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BioProject and BioSample databases at NCBI: facilitating capture and organization of metadata
- Nucleic Acids Res
, 2012
"... As the volume and complexity of data sets archived at NCBI grow rapidly, so does the need to gather and organize the associated metadata. Although metadata has been collected for some archival databases, previously, there was no centralized approach at NCBI for collecting this information and using ..."
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As the volume and complexity of data sets archived at NCBI grow rapidly, so does the need to gather and organize the associated metadata. Although metadata has been collected for some archival databases, previously, there was no centralized approach at NCBI for collecting this information and using it across databases. The BioProject database was recently established to facilitate organization and classification of project data submitted to NCBI, EBI and DDBJ databases. It captures descriptive information about research projects that result in high volume submissions to archival databases, ties together related data across multiple archives and serves as a central portal by which to inform users of data availability. Concomitantly, the BioSample database is being de-veloped to capture descriptive information about the biological samples investigated in projects. BioProject and BioSample records link to corres-ponding data stored in archival repositories. Submissions are supported by a web-based Submission Portal that guides users through a series of forms for input of rich metadata describing their projects and samples. Together, these data-bases offer improved ways for users to query, locate, integrate and interpret the masses of data held in NCBI’s archival repositories. The BioProject and BioSample databases are available at
Systems-level metabolic flux profiling elucidates a complete, bifurcated tricarboxylic acid cycle in Clostridium acetobutylicum
- Journal of Bacteriology
"... Obligatory anaerobic bacteria are major contributors to the overall metabolism of soil and the human gut. The metabolic pathways of these bacteria remain, however, poorly understood. Using isotope tracers, mass spectrometry, and quantitative flux modeling, here we directly map the metabolic pathways ..."
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Obligatory anaerobic bacteria are major contributors to the overall metabolism of soil and the human gut. The metabolic pathways of these bacteria remain, however, poorly understood. Using isotope tracers, mass spectrometry, and quantitative flux modeling, here we directly map the metabolic pathways of Clostridium acetobutylicum, a soil bacterium whose major fermentation products include the biofuels butanol and hydrogen. While genome annotation suggests the absence of most tricarboxylic acid (TCA) cycle enzymes, our results demonstrate that this bacterium has a complete, albeit bifurcated, TCA cycle; oxaloacetate flows to succinate both through citrate/-ketoglutarate and via malate/fumarate. Our investigations also yielded insights into the pathways utilized for glucose catabolism and amino acid biosynthesis and revealed that the organism’s one-carbon metabolism is distinct from that of model microbes, involving reversible pyruvate decarboxylation and the use of pyruvate as the one-carbon donor for biosynthetic reactions. This study represents the first in vivo characterization of the TCA cycle and central metabolism of C. acetobutylicum. Our results establish a role for the full TCA cycle in an obligatory anaerobic organism and demonstrate the importance of complementing genome annotation with isotope tracer studies for determining the metabolic pathways of diverse microbes. In soil ecology, obligatory anaerobic bacteria are key con-tributors to the putrefaction of dead organic matter (18). In the
The structure-function linkage database
- Nucleic Acids Res
, 2014
"... The Structure–Function Linkage Database (SFLD, ..."
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doi:10.1093/nar/gkr1020 ProOpDB: Prokaryotic Operon DataBase
, 2011
"... The Prokaryotic Operon DataBase (ProOpDB, ..."
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FungiDB: an integrated functional genomics database for fungi
, 2011
"... FungiDB ..."
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Translesion-synthesis DNA polymerases participate in replication of the telomeres in
, 2011
"... doi:10.1093/nar/gkr856 ..."
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doi:10.1093/nar/gkr433 GLAMM: Genome-Linked Application for Metabolic Maps
, 2011
"... The Genome-Linked Application for Metabolic Maps (GLAMM) is a unified web interface for visualizing metabolic networks, reconstructing metabolic networks from annotated genome data, visualizing experimental data in the context of metabolic networks and investigating the construction of novel, transg ..."
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The Genome-Linked Application for Metabolic Maps (GLAMM) is a unified web interface for visualizing metabolic networks, reconstructing metabolic networks from annotated genome data, visualizing experimental data in the context of metabolic networks and investigating the construction of novel, transgenic pathways. This simple, user-friendly interface is tightly integrated with the comparative genomics tools of MicrobesOnline [Dehal et al. (2010) Nucleic Acids Research, 38, D396–D400]. GLAMM is available for free to the scientific community at glamm.lbl.gov.
RegPrecise web services interface: programmatic access to the transcriptional regulatory interactions in bacteria reconstructed by comparative genomics
- Nucleic Acids Res
, 2012
"... regulatory interactions in bacteria reconstructed by comparative genomics ..."
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regulatory interactions in bacteria reconstructed by comparative genomics
A high-resolution network model for global gene regulation in Mycobacterium tuberculosis
, 2014
"... The resilience of Mycobacterium tuberculosis (MTB) is largely due to its ability to effectively counter-act and even take advantage of the hostile environ-ments of a host. In order to accelerate the discov-ery and characterization of these adaptive mecha-nisms, we have mined a compendium of 2325 pub ..."
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The resilience of Mycobacterium tuberculosis (MTB) is largely due to its ability to effectively counter-act and even take advantage of the hostile environ-ments of a host. In order to accelerate the discov-ery and characterization of these adaptive mecha-nisms, we have mined a compendium of 2325 pub-licly available transcriptome profiles of MTB to deci-pher a predictive, systems-scale gene regulatory net-work model. The resulting modular organization of 98 % of all MTB genes within this regulatory network was rigorously tested using two independently gen-erated datasets: a genome-wide map of 7248 DNA-binding locations for 143 transcription factors (TFs) and global transcriptional consequences of overex-pressing 206 TFs. This analysis has discovered spe-cific TFs that mediate conditional co-regulation of genes within 240 modules across 14 distinct envi-ronmental contexts. In addition to recapitulating pre-viously characterized regulons, we discovered 454 novel mechanisms for gene regulation during stress, cholesterol utilization and dormancy. Significantly, 183 of these mechanisms act uniquely under con-ditions experienced during the infection cycle to reg-ulate diverse functions including 23 genes that are essential to host-pathogen interactions. These and other insights underscore the power of a rational, model-driven approach to unearth novel MTB biol-ogy that operates under some but not all phases of infection.
Regulation and consequence of serine catabolism in Streptococcus pyogenes
, 2011
"... The Gram-positive bacterium Streptococcus pyogenes (also called group A Streptococcus [GAS]), is found strictly in humans and is capable of causing a wide variety of infections. Here we demonstrate that serine catabolism in GAS is controlled by the transcriptional regulator Spy49_0126c. We have desi ..."
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The Gram-positive bacterium Streptococcus pyogenes (also called group A Streptococcus [GAS]), is found strictly in humans and is capable of causing a wide variety of infections. Here we demonstrate that serine catabolism in GAS is controlled by the transcriptional regulator Spy49_0126c. We have designated this regulator SerR (for serine catabolism regulator). Microarray and transcriptional reporter data show that SerR acts as a transcriptional repressor of multiple operons, including sloR and sdhBA. Purified recom-binant SerR binds to the promoters of both sloR and sdhB, demonstrating that this regulation is direct. Deletion of serR results in a lower culture yield of the mutant than of the wild type when the strains are grown in defined medium unless additional serine is provided, suggesting that regulation of serine metabolism is important for maximizing bacterial growth. Deletion of sloR or sdhB in the serR mutant background restores growth to wild-type levels, suggesting that both operons have roles in serine catabolism. While reports have linked sloR function to streptolysin O expression, transport experiments with radiolabeled L-serine reveal that the sloR operon is required for rapid acquisition of serine, suggesting a novel role for this operon in amino acid metabolism. The Gram-positive bacterium Streptococcus pyogenes, also known as group A Streptococcus (GAS), is a strictly human
