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https://www.readbyqxmd.com/read/27913830/genome-scale-modeling-of-thermophilic-microorganisms
#1
Sanjeev Dahal, Suresh Poudel, R Adam Thompson
Thermophilic microorganisms are of increasing interest for many industries as their enzymes and metabolisms are highly efficient at elevated temperatures. However, their metabolic processes are often largely different from their mesophilic counterparts. These differences can lead to metabolic engineering strategies that are doomed to fail. Genome-scale metabolic modeling is an effective and highly utilized way to investigate cellular phenotypes and to test metabolic engineering strategies. In this review we chronicle a number of thermophilic organisms that have recently been studied with genome-scale models...
December 3, 2016: Advances in Biochemical Engineering/biotechnology
https://www.readbyqxmd.com/read/27911809/unique-attributes-of-cyanobacterial-metabolism-revealed-by-improved-genome-scale-metabolic-modeling-and-essential-gene-analysis
#2
Jared T Broddrick, Benjamin E Rubin, David G Welkie, Niu Du, Nathan Mih, Spencer Diamond, Jenny J Lee, Susan S Golden, Bernhard O Palsson
The model cyanobacterium, Synechococcus elongatus PCC 7942, is a genetically tractable obligate phototroph that is being developed for the bioproduction of high-value chemicals. Genome-scale models (GEMs) have been successfully used to assess and engineer cellular metabolism; however, GEMs of phototrophic metabolism have been limited by the lack of experimental datasets for model validation and the challenges of incorporating photon uptake. Here, we develop a GEM of metabolism in S. elongatus using random barcode transposon site sequencing (RB-TnSeq) essential gene and physiological data specific to photoautotrophic metabolism...
December 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27909940/enhancement-of-rapamycin-production-by-metabolic-engineering-in-streptomyces-hygroscopicus-based-on-genome-scale-metabolic-model
#3
Lanqing Dang, Jiao Liu, Cheng Wang, Huanhuan Liu, Jianping Wen
Rapamycin, as a macrocyclic polyketide with immunosuppressive, antifungal, and anti-tumor activity produced by Streptomyces hygroscopicus, is receiving considerable attention for its significant contribution in medical field. However, the production capacity of the wild strain is very low. Hereby, a computational guided engineering approach was proposed to improve the capability of rapamycin production. First, a genome-scale metabolic model of Streptomyces hygroscopicus ATCC 29253 was constructed based on its annotated genome and biochemical information...
December 1, 2016: Journal of Industrial Microbiology & Biotechnology
https://www.readbyqxmd.com/read/27909649/in-silico-profiling-of-cell-growth-and-succinate-production-in-escherichia-coli-nzn111
#4
Xingxing Jian, Ningchuan Li, Cheng Zhang, Qiang Hua
BACKGROUND: Succinic acid is a valuable product due to its wide-ranging utilities. To improve succinate production and reduce by-products formation, Escherichia coli NZN111 was constructed by insertional inactivation of lactate dehydrogenase (LDH) and pyruvate formate lyase (PFL) encoded by the genes ldhA and pflB, respectively. However, this double-deletion mutant is incapable of anaerobically growing on glucose in rich or minimal medium even with acetate supplementation. A widespread hold view is that the inactivation of NADH-dependent LDH limits the regeneration of NAD(+) and consequently disables proper growth under anaerobic conditions...
2016: Bioresources and Bioprocessing
https://www.readbyqxmd.com/read/27907891/analysis-of-translation-using-polysome-profiling
#5
Héloïse Chassé, Sandrine Boulben, Vlad Costache, Patrick Cormier, Julia Morales
During the past decade, there has been growing interest in the role of translational regulation of gene expression in many organisms. Polysome profiling has been developed to infer the translational status of a specific mRNA species or to analyze the translatome, i.e. the subset of mRNAs actively translated in a cell. Polysome profiling is especially suitable for emergent model organisms for which genomic data are limited. In this paper, we describe an optimized protocol for the purification of sea urchin polysomes and highlight the critical steps involved in polysome purification...
October 7, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27903912/the-complex-evolutionary-history-of-aminoacyl-trna-synthetases
#6
Anargyros Chaliotis, Panayotis Vlastaridis, Dimitris Mossialos, Michael Ibba, Hubert D Becker, Constantinos Stathopoulos, Grigorios D Amoutzias
Aminoacyl-tRNA synthetases (AARSs) are a superfamily of enzymes responsible for the faithful translation of the genetic code and have lately become a prominent target for synthetic biologists. Our large-scale analysis of >2500 prokaryotic genomes reveals the complex evolutionary history of these enzymes and their paralogs, in which horizontal gene transfer played an important role. These results show that a widespread belief in the evolutionary stability of this superfamily is misconceived. Although AlaRS, GlyRS, LeuRS, IleRS, ValRS are the most stable members of the family, GluRS, LysRS and CysRS often have paralogs, whereas AsnRS, GlnRS, PylRS and SepRS are often absent from many genomes...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27903883/function-driven-discovery-of-disease-genes-in-zebrafish-using-an-integrated-genomics-big-data-resource
#7
Hongseok Shim, Ji Hyun Kim, Chan Yeong Kim, Sohyun Hwang, Hyojin Kim, Sunmo Yang, Ji Eun Lee, Insuk Lee
Whole exome sequencing (WES) accelerates disease gene discovery using rare genetic variants, but further statistical and functional evidence is required to avoid false-discovery. To complement variant-driven disease gene discovery, here we present function-driven disease gene discovery in zebrafish (Danio rerio), a promising human disease model owing to its high anatomical and genomic similarity to humans. To facilitate zebrafish-based function-driven disease gene discovery, we developed a genome-scale co-functional network of zebrafish genes, DanioNet (www...
November 16, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27901213/the-rs11191580-variant-of-the-nt5c2-gene-is-associated-with-schizophrenia-and-symptom-severity-in-a-south-chinese-han-population-evidence-from-gwas
#8
Zhen Li, Juan Jiang, Jianxiong Long, Weijun Ling, Guifeng Huang, Xiaojing Guo, Li Su
Objective: Recent genome-wide association studies have identified a significant relationship between the NT5C2 variant rs11191580 and schizophrenia (SCZ) in European populations. This study aimed to validate the association of rs11191580 polymorphism with SCZ risk in a South Chinese Han population. The relationship of this polymorphism with the severity of SCZ clinical symptoms was also explored. Methods: A case-control study was performed in 462 patients with SCZ and 598 healthy controls...
November 24, 2016: Revista Brasileira de Psiquiatria
https://www.readbyqxmd.com/read/27899595/panther-version-11-expanded-annotation-data-from-gene-ontology-and-reactome-pathways-and-data-analysis-tool-enhancements
#9
Huaiyu Mi, Xiaosong Huang, Anushya Muruganujan, Haiming Tang, Caitlin Mills, Diane Kang, Paul D Thomas
The PANTHER database (Protein ANalysis THrough Evolutionary Relationships, http://pantherdb.org) contains comprehensive information on the evolution and function of protein-coding genes from 104 completely sequenced genomes. PANTHER software tools allow users to classify new protein sequences, and to analyze gene lists obtained from large-scale genomics experiments. In the past year, major improvements include a large expansion of classification information available in PANTHER, as well as significant enhancements to the analysis tools...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899586/r-loopdb-a-database-for-r-loop-forming-sequences-rlfs-and-r-loops
#10
Piroon Jenjaroenpun, Thidathip Wongsurawat, Sawannee Sutheeworapong, Vladimir A Kuznetsov
R-loopDB (http://rloop.bii.a-star.edu.sg) was originally constructed as a collection of computationally predicted R-loop forming sequences (RLFSs) in the human genic regions. The renewed R-loopDB provides updates, improvements and new options, including access to recent experimental data. It includes genome-scale prediction of RLFSs for humans, six other animals and yeast. Using the extended quantitative model of RLFSs (QmRLFS), we significantly increased the number of RLFSs predicted in the human genes and identified RLFSs in other organism genomes...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899536/a-comprehensively-curated-genome-scale-two-cell-model-for-the-cyanobacterium-anabaena-sp-pcc-7120
#11
David Malatinszky, Ralf Steuer, Patrik R Jones
Anabaena sp. PCC 7120 is a nitrogen-fixing filamentous cyanobacterium. Under nitrogen limiting conditions, a fraction of the vegetative cells in each filament terminally differentiate to non-growing heterocysts. Heterocysts are metabolically and structurally specialized to enable O2-sensitive nitrogen fixation. The functionality of the filament, as an association of vegetative cells and heterocysts, is postulated to depend on metabolic exchange of electrons, carbon and fixed nitrogen. In the present work, we compile and evaluate a comprehensive curated stoichiometric model of this two-cell system, with the objective function based on the growth of the filament under diazotrophic conditions...
November 29, 2016: Plant Physiology
https://www.readbyqxmd.com/read/27897000/identifying-cancer-specific-metabolic-signatures-using-constraint-based-models
#12
A Schultz, S Mehta, C W Hu, F W Hoff, T M Horton, S M Kornblau, A A Qutub
Cancer metabolism differs remarkably from the metabolism of healthy surrounding tissues, and it is extremely heterogeneous across cancer types. While these metabolic differences provide promising avenues for cancer treatments, much work remains to be done in understanding how metabolism is rewired in malignant tissues. To that end, constraint-based models provide a powerful computational tool for the study of metabolism at the genome scale. To generate meaningful predictions, however, these generalized human models must first be tailored for specific cell or tissue sub-types...
2016: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/27896997/improved-performance-of-gene-set-analysis-on-genome-wide-transcriptomics-data-when-using-gene-activity-state-estimates
#13
Thomas Kamp, Micah Adams, Craig Disselkoen, Nathan Tintle
Gene set analysis methods continue to be a popular and powerful method of evaluating genome-wide transcriptomics data. These approach require a priori grouping of genes into biologically meaningful sets, and then conducting downstream analyses at the set (instead of gene) level of analysis. Gene set analysis methods have been shown to yield more powerful statistical conclusions than single-gene analyses due to both reduced multiple testing penalties and potentially larger observed effects due to the aggregation of effects across multiple genes in the set...
2016: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/27896277/prediction-of-bacillus-calmette-guerin-response-in-patients-with-bladder-cancer-after-transurethral-resection-of-bladder-tumor-by-using-genetic-variation-based-on-genomic-studies
#14
REVIEW
Ning Zhang, Guangliang Jiang, Xu Liu, Rong Na, Xiang Wang, Jianfeng Xu
Purpose. We aimed to comprehensively review contemporary literature on genetic and epigenetic biomarkers associated with the prediction of Bacillus Calmette-Guerin (BCG) response after the transurethral resection of a bladder tumor and to discuss the application of these biomarkers in precision cancer care for bladder cancer. Method. We performed a systematic review of published literatures in the databases PubMed and Embase by using the following key words: bladder cancer, BCG, gene, and methylation. Studies associated with cell lines, animal models, and muscle invasive bladder cancer were excluded...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27893703/generation-of-genome-scale-metabolic-reconstructions-for-773-members-of-the-human-gut-microbiota
#15
Stefanía Magnúsdóttir, Almut Heinken, Laura Kutt, Dmitry A Ravcheev, Eugen Bauer, Alberto Noronha, Kacy Greenhalgh, Christian Jäger, Joanna Baginska, Paul Wilmes, Ronan M T Fleming, Ines Thiele
Genome-scale metabolic models derived from human gut metagenomic data can be used as a framework to elucidate how microbial communities modulate human metabolism and health. We present AGORA (assembly of gut organisms through reconstruction and analysis), a resource of genome-scale metabolic reconstructions semi-automatically generated for 773 human gut bacteria. Using this resource, we identified a defined growth medium for Bacteroides caccae ATCC 34185. We also showed that interactions among modeled species depend on both the metabolic potential of each species and the nutrients available...
November 28, 2016: Nature Biotechnology
https://www.readbyqxmd.com/read/27892966/effect-of-sex-age-and-genetics-on-crossover-interference-in-cattle
#16
Zhiying Wang, Botong Shen, Jicai Jiang, Jinquan Li, Li Ma
Crossovers generated by homologous recombination ensure proper chromosome segregation during meiosis. Crossover interference results in chiasmata being more evenly distributed along chromosomes, but the mechanism underlying crossover interference remains elusive. Based on large pedigrees of Holstein and Jersey cattle with genotype data, we extracted three-generation families, including 147,327 male and 71,687 female meioses in Holstein, and 108,163 male and 37,008 female meioses in Jersey, respectively. We identified crossovers in these meioses and fitted the Housworth-Stahl "interference-escape" model to study crossover interference patterns in the cattle genome...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27890449/independent-evolution-of-genomic-characters-during-major-metazoan-transitions
#17
REVIEW
Oleg Simakov, Takeshi Kawashima
Metazoan evolution encompasses a vast evolutionary time scale spanning over 600 million years. Our ability to infer ancestral metazoan characters, both morphological and functional, is limited by our understanding of the nature and evolutionary dynamics of the underlying regulatory networks. Increasing coverage of metazoan genomes enables us to identify the evolutionary changes of the relevant genomic characters such as the loss or gain of coding sequences, gene duplications, micro- and macro-synteny, and non-coding element evolution in different lineages...
November 24, 2016: Developmental Biology
https://www.readbyqxmd.com/read/27886494/stochastic-predator-prey-dynamics-of-transposons-in-the-human-genome
#18
Chi Xue, Nigel Goldenfeld
Transposable elements, or transposons, are DNA sequences that can jump from site to site in the genome during the life cycle of a cell, usually encoding the very enzymes which perform their excision. However, some transposons are parasitic, relying on the enzymes produced by the regular transposons. In this case, we show that a stochastic model, which takes into account the small copy numbers of the active transposons in a cell, predicts noise-induced predator-prey oscillations with a characteristic time scale that is much longer than the cell replication time, indicating that the state of the predator-prey oscillator is stored in the genome and transmitted to successive generations...
November 11, 2016: Physical Review Letters
https://www.readbyqxmd.com/read/27884101/variancepartition-interpreting-drivers-of-variation-in-complex-gene-expression-studies
#19
Gabriel E Hoffman, Eric E Schadt
BACKGROUND: As large-scale studies of gene expression with multiple sources of biological and technical variation become widely adopted, characterizing these drivers of variation becomes essential to understanding disease biology and regulatory genetics. RESULTS: We describe a statistical and visualization framework, variancePartition, to prioritize drivers of variation based on a genome-wide summary, and identify genes that deviate from the genome-wide trend. Using a linear mixed model, variancePartition quantifies variation in each expression trait attributable to differences in disease status, sex, cell or tissue type, ancestry, genetic background, experimental stimulus, or technical variables...
November 25, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/27883890/a-consensus-genome-scale-reconstruction-of-chinese-hamster-ovary-cell-metabolism
#20
Hooman Hefzi, Kok Siong Ang, Michael Hanscho, Aarash Bordbar, David Ruckerbauer, Meiyappan Lakshmanan, Camila A Orellana, Deniz Baycin-Hizal, Yingxiang Huang, Daniel Ley, Veronica S Martinez, Sarantos Kyriakopoulos, Natalia E Jiménez, Daniel C Zielinski, Lake-Ee Quek, Tune Wulff, Johnny Arnsdorf, Shangzhong Li, Jae Seong Lee, Giuseppe Paglia, Nicolas Loira, Philipp N Spahn, Lasse E Pedersen, Jahir M Gutierrez, Zachary A King, Anne Mathilde Lund, Harish Nagarajan, Alex Thomas, Alyaa M Abdel-Haleem, Juergen Zanghellini, Helene F Kildegaard, Bjørn G Voldborg, Ziomara P Gerdtzen, Michael J Betenbaugh, Bernhard O Palsson, Mikael R Andersen, Lars K Nielsen, Nicole Borth, Dong-Yup Lee, Nathan E Lewis
Chinese hamster ovary (CHO) cells dominate biotherapeutic protein production and are widely used in mammalian cell line engineering research. To elucidate metabolic bottlenecks in protein production and to guide cell engineering and bioprocess optimization, we reconstructed the metabolic pathways in CHO and associated them with >1,700 genes in the Cricetulus griseus genome. The genome-scale metabolic model based on this reconstruction, iCHO1766, and cell-line-specific models for CHO-K1, CHO-S, and CHO-DG44 cells provide the biochemical basis of growth and recombinant protein production...
November 23, 2016: Cell Systems
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