrella patens transcriptome, integrating annotation from the production process of the clustered sequences and from a high-quality annotation pipeline developed during this study. Each transcript is represented as an entity containing full annotations and GO term associations. The whole production, filtering, clustering, and annotation process is being modelled and results in seven datasets, representing the annotated Physcomitrella transcriptome from different perspectives. We were able to annotate 63.4 % of the 26 123 virtual transcripts. The transcript archetype, as covered by our clustered data, is compared to a compilation based on all available Physcomitrella full length CDS. The distribution of the gene ontology annotations (GOA) for the virtual transcriptome of Physcomitrella patens demonstrates consistency in the ratios of the core molecular functions among the plant GOA. However, the metabolism subcategory is over-represented in bryophytes as compared to seed plants. This observation can be taken as an indicator for the wealth of alternative metabolic pathways in moss in comparison to spermatophytes. All resources presented in this study have been made available to the scientific community through a suite of user-friendly web interfaces via www.cosmoss.org and form the basis for assembly and annotation of the moss genome, which will be sequenced in 2005.

3' Untranslated Regions↗

PubMed2005

Pattern profiling and mapping of the fat body transcriptome in Drosophila melanogaster.

In Drosophila, the fat body is a collective name for the masses and sheets of adipose tissue that are distributed throughout the fly body. Thus far, >386,000 Drosophila expressed sequence tags (ESTs) have been deposited to the GenBank database, including 10,443 derived from fat body in flies (data accessed on October 7, 2004). The objective of this study was to map the transcriptome of the fat body in flies and thus provide genomics and bioinformatics tools for developing a Drosophila model for addressing the genetic complexity of obesity in humans. The gene-EST Basic Local Alignment Search Tool (BLAST) matches revealed that these ESTs could represent 12,188 coding genes in the Drosophila genome. Among them, at least 2,261 are expressed in the fat body, including 41 identified as preferentially expressed genes with logarithm of odds >3.0. Self-organizing map analysis revealed a cluster of 290 genes favorably expressed in the fat body compared with genes expressed in five other tissues. Mapping of the fat body transcriptome identified a 1.7-Mb domain on 3L containing 35 genes that were expressed at a much higher level than in other tissues (transcript density factor = 1.0 approximately 2.3).

Animals↗

PubMed2006

Quantitative comparison of the HSV-1 and HSV-2 transcriptomes using DNA microarray analysis.

The genomes of human herpes virus type-1 and type-2 share a high degree of sequence identity; yet, they exhibit important differences in pathology in their natural human host as well as in animal host and cell cultures. Here, we report the comparative analysis of the time and relative abundance profiles of the transcription of each virus type (their transcriptomes) using parallel infections and microarray analysis using HSV-1 probes which hybridize with high efficiency to orthologous HSV-2 transcripts. We have confirmed that orthologous transcripts belong to the same kinetic class; however, the temporal pattern of accumulation of 4 transcripts (U(L)4, U(L)29, U(L)30, and U(L)31) differs in infections between the two virus types. Interestingly, the protein products of these transcripts are all involved in nuclear organization and viral DNA localization. We discuss the relevance of these findings and whether they may have potential roles in the pathological differences of HSV-1 and HSV-2.

Animals↗

PubMed2024

Role of the Pseudomonas plecoglossicida fliL gene in immune response of infected hybrid groupers (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂).

Pseudomonas plecoglossicida, a gram-negative bacterium, is the main pathogen of visceral white-point disease in marine fish, responsible for substantial economic losses in the aquaculture industry. The FliL protein, involved in torque production of the bacterial flagella motor, is essential for the pathogenicity of a variety of bacteria. In the current study, the fliL gene deletion strain (ΔfliL), fliL gene complement strain (C-ΔfliL), and wild-type strain (NZBD9) were compared to explore the influence of the fliL gene on P. plecoglossicida pathogenicity and its role in host immune response. Results showed that fliL gene deletion increased the survival rate (50%) and reduced white spot disease progression in the hybrid groupers. Moreover, compared to the NZBD9 strain, the ΔfliL strain was consistently associated with lower bacterial loads in the grouper spleen, head kidney, liver, and intestine, coupled with reduced tissue damage. Transcriptomic analysis identified 2 238 differentially expressed genes (DEGs) in the spleens of fish infected with the ΔfliL strain compared to the NZBD9 strain. Based on Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, the DEGs were significantly enriched in seven immune system-associated pathways and three signaling molecule and interaction pathways. Upon infection with the ΔfliL strain, the toll-like receptor (TLR) signaling pathway was activated in the hybrid groupers, leading to the activation of transcription factors (NF-κB and AP1) and cytokines. The expression levels of proinflammatory cytokine-related genes IL-1β, IL-12B, and IL-6 and chemokine-related genes CXCL9, CXCL10, and CCL4 were significantly up-regulated. In conclusion, the fliL gene markedly influenced the pathogenicity of P. plecoglossicida infection in the hybrid groupers. Notably, deletion of fliL gene in P. plecoglossicida induced a robust immune response in the groupers, promoting defense against and elimination of pathogens via an inflammatory response involving multiple cytokines.

Animals↗

PubMed2003

Sputnik: a database platform for comparative plant genomics.

Two million plant ESTs, from 20 different plant species, and totalling more than one 1000 Mbp of DNA sequence, represents a formidable transcriptomic resource. Sputnik uses the potential of this sequence resource to fill some of the information gap in the un-sequenced plant genomes and to serve as the foundation for in silicio comparative plant genomics. The complexity of the individual EST collections has been reduced using optimised EST clustering techniques. Annotation of cluster sequences is performed by exploiting and transferring information from the comprehensive knowledgebase already produced for the completed model plant genome (Arabidopsis thaliana) and by performing additional state of-the-art sequence analyses relevant to today's plant biologist. Functional predictions, comparative analyses and associative annotations for 500 000 plant EST derived peptides make Sputnik (http://mips.gsf.de/proj/sputnik/) a valid platform for contemporary plant genomics.

Databases, Nucleic Acid↗

PubMed2006

Identification of candidate maternal-effect genes through comparison of multiple microarray data sets.

Transcriptional profiling by microarray hybridization has become a standard method to analyze global gene expression and has resulted in the availability of enormous amounts of experimental data. Given the number of different microarray platforms currently in use, it is critical to determine how reproducible results are from one platform to another. Additional variability may also arise from tissue collection and protocol differences among laboratories. In an effort to identify genes whose maternal mRNA pools are critical during preimplantation development, we compared published results of three independent studies of the mouse preimplantation embryo transcriptome, each performed in a different laboratory using different microarray platforms. We searched the combined data set for genes whose expression patterns were consistent among the three experiments. Querying for presence or absence at single developmental windows indicates that between 52% and 60% of genes are in agreement among the three experiments. Searching for expression patterns across three developmental windows (oocyte + 1-cell, 2- through 8-cell, and blastocyst stage) revealed approximately 33% agreement among the three experiments, although the majority of these genes were either always present or always absent. Using this approach, we identified 51 genes with a predicted expression pattern of maternal RNA only (not present during 2-cell through 8-cell or at the blastocyst stage). RT-PCR validation indicates 37 (72%) of these candidates have the microarray-predicted expression pattern and represent candidate maternal-effect genes. Based on our analysis, we conclude that data mining microarray experiments in this way greatly enhances candidate gene expression pattern accuracy.

Animals↗

PubMed2002

Translational machinery of channel catfish: I. A transcriptomic approach to the analysis of 32 40S ribosomal protein genes and their expression.

Ribosomal protein (RP) genes have become widely used as markers for phylogenetic studies and comparative genomics. However, they have not been available for evolutionary studies in fish although teleosts are the largest group of vertebrates with more than 23,000 species. Using a transcriptomic approach, we have cloned and sequenced 32 40S RP complementary DNAs (cDNAs) from channel catfish (Ictalurus punctatus), making them one of the most complete sets of 40S RP gene sequences from a single organism. Most 40S RPs in channel catfish are highly similar to their orthologues in mammalian species, but S19, S21, and S25 are highly divergent. Only one type of cDNA was found for all RP genes except S26 and S27, for which two cDNAs were found in channel catfish. Alternatively spliced transcripts for the S3 and alternatively polyadenylated transcripts for S19 and S21 were found. The 32 40S RP genes are generally highly expressed and together they account for 5.33-11.42% of expression depending on the tissues. Expression levels of the RP genes were highly variable both within a single tissue among different RP genes and among tissues with regard to a single RP gene. Taken together, these data strongly suggest post-transcriptional regulation of RP gene expression, particularly in consideration of the stoichiometry of their representation in ribosomes.

Alternative Splicing↗

PubMed2007

Global analysis of chromosome X gene expression in primary cultures of normal ovarian surface epithelial cells and epithelial ovarian cancer cell lines.

The interpretation of loss of heterozygosity (LOH) in cancers is complicated as genes that map to LOH regions may be transcriptionally active (Xa) or inactive (Xi) due to X chromosome inactivation (XCI). We have analyzed the chromosome X transcriptome in four epithelial ovarian cancer (EOC) cell lines (TOV21G, TOV81D, TOV112D, and OV90) and 12 primary cultures of normal ovarian surface epithelial (NOSE) cells in relation to chromosome X integrity. Two-way comparative analysis using HuGeneFL Affymetrix GeneChips of TOV21G, TOV81D and OV90 relative to the NOSE samples was highly correlated (> 89%) in contrast to that of TOV112D (56-69%). TOV112D, followed by TOV21G, exhibited the largest number of up-regulated genes. XIST expression by RT-PCR was not detectable in TOV112D or TOV21G. Allele-specific transcription by cDNA sequence analysis of genes known to be subjected to XCI revealed maintenance of XCI in TOV81D and OV90, but not TOV21G. Biallelic expression could not be assessed in TOV112D due to reduction to hemizygosity of chromosome X. Chromosome X rearrangements were observed in FISH analysis of TOV112D and TOV21G, and both of these EOC cell lines were negative for Barr body analysis. The differentially expressed genes did not appear to map to any particular region of the X chromosome in any EOC cell line. The absence of XIST expression is consistent with Barr body loss in TOV112D and TOV21G. The combined evidence is consistent with two proposed mechanisms to account for absence of Xi in female cancers: Xi loss followed by Xa duplication (exemplified by TOV112D) and transcriptional reactivation of Xi (exemplified by TOV21G). Despite an alteration in XIST expression and differences in allelic content in the EOC cell lines, the chromosome X transcriptome was modified modestly when compared with that of NOSE samples.

Cell Line, Tumor↗

PubMed2006

Transcriptome of a Nitrosomonas europaea mutant with a disrupted nitrite reductase gene (nirK).

Global gene expression was compared between the Nitrosomonas europaea wild type and a nitrite reductase-deficient mutant using a genomic microarray. Forty-one genes were differentially regulated between the wild type and the nirK mutant, including the nirK operon, genes for cytochrome c oxidase, and seven iron uptake genes. Relationships of differentially regulated genes to the nirK mutant phenotype are discussed.

Electron Transport Complex IV↗