Michael R Leuze

Oak Ridge National Laboratory, Oak Ridge, FL, USA

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Publications (8)12.29 Total impact

  • Source
    Article: BESC knowledgebase public portal.
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    ABSTRACT: The BioEnergy Science Center (BESC) is undertaking large experimental campaigns to understand the biosynthesis and biodegradation of biomass and to develop biofuel solutions. BESC is generating large volumes of diverse data, including genome sequences, omics data and assay results. The purpose of the BESC Knowledgebase is to serve as a centralized repository for experimentally generated data and to provide an integrated, interactive and user-friendly analysis framework. The Portal makes available tools for visualization, integration and analysis of data either produced by BESC or obtained from external resources. AVAILABILITY: http://besckb.ornl.gov.
    Bioinformatics 03/2012; 28(5):750-1. · 5.47 Impact Factor
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    Article: Binding Motifs in Bacterial Gene Promoters Modulate Transcriptional Effects of Global Regulators CRP and ArcA.
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    ABSTRACT: Bacterial gene regulation involves transcription factors (TF) that bind to DNA recognition sequences in operon promoters. These recognition sequences, many of which are palindromic, are known as regulatory elements or transcription factor binding sites (TFBS). Some TFs are global regulators that can modulate the expression of hundreds of genes. In this study we examine global regulator half-sites, where a half-site, which we shall call a binding motif (BM), is one half of a palindromic TFBS. We explore the hypothesis that the number of BMs plays an important role in transcriptional regulation, examining empirical data from transcriptional profiling of the CRP and ArcA regulons. We compare the power of BM counts and of full TFBS characteristics to predict induced transcriptional activity. We find that CRP BM counts have a nonlinear effect on CRP-dependent transcriptional activity and predict this activity better than full TFBS quality or location.
    Gene regulation and systems biology 01/2012; 6:93-107.
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    Article: CAZymes Analysis Toolkit (CAT): web service for searching and analyzing carbohydrate-active enzymes in a newly sequenced organism using CAZy database.
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    ABSTRACT: The Carbohydrate-Active Enzyme (CAZy) database provides a rich set of manually annotated enzymes that degrade, modify, or create glycosidic bonds. Despite rich and invaluable information stored in the database, software tools utilizing this information for annotation of newly sequenced genomes by CAZy families are limited. We have employed two annotation approaches to fill the gap between manually curated high-quality protein sequences collected in the CAZy database and the growing number of other protein sequences produced by genome or metagenome sequencing projects. The first approach is based on a similarity search against the entire nonredundant sequences of the CAZy database. The second approach performs annotation using links or correspondences between the CAZy families and protein family domains. The links were discovered using the association rule learning algorithm applied to sequences from the CAZy database. The approaches complement each other and in combination achieved high specificity and sensitivity when cross-evaluated with the manually curated genomes of Clostridium thermocellum ATCC 27405 and Saccharophagus degradans 2-40. The capability of the proposed framework to predict the function of unknown protein domains and of hypothetical proteins in the genome of Neurospora crassa is demonstrated. The framework is implemented as a Web service, the CAZymes Analysis Toolkit, and is available at http://cricket.ornl.gov/cgi-bin/cat.cgi.
    Glycobiology 12/2010; 20(12):1574-84. · 3.58 Impact Factor
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    Article: Shewanella knowledgebase: integration of the experimental data and computational predictions suggests a biological role for transcription of intergenic regions.
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    ABSTRACT: Shewanellae are facultative gamma-proteobacteria whose remarkable respiratory versatility has resulted in interest in their utility for bioremediation of heavy metals and radionuclides and for energy generation in microbial fuel cells. Extensive experimental efforts over the last several years and the availability of 21 sequenced Shewanella genomes made it possible to collect and integrate a wealth of information on the genus into one public resource providing new avenues for making biological discoveries and for developing a system level understanding of the cellular processes. The Shewanella knowledgebase was established in 2005 to provide a framework for integrated genome-based studies on Shewanella ecophysiology. The present version of the knowledgebase provides access to a diverse set of experimental and genomic data along with tools for curation of genome annotations and visualization and integration of genomic data with experimental data. As a demonstration of the utility of this resource, we examined a single microarray data set from Shewanella oneidensis MR-1 for new insights into regulatory processes. The integrated analysis of the data predicted a new type of bacterial transcriptional regulation involving co-transcription of the intergenic region with the downstream gene and suggested a biological role for co-transcription that likely prevents the binding of a regulator of the upstream gene to the regulator binding site located in the intergenic region. Database URL: http://shewanella-knowledgebase.org:8080/Shewanella/ or http://spruce.ornl.gov:8080/Shewanella/
    Database The Journal of Biological Databases and Curation 01/2010; 2010:baq012. · 2.07 Impact Factor
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    Article: Shewregdb: database and visualization environment for experimental and predicted regulatory information in Shewanella oneidensis mr-1.
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    ABSTRACT: Shewanella oneidensis MR-1 is an important model organism for environmental research as it has an exceptional metabolic and respiratory versatility regulated by a complex regulatory network. We have developed a database to collect experimental and computational data relating to regulation of gene and protein expression, and, a visualization environment that enables integration of these data types. The regulatory information in the database includes predictions of DNA regulator binding sites, sigma factor binding sites, transcription units, operons, promoters, and RNA regulators including non-coding RNAs, riboswitches, and different types of terminators. AVAILABILITY: http://shewanella-knowledgebase.org:8080/Shewanella/gbrowserLanding.jsp.
    Bioinformation 01/2009; 4(4):169-72.
  • Article: Hypothesis of stress-induced cellular adaptation as applied to evolution of cellulose-degrading fermenting bacteria
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    ABSTRACT: Recent progress in genomics and molecular biology has challenged the main statements of the evolutionary theory, namely, that mutations in living organisms occur randomly during replication, rate of mutations is independent of the environment, and that adaptive changes acquired by an organism cannot be transferred to offspring. Studies of stationary state mutagenesis in bacteria, tumorigenesis in mammals, and epigenetic effects in different organisms reveal (i) increased rate of mutations under stress; (ii) a higher probability of mutations in genes that are under selection pressure in stressful environment; (iii) the involvement of environmental signal in regulation of DNA replication and repair, and (iv) the transfer of information about the environment to the DNA through inherited epigenetic modifications. Based on these observations we propose a hypothesis of stress induced cellular adaptation and accelerated direct evolution. According to the hypothesis, a sustained stress environment drives a small subpopulation of the living cells to activation of a specific survival strategy characterized by acquisition of beneficial mutations resulted in accelerated development of novel cellular functions. Hallmarks of the strategy, which is also referred to as the Mutator Phenotype, are (i) stress-induced cell proliferation; (ii) increased rate of mutations and their beneficial nature; (iii) silencing of processes involved in alternative survival strategies, including cellular senescence, programmed cell death, and differentiation. Comparison of ethanol tolerant and fast growing mutants of Clostridium thermocellum with the wild type strain using 454 pyrosequencing supports the hypothesis indicating non-random distribution of mutations in the mutants.
    Biotechnology for Fuels and Chemicals.
  • Article: Hypothesis of stress-induced cellular adaptation as applied to evolution of cellulose-degrading fermenting bacteria
    [show abstract] [hide abstract]
    ABSTRACT: Recent progress in genomics and molecular biology has challenged the main statements of the evolutionary theory, namely, that mutations in living organisms occur randomly during replication, rate of mutations is independent of the environment, and that adaptive changes acquired by an organism cannot be transferred to offspring. Studies of stationary state mutagenesis in bacteria, tumorigenesis in mammals, and epigenetic effects in different organisms reveal (i) increased rate of mutations under stress; (ii) a higher probability of mutations in genes that are under selection pressure in stressful environment; (iii) the involvement of environmental signal in regulation of DNA replication and repair, and (iv) the transfer of information about the environment to the DNA through inherited epigenetic modifications. Based on these observations we propose a hypothesis of stress induced cellular adaptation and accelerated direct evolution. According to the hypothesis, a sustained stress environment drives a small subpopulation of the living cells to activation of a specific survival strategy characterized by acquisition of beneficial mutations resulted in accelerated development of novel cellular functions. Hallmarks of the strategy, which is also referred to as the Mutator Phenotype, are (i) stress-induced cell proliferation; (ii) increased rate of mutations and their beneficial nature; (iii) silencing of processes involved in alternative survival strategies, including cellular senescence, programmed cell death, and differentiation. Comparison of ethanol tolerant and fast growing mutants of Clostridium thermocellum with the wild type strain using 454 pyrosequencing supports the hypothesis indicating non-random distribution of mutations in the mutants.
    Biotechnology for Fuels and Chemicals.
  • Article: Vector space model for the generalized parts grouping problem
    Nagiza F. Samatova, Thomas E. Potok, Michael R. Leuze
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    ABSTRACT: The vector perturbation approach is introduced for addressing the generalized parts grouping problem, identifying part families for a general set of suppliers, not just a single supplier. This method is driven by the need for flexible and lean supply chain systems. A vector space model is used to represent a set of operation sequences as opposed to the traditional matrix and integer programming models in group technology. Using this approach, we find that we are able to generate part groups from 90% of the available parts, in which all the operation sequences are preserved. This contrasts the traditional methods using which only 66% of the available parts can be grouped. Furthermore, a vector representation of operation sequences provides an intuitive means for discovering the natural structure of the part data. From these results, we conclude that this technique can dramatically improve the effectiveness of the entire supply chain.
    Robotics and Computer-Integrated Manufacturing 17:73-80. · 1.17 Impact Factor