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1.
BMC Genomics ; 9: 75, 2008 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-18261238

RESUMO

BACKGROUND: The number of prokaryotic genome sequences becoming available is growing steadily and is growing faster than our ability to accurately annotate them. DESCRIPTION: We describe a fully automated service for annotating bacterial and archaeal genomes. The service identifies protein-encoding, rRNA and tRNA genes, assigns functions to the genes, predicts which subsystems are represented in the genome, uses this information to reconstruct the metabolic network and makes the output easily downloadable for the user. In addition, the annotated genome can be browsed in an environment that supports comparative analysis with the annotated genomes maintained in the SEED environment. The service normally makes the annotated genome available within 12-24 hours of submission, but ultimately the quality of such a service will be judged in terms of accuracy, consistency, and completeness of the produced annotations. We summarize our attempts to address these issues and discuss plans for incrementally enhancing the service. CONCLUSION: By providing accurate, rapid annotation freely to the community we have created an important community resource. The service has now been utilized by over 120 external users annotating over 350 distinct genomes.


Assuntos
Biologia Computacional/métodos , Bases de Dados de Ácidos Nucleicos , Genes de RNAr/genética , Genoma Arqueal , Genoma Bacteriano , Fases de Leitura Aberta/genética , Filogenia , Proteínas/genética , RNA de Transferência/genética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Fatores de Tempo , Interface Usuário-Computador
2.
Cancer Res ; 67(19): 9248-57, 2007 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-17909032

RESUMO

Human cancer is controlled by a complex interaction between genetic and environmental factors. Such environmental factors are well defined for smoking-induced lung cancer; however, the roles of specific genes have still to be elucidated. Glutathione transferase pi (GSTP) catalyzes the detoxification of electrophilic diol epoxides produced by the metabolism of polycyclic aromatic hydrocarbons such as benzo[a]pyrene (BaP), a common constituent of tobacco smoke. Activity-altering polymorphisms in Gstp have therefore been speculated to be potential risk modifiers in lung cancer development. To clearly establish a role for GSTP in lung tumorigenesis, we investigated whether deletion of the murine Gstp genes (Gstp1 and Gstp2) alters susceptibility to chemically induced lung tumors following exposure to BaP, 3-methylcholanthrene (3-MC), and urethane. Gstp-null mice were found to have substantially increased numbers of adenomas relative to wild-type mice following exposure to all three compounds (8.3-, 4.3-, and 8.7-fold increase for BaP, 3-MC, and urethane, respectively). In Gstp-null mice, the capacity of pulmonary cytosol to catalyze conjugation of the BaP diol epoxide was significantly reduced. Concomitant with this, a significant increase in the level of BaP DNA adducts was measured in the lungs of null animals; however, no increase in DNA adducts was measured in the case of 3-MC exposure, suggesting that an alternative protective pathway exists. Indeed, significant differences in pulmonary gene expression profiles were also noted between wild-type and null mice. This is the first report to establish a clear correlation between Gstp status and lung cancer in vivo.


Assuntos
Adenoma/induzido quimicamente , Adenoma/enzimologia , Carcinógenos , Glutationa S-Transferase pi/metabolismo , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/enzimologia , 7,8-Di-Hidro-7,8-Di-Hidroxibenzo(a)pireno 9,10-óxido , Animais , Benzo(a)pireno , Adutos de DNA/biossíntese , Feminino , Perfilação da Expressão Gênica , Glutationa S-Transferase pi/deficiência , Glutationa S-Transferase pi/genética , Pulmão/metabolismo , MAP Quinase Quinase 4/metabolismo , Masculino , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Nicotiana , Uretana
3.
Nucleic Acids Res ; 35(Database issue): D347-53, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17145713

RESUMO

The National Microbial Pathogen Data Resource (NMPDR) (http://www.nmpdr.org) is a National Institute of Allergy and Infections Disease (NIAID)-funded Bioinformatics Resource Center that supports research in selected Category B pathogens. NMPDR contains the complete genomes of approximately 50 strains of pathogenic bacteria that are the focus of our curators, as well as >400 other genomes that provide a broad context for comparative analysis across the three phylogenetic Domains. NMPDR integrates complete, public genomes with expertly curated biological subsystems to provide the most consistent genome annotations. Subsystems are sets of functional roles related by a biologically meaningful organizing principle, which are built over large collections of genomes; they provide researchers with consistent functional assignments in a biologically structured context. Investigators can browse subsystems and reactions to develop accurate reconstructions of the metabolic networks of any sequenced organism. NMPDR provides a comprehensive bioinformatics platform, with tools and viewers for genome analysis. Results of precomputed gene clustering analyses can be retrieved in tabular or graphic format with one-click tools. NMPDR tools include Signature Genes, which finds the set of genes in common or that differentiates two groups of organisms. Essentiality data collated from genome-wide studies have been curated. Drug target identification and high-throughput, in silico, compound screening are in development.


Assuntos
Bases de Dados de Ácidos Nucleicos , Genoma Bacteriano , Bactérias/efeitos dos fármacos , Bactérias/metabolismo , Bactérias/patogenicidade , Proteínas de Bactérias/genética , Proteínas de Bactérias/fisiologia , DNA Bacteriano/química , Sistemas de Liberação de Medicamentos , Genes Bacterianos , Genes Essenciais , Genômica , Internet , Homologia de Sequência do Ácido Nucleico , Software , Interface Usuário-Computador
4.
Nucleic Acids Res ; 33(17): 5691-702, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16214803

RESUMO

The release of the 1000th complete microbial genome will occur in the next two to three years. In anticipation of this milestone, the Fellowship for Interpretation of Genomes (FIG) launched the Project to Annotate 1000 Genomes. The project is built around the principle that the key to improved accuracy in high-throughput annotation technology is to have experts annotate single subsystems over the complete collection of genomes, rather than having an annotation expert attempt to annotate all of the genes in a single genome. Using the subsystems approach, all of the genes implementing the subsystem are analyzed by an expert in that subsystem. An annotation environment was created where populated subsystems are curated and projected to new genomes. A portable notion of a populated subsystem was defined, and tools developed for exchanging and curating these objects. Tools were also developed to resolve conflicts between populated subsystems. The SEED is the first annotation environment that supports this model of annotation. Here, we describe the subsystem approach, and offer the first release of our growing library of populated subsystems. The initial release of data includes 180 177 distinct proteins with 2133 distinct functional roles. This data comes from 173 subsystems and 383 different organisms.


Assuntos
Genoma Arqueal , Genoma Bacteriano , Genômica/métodos , Software , Acil Coenzima A/metabolismo , Coenzima A/biossíntese , Biologia Computacional , Internet , Leucina/metabolismo , Proteínas Ribossômicas/classificação , Terminologia como Assunto , Vocabulário Controlado
5.
Biochem J ; 388(Pt 3): 857-67, 2005 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-15717863

RESUMO

Cytochrome P450 reductase is the unique electron donor for microsomal cytochrome P450s; these enzymes play a major role in the metabolism of endogenous and xenobiotic compounds. In mice with a liver-specific deletion of cytochrome P450 reductase, hepatic cytochrome P450 activity is ablated, with consequent changes in bile acid and lipid homoeostasis. In order to gain insights into the metabolic changes resulting from this phenotype, we have analysed changes in hepatic mRNA expression using microarray analysis and real-time PCR. In parallel with the perturbations in bile acid levels, changes in the expression of key enzymes involved in cholesterol and lipid homoeostasis were observed in hepatic cytochrome P450 reductase null mice. This was characterized by a reduced expression of Cyp7b1, and elevation of Cyp7a1 and Cyp8b1 expression. The levels of mRNAs for other cytochrome P450 genes, including Cyp2b10, Cyp2c29, Cyp3a11 and Cyp3a16, were increased, demonstrating that endogenous factors play a role in regulating the expression of these proteins and that the increases are due, at least in part, to altered levels of transcripts. In addition, levels of mRNAs encoding genes involved in glycolysis and lipid transport were also increased; the latter may provide an explanation for the increased hepatic lipid content observed in the hepatic null mice. Serum testosterone and oestradiol levels were lowered, accompanied by significantly decreased expression of Hsd3b2 (3beta-hydroxy-Delta5-steroid dehydrogenase-2), Hsd3b5 (3beta-hydroxy-Delta5-steroid dehydrogenase-5) and Hsd11b1 (11beta-hydroxysteroid dehydrogenase type 1), key enzymes in steroid hormone metabolism. These microarray data provide important insights into the control of metabolic pathways by the cytochrome system.


Assuntos
Deleção de Genes , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Fígado/metabolismo , NADPH-Ferri-Hemoproteína Redutase/deficiência , NADPH-Ferri-Hemoproteína Redutase/metabolismo , Animais , Metabolismo dos Carboidratos , Colesterol/metabolismo , Citoesqueleto/metabolismo , Glicólise/genética , Hormônios/metabolismo , Imunidade/genética , Metabolismo dos Lipídeos , Camundongos , Camundongos Knockout , NADPH-Ferri-Hemoproteína Redutase/genética , Neoplasias/genética , Análise de Sequência com Séries de Oligonucleotídeos , Estresse Oxidativo/genética , Fenótipo , Fosforilação , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , Transdução de Sinais/genética
6.
J Bacteriol ; 186(11): 3660-2, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15150256

RESUMO

The genes encoding thiamine kinase in Escherichia coli (ycfN) and thiamine pyrophosphokinase in Bacillus subtilis (yloS) have been identified. This study completes the identification of the thiamine salvage enzymes in bacteria.


Assuntos
Genes Bacterianos/fisiologia , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Tiamina Pirofosfoquinase/genética , Tiamina/metabolismo , Bacillus subtilis/genética , Escherichia coli/genética , NAD/metabolismo
7.
In Silico Biol ; 3(1-2): 3-15, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12762842

RESUMO

PhoH protein is a putative ATPase belonging to the phosphate regulon in Escherichia coli. EC-PhoH homologs are present in different organisms, but it is not clear if they are functionally related, besides nothing is known about their regulation. To distinguish true functional orthologs of EC-PhoH in different classes of bacteria and to identify their functional role in bacterial metabolic network we performed phylogenetic analysis of these proteins and comparative study of position and regulation of the related genes. Three groups of proteins were identified. Proteins of the first group (BS-PhoH orthologs) are present in most of bacteria and are proposed to be functionally linked to phospholipid metabolism and RNA modification. Proteins of the second group (BS-YlaK orthologs) are present in most of aerobes and Actinobacterial YlaK orthologs are shown to be members of a fatty acid beta-oxidation regulons. EC-PhoH orthologs are classified in a third group, specific for Enterobacteria. Functional role of PhoH homologs in the lipid and RNA metabolism and proposed interrelation of PhoH paralogs in one organism are discussed.


Assuntos
Bactérias/enzimologia , Bactérias/genética , Proteínas de Escherichia coli/classificação , Proteínas de Escherichia coli/genética , Genes Bacterianos/genética , Sequência de Bases , Biologia Computacional , Sequência Conservada , Regulação Bacteriana da Expressão Gênica , Regulação Enzimológica da Expressão Gênica , Genoma Bacteriano
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