Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “functional annotations”

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.

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

At least 1,027 records · Page 57Linked to original sources
PubMed2002

SubtiList: the reference database for the Bacillus subtilis genome.

SubtiList is the reference database dedicated to the genome of Bacillus subtilis 168, the paradigm of Gram-positive endospore-forming bacteria. Developed in the framework of the B.subtilis genome project, SubtiList provides a curated dataset of DNA and protein sequences, combined with the relevant annotations and functional assignments. Information about gene functions and products is continuously updated by linking relevant bibliographic references. Recently, sequence corrections arising from both systematic verifications and submissions by individual scientists were included in the reference genome sequence. SubtiList is based on a generic relational data schema and a World Wide Web interface developed for the handling of bacterial genomes, called GenoList. The World Wide Web interface was designed to allow users to easily browse through genome data and retrieve information according to common biological queries. SubtiList also provides more elaborate tools, such as pattern searching, which are tightly connected to the overall browsing system. SubtiList is accessible at http://genolist.pasteur.fr/SubtiList/. Similar bacterial databases are accessible at http://genolist.pasteur.fr/.

Bacillus subtilis↗
PubMed2004

Computational method for discovery of estrogen responsive genes.

Estrogen has a profound impact on human physiology and affects numerous genes. The classical estrogen reaction is mediated by its receptors (ERs), which bind to the estrogen response elements (EREs) in target gene's promoter region. Due to tedious and expensive experiments, a limited number of human genes are functionally well characterized. It is still unclear how many and which human genes respond to estrogen treatment. We propose a simple, economic, yet effective computational method to predict a subclass of estrogen responsive genes. Our method relies on the similarity of ERE frames across different promoters in the human genome. Matching ERE frames of a test set of 60 known estrogen responsive genes to the collection of over 18,000 human promoters, we obtained 604 candidate genes. Evaluating our result by comparison with the published microarray data and literature, we found that more than half (53.6%, 324/604) of predicted candidate genes are responsive to estrogen. We believe this method can significantly reduce the number of testing potential estrogen target genes and provide functional clues for annotating part of genes that lack functional information.

Computational Biology↗
PubMed2005

InterPro, progress and status in 2005.

InterPro, an integrated documentation resource of protein families, domains and functional sites, was created to integrate the major protein signature databases. Currently, it includes PROSITE, Pfam, PRINTS, ProDom, SMART, TIGRFAMs, PIRSF and SUPERFAMILY. Signatures are manually integrated into InterPro entries that are curated to provide biological and functional information. Annotation is provided in an abstract, Gene Ontology mapping and links to specialized databases. New features of InterPro include extended protein match views, taxonomic range information and protein 3D structure data. One of the new match views is the InterPro Domain Architecture view, which shows the domain composition of protein matches. Two new entry types were introduced to better describe InterPro entries: these are active site and binding site. PIRSF and the structure-based SUPERFAMILY are the latest member databases to join InterPro, and CATH and PANTHER are soon to be integrated. InterPro release 8.0 contains 11 007 entries, representing 2573 domains, 8166 families, 201 repeats, 26 active sites, 21 binding sites and 20 post-translational modification sites. InterPro covers over 78% of all proteins in the Swiss-Prot and TrEMBL components of UniProt. The database is available for text- and sequence-based searches via a webserver (http://www.ebi.ac.uk/interpro), and for download by anonymous FTP (ftp://ftp.ebi.ac.uk/pub/databases/interpro).

Databases, Protein↗
PubMed2026

VicMAG, an open-source tool for visualizing circular metagenome-assembled genomes highlighting bacterial virulence and antimicrobial resistance.

Bacterial pathogens spread in clinical and environmental settings, and mobile genetic elements (MGEs), such as plasmids and phages, mediate the transfer of virulence factor genes (VFGs) and antimicrobial resistance genes (ARGs) among bacterial communities. Metagenomic analysis of environmental and wastewater samples using highly accurate long-read sequencing technologies, such as Pacific Biosciences (PacBio) HiFi sequencing, provides valuable insights into monitoring the regional spread of VFGs and ARGs, including dissemination mediated by MGEs. No visualization tool is currently available for the comprehensive display of numerous resulting circular metagenome-assembled genomes (cMAGs) with functional gene annotations. Here, we developed visualization of circular metagenome-assembled genome (VicMAG), a visualization tool for highly complex cMAGs derived from long-read metagenome assemblies annotated using updated databases of VFGs, ARGs, and MGEs. Using 353 cMAGs from PacBio HiFi sequencing of a wastewater sample, we demonstrated the utility of VicMAG for metagenome visualization. VicMAG provides comprehensive, size-aware visualization of cMAGs representing bacterial chromosomes and plasmids, annotated with VFGs, ARGs, and phages. By simultaneously visualizing all cMAGs in a framework, VicMAG facilitates a holistic understanding of the distribution and genomic context of VFGs and ARGs across complex microbial communities. This tool supports integrated surveillance of bacteria associated with virulence and antimicrobial resistance across clinical, environmental, and One Health contexts.

Metagenome↗
PubMed2005

Temporal and dose-dependent hepatic gene expression patterns in mice provide new insights into TCDD-Mediated hepatotoxicity.

In an effort to further characterize the mechanisms of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated toxicity, comprehensive temporal and dose-response microarray analyses were performed on hepatic tissue from immature ovariectomized C57BL/6 mice treated with TCDD. For temporal analysis, mice were gavaged with 30 microg/kg of TCDD or vehicle and sacrificed after 2, 4, 8, 12, 18, 24, 72, or 168 h. Dose-response mice were gavaged with 0, 0.001, 0.01, 0.1, 1, 10, 100, or 300 microg/kg of TCDD and sacrificed after 24 h. Hepatic gene expression profiles were monitored using custom cDNA microarrays containing 13,362 cDNA clones. Gene expression analysis identified 443 and 315 features which exhibited a significant change at one or more doses or time points, respectively, as determined using an empirical Bayes approach. Functional gene annotation extracted from public databases associated gene expression changes with physiological processes such as oxidative stress and metabolism, differentiation, apoptosis, gluconeogenesis, and fatty acid uptake and metabolism. Complementary histopathology (H&E and Oil Red O stains), clinical chemistry (i.e., alanine aminotransferase [ALT], triglyceride [TG], free fatty acids [FFA], cholesterol) and high-resolution gas chromatography/mass spectrometry assessment of hepatic TCDD levels were also performed in order to phenotypically anchor changes in gene expression to physiological end points. Collectively, the data support a proposed mechanism for TCDD-mediated hepatotoxicity, including fatty liver, which involves mobilization of peripheral fat and inappropriate increases in hepatic uptake of fatty acids.

Alanine Transaminase↗
PubMed2025

Gene and pathway analysis of genome-wide genetic associations of bladder cancer.

BACKGROUND: Although genetic variants associated with bladder cancer (BCa) risk have been identified through hypothesis-driven and genome-wide association studies, a systematic understanding of BCa genetic susceptibility at the gene and pathway levels remains to be achieved. MATERIALS AND METHODS: In this 2-stage functional genomics study, we used 5 independent tools for genome-wide gene mapping and ranking based on BCa genome-wide association studies summary statistics, followed by a meta-analysis of gene-level significance p values, to obtain a consensus gene ranking in terms of association with BCa. Subsequently, we performed preranked gene-set enrichment analysis to identify the functional pathways involved in BCa genetic susceptibility. Joint analysis with gene-set enrichment analysis, based on somatic alteration frequency, was performed to explore the pathway-level relationships between genetic susceptibility and somatic alterations in BCa. RESULTS: Other than the well-known BCa genes (such as FGFR3, MYC, TERT, CCNE1, and TP63), we additionally prioritized a set of novel genes likely to be genetically implicated in BCa development, including SETD2, a possible tumor suppressor gene involved in chromatin remodeling. We further demonstrated convergence between genetic associations and somatic alterations at both the gene (eg, FGFR3 and TERT) and pathway levels (eg, cell cycle and chromatin modification), as well as functional ontologies specifically implicated in germline predisposition to BCa (eg, CD8/TCR signaling, immune checkpoints, and cytokine signaling). CONCLUSIONS: We identified several novel genes associated with BCa and demonstrated that genetic variants contribute to the development of BCa by affecting antitumor immunity, response to toxic exposure, and RNA and protein homeostasis and synergizing with somatic alterations in various cancer-related pathways.

Bladder cancer↗
PubMed2003

Gene expression in autumn leaves.

Two cDNA libraries were prepared, one from leaves of a field-grown aspen (Populus tremula) tree, harvested just before any visible sign of leaf senescence in the autumn, and one from young but fully expanded leaves of greenhouse-grown aspen (Populus tremula x tremuloides). Expressed sequence tags (ESTs; 5,128 and 4,841, respectively) were obtained from the two libraries. A semiautomatic method of annotation and functional classification of the ESTs, according to a modified Munich Institute of Protein Sequences classification scheme, was developed, utilizing information from three different databases. The patterns of gene expression in the two libraries were strikingly different. In the autumn leaf library, ESTs encoding metallothionein, early light-inducible proteins, and cysteine proteases were most abundant. Clones encoding other proteases and proteins involved in respiration and breakdown of lipids and pigments, as well as stress-related genes, were also well represented. We identified homologs to many known senescence-associated genes, as well as seven different genes encoding cysteine proteases, two encoding aspartic proteases, five encoding metallothioneins, and 35 additional genes that were up-regulated in autumn leaves. We also indirectly estimated the rate of plastid protein synthesis in the autumn leaves to be less that 10% of that in young leaves.

Arabidopsis Proteins↗
PubMed2002

A comparison of position-specific score matrices based on sequence and structure alignments.

Sequence comparison methods based on position-specific score matrices (PSSMs) have proven a useful tool for recognition of the divergent members of a protein family and for annotation of functional sites. Here we investigate one of the factors that affects overall performance of PSSMs in a PSI-BLAST search, the algorithm used to construct the seed alignment upon which the PSSM is based. We compare PSSMs based on alignments constructed by global sequence similarity (ClustalW and ClustalW-pairwise), local sequence similarity (BLAST), and local structure similarity (VAST). To assess performance with respect to identification of conserved functional or structural sites, we examine the accuracy of the three-dimensional molecular models predicted by PSSM-sequence alignments. Using the known structures of those sequences as the standard of truth, we find that model accuracy varies with the algorithm used for seed alignment construction in the pattern local-structure (VAST) > local-sequence (BLAST) > global-sequence (ClustalW). Using structural similarity of query and database proteins as the standard of truth, we find that PSSM recognition sensitivity depends primarily on the diversity of the sequences included in the alignment, with an optimum around 30-50% average pairwise identity. We discuss these observations, and suggest a strategy for constructing seed alignments that optimize PSSM-sequence alignment accuracy and recognition sensitivity.

Algorithms↗
PubMed2026

Moderate expression and activity of flocculins underlie the characteristic flocculation phenotype of Saccharomyces pastorianus.

Flocculation is a key technological trait in lager brewing, governing fermentation performance, yeast recovery, and beer quality. In the allo-aneuploid hybrid yeast Saccharomyces pastorianus, the genetic basis of flocculation remains poorly resolved due to its complex dual sub-genome architecture. Here, we systematically re-annotated and functionally characterized the complete FLO gene repertoire of the Group II strain CBS 1483. Thirteen FLO genes were identified, including allelic variants and a previously uncharacterized adhesin, Flo12, containing a Hyphal_reg_CWP domain instead of the canonical PA14 lectin-binding domain. Structural modeling revealed strong conservation of Ca²+-binding residues in PA14 domains, alongside repeat-region diversification likely contributing to functional variability. Using optogenetic expression in a FLO-null background, we demonstrated that SpcI-FLO9-1 and SpcI-FLO9-2_1 are the strongest drivers of flocculation, exhibiting NewFlo-like sugar sensitivity. Transcriptomic analysis during 17°P wort fermentation showed dynamic induction of these genes coinciding with flocculation onset. Surprisingly, deletion of both loci in CBS 1483 did not abolish but only delayed sedimentation in wort, accompanied by improved maltose utilization and attenuation. These findings reveal functional redundancy and compensatory mechanisms within the FLO network of lager yeast, highlighting the genetic complexity underlying flocculation, and providing a molecular framework to inform yeast selection, strain development, and optimization of the lager fermentation processes.IMPORTANCEFlocculation, the process by which yeast cells aggregate and settle, is essential for producing clear, high-quality lager beer, and for efficient yeast recovery during brewing. However, the genetic basis of this trait in lager yeast has remained poorly understood because these strains possess unusually complex hybrid genomes. In this study, we systematically identified and characterized the complete set of flocculation genes in the industrial lager yeast Saccharomyces pastorianus CBS 1483. We demonstrated that lager yeast flocculation is not controlled by a single dominant gene, but instead emerges from the combined action of several moderately active adhesion proteins that are expressed at low levels during fermentation. Surprisingly, deleting the two strongest candidate genes only delayed, rather than eliminated, sedimentation, revealing a robust compensatory network that preserves brewing performance. These findings refine the current understanding of yeast flocculation and provide a molecular framework for developing brewing strains with improved fermentation efficiency, product consistency, and flavor quality.

Saccharomyces pastorianus↗
PubMed2005

Trade-offs in detecting evolutionarily constrained sequence by comparative genomics.

As whole-genome sequencing efforts extend beyond more traditional model organisms to include a deep diversity of species, comparative genomic analyses will be further empowered to reveal insights into the human genome and its evolution. The discovery and annotation of functional genomic elements is a necessary step toward a detailed understanding of our biology, and sequence comparisons have proven to be an integral tool for that task. This review is structured to broadly reflect the statistical challenges in discriminating these functional elements from the bulk of the genome that has evolved neutrally. Specifically, we review the comparative genomics literature in terms of specificity, sensitivity, and phylogenetic scope, as well as the trade-offs that relate these factors in standard analyses. We consider the impact of an expanding diversity of orthologous sequences on our ability to resolve functional elements. This impact is assessed through both recent comparative analyses of deep alignments and mathematical modeling.

Animals↗
PubMed2003

Identification of temporal patterns of gene expression in the uteri of immature, ovariectomized mice following exposure to ethynylestradiol.

Estrogen induction of uterine wet weight provides an excellent model to investigate relationships between changes in global gene expression and well-characterized physiological responses. In this study, time course microarray GeneChip data were analyzed using a novel approach to identify temporal changes in uterine gene expression following treatment of immature ovariectomized C57BL/6 mice with 0.1 mg/kg 17alpha-ethynylestradiol. Functional gene annotation information from public databases facilitated the association of changes in gene expression with physiological outcomes, which allowed detailed mechanistic inferences to be drawn regarding cell cycle control and proliferation, transcription and translation, structural tissue remodeling, and immunologic responses. These systematic approaches confirm previously established responses, identify novel estrogen-regulated transcriptional effects, and disclose the coordinated activation of multiple modes of action that support the uterotrophic response elicited by estrogen. In particular, it was possible to elucidate the physiological significance of the dramatic induction of arginase, a classic estrogenic response, by elucidating its mechanistic relevance and delineating the role of arginine and ornithine utilization in the estrogen-stimulated induction of uterine wet weight.

Animals↗
PubMed2006

Microarray analysis of gene expression: considerations in data mining and statistical treatment.

DNA microarray represents a powerful tool in biomedical discoveries. Harnessing the potential of this technology depends on the development and appropriate use of data mining and statistical tools. Significant current advances have made microarray data mining more versatile. Researchers are no longer limited to default choices that generate suboptimal results. Conflicting results in repeated experiments can be resolved through attention to the statistical details. In the current dynamic environment, there are many choices and potential pitfalls for researchers who intend to incorporate microarrays as a research tool. This review is intended to provide a simple framework to understand the choices and identify the pitfalls. Specifically, this review article discusses the choice of microarray platform, preprocessing raw data, differential expression and validation, clustering, annotation and functional characterization of genes, and pathway construction in light of emergent concepts and tools.

Cluster Analysis↗
PubMed2002

FunSpec: a web-based cluster interpreter for yeast.

BACKGROUND: For effective exposition of biological information, especially with regard to analysis of large-scale data types, researchers need immediate access to multiple categorical knowledge bases and need summary information presented to them on collections of genes, as opposed to the typical one gene at a time. RESULTS: We present here a web-based tool (FunSpec) for statistical evaluation of groups of genes and proteins (e.g. co-regulated genes, protein complexes, genetic interactors) with respect to existing annotations (e.g. functional roles, biochemical properties, localization). FunSpec is available online at http://funspec.med.utoronto.ca CONCLUSION: FunSpec is helpful for interpretation of any data type that generates groups of related genes and proteins, such as gene expression clustering and protein complexes, and is useful for predictive methods employing "guilt-by-association."

Cluster Analysis↗
PubMed2004

A fast algorithm for determining the best combination of local alignments to a query sequence.

BACKGROUND: Existing sequence alignment algorithms assume that similarities between DNA or amino acid sequences are linearly ordered. That is, stretches of similar nucleotides or amino acids are in the same order in both sequences. Recombination perturbs this order. An algorithm that can reconstruct sequence similarity despite rearrangement would be helpful for reconstructing the evolutionary history of recombined sequences. RESULTS: We propose a graph-based algorithm for combining multiple local alignments to a query sequence into the single combination of alignments that either covers the maximal portion of the query or results in the single highest alignment score to the query. This algorithm can help study the process of genome rearrangement, improve functional gene annotation, and reconstruct the evolutionary history of recombined proteins. The algorithm takes O(n2) time, where n is the number of local alignments considered. CONCLUSIONS: We discuss two example applications of the algorithm. The algorithm is able to provide useful reconstructions of the metazoan mitochondrial genome. It is also able to increase the percentage of a query sequence's amino acid residues for which similar stretches of amino acids can be found in sequence databases.

Algorithms↗
PubMed2005

stam--a Bioconductor compliant R package for structured analysis of microarray data.

BACKGROUND: Genome wide microarray studies have the potential to unveil novel disease entities. Clinically homogeneous groups of patients can have diverse gene expression profiles. The definition of novel subclasses based on gene expression is a difficult problem not addressed systematically by currently available software tools. RESULTS: We present a computational tool for semi-supervised molecular disease entity detection. It automatically discovers molecular heterogeneities in phenotypically defined disease entities and suggests alternative molecular sub-entities of clinical phenotypes. This is done using both gene expression data and functional gene annotations. We provide stam, a Bioconductor compliant software package for the statistical programming environment R. We demonstrate that our tool detects gene expression patterns, which are characteristic for only a subset of patients from an established disease entity. We call such expression patterns molecular symptoms. Furthermore, stam finds novel sub-group stratifications of patients according to the absence or presence of molecular symptoms. CONCLUSION: Our software is easy to install and can be applied to a wide range of datasets. It provides the potential to reveal so far indistinguishable patient sub-groups of clinical relevance.

Calibration↗
PubMed2006

Microarray expression analysis of meiosis and microsporogenesis in hexaploid bread wheat.

BACKGROUND: Our understanding of the mechanisms that govern the cellular process of meiosis is limited in higher plants with polyploid genomes. Bread wheat is an allohexaploid that behaves as a diploid during meiosis. Chromosome pairing is restricted to homologous chromosomes despite the presence of homoeologues in the nucleus. The importance of wheat as a crop and the extensive use of wild wheat relatives in breeding programs has prompted many years of cytogenetic and genetic research to develop an understanding of the control of chromosome pairing and recombination. The rapid advance of biochemical and molecular information on meiosis in model organisms such as yeast provides new opportunities to investigate the molecular basis of chromosome pairing control in wheat. However, building the link between the model and wheat requires points of data contact. RESULTS: We report here a large-scale transcriptomics study using the Affymetrix wheat GeneChip(R) aimed at providing this link between wheat and model systems and at identifying early meiotic genes. Analysis of the microarray data identified 1,350 transcripts temporally-regulated during the early stages of meiosis. Expression profiles with annotated transcript functions including chromatin condensation, synaptonemal complex formation, recombination and fertility were identified. From the 1,350 transcripts, 30 displayed at least an eight-fold expression change between and including pre-meiosis and telophase II, with more than 50% of these having no similarities to known sequences in NCBI and TIGR databases. CONCLUSION: This resource is now available to support research into the molecular basis of pairing and recombination control in the complex polyploid, wheat.

Chromosome Pairing↗
PubMed2006

In vivo-in vitro toxicogenomic comparison of TCDD-elicited gene expression in Hepa1c1c7 mouse hepatoma cells and C57BL/6 hepatic tissue.

BACKGROUND: In vitro systems have inherent limitations in their ability to model whole organism gene responses, which must be identified and appropriately considered when developing predictive biomarkers of in vivo toxicity. Systematic comparison of in vitro and in vivo temporal gene expression profiles were conducted to assess the ability of Hepa1c1c7 mouse hepatoma cells to model hepatic responses in C57BL/6 mice following treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). RESULTS: Gene expression analysis and functional gene annotation indicate that Hepa1c1c7 cells appropriately modeled the induction of xenobiotic metabolism genes in vivo. However, responses associated with cell cycle progression and proliferation were unique to Hepa1c1c7 cells, consistent with the cell cycle arrest effects of TCDD on rapidly dividing cells. In contrast, lipid metabolism and immune responses, representative of whole organism effects in vivo, were not replicated in Hepa1c1c7 cells. CONCLUSION: These results identified inherent differences in TCDD-mediated gene expression responses between these models and highlighted the limitations of in vitro systems in modeling whole organism responses, and additionally identified potential predictive biomarkers of toxicity.

Animals↗
PubMed2006

High-throughput isolation of ultra-pure plasmid DNA by a robotic system.

BACKGROUND: With the availability of complete genomes, a systematic inventory of cellular processes becomes achievable. This requires assessing the function of all individual genes. Transfection of plasmid DNA into cell culture cells is an essential technique for this aim as it allows functional overexpression or downregulation of genes. While many robotic systems isolate plasmids for sequencing purposes, for more demanding applications such as transfections there is a shortage of robots for the high-throughput isolation of plasmid DNA. RESULTS: Here we describe a custom-made, automated device, which uses a special protocol to isolate plasmid DNAs with a purity sufficient for efficient transfections into mammalian cells. Approximately 1,600 ultra pure plasmids can be isolated in a 96-well plate format within 12 hours. As a unique feature the robot comprises the integration of a centrifuge instead of expensive columns, the use of a custom-made pipetting head with a movable gripper, especially designed shaking platforms and an acetone wash facility. CONCLUSION: Using this robot we demonstrate how centrifugation steps with multiple precipitations, most notably through a precipitation step of SDS in isopropanol, lead to high purity plasmid DNA and make possible high-throughput transfections into mammalian cells for functional gene annotations.

Chemical Fractionation↗