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At least 649 records · Page 36Linked to original sources
PubMed2001

The University of Minnesota Biocatalysis/Biodegradation Database: emphasizing enzymes.

The University of Minnesota Biocatalysis/Biodegradation Database (UM-BBD, http://umbbd.ahc.umn.edu/) provides curated information on microbial catabolic enzymes and their organization into metabolic pathways. Currently, it contains information on over 400 enzymes. In the last year the enzyme page was enhanced to contain more internal and external links; it also displays the different metabolic pathways in which each enzyme participates. In collaboration with the Nomenclature Commission of the International Union of Biochemistry and Molecular Biology, 35 UM-BBD enzymes were assigned complete EC codes during 2000. Bacterial oxygenases are heavily represented in the UM-BBD; they are known to have broad substrate specificity. A compilation of known reactions of naphthalene and toluene dioxygenases were recently added to the UM-BBD; 73 and 108 were listed respectively. In 2000 the UM-BBD is mirrored by two prestigious groups: the European Bioinformatics Institute and KEGG (the Kyoto Encyclopedia of Genes and Genomes). Collaborations with other groups are being developed. The increased emphasis on UM-BBD enzymes is important for predicting novel metabolic pathways that might exist in nature or could be engineered. It also is important for current efforts in microbial genome annotation.

Bacteria↗
PubMed2002

Transcriptome analysis of Escherichia coli using high-density oligonucleotide probe arrays.

Microarrays traditionally have been used to analyze the expression behavior of large numbers of coding transcripts. Here we present a comprehensive approach for high-throughput transcript discovery in Escherichia coli focused mainly on intergenic regions which, together with analysis of coding transcripts, provides us with a more complete insight into the organism's transcriptome. Using a whole genome array, we detected expression for 4052 coding transcripts and identified 1102 additional transcripts in the intergenic regions of the E.coli genome. Further classification reveals 317 novel transcripts with unknown function. Our results show that, despite sophisticated approaches to genome annotation, many cellular transcripts remain unidentified. Through the experimental identification of all RNAs expressed under a specific condition, we gain a more thorough understanding of all cellular processes.

3' Untranslated Regions↗
PubMed2003

Identification of stop codon readthrough genes in Saccharomyces cerevisiae.

We specifically sought genes within the yeast genome controlled by a non-conventional translation mechanism involving the stop codon. For this reason, we designed a computer program using the yeast database genomic regions, and seeking two adjacent open reading frames separated only by a unique stop codon (called SORFs). Among the 58 SORFs identified, eight displayed a stop codon bypass level ranging from 3 to 25%. For each of the eight sequences, we demonstrated the presence of a poly(A) mRNA. Using isogenic [PSI(+)] and [psi(-)] yeast strains, we showed that for two of the sequences the mechanism used is a bona fide readthrough. However, the six remaining sequences were not sensitive to the PSI state, indicating either a translation termination process independent of eRF3 or a new stop codon bypass mechanism. Our results demonstrate that the presence of a stop codon in a large ORF may not always correspond to a sequencing error, or a pseudogene, but can be a recoding signal in a functional gene. This emphasizes that genome annotation should take into account the fact that recoding signals could be more frequently used than previously expected.

Base Sequence↗
PubMed2003

PatSearch: A program for the detection of patterns and structural motifs in nucleotide sequences.

Regulation of gene expression at transcriptional and post-transcriptional level involves the interaction between short DNA or RNA tracts and the corresponding trans-acting protein factors. Detection of such cis-acting elements in genome-wide screenings may significantly contribute to genome annotation and comparative analysis as well as to target functional characterization experiments. We present here PatSearch, a flexible and fast pattern matcher able to search for specific combinations of oligonucleotide consensus sequences, secondary structure elements and position-weight matrices. It can also allow for mismatches/mispairings below a user fixed threshold. We report three different applications of the program in the search of complex patterns such as those of the iron responsive element hairpin-loop structure, the p53 responsive element and a promoter module containing CAAT-, TATA- and cap-boxes. PatSearch is available on the web at http://bighost.area.ba.cnr.it/BIG/PatSearch/.

Base Sequence↗
PubMed2003

PSORT-B: Improving protein subcellular localization prediction for Gram-negative bacteria.

Automated prediction of bacterial protein subcellular localization is an important tool for genome annotation and drug discovery. PSORT has been one of the most widely used computational methods for such bacterial protein analysis; however, it has not been updated since it was introduced in 1991. In addition, neither PSORT nor any of the other computational methods available make predictions for all five of the localization sites characteristic of Gram-negative bacteria. Here we present PSORT-B, an updated version of PSORT for Gram-negative bacteria, which is available as a web-based application at http://www.psort.org. PSORT-B examines a given protein sequence for amino acid composition, similarity to proteins of known localization, presence of a signal peptide, transmembrane alpha-helices and motifs corresponding to specific localizations. A probabilistic method integrates these analyses, returning a list of five possible localization sites with associated probability scores. PSORT-B, designed to favor high precision (specificity) over high recall (sensitivity), attained an overall precision of 97% and recall of 75% in 5-fold cross-validation tests, using a dataset we developed of 1443 proteins of experimentally known localization. This dataset, the largest of its kind, is freely available, along with the PSORT-B source code (under GNU General Public License).

Bacterial Proteins↗
PubMed2004

The TIGR Plant Repeat Databases: a collective resource for the identification of repetitive sequences in plants.

In a number of higher plants, a substantial portion of the genome is composed of repetitive sequences that can hinder genome annotation and sequencing efforts. To better understand the nature of repetitive sequences in plants and provide a resource for identifying such sequences, we constructed databases of repetitive sequences for 12 plant genera: Arabidopsis, Brassica, Glycine, Hordeum, Lotus, Lycopersicon, Medicago, Oryza, Solanum, Sorghum, Triticum and Zea (www.tigr.org/tdb/e2k1/plant. repeats/index.shtml). The repetitive sequences within each database have been coded into super-classes, classes and sub-classes based on sequence and structure similarity. These databases are available for sequence similarity searches as well as downloadable files either as entire databases or subsets of each database. To further the utility for comparative studies and to provide a resource for searching for repetitive sequences in other genera within these families, repetitive sequences have been combined into four databases to represent the Brassicaceae, Fabaceae, Gramineae and Solanaceae families. Collectively, these databases provide a resource for the identification, classification and analysis of repetitive sequences in plants.

Computational Biology↗
PubMed2004

LEON: multiple aLignment Evaluation Of Neighbours.

Sequence alignments are fundamental to a wide range of applications, including database searching, functional residue identification and structure prediction techniques. These applications predict or propagate structural/functional/evolutionary information based on a presumed homology between the aligned sequences. If the initial hypothesis of homology is wrong, no subsequent application, however sophisticated, can be expected to yield accurate results. Here we present a novel method, LEON, to predict homology between proteins based on a multiple alignment of complete sequences (MACS). In MACS, weak signals from distantly related proteins can be considered in the overall context of the family. Intermediate sequences and the combination of individual weak matches are used to increase the significance of low-scoring regions. Residue composition is also taken into account by incorporation of several existing methods for the detection of compositionally biased sequence segments. The accuracy and reliability of the predictions is demonstrated in large-scale comparisons with structural and sequence family databases, where the specificity was shown to be >99% and the sensitivity was estimated to be approximately 76%. LEON can thus be used to reliably identify the complex relationships between large multidomain proteins and should be useful for automatic high-throughput genome annotations, 2D/3D structure predictions, protein-protein interaction predictions etc.

Algorithms↗
PubMed2006

TreeDomViewer: a tool for the visualization of phylogeny and protein domain structure.

Phylogenetic analysis and examination of protein domains allow accurate genome annotation and are invaluable to study proteins and protein complex evolution. However, two sequences can be homologous without sharing statistically significant amino acid or nucleotide identity, presenting a challenging bioinformatics problem. We present TreeDomViewer, a visualization tool available as a web-based interface that combines phylogenetic tree description, multiple sequence alignment and InterProScan data of sequences and generates a phylogenetic tree projecting the corresponding protein domain information onto the multiple sequence alignment. Thereby it makes use of existing domain prediction tools such as InterProScan. TreeDomViewer adopts an evolutionary perspective on how domain structure of two or more sequences can be aligned and compared, to subsequently infer the function of an unknown homolog. This provides insight into the function assignment of, in terms of amino acid substitution, very divergent but yet closely related family members. Our tool produces an interactive scalar vector graphics image that provides orthological relationship and domain content of proteins of interest at one glance. In addition, PDF, JPEG or PNG formatted output is also provided. These features make TreeDomViewer a valuable addition to the annotation pipeline of unknown genes or gene products. TreeDomViewer is available at http://www.bioinformatics.nl/tools/treedom/.

Computer Graphics↗
PubMed2006

metaSHARK: a WWW platform for interactive exploration of metabolic networks.

The metaSHARK (metabolic search and reconstruction kit) web server offers users an intuitive, fully interactive way to explore the KEGG metabolic network via a WWW browser. Metabolic reconstruction information for specific organisms, produced by our automated SHARKhunt tool or from other programs or genome annotations, may be uploaded to the website and overlaid on the generic network. Additional data from gene expression experiments can also be incorporated, allowing the visualization of differential gene expression in the context of the predicted metabolic network. metaSHARK is available at http://bioinformatics.leeds.ac.uk/shark/.

Animals↗
PubMed2006

PATRIC: the VBI PathoSystems Resource Integration Center.

The PathoSystems Resource Integration Center (PATRIC) is one of eight Bioinformatics Resource Centers (BRCs) funded by the National Institute of Allergy and Infection Diseases (NIAID) to create a data and analysis resource for selected NIAID priority pathogens, specifically proteobacteria of the genera Brucella, Rickettsia and Coxiella, and corona-, calici- and lyssaviruses and viruses associated with hepatitis A and E. The goal of the project is to provide a comprehensive bioinformatics resource for these pathogens, including consistently annotated genome, proteome and metabolic pathway data to facilitate research into counter-measures, including drugs, vaccines and diagnostics. The project's curation strategy has three prongs: 'breadth first' beginning with whole-genome and proteome curation using standardized protocols, a 'targeted' approach addressing the specific needs of researchers and an integrative strategy to leverage high-throughput experimental data (e.g. microarrays, proteomics) and literature. The PATRIC infrastructure consists of a relational database, analytical pipelines and a website which supports browsing, querying, data visualization and the ability to download raw and curated data in standard formats. At present, the site warehouses complete sequences for 17 bacterial and 332 viral genomes. The PATRIC website (https://patric.vbi.vt.edu) will continually grow with the addition of data, analysis and functionality over the course of the project.

Bioterrorism↗
PubMed2000

Phylogeny of related functions: the case of polyamine biosynthetic enzymes.

Genome annotation requires explicit identification of gene function. This task frequently uses protein sequence alignments with examples having a known function. Genetic drift, co-evolution of subunits in protein complexes and a variety of other constraints interfere with the relevance of alignments. Using a specific class of proteins, it is shown that a simple data analysis approach can help solve some of the problems posed. The origin of ureohydrolases has been explored by comparing sequence similarity trees, maximizing amino acid alignment conservation. The trees separate agmatinases from arginases but suggest the presence of unknown biases responsible for unexpected positions of some enzymes. Using factorial correspondence analysis, a distance tree between sequences was established, comparing regions with gaps in the alignments. The gap tree gives a consistent picture of functional kinship, perhaps reflecting some aspects of phylogeny, with a clear domain of enzymes encoding two types of ureohydrolases (agmatinases and arginases) and activities related to, but different from ureohydrolases. Several annotated genes appeared to correspond to a wrong assignment if the trees were significant. They were cloned and their products expressed and identified biochemically. This substantiated the validity of the gap tree. Its organization suggests a very ancient origin of ureohydrolases. Some enzymes of eukaryotic origin are spread throughout the arginase part of the trees: they might have been derived from the genes found in the early symbiotic bacteria that became the organelles. They were transferred to the nucleus when symbiotic genes had to escape Muller's ratchet. This work also shows that arginases and agmatinases share the same two manganese-ion-binding sites and exhibit only subtle differences that can be accounted for knowing the three-dimensional structure of arginases. In the absence of explicit biochemical data, extreme caution is needed when annotating genes having similarities to ureohydrolases.

Amino Acid Sequence↗
PubMed2005

Effects of growth phase and the developmentally significant bldA-specified tRNA on the membrane-associated proteome of Streptomyces coelicolor.

Previous proteomic analyses of Streptomyces coelicolor by two-dimensional electrophoresis and protein mass fingerprinting focused on extracts from total cellular material. Here, the membrane-associated proteome of cultures grown in a liquid minimal medium was partially characterized. The products of some 120 genes were characterized from the membrane fraction, with 70 predicted to possess at least one transmembrane helix. A notably high proportion of ABC transporter systems was represented; the specific types detected provided a snapshot of the nutritional requirements of the mycelium. The membrane-associated proteins did not change very much in abundance in different phases of growth in liquid minimal medium. Identification of gene products not expected to be present in membrane protein extracts led to a reconsideration of the genome annotation in two cases, and supplemented scarce information on 11 hypothetical/conserved hypothetical proteins of unknown function. The wild-type membrane proteome was compared with that of a bldA mutant lacking the only tRNA capable of efficient translation of the rare UUA (leucine) codon. Such mutants are unaffected in vegetative growth but are defective in many aspects of secondary metabolism and morphological differentiation. There were a few clear changes in the membrane proteome of the mutant. In particular, two hypothetical proteins (SCO4244 and SCO4252) were completely absent from the bldA mutant, and this was associated with the TTA-containing regulatory gene SCO4263. Evidence for the control of a cluster of function-unknown genes by the SCO4263 regulator revealed a new aspect of the pleiotropic bldA phenotype.

Base Sequence↗
PubMed2025

Spatial Metabolomics Reveals the Role of Penicillic Acid in Cheese Rind Microbiome Disruption by a Spoilage Fungus.

Microbial interactions in cheese rinds influence community structure, food safety, and product quality. But the chemical mechanisms that mediate microbial interactions in cheeses and other fermented foods are generally not known. Here, we investigate how the spoilage mold Aspergillus westerdijkiae chemically inhibits beneficial cheese-rind bacteria using a combination of omics technologies. In cheese rind community and co-culture experiments, A. westerdijkiae strongly inhibited most cheese rind community members. In co-culture with Staphylococcus equorum, A. westerdijkiae strongly affected bacterial gene expression, including upregulation of a putative bceAB gene cluster that is associated with resistance to antimicrobial compounds in other bacteria. Mass spectrometry imaging (MSI) revealed spatially localized production of secondary metabolites, including penicillic acid and ochratoxin B at the fungal-bacterial interface. Integration of LC-MS/MS and genome annotations confirmed the presence of additional bioactive metabolites, such as notoamides and circumdatins. Fungal metabolic responses varied by bacterial partner, suggesting species-specific chemical strategies. Notably, penicillic acid levels increased 2.5-fold during interaction with Brachybacterium, and experiments with purified penicillic acid showed inhibition of a range of cheese rind bacteria. These findings show that A. westerdijkiae deploys a context-dependent arsenal of mycotoxins and other metabolites, disrupting microbial community assembly in cheese rinds.

Aspergillus westerdijkiae↗
PubMed2000

Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells.

Three hundred cDNAs containing putatively entire open reading frames (ORFs) for previously undefined genes were obtained from CD34+ hematopoietic stem/progenitor cells (HSPCs), based on EST cataloging, clone sequencing, in silico cloning, and rapid amplification of cDNA ends (RACE). The cDNA sizes ranged from 360 to 3496 bp and their ORFs coded for peptides of 58-752 amino acids. Public database search indicated that 225 cDNAs exhibited sequence similarities to genes identified across a variety of species. Homology analysis led to the recognition of 50 basic structural motifs/domains among these cDNAs. Genomic exon-intron organization could be established in 243 genes by integration of cDNA data with genome sequence information. Interestingly, a new gene named as HSPC070 on 3p was found to share a sequence of 105bp in 3' UTR with RAF gene in reversed transcription orientation. Chromosomal localizations were obtained using electronic mapping for 192 genes and with radiation hybrid (RH) for 38 genes. Macroarray technique was applied to screen the gene expression patterns in five hematopoietic cell lines (NB4, HL60, U937, K562, and Jurkat) and a number of genes with differential expression were found. The resource work has provided a wide range of information useful not only for expression genomics and annotation of genomic DNA sequence, but also for further research on the function of genes involved in hematopoietic development and differentiation.

Alternative Splicing↗
PubMed2002

Temperature-regulated transcription in the pathogenic fungus Cryptococcus neoformans.

The basidiomycete fungus Cryptococcus neoformans is an opportunistic pathogen of worldwide importance that causes meningitis, leading to death in immunocompromised individuals. Unlike many basidiomycete fungi, C. neoformans is thermotolerant, and its ability to grow at 37 degrees C is considered to be a virulence factor. We used serial analysis of gene expression (SAGE) to characterize the transcriptomes of C. neoformans strains that represent two varieties with different polysaccharide capsule serotypes. These include a serotype D strain of the C. neoformans variety neoformans and a serotype A strain of variety grubii. In this report, we describe the construction and characterization of SAGE libraries from each strain grown at 25 degrees C and 37 degrees C. The SAGE data reveal transcriptome differences between the two strains, even at this early stage of analysis, and identify sets of genes with higher transcript levels at 25 degrees C or 37 degrees C. Notably, growth at the lower temperature increased transcript levels for histone genes, indicating a general influence of temperature on chromatin structure. At 37 degrees C, we noted elevated transcript levels for several genes encoding heat shock proteins and translation machinery. Some of these genes may play a role in temperature-regulated phenotypes in C. neoformans, such as the adaptation of the fungus to growth in the host and the dimorphic transition between budding and filamentous growth. Overall, this work provides the most comprehensive gene expression data available for C. neoformans; this information will be a critical resource both for gene discovery and genome annotation in this pathogen.

Blotting, Northern↗
PubMed2002

Cloning and sequencing of cDNAs for hypothetical genes from chromosome 2 of Arabidopsis.

About 25% of the genes in the fully sequenced and annotated Arabidopsis genome have structures that are predicted solely by computer algorithms with no support from either nucleic acid or protein homologs from other species or expressed sequence matches from Arabidopsis. These are referred to as "hypothetical genes." On chromosome 2, sequenced by The Institute for Genomic Research, there are approximately 800 hypothetical genes among a total of approximately 4,100 genes. To test their expression under various growth conditions and in specific tissues, we used six cDNA populations prepared from cold-treated, heat-treated, and pathogen (Xanthomonas campestris pv campestris)-infected plants, callus, roots, and young seedlings. To date, 169 hypothetical genes were tested, and 138 of them are found to be expressed in one or more of the six cDNA populations. By sequencing multiple clones from each 5'- and 3'-rapid amplification of cDNA ends (RACE) product and assembling the sequences, we generated full-length sequences for 16 of these genes. For 14 genes, there was one full-length assembly that precisely supported the intron-exon boundaries of their gene predictions, adding only 5'- and 3'-untranslated region sequences. However, for three of these genes, the other assemblies represent additional exons and alternatively spliced or unspliced introns. For the remaining two genes, the cDNA sequences reveal major differences with predicted gene structures. In addition, a total of six genes displayed more than one polyadenylation site. These data will be used to update gene models in The Institute for Genomic Research annotation database ATH1.

Alternative Splicing↗
PubMed2002

Sequence conserved for subcellular localization.

The more proteins diverged in sequence, the more difficult it becomes for bioinformatics to infer similarities of protein function and structure from sequence. The precise thresholds used in automated genome annotations depend on the particular aspect of protein function transferred by homology. Here, we presented the first large-scale analysis of the relation between sequence similarity and identity in subcellular localization. Three results stood out: (1) The subcellular compartment is generally more conserved than what might have been expected given that short sequence motifs like nuclear localization signals can alter the native compartment; (2) the sequence conservation of localization is similar between different compartments; and (3) it is similar to the conservation of structure and enzymatic activity. In particular, we found the transition between the regions of conserved and nonconserved localization to be very sharp, although the thresholds for conservation were less well defined than for structure and enzymatic activity. We found that a simple measure for sequence similarity accounting for pairwise sequence identity and alignment length, the HSSP distance, distinguished accurately between protein pairs of identical and different localizations. In fact, BLAST expectation values outperformed the HSSP distance only for alignments in the subtwilight zone. We succeeded in slightly improving the accuracy of inferring localization through homology by fine tuning the thresholds. Finally, we applied our results to the entire SWISS-PROT database and five entirely sequenced eukaryotes.

Amino Acid Sequence↗
PubMed2001

Identification of related proteins with weak sequence identity using secondary structure information.

Molecular modeling of proteins is confronted with the problem of finding homologous proteins, especially when few identities remain after the process of molecular evolution. Using even the most recent methods based on sequence identity detection, structural relationships are still difficult to establish with high reliability. As protein structures are more conserved than sequences, we investigated the possibility of using protein secondary structure comparison (observed or predicted structures) to discriminate between related and unrelated proteins sequences in the range of 10%-30% sequence identity. Pairwise comparison of secondary structures have been measured using the structural overlap (Sov) parameter. In this article, we show that if the secondary structures likeness is >50%, most of the pairs are structurally related. Taking into account the secondary structures of proteins that have been detected by BLAST, FASTA, or SSEARCH in the noisy region (with high E: value), we show that distantly related protein sequences (even with <20% identity) can be still identified. This strategy can be used to identify three-dimensional templates in homology modeling by finding unexpected related proteins and to select proteins for experimental investigation in a structural genomic approach, as well as for genome annotation.

Algorithms↗