SEARCH · Search PubMed

Results for “Cell annotation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 181 records · Page 10Linked to original sources

PubMed2006

Predicting the subcellular localization of viral proteins within a mammalian host cell.

BACKGROUND: The bioinformatic prediction of protein subcellular localization has been extensively studied for prokaryotic and eukaryotic organisms. However, this is not the case for viruses whose proteins are often involved in extensive interactions at various subcellular localizations with host proteins. RESULTS: Here, we investigate the extent of utilization of human cellular localization mechanisms by viral proteins and we demonstrate that appropriate eukaryotic subcellular localization predictors can be used to predict viral protein localization within the host cell. CONCLUSION: Such predictions provide a method to rapidly annotate viral proteomes with subcellular localization information. They are likely to have widespread applications both in the study of the functions of viral proteins in the host cell and in the design of antiviral drugs.

Computational Biology↗

PubMed2005

Transcriptome profiling of vertical stem segments provides insights into the genetic regulation of secondary growth in hybrid aspen trees.

In order to better understand the genetic regulation of secondary growth in hybrid aspen (Populus tremula L.xP. alba L.), we carried out a series of cDNA-amplified fragment length polymorphism (AFLP)-based transcriptome analyses in vertical stem segments that represent a gradient of developmental stages with regard to secondary growth. This approach allowed us to screen >80% of the transcriptome expressed in six samples and identify genes differentially expressed with the progress of secondary growth, in a tissue-specific manner. Of the 76,800 transcript-derived fragments (TDFs) analyzed, 271 TDFs were selected and sequenced based on their differential expression patterns. Many of the xylem-up-regulated genes were involved in cell wall and lignin biosynthesis, while the bark-up-regulated genes had diverse functional roles. About 25% of the xylem-up-regulated TDFs analyzed were involved in the phenylpropanoid biosynthesis pathway, which produces the cell wall polymer lignin and various wood extractives. In addition, many of the TDFs showing secondary xylem-specific expression were annotated as genes not previously reported in Populus, including novel cell death proteins, cytoskeleton-interacting proteins, transporters and putative transcription factors.

Blotting, Northern↗

PubMed2026

Enzyme-Metabolite Network Analysis of Endometrial Cancer-Derived Extracellular Vesicles Through Integrated Proteomics and Metabolomics.

Endometrial cancer (EC) is the most common gynecological malignancy in high-income countries. Extracellular vesicles (EVs) are key mediators of intercellular communication and metabolic reprogramming, but their molecular cargo in EC remains poorly characterized. EVs were isolated from four EC cell lines representing Type I and Type II subtypes (AN3CA, ISHIKAWA, HEC1A, and KLE). Untargeted metabolomics was performed by HILIC-LC-MS/MS, proteomics by data-independent acquisition (DIA) mass spectrometry, and multi-omics integration using MetaboAnalyst and OmicsNet. Metabolomic profiling identified 1463 annotated features and revealed significant differences among EC cell lines (PERMANOVA, p = 0.002). Twenty-eight differentially abundant metabolites, including lactic acid, succinic acid, and uric acid, were identified. Proteomic analysis quantified 8513 proteins with subtype-specific expression patterns. Integrated analysis revealed seven significantly enriched pathways, including glycolysis/gluconeogenesis, central carbon metabolism in cancer, and the pentose phosphate pathway. Increased LDHA abundance in metastatic AN3CA-derived EVs was confirmed by Western blot (p = 0.047). EC-derived EVs display subtype- and metastatic-status-specific metabolo-proteomic signatures, with glycolysis, TCA cycle remodeling, and central carbon metabolism as convergent pathway signatures of molecular reprogramming. These findings establish a multi-omics framework for characterizing EV cargo in EC and identify candidate enzyme-metabolite nodes for future biomarker validation in patient-derived specimens.

Female↗

PubMed2006

Contribution of penicillin-binding protein homologs to antibiotic resistance, cell morphology, and virulence of Listeria monocytogenes EGDe.

Seven open reading frames, annotated as potential penicillin-binding-protein-encoding genes (lmo0441, lmo0540, lmo1438, lmo1892, lmo2039, lmo2229, and lmo2754), were targeted for insertional mutagenesis in Listeria monocytogenes EGDe. These genes were found to contribute in various degrees to beta-lactam resistance, cell morphology, or the virulence potential of this organism.

Amino Acid Sequence↗

PubMed2023

Dandelion uses the single-cell adaptive immune receptor repertoire to explore lymphocyte developmental origins.

Assessment of single-cell gene expression (single-cell RNA sequencing) and adaptive immune receptor (AIR) sequencing (scVDJ-seq) has been invaluable in studying lymphocyte biology. Here we introduce Dandelion, a computational pipeline for scVDJ-seq analysis. It enables the application of standard V(D)J analysis workflows to single-cell datasets, delivering improved V(D)J contig annotation and the identification of nonproductive and partially spliced contigs. We devised a strategy to create an AIR feature space that can be used for both differential V(D)J usage analysis and pseudotime trajectory inference. The application of Dandelion improved the alignment of human thymic development trajectories of double-positive T cells to mature single-positive CD4/CD8 T cells, generating predictions of factors regulating lineage commitment. Dandelion analysis of other cell compartments provided insights into the origins of human B1 cells and ILC/NK cell development, illustrating the power of our approach. Dandelion is available at https://www.github.com/zktuong/dandelion .

Humans↗

PubMed2005

Differences in vascular bed disease susceptibility reflect differences in gene expression response to atherogenic stimuli.

Atherosclerosis occurs predominantly in arteries and only rarely in veins. The goal of this study was to test whether differences in the molecular responses of venous and arterial endothelial cells (ECs) to atherosclerotic stimuli might contribute to vascular bed differences in susceptibility to atherosclerosis. We compared gene expression profiles of primary cultured ECs from human saphenous vein (SVEC) and coronary artery (CAEC) exposed to atherogenic stimuli. In addition to identifying differentially expressed genes, we applied statistical analysis of gene ontology and pathway annotation terms to identify signaling differences related to cell type and stimulus. Differential gene expression of untreated venous and arterial endothelial cells yielded 285 genes more highly expressed in untreated SVEC (P<0.005 and fold change >1.5). These genes represented various atherosclerosis-related pathways including responses to proliferation, oxidoreductase activity, antiinflammatory responses, cell growth, and hemostasis functions. Moreover, stimulation with oxidized LDL induced dramatically greater gene expression responses in CAEC compared with SVEC, relating to adhesion, proliferation, and apoptosis pathways. In contrast, interleukin 1beta and tumor necrosis factor alpha activated similar gene expression responses in both CAEC and SVEC. The differences in functional response and gene expression were further validated by an in vitro proliferation assay and in vivo immunostaining of alphabeta-crystallin protein. Our results strongly suggest that different inherent gene expression programs in arterial versus venous endothelial cells contribute to differences in atherosclerotic disease susceptibility.

Atherosclerosis↗

PubMed2004

Gene expression alterations over large chromosomal regions in cancers include multiple genes unrelated to malignant progression.

In solid tumors, the relationship between DNA copy number and global expression over large chromosomal regions has not been systematically explored. We used a 12,626-gene expression array analysis of head and neck squamous cell carcinoma and normal oral mucosa and annotated gene expression levels to specific chromosomal loci. Expression alterations correlated with reported data using comparative genomic hybridization. When genes with significant differences in expression between normal and malignant lesions, as defined by significance analysis of microarrays (SAM), were compared to nonsignificant genes, similar chromosomal patterns of alteration in expression were noted. Individual tumors underwent microsatellite analysis and chi(2) analysis of expression at 3p and 22q. Significant 3p underexpression and 22q overexpression were found in all primary tumors with 3p and 22q allelic imbalance, respectively, whereas no tumor without allelic imbalance on these chromosomal arms demonstrated expression differences. Loss and gain of chromosomal material in solid cancers can alter gene expression over large chromosomal regions, including multiple genes unrelated to malignant progression.

Allelic Imbalance↗

PubMed2001

Genome and genetic resources from the Cancer Genome Anatomy Project.

The Cancer Genome Anatomy Project (CGAP) is a collaborative network of cancer researchers with a common goal: to decipher the genetic changes that occur during cancer formation and progression. The project brings together several recent technologies capable of high-throughput analysis to help achieve this goal. Automated sequencing of cDNA libraries is a primary focus and is geared towards providing a comprehensive and annotated set of human and mouse transcribed sequences. This effort includes full-length transcript sequence generated by CGAP's new Mammalian Gene Collection initiative. Single nucleotide polymorphisms (SNPs) within human gene sequences (Genetic Annotation Initiative) and chromosomal rearrangements within cancer cells (Cancer Chromosome Aberration Project) are also being cataloged as part of CGAP. Finally, to help determine gene expression patterns related to cancer, CGAP provides a quantitative catalog of data through its SAGEmap initiative. The genome and genetic analysis tools listed in this review are all freely distributed by CGAP (http://cgap.nci.nih.gov/) without restriction.

Animals↗

PubMed2006

WormBase: new content and better access.

WormBase (http://wormbase.org), a model organism database for Caenorhabditis elegans and other related nematodes, continues to evolve and expand. Over the past year WormBase has added new data on C.elegans, including data on classical genetics, cell biology and functional genomics; expanded the annotation of closely related nematodes with a new genome browser for Caenorhabditis remanei; and deployed new hardware for stronger performance. Several existing datasets including phenotype descriptions and RNAi experiments have seen a large increase in new content. New datasets such as the C.remanei draft assembly and annotations, the Vancouver Fosmid library and TEC-RED 5' end sites are now available as well. Access to and searching WormBase has become more dependable and flexible via multiple mirror sites and indexing through Google.

Animals↗

PubMed2026

Unraveling 'F' factor: towards a genetic-clinical framework for the musculoskeletal-heart crosstalk in metabolic aging.

BACKGROUND: The rising co-occurrence of cardiometabolic diseases and musculoskeletal degeneration poses a critical challenge to healthy aging, yet the shared biological mechanisms underlying this multimorbidity remain poorly defined. This study aimed to establish an integrative clinical-genetic framework to elucidate the common frailty factor, the 'F' factor, that captures the systemic vulnerability linking cardiometabolic multimorbidity (CMM) and musculoskeletal aging. METHODS: Utilizing the prospective China Health and Retirement Longitudinal Study (CHARLS) cohort, we developed and validated novel Frailty-Integrated Indices for CMM risk prediction, evaluated with machine learning models interpreted via SHapley Additive exPlanations (SHAP). Independently, we applied genomic structural equation modeling (Genomic-SEM) to integrate genome-wide association data from six traits-coronary artery disease, type 2 diabetes, hypertension, bone mineral density, frailty, and telomere length-to model a shared latent genetic factor ('F' factor). This was followed by multivariate GWAS, fine-mapping, transcriptome-wide association study (TWAS), gene-based analysis, and functional annotation to prioritize causal genes, pathways, and cell types. RESULTS: Clinically, several Frailty-Integrated Indices significantly improved CMM risk prediction, with the optimal model achieving an AUC of 0.727. Genetically, we modeled a significant shared latent genetic factor ('F' factor), pinpointing novel risk loci and implicating key genes such as APOE and SLC22A3. These genes were enriched in pathways including cellular senescence and cholesterol metabolism and showed specific expression patterns in developmental brain stages and across multi-organ endothelial cells. CONCLUSION: Our findings provide converging evidence for Musculoskeletal‑Heart crosstalk of metabolic aging and inferred the 'F' factor as a genetic correlate of a transdiagnostic state, which links genetic predisposition to metabolic dysregulation, and systemic functional decline. This work provides a multi-level biological characterization of multimorbidity liability, informing early-risk detection and preventive strategies for complex aging-related comorbidities.

Humans↗

PubMed2026

An inflammatory bowel disease-linked lncRNA suppresses transcription factor T-BET expression in T cells to limit intestinal inflammation.

Among the tens of thousands of annotated long noncoding RNAs (lncRNAs) in the human genome, only a small fraction have been functionally characterized. Here, we show that a well-established inflammatory bowel disease (IBD) risk locus encoded a conserved lncRNA, lnc15 (2310015A10Rik/ENSMUSG00000097729), whose structure was destabilized by risk-associated variants, leading to its degradation. Deletion of lnc15 in mice resulted in molecular features of inflammation under steady-state conditions and conferred heightened susceptibility to experimental colitis. Lnc15 was abundantly expressed in T cells, with highest expression in regulatory T (Treg) cells. Mechanistically, lnc15 suppressed the transcription factor T-BET by recruiting the CCR4-NOT RNA degradation complex to Tbx21 mRNA. Our study identifies that lnc15 simultaneously enhances Treg cell suppressive function and impairs conventional T cell pathogenicity in the context of intestinal inflammation. Collectively, these findings identify lnc15 as a functional lncRNA that links noncoding genetic variation to immune regulation and prevention of mucosal inflammation. VIDEO ABSTRACT.

RNA, Long Noncoding↗

PubMed2003

Differential gene expression of human stem progenitor cells derived from early stages of in utero human hematopoiesis.

Hematopoietic stem progenitor cells (HSPCs) are highly enriched in a rare subset of Lin-CD34+CD38- cells. Independent of stage of human development, HSPC function segregates to the subset of Lin-CD34+CD38- cells. However, fetal-derived HSPCs demonstrate distinct self-renewal and differentiation capacities compared with their adult counterparts. Here, to characterize the molecular nature of fetal HSPCs, suppressive subtractive hybridization was used to compare gene expression of HSPCs isolated from fetal blood (FB-HSPCs) versus adult mobilized peripheral blood (MPB-HSPCs). We identified 97 differentially expressed genes that could be annotated into distinct groups that include transcription factors, cell cycle regulators, and genes involved in signal transduction. Candidate regulators, such as Lim only domain-2 (LMO2), nuclear factor-kappa B (NF-kappaB), tripartite motif 28 (Trim28), and N-myc protooncogene (MYCN), and a novel homeobox gene product were among transcripts that were found to be differentially expressed and could be associated with specific proliferation and differentiation properties unique to FB-HSPCs. Interestingly, the majority of genes associated with signal transduction belong to Ras pathway, highlighting the significance of Ras signaling in FB-HSPCs. Genes differentially expressed in FB-HSPCs versus adult MPB-HSPCs were verified using quantitative real-time polymerase chain reaction (Q-PCR). This approach also resulted in the identification of a transcript that is highly expressed in FB-HSPCs but not detectable in more differentiated Lin-CD34+CD38+ FB progenitors. Our investigation represents the first study to compare phenotypically similar, but functionally distinct, HSPC populations and to provide a gene profile of unique human HSPCs with higher proliferative capacity derived from early in utero human blood development.

Base Sequence↗

PubMed2025

Bayesian reconstruction and differential testing of excised introns.

MOTIVATION: Characterizing the differential excision of introns is critical for understanding the functional complexity of a cell or tissue, from normal developmental processes to disease pathogenesis. Most transcript reconstruction methods infer full-length transcripts from high-throughput sequencing data. However, this is a challenging task due to incomplete annotations and the heterogeneous expression of transcripts across cell-types, tissues, and experimental conditions. Several recent methods circumvent these difficulties by considering local splicing events, but these methods lose transcript-level splicing information and may conflate similar, but distinct transcripts. RESULTS: In this work, we formalize a new transcript reconstruction problem that interpolates between the full-length and local splicing perspectives by considering sequences of exon-exon junctions (SEEJs) that co-occur in transcripts. We then present a hierarchical Bayesian admixture model and posterior inference algorithms for computing SEEJs (BSEEJ), and a generalized linear model for characterizing differential SEEJ usage based on model parameter estimates. We show that BSEEJ achieves high F1 score for reconstruction tasks and improved accuracy and sensitivity in differential splicing when compared with six transcript and local splicing methods on simulated data. Lastly, we evaluate BSEEJ on experimental data based on transcript reconstruction, novelty of transcripts produced, model sensitivity to hyperparameters, and a functional analysis of differentially expressed SEEJs. AVAILABILITY AND IMPLEMENTATION: BSEEJ is freely available at https://github.com/bayesomicslab/BSEEJ.

Bayes Theorem↗

PubMed2006

Global profiles of gene expression induced by adrenocorticotropin in Y1 mouse adrenal cells.

ACTH regulates the steroidogenic capacity, size, and structural integrity of the adrenal cortex through a series of actions involving changes in gene expression; however, only a limited number of ACTH-regulated genes have been identified, and these only partly account for the global effects of ACTH on the adrenal cortex. In this study, a National Institute on Aging 15K mouse cDNA microarray was used to identify genome-wide changes in gene expression after treatment of Y1 mouse adrenocortical cells with ACTH. ACTH affected the levels of 1275 annotated transcripts, of which 46% were up-regulated. The up-regulated transcripts were enriched for functions associated with steroid biosynthesis and metabolism; the down- regulated transcripts were enriched for functions associated with cell proliferation, nuclear transport and RNA processing, including alternative splicing. A total of 133 different transcripts, i.e. only 10% of the ACTH-affected transcripts, were represented in the categories above; most of these had not been described as ACTH-regulated previously. The contributions of protein kinase A and protein kinase C to these genome-wide effects of ACTH were evaluated in microarray experiments after treatment of Y1 cells and derivative protein kinase A-defective mutants with pharmacological probes of each pathway. Protein kinase A-dependent signaling accounted for 56% of the ACTH effect; protein kinase C-dependent signaling accounted for an additional 6%. These results indicate that ACTH affects the expression profile of Y1 adrenal cells principally through cAMP- and protein kinase A- dependent signaling. The large number of transcripts affected by ACTH anticipates a broader range of actions than previously appreciated.

Adrenal Cortex↗

PubMed2004

Transcriptome variations in human CaCo-2 cells: a model for enterocyte differentiation and its link to iron absorption.

Complete clinical expression of the HFE1 hemochromatosis is very likely modulated by genes linked to duodenal iron absorption, whose level is conditioned by unknown processes taking place during enterocyte differentiation. We carried out a transcriptomic study on CaCo-2 cells used as a model of enterocyte differentiation in vitro. Of the 720 genes on the microarrays, 80, 50, and 56 were significantly down-regulated up-regulated, and invariant during differentiation. With regard to iron metabolism, we showed that HEPH, SLC11A2, SLC11A3, and TF are significantly up-regulated, while ATP7B and SLC39A1 (and SFT) are down-regulated and ACO1, dCYTb, FECH, and FTH1 show constant expression. Ontological annotations highlight the decrease in the expression of cell cycle and DNA metabolism associated genes as well as transcription, protein metabolism, signal transduction, and nucleocytoplasmic transport associated genes, whereas there are increases in the expression of genes linked to cell adhesion, lipid and xenobiotic metabolism, iron transport and homeostasis, and immune response.

Caco-2 Cells↗

PubMed2005

IMGT unique numbering for immunoglobulin and T cell receptor constant domains and Ig superfamily C-like domains.

IMGT, the international ImMunoGeneTics information system (http://imgt.cines.fr) provides a common access to expertly annotated data on the genome, proteome, genetics and structure of immunoglobulins (IG), T cell receptors (TR), major histocompatibility complex (MHC), and related proteins of the immune system (RPI) of human and other vertebrates. The NUMEROTATION concept of IMGT-ONTOLOGY has allowed to define a unique numbering for the variable domains (V-DOMAINs) and for the V-LIKE-DOMAINs. In this paper, this standardized characterization is extended to the constant domains (C-DOMAINs), and to the C-LIKE-DOMAINs, leading, for the first time, to their standardized description of mutations, allelic polymorphisms, two-dimensional (2D) representations and tridimensional (3D) structures. The IMGT unique numbering is, therefore, highly valuable for the comparative, structural or evolutionary studies of the immunoglobulin superfamily (IgSF) domains, V-DOMAINs and C-DOMAINs of IG and TR in vertebrates, and V-LIKE-DOMAINs and C-LIKE-DOMAINs of proteins other than IG and TR, in any species.

Amino Acid Sequence↗

PubMed2006

Identifying illness parameters in fatiguing syndromes using classical projection methods.

OBJECTIVES: To examine the potential of multivariate projection methods in identifying common patterns of change in clinical and gene expression data that capture the illness state of subjects with unexplained fatigue and nonfatigued control participants. METHODS: Data for 111 female subjects was examined. A total of 59 indicators, including multidimensional fatigue inventory (MFI), medical outcome Short Form 36 (SF-36), Centers for Disease Control and Prevention (CDC) symptom inventory and cognitive response described illness. Partial least squares (PLS) was used to construct two feature spaces: one describing the symptom space from gene expression in peripheral blood mononuclear cells (PBMC) and one based on 117 clinical variables. Multiplicative scatter correction followed by quantile normalization was applied for trend removal and range adjustment of microarray data. Microarray quality was assessed using mean Pearson correlation between samples. Benjamini-Hochberg multiple testing criteria served to identify significantly expressed probes. RESULTS: A single common trend in 59 symptom constructs isolates of nonfatigued subjects from the overall group. This segregation is supported by two co-regulation patterns representing 10% of the overall microarray variation. Of the 39 principal contributors, the 17 probes annotated related to basic cellular processes involved in cell signaling, ion transport and immune system function. The single most influential gene was sestrin 1 (SESN1), supporting recent evidence of oxidative stress involvement in chronic fatigue syndrome (CFS). Dominant variables in the clinical feature space described heart rate variability (HRV) during sleep. Potassium and free thyroxine (T4) also figure prominently. CONCLUSION: Combining multiple symptom, gene or clinical variables into composite features provides better discrimination of the illness state than even the most influential variable used alone. Although the exact mechanism is unclear, results suggest a common link between oxidative stress, immune system dysfunction and potassium imbalance in CFS patients leading to impaired sympatho-vagal balance strongly reflected in abnormal HRV.

Adult↗

PubMed2006

Analysis of the interaction of extracellular matrix and phenotype of bladder cancer cells.

BACKGROUND: The extracellular matrix has a major effect upon the malignant properties of bladder cancer cells both in vitro in 3-dimensional culture and in vivo. Comparing gene expression of several bladder cancer cells lines grown under permissive and suppressive conditions in 3-dimensional growth on cancer-derived and normal-derived basement membrane gels respectively and on plastic in conventional tissue culture provides a model system for investigating the interaction of malignancy and extracellular matrix. Understanding how the extracellular matrix affects the phenotype of bladder cancer cells may provide important clues to identify new markers or targets for therapy. METHODS: Five bladder cancer cell lines and one immortalized, but non-tumorigenic, urothelial line were grown on Matrigel, a cancer-derived ECM, on SISgel, a normal-derived ECM, and on plastic, where the only ECM is derived from the cells themselves. The transcriptomes were analyzed on an array of 1186 well-annotated cancer derived cDNAs containing most of the major pathways for malignancy. Hypervariable genes expressing more variability across cell lines than a set expressing technical variability were analyzed further. Expression values were clustered, and to identify genes most likely to represent biological factors, statistically over-represented ontologies and transcriptional regulatory elements were identified. RESULTS: Approximately 400 of the 1186 total genes were expressed 2 SD above background. Approximately 100 genes were hypervariable in cells grown on each ECM, but the pattern was different in each case. A core of 20 were identified as hypervariable under all 3 growth conditions, and 33 were hypervariable on both SISgel and Matrigel, but not on plastic. Clustering of the hypervariable genes showed very different patterns for the same 6 cell types on the different ECM. Even when loss of cell cycle regulation was identified, different genes were involved, depending on the ECM. Under the most permissive conditions of growth where the malignant phenotype was fully expressed, activation of AKT was noted. TGFbeta1 signaling played a major role in the response of bladder cancer cells to ECM. Identification of TREs on genes that clustered together suggested some clustering was driven by specific transcription factors. CONCLUSION: The extracellular matrix on which cancer cells are grown has a major effect on gene expression. A core of 20 malignancy-related genes were not affected by matrix, and 33 were differentially expressed on 3-dimensional culture as opposed to plastic. Other than these genes, the patterns of expression were very different in cells grown on SISgel than on Matrigel or even plastic, supporting the hypothesis that growth of bladder cancer cells on normal matrix suppresses some malignant functions. Unique underlying regulatory networks were driving gene expression and could be identified by the approach outlined here.

Cell Line, Tumor↗