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https://www.readbyqxmd.com/read/29457794/recon3d-enables-a-three-dimensional-view-of-gene-variation-in-human-metabolism
#1
Elizabeth Brunk, Swagatika Sahoo, Daniel C Zielinski, Ali Altunkaya, Andreas Dräger, Nathan Mih, Francesco Gatto, Avlant Nilsson, German Andres Preciat Gonzalez, Maike Kathrin Aurich, Andreas Prlić, Anand Sastry, Anna D Danielsdottir, Almut Heinken, Alberto Noronha, Peter W Rose, Stephen K Burley, Ronan M T Fleming, Jens Nielsen, Ines Thiele, Bernhard O Palsson
Genome-scale network reconstructions have helped uncover the molecular basis of metabolism. Here we present Recon3D, a computational resource that includes three-dimensional (3D) metabolite and protein structure data and enables integrated analyses of metabolic functions in humans. We use Recon3D to functionally characterize mutations associated with disease, and identify metabolic response signatures that are caused by exposure to certain drugs. Recon3D represents the most comprehensive human metabolic network model to date, accounting for 3,288 open reading frames (representing 17% of functionally annotated human genes), 13,543 metabolic reactions involving 4,140 unique metabolites, and 12,890 protein structures...
February 19, 2018: Nature Biotechnology
https://www.readbyqxmd.com/read/29456625/alignment-of-microbial-fitness-with-engineered-product-formation-obligatory-coupling-between-acetate-production-and-photoautotrophic-growth
#2
Wei Du, Joeri A Jongbloets, Coco van Boxtel, Hugo Pineda Hernández, David Lips, Brett G Oliver, Klaas J Hellingwerf, Filipe Branco Dos Santos
Background: Microbial bioengineering has the potential to become a key contributor to the future development of human society by providing sustainable, novel, and cost-effective production pipelines. However, the sustained productivity of genetically engineered strains is often a challenge, as spontaneous non-producing mutants tend to grow faster and take over the population. Novel strategies to prevent this issue of strain instability are urgently needed. Results: In this study, we propose a novel strategy applicable to all microbial production systems for which a genome-scale metabolic model is available that aligns the production of native metabolites to the formation of biomass...
2018: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/29451365/the-genome-of-the-freshwater-monogonont-rotifer-brachionus-calyciflorus
#3
Hui-Su Kim, Bo-Young Lee, Jeonghoon Han, Chang-Bum Jeong, Dae-Sik Hwang, Min-Chul Lee, Hye-Min Kang, Duck-Hyun Kim, Hee-Jin Kim, Spiros Papakostas, Steven A J Declerck, Ik-Young Choi, Atsushi Hagiwara, Heum Gi Park, Jae-Seong Lee
Monogononta is the most speciose class of rotifers, with more than 2000 species. The monogonont genus Brachionus is widely distributed at a global scale, and a few of its species are commonly used as ecological and evolutionary models to address questions related to aquatic ecology, cryptic speciation, evolutionary ecology, the evolution of sex, and ecotoxicology. With the importance of Brachionus species in many areas of research, it is remarkable that the genome has not been characterized. This study aims to address this lacuna by presenting, for the first time, the whole genome assembly of the freshwater species Brachionus calyciflorus...
February 16, 2018: Molecular Ecology Resources
https://www.readbyqxmd.com/read/29450107/macrogenomic-engineering-via-modulation-of-the-scaling-of-chromatin-packing-density
#4
Luay M Almassalha, Greta M Bauer, Wenli Wu, Lusik Cherkezyan, Di Zhang, Alexis Kendra, Scott Gladstein, John E Chandler, David VanDerway, Brandon-Luke L Seagle, Andrey Ugolkov, Daniel D Billadeau, Thomas V O'Halloran, Andrew P Mazar, Hemant K Roy, Igal Szleifer, Shohreh Shahabi, Vadim Backman
Many human diseases result from the dysregulation of the complex interactions between tens to thousands of genes. However, approaches for the transcriptional modulation of many genes simultaneously in a predictive manner are lacking. Here, through the combination of simulations, systems modelling and in vitro experiments, we provide a physical regulatory framework based on chromatin packing-density heterogeneity for modulating the genomic information space. Because transcriptional interactions are essentially chemical reactions, they depend largely on the local physical nanoenvironment...
November 2017: Nature Biomedical Engineering
https://www.readbyqxmd.com/read/29449860/adaptive-genetic-divergence-despite-significant-isolation-by-distance-in-populations-of-taiwan-cow-tail-fir-keteleeria-davidiana-var-formosana
#5
Kai-Ming Shih, Chung-Te Chang, Jeng-Der Chung, Yu-Chung Chiang, Shih-Ying Hwang
Double digest restriction site-associated DNA sequencing (ddRADseq) is a tool for delivering genome-wide single nucleotide polymorphism (SNP) markers for non-model organisms useful in resolving fine-scale population structure and detecting signatures of selection. This study performs population genetic analysis, based on ddRADseq data, of a coniferous species, Keteleeria davidiana var. formosana , disjunctly distributed in northern and southern Taiwan, for investigation of population adaptive divergence in response to environmental heterogeneity...
2018: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29448159/polyploid-arabidopsis-species-originated-around-recent-glaciation-maxima
#6
REVIEW
Polina Yu Novikova, Nora Hohmann, Yves Van de Peer
Polyploidy may provide adaptive advantages and is considered to be important for evolution and speciation. Polyploidy events are found throughout the evolutionary history of plants, however they do not seem to be uniformly distributed along the time axis. For example, many of the detected ancient whole-genome duplications (WGDs) seem to cluster around the K/Pg boundary (∼66Mya), which corresponds to a drastic climate change event and a mass extinction. Here, we discuss more recent polyploidy events using Arabidopsis as the most developed plant model at the level of the entire genus...
February 12, 2018: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/29447218/findprimarypairs-an-efficient-algorithm-for-predicting-element-transferring-reactant-product-pairs-in-metabolic-networks
#7
Jon Lund Steffensen, Keith Dufault-Thompson, Ying Zhang
The metabolism of individual organisms and biological communities can be viewed as a network of metabolites connected to each other through chemical reactions. In metabolic networks, chemical reactions transform reactants into products, thereby transferring elements between these metabolites. Knowledge of how elements are transferred through reactant/product pairs allows for the identification of primary compound connections through a metabolic network. However, such information is not readily available and is often challenging to obtain for large reaction databases or genome-scale metabolic models...
2018: PloS One
https://www.readbyqxmd.com/read/29445022/whole-genome-duplication-and-transposable-element-proliferation-drive-genome-expansion-in-corydoradinae-catfishes
#8
Sarah Marburger, Markos A Alexandrou, John B Taggart, Simon Creer, Gary Carvalho, Claudio Oliveira, Martin I Taylor
Genome size varies significantly across eukaryotic taxa and the largest changes are typically driven by macro-mutations such as whole genome duplications (WGDs) and proliferation of repetitive elements. These two processes may affect the evolutionary potential of lineages by increasing genetic variation and changing gene expression. Here, we elucidate the evolutionary history and mechanisms underpinning genome size variation in a species-rich group of Neotropical catfishes (Corydoradinae) with extreme variation in genome size-0...
February 14, 2018: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/29444910/the-neuroendocrine-phenotype-genomic-profile-and-therapeutic-sensitivity-of-gepnet-cell-lines
#9
Tobias Hofving, Yvonne Arvidsson, Bilal Almobarak, Linda Inge, Roswitha Pfragner, Marta Persson, Göran Stenman, Erik Kristiansson, Viktor Johanson, Ola Nilsson
Experimental models of neuroendocrine tumour disease are scarce, and no comprehensive characterisation of existing gastroenteropancreatic neuroendocrine tumour (GEPNET) cell lines has been reported. In this study, we aimed to define the molecular characteristics and therapeutic sensitivity of these cell lines. We therefore performed immunophenotyping, copy number profiling, whole-exome sequencing and a large-scale inhibitor screening of seven GEPNET cell lines. Four cell lines, GOT1, P-STS, BON-1 and QGP-1, displayed a neuroendocrine phenotype while three others, KRJ-I, L-STS and H-STS, did not...
March 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29444634/evaluation-of-reaction-gap-filling-accuracy-by-randomization
#10
Mario Latendresse, Peter D Karp
BACKGROUND: Completion of genome-scale flux-balance models using computational reaction gap-filling is a widely used approach, but its accuracy is not well known. RESULTS: We report on computational experiments of reaction gap filling in which we generated degraded versions of the EcoCyc-20.0-GEM model by randomly removing flux-carrying reactions from a growing model. We gap-filled the degraded models and compared the resulting gap-filled models with the original model...
February 14, 2018: BMC Bioinformatics
https://www.readbyqxmd.com/read/29444205/ssbio-a-python-framework-for-structural-systems-biology
#11
Nathan Mih, Elizabeth Brunk, Ke Chen, Edward Catoiu, Anand Sastry, Erol Kavvas, Jonathan M Monk, Zhen Zhang, Bernhard O Palsson, Alfonso Valencia
Summary: Working with protein structures at the genome-scale has been challenging in a variety of ways. Here, we present ssbio, a Python package that provides a framework to easily work with structural information in the context of genome-scale network reconstructions, which can contain thousands of individual proteins. The ssbio package provides an automated pipeline to construct high quality genomescale models with protein structures (GEM-PROs), wrappers to popular third-party programs to compute associated protein properties, and methods to visualize and annotate structures directly in Jupyter notebooks, thus lowering the barrier of linking 3D structural data with established systems workflows...
February 12, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29435254/multiscale-landscape-genomic-models-to-detect-signatures-of-selection-in-the-alpine-plant-biscutella-laevigata
#12
Kevin Leempoel, Christian Parisod, Céline Geiser, Stéphane Joost
Plant species are known to adapt locally to their environment, particularly in mountainous areas where conditions can vary drastically over short distances. The climate of such landscapes being largely influenced by topography, using fine-scale models to evaluate environmental heterogeneity may help detecting adaptation to micro-habitats. Here, we applied a multiscale landscape genomic approach to detect evidence of local adaptation in the alpine plant Biscutella laevigata. The two gene pools identified, experiencing limited gene flow along a 1-km ridge, were different in regard to several habitat features derived from a very high resolution (VHR) digital elevation model (DEM)...
February 2018: Ecology and Evolution
https://www.readbyqxmd.com/read/29434275/quantification-of-glioblastoma-mass-effect-by-lateral-ventricle-displacement
#13
Tyler C Steed, Jeffrey M Treiber, Michael G Brandel, Kunal S Patel, Anders M Dale, Bob S Carter, Clark C Chen
Mass effect has demonstrated prognostic significance for glioblastoma, but is poorly quantified. Here we define and characterize a novel neuroimaging parameter, lateral ventricle displacement (LVd), which quantifies mass effect in glioblastoma patients. LVd is defined as the magnitude of displacement from the center of mass of the lateral ventricle volume in glioblastoma patients relative to that a normal reference brain. Pre-operative MR images from 214 glioblastoma patients from The Cancer Imaging Archive (TCIA) were segmented using iterative probabilistic voxel labeling (IPVL)...
February 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29429966/transformation-of-summary-statistics-from-linear-mixed-model-association-on-all-or-none-traits-to-odds-ratio
#14
Luke R Lloyd-Jones, Matthew R Robinson, Jian Yang, Peter M Visscher
Genome-wide association studies (GWAS) have identified thousands of loci that are robustly associated with complex diseases. The use of linear mixed model (LMM) methodology for GWAS is becoming more prevalent due to its ability to control for population structure and cryptic relatedness and increase power. The odds ratio (OR) is a common measure of the association of a disease with an exposure (e.g., a genetic variant) and is readably available from logistic regression. However, when the LMM is applied to all-or-none traits it provides estimates of genetic effects on the observed 0-1 scale, a different scale to that in logistic regression...
February 2, 2018: Genetics
https://www.readbyqxmd.com/read/29427605/a-mathematical-framework-for-yield-versus-rate-optimization-in-constraint-based-modeling-and-applications-in-metabolic-engineering
#15
Steffen Klamt, Stefan Müller, Georg Regensburger, Jürgen Zanghellini
BACKGROUND: The optimization of metabolic rates (as linear objective functions) represents the methodical core of flux-balance analysis techniques which have become a standard tool for the study of genome-scale metabolic models. Besides (growth and synthesis) rates, metabolic yields are key parameters for the characterization of biochemical transformation processes, especially in the context of biotechnological applications. However, yields are ratios of rates, and hence the optimization of yields (as nonlinear objective functions) under arbitrary linear constraints is not possible with current flux-balance analysis techniques...
February 7, 2018: Metabolic Engineering
https://www.readbyqxmd.com/read/29425498/hybridization-kinetics-explains-crispr-cas-off-targeting-rules
#16
Misha Klein, Behrouz Eslami-Mossallam, Dylan Gonzalez Arroyo, Martin Depken
Due to their specificity, efficiency, and ease of programming, CRISPR-associated nucleases are popular tools for genome editing. On the genomic scale, these nucleases still show considerable off-target activity though, posing a serious obstacle to the development of therapies. Off targeting is often minimized by choosing especially high-specificity guide sequences, based on algorithms that codify empirically determined off-targeting rules. A lack of mechanistic understanding of these rules has so far necessitated their ad hoc implementation, likely contributing to the limited precision of present algorithms...
February 6, 2018: Cell Reports
https://www.readbyqxmd.com/read/29424663/a-large-scale-mutational-analysis-of-two-component-signaling-systems-of-lonsdalea-quercina-revealed-that-kdpd-kdpe-regulates-bacterial-virulence-against-host-poplar-trees
#17
Ruo-Lan Yang, Chao-Ying Deng, Jin-Wei Wei, Wei He, Ai-Ning Li, Wei Qian
Poplar, which is a dominant species in plant communities distributed in the northern hemisphere, is commonly used as a model plant in forestry studies. Poplar production can be inhibited by infections caused by bacteria, including Lonsdalea quercina subsp. populi, which is a Gram-negative bacterium responsible for bark canker disease. However, the molecular basis of the pathogenesis remains uncharacterized. In this study, we annotated the two-component signal transduction systems (TCSs) encoded by the L. quercina subsp...
February 9, 2018: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/29423846/molecular-cloning-and-characterization-of-small-viral-genome-in-fission-yeast
#18
Ge Li, Richard Y Zhao
Fission yeast is a single-cell eukaryote that has been used extensively as a model organism to study cell biology and virology of higher eukaryotes including plants and humans. In particular, it is a very well-tested model to study evolutionary highly conserved cellular activities such as cell proliferation, cell cycle regulation, and cell death. Some of the advantages of using fission yeast as a surrogate system: easy to carry out functional and genome-wide analysis of small viral genome, easy to maintain in the laboratory with a relatively short doubling time...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29420686/marginal-false-discovery-rates-for-penalized-regression-models
#19
Patrick J Breheny
Penalized regression methods are an attractive tool for high-dimensional data analysis, but their widespread adoption has been hampered by the difficulty of applying inferential tools. In particular, the question "How reliable is the selection of those features?" has proved difficult to address. In part, this difficulty arises from defining false discoveries in the classical, fully conditional sense, which is possible in low dimensions but does not scale well to high-dimensional settings. Here, we consider the analysis of marginal false discovery rates (mFDRs) for penalized regression methods...
February 6, 2018: Biostatistics
https://www.readbyqxmd.com/read/29419727/identification-of-differentially-methylated-sites-with-weak-methylation-effects
#20
Hong Tran, Hongxiao Zhu, Xiaowei Wu, Gunjune Kim, Christopher R Clarke, Hailey Larose, David C Haak, Shawn D Askew, Jacob N Barney, James H Westwood, Liqing Zhang
Deoxyribonucleic acid (DNA) methylation is an epigenetic alteration crucial for regulating stress responses. Identifying large-scale DNA methylation at single nucleotide resolution is made possible by whole genome bisulfite sequencing. An essential task following the generation of bisulfite sequencing data is to detect differentially methylated cytosines (DMCs) among treatments. Most statistical methods for DMC detection do not consider the dependency of methylation patterns across the genome, thus possibly inflating type I error...
February 8, 2018: Genes
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