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genome scale model

Julia Engelhorn, Frank Wellmer, Cristel C Carles
Covalent histone modifications and their effects on chromatin state and accessibility play a key role in the regulation of gene expression in eukaryotes. To gain insights into their functions during plant growth and development, the distribution of histone modifications can be analyzed at a genome-wide scale through chromatin immunoprecipitation assays followed by sequencing of the isolated genomic DNA. Here, we present a protocol for systematic analysis of the distribution and dynamic changes of selected histone modifications, during flower development in the model plant Arabidopsis thaliana...
2018: Methods in Molecular Biology
Amanda J Lea, Tauras P Vilgalys, Paul A P Durst, Jenny Tung
Genome-scale bisulfite sequencing approaches have opened the door to ecological and evolutionary studies of DNA methylation in many organisms. These approaches can be powerful. However, they introduce new methodological and statistical considerations, some of which are particularly relevant to non-model systems. Here, we highlight how these considerations influence a study's power to link methylation variation with a predictor variable of interest. Relative to current practice, we argue that sample sizes will need to increase to provide robust insights...
August 2017: Nature ecology & evolution
Christian Rödelsperger, Jan M Meyer, Neel Prabh, Christa Lanz, Felix Bemm, Ralf J Sommer
The nematode Pristionchus pacificus is an established model for integrative evolutionary biology and comparative studies with Caenorhabditis elegans. While an existing genome draft facilitated the identification of several genes controlling various developmental processes, its high degree of fragmentation complicated virtually all genomic analyses. Here, we present a de novo genome assembly from single-molecule, long-read sequencing data consisting of 135 P. pacificus contigs. When combined with a genetic linkage map, 99% of the assembly could be ordered and oriented into six chromosomes...
October 17, 2017: Cell Reports
Eva-Maria Holstein, Conor Lawless, Peter Banks, David Lydall
We provide a detailed protocol for robot-assisted, genome-wide measurement of fitness in the model yeast Saccharomyces cerevisiae using Quantitative Fitness Analysis (QFA). We first describe how we construct thousands of double or triple mutant yeast strains in parallel using Synthetic Genetic Array (SGA) procedures. Strains are inoculated onto solid agar surfaces by liquid spotting followed by repeated photography of agar plates. Growth curves are constructed and the fitness of each strain is estimated. Robot-assisted QFA, can be used to identify genetic interactions and chemical sensitivity/resistance in genome-wide experiments, but QFA can also be used in smaller scale, manual workflows...
2018: Methods in Molecular Biology
Jiang Shu, Bruno Vieira Resende E Silva, Tian Gao, Zheng Xu, Juan Cui
MicroRNA is responsible for the fine-tuning of fundamental cellular activities and human disease development. The altered availability of microRNAs, target mRNAs, and other types of endogenous RNAs competing for microRNA interactions reflects the dynamic and conditional property of microRNA-mediated gene regulation that remains under-investigated. Here we propose a new integrative method to study this dynamic process by considering both competing and cooperative mechanisms and identifying functional modules where different microRNAs co-regulate the same functional process...
October 17, 2017: Scientific Reports
David Gilbert, Monika Heiner, Yasoda Jayaweera, Christian Rohr
The analysis of the dynamic behaviour of genome-scale models of metabolism (GEMs) currently presents considerable challenges because of the difficulties of simulating such large and complex networks. Bacterial GEMs can comprise about 5000 reactions and metabolites, and encode a huge variety of growth conditions; such models cannot be used without sophisticated tool support. This article is intended to aid modellers, both specialist and non-specialist in computerized methods, to identify and apply a suitable combination of tools for the dynamic behaviour analysis of large-scale metabolic designs...
October 13, 2017: Briefings in Bioinformatics
Sonia Irigoyen, Renesh H Bedre, Karen-Beth G Scholthof, Kranthi K Mandadi
Alternative splicing (AS) promotes transcriptome and proteome diversity in plants, which influences growth and development, and host responses to stress. Advancements in next-generation sequencing, bioinformatics, and computational biology tools have allowed biologists to investigate AS landscapes on a genome-wide scale in several plant species. Furthermore, the development of Brachypodium distachyon (Brachypodium) as a model system for grasses has facilitated comparative studies of AS within the Poaceae. These analyses revealed a plethora of genes in several biological processes that are alternatively spliced and identified conserved AS patterns among monocot and dicot plants...
2018: Methods in Molecular Biology
Julie Laniau, Clémence Frioux, Jacques Nicolas, Caroline Baroukh, Maria-Paz Cortes, Jeanne Got, Camille Trottier, Damien Eveillard, Anne Siegel
BACKGROUND: The emergence of functions in biological systems is a long-standing issue that can now be addressed at the cell level with the emergence of high throughput technologies for genome sequencing and phenotyping. The reconstruction of complete metabolic networks for various organisms is a key outcome of the analysis of these data, giving access to a global view of cell functioning. The analysis of metabolic networks may be carried out by simply considering the architecture of the reaction network or by taking into account the stoichiometry of reactions...
2017: PeerJ
Christina Lehermeier, Simon Teyssèdre, Chris-Carolin Schön
A crucial step in plant breeding is the selection and combination of parents to form new crosses. Genome-based prediction guides the selection of high-performing parental lines in many crop breeding programs which ensures a high mean performance of progeny. To warrant maximum selection progress, a new cross should also provide a large progeny variance. The usefulness concept as measure of the gain that can be obtained from a specific cross accounts for variation in progeny variance. Here, it is shown that genetic gain can be considerably increased when crosses are selected based on their genomic usefulness criterion compared to selection based on mean genomic estimated breeding values...
October 16, 2017: Genetics
Matthias Hoetzinger, Martin W Hahn
BACKGROUND: In many prokaryotic genera a clustered phylogeny is observed, akin to the occurrence of species in sexually reproducing organisms. For some taxa, homologous recombination has been invoked as the underlying mechanism providing genomic cohesion among conspecific individuals. Whether this mechanism is applicable to prokaryotes in freshwaters with low habitat connectivity - i.e. elevated geographic barriers to gene flow - is unclear. To investigate further we studied genomic trends within the globally abundant PnecC cluster (genus Polynucleobacter, Betaproteobacteria) and analyzed homologous recombination within the affiliated species P...
October 16, 2017: BMC Genomics
Siu H J Chan, Jingyi Cai, Lin Wang, Margaret N Simons-Senftle, Costas D Maranas
Motivation: In a genome-scale metabolic model, the biomass produced is defined to have a molecular weight (MW) of 1 g mmol -1 . This is critical for correctly predicting growth yields, contrasting multiple models and more importantly modeling microbial communities. However, the standard is rarely verified in the current practice and the chemical formulae of biomass components such as proteins, nucleic acids and lipids are often represented by undefined side groups (e.g. X, R). Results: We introduced a systematic procedure for checking the biomass weight and ensuring complete mass balance of a model...
July 14, 2017: Bioinformatics
Charles S P Foster, Simon Y W Ho
Evolutionary timescales can be inferred from molecular sequence data using a Bayesian phylogenetic approach. In these methods, the molecular clock is often calibrated using fossil data. The uncertainty in these fossil calibrations is important because it determines the limiting posterior distribution for divergence-time estimates as the sequence length tends to infinity. Here we investigate how the accuracy and precision of Bayesian divergence-time estimates improve with the increased clock-partitioning of genome-scale data into clock-subsets...
September 25, 2017: Genome Biology and Evolution
Lucia Grenga, Govind Chandra, Gerhard Saalbach, Carla V Galmozzi, Günter Kramer, Jacob G Malone
The ability of bacteria to respond to environmental change is based on the ability to coordinate, redirect and fine-tune their genetic repertoire as and when required. While we can learn a great deal from reductive analysis of individual pathways and global approaches to gene regulation, a deeper understanding of these complex signaling networks requires the simultaneous consideration of several regulatory layers at the genome scale. To highlight the power of this approach we analyzed the Hfq transcriptional/translational regulatory network in the model bacterium Pseudomonas fluorescens...
2017: Frontiers in Microbiology
Yun Heacock-Kang, Zhenxin Sun, Jan Zarzycki-Siek, Ian A McMillan, Michael H Norris, Andrew P Bluhm, Darlene Cabanas, Dawson Fogen, Hung Vo, Stuart P Donachie, Bradley R Borlee, Christopher D Sibley, Shawn Lewenza, Michael J Schurr, Herbert P Schweizer, Tung T Hoang
Bacterial cooperative associations and dynamics in the biofilm microenvironments are of special interest in recent years. Knowledge of localized gene-expression and corresponding bacterial behaviors within the biofilm architecture at a global scale has been limited, due to a lack of robust technology to study limited number of cells in stratified layers of biofilms. With our recent pioneering developments in single bacterial cell transcriptomic analysis technology, we generated herein an unprecedented spatial transcriptome map of the mature in vitro Pseudomonas aeruginosa biofilm model, revealing contemporaneous yet altered bacterial behaviors at different layers within the biofilm architecture (i...
October 14, 2017: Molecular Microbiology
Jack Kuipers, Katharina Jahn, Benjamin J Raphael, Niko Beerenwinkel
Intra-tumor heterogeneity poses substantial challenges for cancer treatment. A tumor's composition can be deduced by reconstructing its mutational history. Central to current approaches is the infinite sites assumption that every genomic position can only mutate once over the lifetime of a tumor. The validity of this assumption has never been quantitatively assessed. We developed a rigorous statistical framework to test the infinite sites assumption with single-cell sequencing data. Our framework accounts for the high noise and contamination present in such data...
October 13, 2017: Genome Research
Jiayi Sun, James G Jeffryes, Christopher S Henry, Steven D Bruner, Andrew D Hanson
The necessarily sharp focus of metabolic engineering and metabolic synthetic biology on pathways and their fluxes has tended to divert attention from the damaging enzymatic and chemical side-reactions that pathway metabolites can undergo. Although historically overlooked and underappreciated, such metabolite damage reactions are now known to occur throughout metabolism and to generate (formerly enigmatic) peaks detected in metabolomics datasets. It is also now known that metabolite damage is often countered by dedicated repair enzymes that undo or prevent it...
October 10, 2017: Metabolic Engineering
Konstantinos Angelis, Sandra Álvarez-Carretero, Mario Dos Reis, Ziheng Yang
The explosive growth of molecular sequence data has made it possible to estimate species divergence times under relaxed-clock models using genome-scale data sets with many gene loci. In order to improve both model realism and to best extract information about relative divergence times in the sequence data, it is important to account for the heterogeneity in the evolutionary process across genes or genomic regions. Partitioning is a commonly used approach to achieve those goals. We group sites that have similar evolutionary characteristics into the same partition and those with different characteristics into different partitions, and then use different models or different values of model parameters for different partitions to account for the among-partition heterogeneity...
July 4, 2017: Systematic Biology
David A Duchêne, Jason G Bragg, Sebastián Duchêne, Linda E Neaves, Sally Potter, Craig Moritz, Rebecca N Johnson, Simon Y W Ho, Mark D B Eldridge
A fundamental challenge in resolving evolutionary relationships across the Tree of Life is to account for heterogeneity in the evolutionary signal across loci. Studies of marsupial mammals have demonstrated that this heterogeneity can be substantial, leaving considerable uncertainty in the evolutionary timescale and relationships within the group. Using simulations and a new phylogenomic data set comprising nucleotide sequences of 1550 loci from 18 of the 22 extant marsupial families, we demonstrate the power of a method for identifying clusters of loci that support different phylogenetic trees...
September 22, 2017: Systematic Biology
Ksenia Arkhipova, Timofey Skvortsov, John P Quinn, John W McGrath, Christopher Cr Allen, Bas E Dutilh, Yvonne McElarney, Leonid A Kulakov
Recent work has vastly expanded the known viral genomic sequence space, but the seasonal dynamics of viral populations at the genome level remain unexplored. Here we followed the viral community in a freshwater lake for 1 year using genome-resolved viral metagenomics, combined with detailed analyses of the viral community structure, associated bacterial populations and environmental variables. We reconstructed 8950 complete and partial viral genomes, the majority of which were not persistent in the lake throughout the year, but instead continuously succeeded each other...
October 13, 2017: ISME Journal
Shenqi Wang, On Sun Lau
In multicellular organisms, the initiation and maintenance of specific cell types often require the activity of cell type-specific transcriptional regulators. Understanding their roles in gene regulation is crucial but probing their DNA targets in vivo, especially in a genome-wide manner, remains a technical challenge with their limited expression. To improve the sensitivity of chromatin immunoprecipitation (ChIP) for detecting the cell type-specific signals, we have developed the Maximized Objects for Better Enrichment (MOBE)-ChIP, where ChIP is performed at a substantially larger experimental scale and under low background conditions...
2018: Methods in Molecular Biology
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