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PubMed2005

The CATH Domain Structure Database and related resources Gene3D and DHS provide comprehensive domain family information for genome analysis.

The CATH database of protein domain structures (http://www.biochem.ucl.ac.uk/bsm/cath/) currently contains 43,229 domains classified into 1467 superfamilies and 5107 sequence families. Each structural family is expanded with sequence relatives from GenBank and completed genomes, using a variety of efficient sequence search protocols and reliable thresholds. This extended CATH protein family database contains 616,470 domain sequences classified into 23,876 sequence families. This results in the significant expansion of the CATH HMM model library to include models built from the CATH sequence relatives, giving a 10% increase in coverage for detecting remote homologues. An improved Dictionary of Homologous superfamilies (DHS) (http://www.biochem.ucl.ac.uk/bsm/dhs/) containing specific sequence, structural and functional information for each superfamily in CATH considerably assists manual validation of homologues. Information on sequence relatives in CATH superfamilies, GenBank and completed genomes is presented in the CATH associated DHS and Gene3D resources. Domain partnership information can be obtained from Gene3D (http://www.biochem.ucl.ac.uk/bsm/cath/Gene3D/). A new CATH server has been implemented (http://www.biochem.ucl.ac.uk/cgi-bin/cath/CathServer.pl) providing automatic classification of newly determined sequences and structures using a suite of rapid sequence and structure comparison methods. The statistical significance of matches is assessed and links are provided to the putative superfamily or fold group to which the query sequence or structure is assigned.

Databases, Nucleic Acid↗
PubMed2004

[The application of human mutation databases].

Researches on genome mutation are becoming more and more important with the finish of human genome DNA draft. This review is to classify the existing human mutation databases, including mutation database, SNP(single nucleotide polymorphisms) databases, mutation databases about disease, mutation databases about proteins, mutation databases about map and mutation information about specific gene. We also give advice on how to utilize these mutation databases, and discuss problems of existing databases.

Databases, Factual↗
PubMed1998

CyanoBase, a www database containing the complete nucleotide sequence of the genome of Synechocystis sp. strain PCC6803.

CyanoBase (http://www.kazusa.or.jp/cyano/) is a database containing genomic information on the cyanobacterium Synechocystis sp. strain PCC6803. It furnishes an annotation to each of the 3168 protein genes deduced from the entire nucleotide sequence of this genome. Information on the genome can be directly accessed through three different menus: a clickable physical map of the genome, a gene classification list, and a keyword search menu, all of which are accessible from the main page of the database. The entry page for a gene annotation contains the following information: the location of the gene on the genome, the nucleotide and deduced amino acid sequence of the gene, the result of a similarity search, and the classification of the deduced gene product according to its function. This page has reverse-links to the local physical map and gene classification list so that relevant genes can be searched in terms of their location on the genome and their function. In addition, the main page of CyanoBase provides engines for similarity searches between a query sequence and the entire genome sequence and for keyword searches, in addition to numerous links to pages containing related information.

Bacterial Proteins↗
PubMed2004

The Gene Ontology (GO) database and informatics resource.

The Gene Ontology (GO) project (http://www. geneontology.org/) provides structured, controlled vocabularies and classifications that cover several domains of molecular and cellular biology and are freely available for community use in the annotation of genes, gene products and sequences. Many model organism databases and genome annotation groups use the GO and contribute their annotation sets to the GO resource. The GO database integrates the vocabularies and contributed annotations and provides full access to this information in several formats. Members of the GO Consortium continually work collectively, involving outside experts as needed, to expand and update the GO vocabularies. The GO Web resource also provides access to extensive documentation about the GO project and links to applications that use GO data for functional analyses.

Animals↗
PubMed2025

Whole-genome sequencing identifies genetic diversity and adaptive signatures of hypoxia and ultraviolet radiation in Chinese chickens.

INTRODUCTION: Domestic chickens primarily descended from the wild red junglefowl, play a crucial role in global egg and meat production. China hosts diverse indigenous chicken populations that have adapted to various environmental conditions, including high-altitude with hypoxic and ultraviolet radiation stress. METHOD: We analyzed whole-genome sequences of 118 birds from five Indigenous Chinese chicken populations and 295 chicken genomes from publicly available databases to identify genomic diversity, admixture, and selection signatures of chickens adapted to high-altitude environments. Selection signatures were identified using nucleotide diversity (π), Tajima's D, XPEHH, and XP-CLR, selection scan methods. RESULTS: We observed a reduction in genetic diversity and historical declines in effective population size in high-altitude chicken, suggesting ongoing selection pressures shaping these populations. Selection scans identified nine genomic regions under strong positive selection, enriched for genes associated with hypoxia and ultraviolet radiation. Notably, five genes (TPK1, BAZ2B, MARCHF7, LLGL2, and RCAN3) were repeatedly detected across multiple selection signature analyses. RNA-seq analysis further confirmed the differential expression of these genes in the lung and heart tissues of chickens adapted to high and low altitudes, reinforcing their role in physiological adaptation to hypoxic environments. Altitude adaptation is driven by the selection of genes involved in oxygen metabolism, cellular stress response, and energy regulation. CONCLUSION: Our study provides compelling genetic evidence for differentiation between high and low and high-altitude Chinese chicken populations. These findings also ensure our understanding of local adaptation in poultry and establish a genomic framework for breeding strategies to improve environmental resilience to altitude-related stressors.

Animals↗
PubMed2002

PASS2: a semi-automated database of protein alignments organised as structural superfamilies.

PASS2 is a nearly automated version of CAMPASS and contains sequence alignments of proteins grouped at the level of superfamilies. This database has been created to fall in correspondence with SCOP database (1.53 release) and currently consists of 110 multi-member superfamilies and 613 superfamilies corresponding to single members. In multi-member superfamilies, protein chains with no more than 25% sequence identity have been considered for the alignment and hence the database aims to address sequence alignments which represent 26 219 protein domains under the SCOP 1.53 release. Structure-based sequence alignments have been obtained by COMPARER and the initial equivalences are provided automatically from a MALIGN alignment and subsequently augmented using STAMP4.0. The final sequence alignments have been annotated for the structural features using JOY4.0. Several interesting links are provided to other related databases and genome sequence relatives. Availability of reliable sequence alignments of distantly related proteins, despite poor sequence identity and single-member superfamilies, permit better sampling of structures in libraries for fold recognition of new sequences and for the understanding of protein structure-function relationships of individual superfamilies. The database can be queried by keywords and also by sequence search, interfaced by PSI-BLAST methods. Structure-annotated sequence alignments and several structural accessory files can be retrieved for all the superfamilies including the user-input sequence. The database can be accessed from http://www.ncbs.res.in/%7Efaculty/mini/campass/pass.html.

Amino Acid Sequence↗
PubMed2005

Genome-wide detection and analysis of cell wall-bound proteins with LPxTG-like sorting motifs.

Surface proteins of gram-positive bacteria often play a role in adherence of the bacteria to host tissue and are frequently required for virulence. A specific subgroup of extracellular proteins contains the cell wall-sorting motif LPxTG, which is the target for cleavage and covalent coupling to the peptidoglycan by enzymes called sortases. A comprehensive set of putative sortase substrates was identified by in silico analysis of 199 completely sequenced prokaryote genomes. A combination of detection methods was used, including secondary structure prediction, pattern recognition, sequence homology, and genome context information. With the hframe algorithm, putative substrates were identified that could not be detected by other methods due to errors in open reading frame calling, frameshifts, or sequencing errors. In total, 732 putative sortase substrates encoded in 49 prokaryote genomes were identified. We found striking species-specific variation for the LPxTG motif. A hidden Markov model (HMM) based on putative sortase substrates was created, which was subsequently used for the automatic detection of sortase substrates in recently completed genomes. A database was constructed, LPxTG-DB (http://bamics3.cmbi.kun.nl/sortase_substrates), containing for each genome a list of putative sortase substrates, sequence information of these substrates, the organism-specific HMMs based on the consensus sequence of the sortase recognition motif, and a graphic representation of this consensus.

Algorithms↗
PubMed2025

Interconnected study of molecular pathways: miR-137 as a central element at the intersection of lipid metabolism and prostate carcinogenesis.

OBJECTIVE: To evaluate the roles of miR-137 and its target genes in lipid metabolism and prostate tumorigenesis. METHODS: We used a series of bioinformatic approaches to establish the relationship between miR-137 and its target genes. We mapped the metabolic pathways of interest in the Reactome database and identified the central target genes of miR-137 in this pathway using four platforms: Reactome, miRDB, miRmap, and TargetScan. To assess the expression and association with clinical parameters, we obtained information from the UALCAN, OncoDB, and GEPIA2 databases using a dataset of patients with prostate cancer from The Cancer Genome Atlas. For functional enrichment analysis and construction of the protein-protein interaction network, we used the Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and STRING. RESULTS: Our in silico study of The Cancer Genome Atlas database revealed that miR-137 is underexpressed in tumor tissues, and its reduction is associated with poor prognosis. An intriguing set of eight genes within the PPARα pathway: PPARGC1A, PPARGC1B, NCOA1, NCOA2, NCOA3, MED1, MED27, and ESRRA displayed synergy, positive correlations, and synchronized expression patterns in adipose, hepatic, and prostatic tissues, all linked to the enigmatic processes of metabolic regulation. Among the highlighted genes, ESRRA was overexpressed in the malignant environment, whereas its counterparts remained underexpressed. The plot was thickened with associations between the expression of NCOA1, NCOA3, and MED27, lymph node involvement, and the overexpression of several genes linked to advanced prostate cancer stages. An intriguing pattern emerged, with patients exhibiting reduced disease-free survival overexpressing NCOA2, NCOA3, MED27, and ESRRA. CONCLUSION: This study elucidates the possibility that miR-137 subtly modulates metabolic genes in prostate cancer, suggesting its latent therapeutic potential as a biomarker for disease progression. BACKGROUND: ■ The reduction of miR-137 in tumor tissues is associated with a worse prognosis. BACKGROUND: ■ miR-137 has eight oncogenically relevant target genes acting in the PPARα lipid pathway. BACKGROUND: ■ NCOA1, NCOA3, MED27, and ESRRA are associated with advanced prostate cancer. BACKGROUND: ■ miR-137 exhibits significant clinical potential by repressing the activation of pathways that influence prostate tumorigenesis in hyperstimulated metabolic environments. BACKGROUND: Prostate cancer progression is sustained by the simultaneous activation of pathways involving lipid uptake and de novo synthesis. In this context, miR-137 inhibits adipogenic differentiation and may reduce lipid uptake by tumor cells by modulating the PPAR/ p160/ESRRA axis, considerably attenuating metabolic effects and suppressing prostate tumorigenesis.

Male↗
PubMed2003

Sputnik: a database platform for comparative plant genomics.

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

Databases, Nucleic Acid↗
PubMed2004

A genome-wide and nonredundant mouse transcription factor database.

Here we describe the development of a genome-wide and nonredundant mouse transcription factor database and its viewer (http://genome.gsc.riken.gp/TFdb/). We systematically selected transcription factors with DNA-binding properties and their regulators on the basis of their LocusLink and Gene Ontology annotations. We also incorporated into our database information regarding the corresponding available cDNA clones and their structural properties. Because of these features, our database is unique and may provide useful information for systematic genome-wide studies of transcriptional regulation.

Animals↗
PubMed2005

openSputnik--a database to ESTablish comparative plant genomics using unsaturated sequence collections.

The public expressed sequence tag collections are continually being enriched with high-quality sequences that represent an ever-expanding range of taxonomically diverse plant species. While these sequence collections provide biased insight into the populations of expressed genes available within individual species and their associated tissues, the information is conceivably of wider relevance in a comparative context. When we consider the available expressed sequence tag (EST) collections of summer 2004, most of the major plant taxonomic clades are at least superficially represented. Investigation of the five million available plant ESTs provides a wealth of information that has applications in modelling the routes of plant genome evolution and the identification of lineage-specific genes and gene families. Over four million ESTs from over 50 distinct plant species have been collated within an EST analysis pipeline called openSputnik. The ESTs were resolved down into approximately one million unigene sequences. These have been annotated using orthology-based annotation transfer from reference plant genomes and using a variety of contemporary bioinformatics methods to assign peptide, structural and functional attributes. The openSputnik database is available at http://sputnik.btk.fi.

Cluster Analysis↗
PubMed2004

Comparative methods for the analysis of gene-expression evolution: an example using yeast functional genomic data.

Understanding the evolution of gene function is a primary challenge of modern evolutionary biology. Despite an expanding database from genomic and developmental studies, we are lacking quantitative methods for analyzing the evolution of some important measures of gene function, such as gene-expression patterns. Here, we introduce phylogenetic comparative methods to compare different models of gene-expression evolution in a maximum-likelihood framework. We find that expression of duplicated genes has evolved according to a nonphylogenetic model, where closely related genes are no more likely than more distantly related genes to share common expression patterns. These results are consistent with previous studies that found rapid evolution of gene expression during the history of yeast. The comparative methods presented here are general enough to test a wide range of evolutionary hypotheses using genomic-scale data from any organism.

Evolution, Molecular↗
PubMed2004

Empirical analysis of protein insertions and deletions determining parameters for the correct placement of gaps in protein sequence alignments.

To understand how protein segments are inserted and deleted during divergent evolution, a set of pairwise alignments contained exactly one gap, and therefore arising from the first insertion-deletion (indel) event in the time separating the homologs, was examined. The alignments showed that "structure breaking" amino acids (PGDNS) were preferred within and flanking gapped regions, as are two residues with hydrophilic side-chains (QE) that frequently occur at the surface of protein folds. Conversely, hydrophobic residues (FMILYVW) occur infrequently within and flanking the gapped region. These preferences are modestly different in protein pairs separated by an episode of adaptive evolution, than in pairs diverging under strong functional constraints. Surprisingly, regions near an indel have not evolved more rapidly than the sequence pair overall, showing no evidence that an indel event must be compensated by local amino acid replacement. The gap-lengths are best approximated by a Zipfian distribution, with the probability of a gap of length L decreasing as a function of L(-1.8). These features are largely independent of the length of the gap and the extent of divergence (measured by both silent and non-silent sequence changes) separating the two proteins. Surprisingly, amino acid repeats were discovered in more than a third of the polypeptide segments in and around the gap. These correspond to repeats in the DNA sequence. This suggests that a signature of the mechanism by which indels occur in the DNA sequence remains in the encoded protein sequences. These data suggest specific tools to score gap placement in an alignment. They also suggest tools that distinguish true indels from gaps created by mistaken gene finding, including under-predicted and over-predicted introns. By providing mechanisms to identify errors, the tools will enhance the value of genome sequence databases in support of integrated paleogenomics strategies used to extract functional information in a post-genomic environment.

Amino Acid Sequence↗
PubMed2003

Mutagenesis of Streptococcus equi and Streptococcus suis by transposon Tn917.

Genetic tools for studying streptococci are much less sophisticated than those that are available for many other bacterial genera. In this paper, we describe the development of a transposon mutagenesis system that we have used to mutate two important veterinary streptococci, Streptococcus equi and Streptococcus suis. The system uses a temperature-sensitive suicide vector to deliver Tn917 via electroporation, transposing Tn917 into the chromosomal DNA of the two streptococci. The transposon insertions can be rescued from the streptococcal chromosomes by plasmid rescue and selection in E. coli, with subsequent insertion site analysis by DNA sequencing. Transposition appeared to have occurred in an essentially random fashion when chromosomal DNA of S. suis and S. equi mutants was analysed by Southern blotting. However, when analysis of 60 S. equi mutants was carried out using the S. equi genome sequence database, 60% of transposon insertions had occurred within a 15 kb region of the genome whereas the other insertions appeared to have occurred essentially randomly. This finding suggests that Southern blot analysis for assessing the randomness of transposon libraries may need to be interpreted with caution. However, this observation notwithstanding, the Tn917 based system described in this paper will facilitate the study of S. suis and S. equi.

Animals↗
PubMed2006

AthaMap web tools for the analysis and identification of co-regulated genes.

The AthaMap database generates a map of cis-regulatory elements for the whole Arabidopsis thaliana genome. This database has been extended by new tools to identify common cis-regulatory elements in specific regions of user-provided gene sets. A resulting table displays all cis-regulatory elements annotated in AthaMap including positional information relative to the respective gene. Further tables show overviews with the number of individual transcription factor binding sites (TFBS) present and TFBS common to the whole set of genes. Over represented cis-elements are easily identified. These features were used to detect specific enrichment of drought-responsive elements in cold-induced genes. For identification of co-regulated genes, the output table of the colocalization function was extended to show the closest genes and their relative distances to the colocalizing TFBS. Gene sets determined by this function can be used for a co-regulation analysis in microarray gene expression databases such as Genevestigator or PathoPlant. Additional improvements of AthaMap include display of the gene structure in the sequence window and a significant data increase. AthaMap is freely available at http://www.athamap.de/.

Arabidopsis↗
PubMedDate not supplied

Simultaneous measurement of hundreds of liver proteins: application in assessment of liver function.

Proteins implement most biological functions at the molecular level. As one might expect based on this fact, it appears that the altered functional states associated with toxic effects involve changes in the abundance or structure of proteins. Although numerous specific assays exist to measure changes in the abundance of individual proteins, practical limitations have prevented widespread use of multiple protein assays for the global characterization of toxicity. Recent developments in protein analytical technology are rapidly changing this picture. Two-dimensional gel electrophoresis, a technique capable of resolving and quantitating hundreds of proteins simultaneously, is becoming an automated, high-throughput tool. In parallel, techniques have been developed that allow the resulting deluge of protein measurements to be organized into a prototype Molecular Effects Database describing xenobiotic effects in rodent liver. This database can detect, classify, and characterize a broad range of liver toxicity mechanisms. It currently contains approximately 10 million protein measurements, including data on the liver effects of 43 compounds, with a further 50 compounds to be added in 1995. Observed effects range from very broad (sex steroids alter levels of 45% of all liver proteins) to very specific (e.g., hepatic hydroxymethyl glutaryl coenzyme A reductase inhibitors). Companion 2-dimensional databases describing rodent brain and kidney have been initiated, as have linkages to the genomic sequence databases. Assimilation of this approach into research and regulatory toxicology poses an interesting challenge--one that is likely to lead to a radically more sophisticated understanding of toxicity and its biological basis.

Animals↗
PubMed2002

Primer on medical genomics. Part IV: Expression proteomics.

Proteomics, simply defined, is the study of proteomes. More completely, proteomics is defined as the study of all proteins, including their relative abundance, distribution, posttranslational modifications, functions, and interactions with other macromolecules, in a given cell or organism within a given environment and at a specific stage in the cell cycle. Proteins carry out the biological functions encoded by genes; hence, once the initial stage of genome sequencing and gene discovery is completed, a study of the proteome must be undertaken to address fundamental biological questions. The 3 broad areas are expression proteomics, which catalogues the relative abundance of proteins; cell-mapping or cellular proteomics, which delineates functional protein-protein interactions and organelle-specific protein distribution; and structural proteomics, which characterizes the 3-dimensional structure of proteins. With these approaches, proteins are studied on a global scale using a synergistic combination of powerful, high-throughput technologies, including 2-dimensional polyacrylamide gel electrophoresis, mass spectrometry, multidimensional liquid chromatography, and bioinformatics. Mass spectrometry, which provides highly accurate molecular mass measurements, has emerged as the analytical technology of choice for protein identification, characterization, and sequencing. This task has been made considerably easier with the availability of complete, nonredundant, and annotated genome sequence databases for many organisms. This article reviews the area of expression proteomics.

Biotechnology↗