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Results for “comparative transcriptomics”

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PubMed2006

Evaluation of gene expression analysis using RNA-targeted partial genome arrays.

Highly parallel cDNA targeting microarrays have been established over the last years as the quasi-standard for genome wide expression profiling in pro- and eukaryotes. Protocols for the direct detection of RNA or aRNA (amplified RNA) are currently emerging. This allows to circumvent the bias introduced by enzymatic target molecule preparation. To systematically evaluate the extent of non-specific target binding on oligonucleotide microarrays designed for total RNA expression profiling, a model system of 70-mer probes targeting genes involved in magnetosome formation (mam genes) of the bacterium Magnetospirillum gryphiswaldense was established utilizing wild-type strain MSR-1 and an isogenic deletion mutant MSR-1B that lacks all mam genes. An optimized protocol for the direct chemical labelling of total cellular RNAs was used. A linear correlation between the amount of applied RNA and the mean global background intensity was found which enables a simple and unbiased way of normalizing the data. The results obtained with the mam deletion mutant MSR-1B revealed a significant number of false positive signals, even under optimal hybridization conditions. This indicates a high degree of non-specific binding in microarray experiments when using longer oligo- or polynucleotides and RNA as target molecule. Comparative microarray analysis of an MSR-1B culture and two MSR-1 wild-type cultures grown under different conditions was done via a three-colour hybridization assay. The additional information provided by the MSR-1B transcriptome revealed differential gene expression in the two MSR-1 cultures, which was otherwise undetectable.

Gene Expression Profiling↗

PubMed2005

The rat blood-brain barrier transcriptome.

The blood-brain barrier (BBB) is the cellular interface between the circulating blood and neural environment, and is created by apposed endothelial cells and their intercellular tight junctions. Many aspects of how the BBB functions at the molecular level remain unresolved; therefore, we report for the first time a comprehensive gene expression profile of rat brain microvessels using serial analysis of gene expression (SAGE). We assembled a full and quantitative SAGE catalog containing 101,364 tags, of which 33% of the tags matched known genes, 51% matched expressed sequence tags (ESTs) in the Unigene database, and 16% of the tags were unassigned. The transcriptome catalog contains many new and novel transcripts among known BBB genes. A large compliment of junctional proteins and an extensive assortment of facilitated carrier and ATP-dependent transporters are included. To identify microvessel-enriched transcripts, we compared the microvessel SAGE catalog to cortex and hippocampus SAGE catalogs. This resulted in identification of 864 genes, including several known for their abundant expression at the BBB, such as the transferrin receptor (TrnR). Sorting enriched genes based on function revealed groups that encode transporters (11%), receptors (5%), proteins involved in vesicle trafficking (4%), structural proteins (10%), and components of signal transduction pathways (17%). This genomic repertoire emphasizes the unique cellular phenotype existing within the brain and further implicates the BBB as a mediator between the brain and periphery. These results may provide a useful resource and reference point from which to determine the effects of different physiological, developmental, and disease processes on BBB gene expression.

Animals↗

PubMed2004

AnoXcel: an Anopheles gambiae protein database.

The proteome of the mosquito Anopheles gambiae was organized on a hyperlinked spreadsheet format containing one protein per row and several pieces of information in each column. The information for each protein ranges from the presence or absence of signal peptide indicative of secretion, presence of transmembrane domains, similarities to several databases, chromosomal location, and relatedness to other An. gambiae proteins, etc. Hosted by AnoBase (http://www.anobase.org/), the whole spreadsheet or segments of it can be downloaded or searched from http://www.anobase.org/AnoBase/Genes/Ano-Xcel by the scientist dealing with the annotation of proteome subsets such as those deriving from transcriptomes, nucleotide microarrays or high throughput mass spectrometry data.

Animals↗

PubMed2006

Quantitative proteomics and its applications for systems biology.

Here we discuss the current state of research in the rapidly growing field of quantitative proteomics and its applications to systems biology. Quantitative proteomics can be successfully used for characterizing alterations in protein abundance, finding novel protein-protein and protein-peptide interactions, investigating formation of large macromolecular complexes, and elucidating temporal changes in organellar protein composition and phosphorylation in signal transduction cascades. Further, quantitative proteomics can directly compare activation of entire signaling networks in response to individual stimuli and discover critical differences in their circuits that account for alterations of cell response. Maturation of proteomic bioinformatics applications and continuous improvements in proteomics and related genomics and transcriptomics technologies now allows us to investigate cellular mechanisms at the integrative system level.

Animals↗

PubMed2004

Toxicogenomics of subchronic hexachlorobenzene exposure in Brown Norway rats.

Hexachlorobenzene (HCB) is a persistent environmental pollutant with toxic effects in man and rat. Reported adverse effects are hepatic porphyria, neurotoxicity, and adverse effects on the reproductive and immune system. To obtain more insight into HCB-induced mechanisms of toxicity, we studied gene expression levels using DNA microarrays. For 4 weeks, Brown Norway rats were fed a diet supplemented with 0, 150, or 450 mg HCB/kg. Spleen, mesenteric lymph nodes (MLN), thymus, blood, liver, and kidney were collected and analyzed using the Affymetrix rat RGU-34A GeneChip microarray. Most significant (p < 0.001) changes, compared to the control group, occurred in spleen, followed by liver, kidney, blood, and MLN, but only a few genes were affected in thymus. This was to be expected, as the thymus is not a target organ of HCB. Transcriptome profiles confirmed known effects of HCB such as stimulatory effects on the immune system and induction of enzymes involved in drug metabolism, porphyria, and the reproductive system. In line with previous histopathological findings were increased transcript levels of markers for granulocytes and macrophages. New findings include the upregulation of genes encoding proinflammatory cytokines, antioxidants, acute phase proteins, mast cell markers, complements, chemokines, and cell adhesion molecules. Generally, gene expression data provide evidence that HCB induces a systemic inflammatory response, accompanied by oxidative stress and an acute phase response. In conclusion, this study confirms previously observed (immuno)toxicological effects of HCB but also reveals several new and mechanistically relevant gene products. Thus, transcriptome profiles can be used as markers for several of the processes that occur after HCB exposure.

Acute-Phase Reaction↗

PubMed2026

Liver transcriptome analysis revealed multiple immune processes and lipid metabolism pathways involved in the defense response of the turbot (Scophthalmus maximus) against Aeromonas salmonicida.

Aeromonas salmonicida is a significant pathogen causing notable economic losses in Scophthalmus maximus aquaculture. This study utilized Illumina sequencing technology to examine the transcriptional response characteristics of S. maximus liver at 24 h following A. salmonicida infection. A total of 2363 differentially expressed genes (DEGs) were identified when compared to the negative control group. The immunity-related Toll-like receptor signaling pathway, NOD-like receptor signaling pathway, as well as metabolism-related PPAR signaling pathway and insulin signaling pathway, were notably enriched. Significant differences exist in the expression of key genes within the PPAR pathway, particularly cd36, acsl4a, pparαa, and plin2, all of which mediate the interaction between lipid metabolism and the immune response. These results offer valuable insights into the immunometabolic regulatory mechanism of S. maximus response to A. salmonicida infection.

Animals↗

PubMed2026

Causal assessment of Bayesian gene regulatory networks from single-cell transcriptomics.

Gene regulatory network (GRN) inference is an essential tool for revealing dysregulated relationships between genes in different cell types from single-cell transcriptomic (SCT) data. GRNs based on Bayesian networks (BNs) learned from SCT data can elucidate directed regulatory relationships representing complex disease mechanisms and their interplay through graphical modeling. However, software for learning BNs from SCT data is not widely available, nor is software for evaluating the BNs' structural accuracy in representing causal relationships between genes. Here, we describe the scstruc R package. This package provides a suite of BN structure learning algorithms specifically designed to handle SCT data, to evaluate the resulting networks based on the causal relationships they represent regardless of the availability of established molecular interaction networks, and to compare regulatory relationships between conditions. We demonstrated that scstruc can identify biologically relevant differential regulatory relationships between groups on a per-cell basis.

Bayesian networks↗

PubMed2026

Comprehensive identification and evolutionary analysis of the Wnt gene family in bivalves: Insights into the larval development of the noble scallop Chlamys nobilis.

The Wnt gene family regulates fundamental developmental processes in metazoans, but its evolutionary composition and developmental deployment in bivalves remain largely unresolved. Here, we performed a comparative genomic analysis of Wnt genes in 19 bivalve species and examined developmental expression profiles in the noble scallop Chlamys nobilis, with Crassostrea gigas and Chlamys farreri used for cross-species comparison. A total of 235 Wnt genes were identified and assigned to 12 subfamilies. No reliable Wnt3 ortholog was detected in any analyzed bivalve, supporting the view that Wnt3 loss occurred early during lophotrochozoan evolution rather than representing a lineage-specific absence. Most Wnt proteins retained the conserved WNT domain, indicating strong structural conservation, whereas lineage-specific copy-number variation and gene loss were observed among species. C. farreri and C. gigas each retained 12 Wnt genes and lacked Wnt3, whereas C. nobilis lacked Wnt3, Wnt7, and Wnt16. Developmental transcriptome analysis and RT-qPCR revealed clear stage-specific expression patterns. In C. gigas, Wnt2/10/A were highly expressed during earlydevelopment and peaked around the D-shaped larval stage, while Wnt8 and Wnt11 showed distinct stage-specific peaks. By contrast, Wnt1/5/6/9 were more active during later larval development or juvenile formation. These results provide a comparative framework for bivalve Wnt evolution and identify candidate Wnt genes potentially involved in larval development and aquaculture-relevant developmental transitions.

Animals↗

PubMed2006

Multivariate analysis of microarray data by principal component discriminant analysis: prioritizing relevant transcripts linked to the degradation of different carbohydrates in Pseudomonas putida S12.

The value of the multivariate data analysis tools principal component analysis (PCA) and principal component discriminant analysis (PCDA) for prioritizing leads generated by microarrays was evaluated. To this end, Pseudomonas putida S12 was grown in independent triplicate fermentations on four different carbon sources, i.e. fructose, glucose, gluconate and succinate. RNA isolated from these samples was analysed in duplicate on an anonymous clone-based array to avoid bias during data analysis. The relevant transcripts were identified by analysing the loadings of the principal components (PC) and discriminants (D) in PCA and PCDA, respectively. Even more specifically, the relevant transcripts for a specific phenotype could also be ranked from the loadings under an angle (biplot) obtained after PCDA analysis. The leads identified in this way were compared with those identified using the commonly applied fold-difference and hierarchical clustering approaches. The different data analysis methods gave different results. The methods used were complementary and together resulted in a comprehensive picture of the processes important for the different carbon sources studied. For the more subtle, regulatory processes in a cell, the PCDA approach seemed to be the most effective. Except for glucose and gluconate dehydrogenase, all genes involved in the degradation of glucose, gluconate and fructose were identified. Moreover, the transcriptomics approach resulted in potential new insights into the physiology of the degradation of these carbon sources. Indications of iron limitation were observed with cells grown on glucose, gluconate or succinate but not with fructose-grown cells. Moreover, several cytochrome- or quinone-associated genes seemed to be specifically up- or downregulated, indicating that the composition of the electron-transport chain in P. putida S12 might change significantly in fructose-grown cells compared to glucose-, gluconate- or succinate-grown cells.

Carbohydrate Metabolism↗

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↗

PubMed2005

Transcriptional responses in mouse lungs induced by vaccination with Mycobacterium bovis BCG and infection with Mycobacterium tuberculosis.

Transcriptome analyses enable the assessment of signature alterations in whole tissues and organs undergoing pathological processes. We analyzed gene expression profiles of lungs from mice infected with Mycobacterium tuberculosis or vaccinated with Mycobacterium bovis bacille Calmette-Guérin (BCG). We compared high-dose systemic and low-dose aerosol M. tuberculosis infections as well as systemic BCG vaccination. Expression profiles in lungs were analyzed at day (d) 1 and d 30 post infection / vaccination using a custom tailored 'in situ' synthesized 60-mer oligonucleotide microarray with focus on immunologically relevant genes. At d 1, a small number of genes were differentially regulated, whereas at d 30, a discrete expression pattern was identified in the lung. Differential gene expression profiles between M. tuberculosis infection and BCG vaccination indicate differences in naturally and vaccine induced pulmonary immune responses. The shared signature of systemic and aerosol M. tuberculosis infection revealed dominance of genes related to or controlled by interferon gamma (IFN-gamma). We assume that differential gene expression profiles after M. tuberculosis infection are strongly influenced by differences in cellular composition of the lung due to migration of immune cells, primarily neutrophils, basophils, eosinophils and monocytes to the site of infection.

Animals↗

PubMed2026

IBAS: Interaction-bridged association studies discovering novel genes underlying complex traits.

Genetic contributions to complex traits are often mediated through coordinated gene-gene interaction networks, yet most existing association frameworks focus on marginal single-gene effects and overlook higher-order dependency structures. Direct modeling of interactions remains challenging due to combinatorial complexity and statistical instability. We introduce Interaction-Bridged Association Study (IBAS), a general framework that incorporates pathway-level interaction patterns into genotype-phenotype association analysis without explicitly enumerating interactions. IBAS leverages transcriptomic reference data to construct low-dimensional representations of pathway activity, which guide SNP-weighting and gene-level association testing within a kernel-based framework. In perturbation-based simulations, IBAS demonstrates improved stability and reproducibility compared to conventional TWAS and gene-based methods, while maintaining well-calibrated Type I error under phenotype permutation. Application to the WTCCC datasets identifies both known and novel genes across multiple complex diseases, including candidates with modest marginal effects missed by standard approaches. These findings are supported by replication in an independent cohort, and analyses across multiple reference tissues revealing both shared and tissue-specific signals. Overall, IBAS provides a statistically robust and computationally tractable framework for incorporating interaction effects into association mapping, extending beyond the single-gene paradigm and enabling more comprehensive characterization of complex trait. IBAS is available on GitHub at: https://github.com/QingrunZhangLab/IBAS.

Polymorphism, Single Nucleotide↗

PubMed2002

Moss transcriptome and beyond.

The ancient land plant Physcomitrella patens is a model system that is becoming increasingly important for plant functional genomics because gene knockouts can be produced with relative ease. Recently, several EST-sequencing projects have been launched as a first step towards a thorough functional characterization of the moss. However, for careful comparison with other plant model systems, the complete genomic sequence is needed as well as the transcriptome.

Arabidopsis↗

PubMed2024

ASXL1 truncating variants in BOS and myeloid leukemia drive shared disruption of Wnt-signaling pathways but have differential isoform usage of RUNX3.

BACKGROUND: Rare variants in epigenes (a.k.a. chromatin modifiers), a class of genes that control epigenetic regulation, are commonly identified in both pediatric neurodevelopmental syndromes and as somatic variants in cancer. However, little is known about the extent of the shared disruption of signaling pathways by the same epigene across different diseases. To address this, we study an epigene, Additional Sex Combs-like 1 (ASXL1), where truncating heterozygous variants cause Bohring-Opitz syndrome (BOS, OMIM #605039), a germline neurodevelopmental disorder, while somatic variants are driver events in acute myeloid leukemia (AML). No BOS patients have been reported to have AML. METHODS: This study explores common pathways dysregulated by ASXL1 variants in patients with BOS and AML. We analyzed whole blood transcriptomic and DNA methylation data from patients with BOS and AML with ASXL1-variant (AML-ASXL1) and examined differential exon usage and cell proportions. RESULTS: Our analyses identified common molecular signatures between BOS and AML-ASXL1 and highlighted key biomarkers, including VANGL2, GRIK5 and GREM2, that are dysregulated across samples with ASXL1 variants, regardless of disease type. Notably, our data revealed significant de-repression of posterior homeobox A (HOXA) genes and upregulation of Wnt-signaling and hematopoietic regulator HOXB4. While we discovered many shared epigenetic and transcriptomic features, we also identified differential splice isoforms in RUNX3 where the long isoform, p46, is preferentially expressed in BOS, while the shorter p44 isoform is expressed in AML-ASXL1. CONCLUSION: Our findings highlight the strong effects of ASXL1 variants that supersede cell-type and even disease states. This is the first direct comparison of transcriptomic and methylation profiles driven by pathogenic variants in a chromatin modifier gene in distinct diseases. Similar to RASopathies, in which pathogenic variants in many genes lead to overlapping phenotypes that can be treated by inhibiting a common pathway, our data identifies common pathways for ASXL1 variants that can be targeted for both disease states. Comparative approaches of high-penetrance genetic variants across cell types and disease states can identify targetable pathways to treat multiple diseases. Finally, our work highlights the connections of epigenes, such as ASXL1, to an underlying stem-cell state in both early development and in malignancy.

Humans↗

PubMed2026

Characterization of the genomic and transcriptomic landscape of invasive non-mucinous lung adenocarcinoma based on IASLC grading.

BACKGROUND: The IASLC grading system has prognostic utility and potential therapeutic implications in invasive non-mucinous lung adenocarcinoma (LUAD), but the molecular basis underlying the grading spectrum remains unclear. METHODS: We performed whole-genome sequencing in 138 Chinese patients with invasive non-mucinous LUAD and RNA sequencing of 96 matched tumor-normal tissue pairs to systematically characterize the molecular features across grades, including coding driver events, mutational signatures, non-coding regulatory disruptions, and transcriptional programs. RESULTS: Compared with Grade 1-2 tumors, Grade 3 LUADs exhibited heightened invasive potential, manifested by more advanced stage, more frequent spread through air spaces, and independently worse survival. Grade 3 tumors had elevated tumor mutational burden and were enriched for alterations in genome maintenance and cell-cycle genes, including TP53, as well as genes implicated in DNA damage response, including ZFHX4. APOBEC-associated mutagenesis was selectively enriched in Grade 3 tumors independent of smoking status, consistent with an instability-associated phenotype. Recurrent non-coding regulatory disruptions affected lung lineage-defining genes, particularly surfactant-associated genes, and were correlated with reduced expression. Transcriptomic profiling revealed epithelial dedifferentiation, loss of pulmonary homeostatic programs, and activation of proliferative and stress-related pathways. Notably, MUC16 emerged as a convergent event linking genomic and transcriptional dysregulation, with coding mutations associated with higher expression and increased expression in Grade 3 tumors correlating with the proportion of high-grade histologic patterns. CONCLUSIONS: These findings provide a molecular framework for the IASLC grading spectrum and identify Grade 3 LUAD as a distinct instability-associated and dedifferentiated biological state.

IASLC grading↗

PubMed2006

Comparative transcriptional profiling of the lung reveals shared and distinct features of Streptococcus pneumoniae and influenza A virus infection.

Pneumonia is the most common cause of death from infectious disease in the western hemisphere. Pathophysiological and protective processes are initiated by pattern recognition of microbial structures. To provide the molecular framework for a better understanding of processes relevant to host defence in pneumonia, we performed pulmonary transcriptome analysis in mice infected with the major bacterial and viral agents of community-acquired pneumonia, Streptococcus pneumoniae and influenza A virus. We detected differential expression of 1300 genes after infection with either pathogen. Of these, approximately 36% or 30% were specific for pneumococcal or influenza infection, respectively, yielding pathogen-specific as well as shared inflammatory transcriptional signatures. These results not only reveal a differential response on the cytokine and chemokine levels but also emphasize the important role of genes implicated in regulation and fine tuning of inflammation. As one, albeit unexpected, key feature of pneumococcal pneumonia we discovered down-regulation of B-cell responses, probably reflecting a pneumococcal virulence strategy. The pathophysiological consequences of influenza A virus infection were reflected by the emerging protective T-cell response and differential induction of genes involved in tissue regeneration and proliferation. These data provide new insights into pathogenesis of the most common forms of pneumonia, highlighting the value of transcriptional profiling for the elucidation of underlying mechanisms.

Animals↗

PubMed2002

Sugar-coated microarrays: a novel slide surface for the high-throughput analysis of glycans.

The development of DNA and protein microarrays represents a significant advance in transcriptomics and proteomics research. Such arrays allow the high-throughput, parallel analysis of protein occurrence and interactions and gene expression. However, this advance has not been matched by equivalent technology for analysis of glycomes. One reason for this is that compared to proteins, it is difficult to reliably immobilise populations of chemically and structurally diverse glycans. We describe the development of a new microarray slide surface to which diverse glycan structures can be directly immobilised without prior derivatisation of the slide surface or any modification of the arrayed samples. The slides can be used to produce comprehensive microarrays of carbohydrates, glycoproteins and proteoglycans using isolated samples or cell extracts. Using standard microarray equipment, a series of carbohydrate microarrays were generated and probed with a panel of monoclonal antibodies with specificities for glycan epitopes. The arrays were highly reproducible, stable, and could be stored dry for several months. Glycans play central roles in development, carcinogenesis, cell adhesion, and immunity and are increasingly the subject of therapeutic approaches. We anticipate that the development of carbohydrate microarrays will be important for the high-throughput analysis of glycans and their molecular interactions.

Animals↗

PubMed2025

Human-specific features of the cerebellum and ZP2-regulated synapse development.

Understanding the unique features of the human brain compared to non-human primates has long intrigued humankind. The cerebellum refines motor coordination and cognitive functions, contributing to the evolutionary development of human adaptability and dexterity. To identify shared and divergent features across primates, we conducted single-nucleus transcriptomic and chromatin accessibility profiling of the adult cerebellar cortex in humans, chimpanzees, macaques, and marmosets. We revealed human-specific transcriptomic and regulatory features, particularly those involved in synaptogenesis. Notably, we identified an enrichment of the sperm receptor zona pellucida glycoprotein 2 (ZP2) and its potential interactors, known for their roles in gamete interaction, in human granule cells. Experimental data show that ZP2 expression in human granule cells is induced by pontine mossy fibers, reducing synaptic proteins at pontocerebellar glomerular synapses, and decreasing cerebellar neuron electrophysiological activity. This unexpected co-option of ZP2 in human-specific synapse regulation provides insights into the evolutionary specialization of the human cerebellum.

Brain evolution↗