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Combinatorial genomics

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https://www.readbyqxmd.com/read/28332231/development-of-humanized-mice-in-the-age-of-genome-editing
#1
Vishnu Hosur, Benjamin E Low, Cindy Avery, Leonard D Shultz, Michael V Wiles
Mice are the most commonly used model organisms to study human disease. Many genetic human diseases can be recapitulated by modifying the mouse genome, which permits testing of existing and novel therapeutics, including combinatorial therapeutics, without putting humans at risk. Specifically, the development of "humanized" mice, i.e., severely immunodeficient mice engrafted with functional human hematopoietic and immune cells and tissues, has revolutionized our ability to study and model human diseases in preclinical in vivo systems...
March 22, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28328998/combinatorial-selection-for-replicable-rna-by-q%C3%AE-replicase-while-maintaining-encoded-gene-function
#2
Mio Yumura, Natsuko Yamamoto, Katsushi Yokoyama, Hirotada Mori, Tetsuya Yomo, Norikazu Ichihashi
Construction of a complex artificial self-replication system is challenging in the field of in vitro synthetic biology. Recently, we developed a translation-coupled RNA replication system, wherein an artificial genomic RNA replicates with the Qβ RNA replicase gene encoded on itself. The challenge is to introduce additional genes into the RNA to develop a complex system that mimics natural living systems. However, most RNA sequence encoding genes are not replicable by the Qβ replicase owing to its requirement for strong secondary structures throughout the RNA sequence that are absent in most genes...
2017: PloS One
https://www.readbyqxmd.com/read/28327091/knn-mdr-a-learning-approach-for-improving-interactions-mapping-performances-in-genome-wide-association-studies
#3
Sinan Abo Alchamlat, Frédéric Farnir
BACKGROUND: Finding epistatic interactions in large association studies like genome-wide association studies (GWAS) with the nowadays-available large volume of genomic data is a challenging and largely unsolved issue. Few previous studies could handle genome-wide data due to the intractable difficulties met in searching a combinatorial explosive search space and statistically evaluating epistatic interactions given a limited number of samples. Our work is a contribution to this field...
March 21, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28299656/roles-of-the-runx1-enhancer-in-normal-hematopoiesis-and-leukemogenesis
#4
Wei-Siang Liau, Phuong Cao Thi Ngoc, Takaomi Sanda
Enhancers are regulatory elements in genomic DNA that contain specific sequence motifs that are bound by DNA-binding transcription factors. The activity of enhancers is tightly regulated in an integrated and combinatorial manner, thus yielding complex patterns of transcription in different tissues. Identifying enhancers is crucial to understanding the physiological and pathogenic roles of their target genes. The RUNX1 intronic enhancer, eR1, acts in cis to regulate RUNX1 gene expression in hematopoietic stem cells (HSCs) and hemogenic endothelial cells...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28299197/new-insights-into-bacterial-type-ii-polyketide-biosynthesis
#5
REVIEW
Zhuan Zhang, Hai-Xue Pan, Gong-Li Tang
Bacterial aromatic polyketides, exemplified by anthracyclines, angucyclines, tetracyclines, and pentangular polyphenols, are a large family of natural products with diverse structures and biological activities and are usually biosynthesized by type II polyketide synthases (PKSs). Since the starting point of biosynthesis and combinatorial biosynthesis in 1984-1985, there has been a continuous effort to investigate the biosynthetic logic of aromatic polyketides owing to the urgent need of developing promising therapeutic candidates from these compounds...
2017: F1000Research
https://www.readbyqxmd.com/read/28298224/transcriptional-reprogramming-in-yeast-using-dcas9-and-combinatorial-grna-strategies
#6
Emil D Jensen, Raphael Ferreira, Tadas Jakočiūnas, Dushica Arsovska, Jie Zhang, Ling Ding, Justin D Smith, Florian David, Jens Nielsen, Michael K Jensen, Jay D Keasling
BACKGROUND: Transcriptional reprogramming is a fundamental process of living cells in order to adapt to environmental and endogenous cues. In order to allow flexible and timely control over gene expression without the interference of native gene expression machinery, a large number of studies have focused on developing synthetic biology tools for orthogonal control of transcription. Most recently, the nuclease-deficient Cas9 (dCas9) has emerged as a flexible tool for controlling activation and repression of target genes, by the simple RNA-guided positioning of dCas9 in the vicinity of the target gene transcription start site...
March 15, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28287094/enlightening-discriminative-network-functional-modules-behind-principal-component-analysis-separation-in-differential-omic-science-studies
#7
Sara Ciucci, Yan Ge, Claudio Durán, Alessandra Palladini, Víctor Jiménez-Jiménez, Luisa María Martínez-Sánchez, Yuting Wang, Susanne Sales, Andrej Shevchenko, Steven W Poser, Maik Herbig, Oliver Otto, Andreas Androutsellis-Theotokis, Jochen Guck, Mathias J Gerl, Carlo Vittorio Cannistraci
Omic science is rapidly growing and one of the most employed techniques to explore differential patterns in omic datasets is principal component analysis (PCA). However, a method to enlighten the network of omic features that mostly contribute to the sample separation obtained by PCA is missing. An alternative is to build correlation networks between univariately-selected significant omic features, but this neglects the multivariate unsupervised feature compression responsible for the PCA sample segregation...
March 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28282941/conservation-of-the-keap1-nrf2-system-an-evolutionary-journey-through-stressful-space-and-time
#8
REVIEW
Yuji Fuse, Makoto Kobayashi
The Keap1-Nrf2 system is an evolutionarily conserved defense mechanism against oxidative and xenobiotic stress. Its regulatory mechanisms, e.g., stress-sensing mechanism, proteasome-based regulation of Nrf2 activity and selection of target genes, have been elucidated mainly in mammals. In addition, emerging model animals, such as zebrafish, fruit fly and Caenorhabditis elegans, have been shown to have similar anti-stress systems to mammals, suggesting that analogous defense systems are widely conserved throughout the animal kingdom...
March 9, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28267569/the-challenge-of-detecting-indels-in-bacterial-genomes-from-short-read-sequencing-data
#9
Matthias Steglich, Ulrich Nübel
We tested the capabilities of four different software tools to detect insertions and deletions (indels) in a bacterial genome on the basis of short sequencing reads. We included tools applying the gapped-alignment (VarScan, FreeBayes) or split-read (Pindel) methods, respectively, and a combinatorial approach with local de-novo assembly (ScanIndel). Tests were performed with 151-basepair, paired-end sequencing reads simulated from a bacterial (Clostridioides difficile R20291) genome sequence with predefined indels (indel length, 1-2321bp)...
March 4, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28260195/nature-s-combinatorial-biosynthesis-and-recently-engineered-production-of-nucleoside-antibiotics-in-streptomyces
#10
REVIEW
Shawn Chen, William A Kinney, Steven Van Lanen
Modified nucleosides produced by Streptomyces and related actinomycetes are widely used in agriculture and medicine as antibacterial, antifungal, anticancer and antiviral agents. These specialized small-molecule metabolites are biosynthesized by complex enzymatic machineries encoded within gene clusters in the genome. The past decade has witnessed a burst of reports defining the key metabolic processes involved in the biosynthesis of several distinct families of nucleoside antibiotics. Furthermore, genome sequencing of various Streptomyces species has dramatically increased over recent years...
April 2017: World Journal of Microbiology & Biotechnology
https://www.readbyqxmd.com/read/28250805/playing-hide-and-seek-with-repeats-in-local-and-global-de-novo-transcriptome-assembly-of-short-rna-seq-reads
#11
Leandro Lima, Blerina Sinaimeri, Gustavo Sacomoto, Helene Lopez-Maestre, Camille Marchet, Vincent Miele, Marie-France Sagot, Vincent Lacroix
BACKGROUND: The main challenge in de novo genome assembly of DNA-seq data is certainly to deal with repeats that are longer than the reads. In de novo transcriptome assembly of RNA-seq reads, on the other hand, this problem has been underestimated so far. Even though we have fewer and shorter repeated sequences in transcriptomics, they do create ambiguities and confuse assemblers if not addressed properly. Most transcriptome assemblers of short reads are based on de Bruijn graphs (DBG) and have no clear and explicit model for repeats in RNA-seq data, relying instead on heuristics to deal with them...
2017: Algorithms for Molecular Biology: AMB
https://www.readbyqxmd.com/read/28249909/morphoproteomics-identifies-sirt1-and-ezh2-pathways-as-commonalities-in-b-cell-acute-lymphoblastic-leukemia-pathogenetic-implications-and-opportunities-for-therapeutic-intervention
#12
Robert E Brown, Kristine E Konopka, Priya Weerasinghe, Vanya Jaitly, Amitava Dasgupta, Mary F McGuire, Nghia D Nguyen
B-cell acute lymphoblastic leukemia (ALL) represents a malignant process in which bone marrow-derived lymphoblasts retain their undifferentiated state. Genetic testing has revealed either no identifiable cytogenetic and genomic abnormalities in such patients or a wide range of aberrations that may or may not contribute to the block in differentiation and the associated proliferation of the malignant lymphoblasts in cases of B-cell ALL. In this study, we applied morphoproteomics to a representative spectrum of cases of newly diagnosed B-cell ALL in order to identify pathways that are known to be associated with the maintenance of the undifferentiated state while promoting proliferation...
January 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/28246379/the-antibiotic-resistance-crisis-with-a-focus-on-the-united-states
#13
REVIEW
Evan Martens, Arnold L Demain
Beginning with the discovery of penicillin by Alexander Fleming in the late 1920s, antibiotics have revolutionized the field of medicine. They have saved millions of lives each year, alleviated pain and suffering, and have even been used prophylactically for the prevention of infectious diseases. However, we have now reached a crisis where many antibiotics are no longer effective against even the simplest infections. Such infections often result in an increased number of hospitalizations, more treatment failures and the persistence of drug-resistant pathogens...
March 1, 2017: Journal of Antibiotics
https://www.readbyqxmd.com/read/28242493/c-elegans-as-a-model-system-to-accelerate-discovery-for-parkinson-disease
#14
REVIEW
Bryan A Martinez, Kim A Caldwell, Guy A Caldwell
The nematode Caenorhabditis elegans possesses a wealth of opportunities to explore mechanisms which regulate metazoan complexity, basic cellular biology, and neuronal system attributes. Together, these provide a basis for tenable understanding of neurodegenerative disorders such as Parkinson disease (PD) through functional genomic analysis and pharmacological manipulation for the discovery of previously unknown genetic and environmental risk factors. The application of C. elegans has proven prescient in terms of the elucidation of functional effectors of cellular mechanisms underlying PD that translate to mammals...
February 24, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28237795/iterative-modeling-reveals-evidence-of-sequential-transcriptional-control-mechanisms
#15
Christine S Cheng, Marcelo S Behar, Gajendra W Suryawanshi, Kristyn E Feldman, Roberto Spreafico, Alexander Hoffmann
Combinatorial control of gene expression is presumed to be mediated by molecular interactions between coincident transcription factors (TFs). While information on the genome-wide locations of TFs is available, the genes they regulate and whether they function combinatorially often remain open questions. Here, we developed a mechanistic, rather than statistical, modeling approach to elucidate TF control logic from gene expression data. Applying this approach to hundreds of genes in 85 datasets measuring the transcriptional responses of murine fibroblasts and macrophages to cytokines and pathogens, we found that stimulus-responsive TFs generally function sequentially in logical OR gates or singly...
March 22, 2017: Cell Systems
https://www.readbyqxmd.com/read/28221768/formation-of-nitrogenase-nifdk-tetramers-in-the-mitochondria-of-saccharomyces-cerevisiae
#16
Stefan Burén, Eric M Young, Elizabeth A Sweeny, Gema López-Torrejón, Marcel Veldhuizen, Christopher A Voigt, Luis M Rubio
Transferring the prokaryotic enzyme nitrogenase into a eukaryotic host with the final aim of developing N2 fixing cereal crops would revolutionize agricultural systems worldwide. Targeting it to mitochondria has potential advantages because of the organelle's high O2 consumption and the presence of bacterial-type iron-sulfur cluster biosynthetic machinery. In this study, we constructed 96 strains of Saccharomyces cerevisiae where transcriptional units comprising nine Azotobacter vinelandii nif genes (nifHDKUSMBEN) were integrated into the genome...
February 21, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28219948/genomic-integration-of-wnt-%C3%AE-catenin-and-bmp-smad1-signaling-coordinates-foregut-and-hindgut-transcriptional-program
#17
Mariana L Stevens, Praneet Chaturvedi, Scott A Rankin, Melissa Macdonald, Sajjeev Jagannathan, Masashi Yukawa, Artem Barski, Aaron M Zorn
Digestive system development is orchestrated by combinatorial signaling interactions between endoderm and mesoderm, but how these signals are integrated in the genome is poorly understood. Here we identified the transcriptomes of Xenopus foregut and hindgut progenitors, which are conserved with mammals. Using RNA-seq and ChIP-seq we show that BMP/Smad1 regulates dorsal-ventral gene expression in both the endoderm and mesoderm, whereas Wnt/β-catenin acts as a genome-wide toggle between foregut and hindgut programs...
February 20, 2017: Development
https://www.readbyqxmd.com/read/28217858/golden-gate-assembly-system-dedicated-to-complex-pathway-manipulation-in-yarrowia-lipolytica
#18
Ewelina Celińska, Rodrigo Ledesma-Amaro, Macarena Larroude, Tristan Rossignol, Cyrille Pauthenier, Jean-Marc Nicaud
In this study, we have adopted Golden Gate modular cloning strategy to develop a robust and versatile DNA assembly platform for the nonconventional yeast Yarrowia lipolytica. To this end, a broad set of destination vectors and interchangeable building blocks have been constructed. The DNA modules were assembled on a scaffold of predesigned 4 nt overhangs covering three transcription units (each bearing promoter, gene and terminator), selection marker gene and genomic integration targeting sequences, constituting altogether thirteen elements...
March 2017: Microbial Biotechnology
https://www.readbyqxmd.com/read/28216108/crispr-enabled-trackable-genome-engineering-for-isopropanol-production-in-escherichia-coli
#19
Liya Liang, Rongming Liu, Andrew D Garst, Thomas Lee, Violeta Sànchez I Nogué, Gregg T Beckham, Ryan T Gill
Isopropanol is an important target molecule for sustainable production of fuels and chemicals. Increases in DNA synthesis and synthetic biology capabilities have resulted in the development of a range of new strategies for the more rapid design, construction, and testing of production strains. Here, we report on the use of such capabilities to construct and test 903 different variants of the isopropanol production pathway in Escherichia coli. We first constructed variants to explore the effect of codon optimization, copy number, and translation initiation rates on isopropanol production...
February 16, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28201946/sorting-permutations-by-prefix-and-suffix-rearrangements
#20
Carla Negri Lintzmayer, Guillaume Fertin, Zanoni Dias
Some interesting combinatorial problems have been motivated by genome rearrangements, which are mutations that affect large portions of a genome. When we represent genomes as permutations, the goal is to transform a given permutation into the identity permutation with the minimum number of rearrangements. When they affect segments from the beginning (respectively end) of the permutation, they are called prefix (respectively suffix) rearrangements. This paper presents results for rearrangement problems that involve prefix and suffix versions of reversals and transpositions considering unsigned and signed permutations...
February 2017: Journal of Bioinformatics and Computational Biology
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