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Combinatorial genomics

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https://www.readbyqxmd.com/read/28431213/genome-mining-unearths-a-hybrid-nonribosomal-peptide-synthetase-like-pteridine-synthase-biosynthetic-gene-cluster
#1
Hyun Bong Park, Corey E Perez, Karl W Barber, Jesse Rinehart, Jason M Crawford
Nonribosomal peptides represent a large class of metabolites with pharmaceutical relevance. Pteridines, such as pterins, folates, and flavins, are heterocyclic metabolites that often serve as redox-active cofactors. The biosynthetic machineries for construction of these distinct classes of small molecules operate independently in the cell. Here, we discovered an unprecedented nonribosomal peptide synthetase-like-pteridine synthase hybrid biosynthetic gene cluster in Photorhabdus luminescens using genome synteny analysis...
March 15, 2017: ELife
https://www.readbyqxmd.com/read/28411843/the-molecular-revolution-in-cutaneous-biology-emerging-landscape-in-genomic-dermatology-new-mechanistic-ideas-gene-editing-and-therapeutic-breakthroughs
#2
REVIEW
Matthias Titeux, Araksya Izmiryan, Alain Hovnanian
Stunning technological advances in genomics have led to spectacular breakthroughs in the understanding of the underlying defects, biological pathways and therapeutic targets of skin diseases leading to new therapeutic interventions. Next-generation sequencing has revolutionized the identification of disease-causing genes and has a profound impact in deciphering gene and protein signatures in rare and frequent skin diseases. Gene addition strategies have shown efficacy in junctional EB and in recessive dystrophic EB (RDEB)...
May 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28395144/landscape-of-histone-modifications-in-a-sponge-reveals-the-origin-of-animal-cis-regulatory-complexity
#3
Federico Gaiti, Katia Jindrich, Selene L Fernandez-Valverde, Kathrein E Roper, Bernard M Degnan, Miloš Tanurdžić
Combinatorial patterns of histone modifications regulate developmental and cell type-specific gene expression and underpin animal complexity, but it is unclear when this regulatory system evolved. By analysing histone modifications in a morphologically-simple, early branching animal, the sponge Amphimedon queenslandica, we show that the regulatory landscape used by complex bilaterians was already in place at the dawn of animal multicellularity. This includes distal enhancers, repressive chromatin and transcriptional units marked by H3K4me3 that vary with levels of developmental regulation...
April 11, 2017: ELife
https://www.readbyqxmd.com/read/28387573/metformin-inhibits-rankl-and-sensitizes-cancer-stem-cells-to-denosumab
#4
Elisabet Cuyàs, Begoña Martin-Castillo, Joaquim Bosch-Barrera, Javier A Menendez
The increased propensity of BRCA1 mutation carriers to develop aggressive breast tumors with stem-like properties begins to be understood in terms of osteoprotegerin (OPG)-unrestricted cross-talk between RANKL-overproducing progesterone-sensor cells and cancer-initiating RANK(+) responder cells that reside within pre-malignant BRCA1(mut/+) breast epithelial tissue. We recently proposed that, in the absence of hormone influence, cancer-initiating cells might remain responsive to RANKL stimulation, and hence to the therapeutic effects of the anti-RANKL antibody denosumab because genomic instability induced by BRCA1 haploinsufficiency might suffice to cell-autonomously hyperactivate RANKL gene expression...
April 7, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28381708/analysis-of-drug-resistance-using-experimental-evolution
#5
Chikara Furusawa
 The emergence of drug-resistant bacteria is a growing concern for global public health. One possible strategy to deal with the problem of resistant bacteria is to understand the dynamics of adaptive evolution under antibiotics and then develop methods to suppress such adaptive evolution. For this purpose, we performed experimental evolution of Escherichia coli under various antibiotics and obtained resistant strains. The phenotypic changes in these resistant strains were quantified by transcriptome analysis, and the genomic changes were analyzed using next-generation sequencers...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28377533/nonselective-bottlenecks-control-the-divergence-and-diversification-of-phase-variable-bacterial-populations
#6
Jack Aidley, Shweta Rajopadhye, Nwanekka M Akinyemi, Lea Lango-Scholey, Christopher D Bayliss
Phase variation occurs in many pathogenic and commensal bacteria and is a major generator of genetic variability. A putative advantage of phase variation is to counter reductions in variability imposed by nonselective bottlenecks during transmission. Genomes of Campylobacter jejuni, a widespread food-borne pathogen, contain multiple phase-variable loci whose rapid, stochastic variation is generated by hypermutable simple sequence repeat tracts. These loci can occupy a vast number of combinatorial expression states (phasotypes) enabling populations to rapidly access phenotypic diversity...
April 4, 2017: MBio
https://www.readbyqxmd.com/read/28377102/can-we-predict-gene-expression-by-understanding-proximal-promoter-architecture
#7
REVIEW
Łukasz Huminiecki, Jarosław Horbańczuk
We review computational predictions of expression from the promoter architecture - the set of transcription factors that can bind the proximal promoter. We focus on spatial expression patterns in animals with complex body plans and many distinct tissue types. This field is ripe for change as functional genomics datasets accumulate for both expression and protein-DNA interactions. While there has been some success in predicting the breadth of expression (i.e., the fraction of tissue types a gene is expressed in), predicting tissue specificity remains challenging...
April 1, 2017: Trends in Biotechnology
https://www.readbyqxmd.com/read/28373393/predictive-models-of-spatial-transcriptional-response-to-high-salinity
#8
Sahra Uygun, Alexander E Seddon, Christina B Azodi, Shin-Han Shiu
Plants are exposed to a variety of environmental conditions, and their ability to respond to environment variation depends on the proper regulation of gene expression in an organ, tissue, and cell type specific manner. Although our knowledge is accumulating on how stress responses are regulated, a genome-wide model of how plant transcription factors (TFs) and cis-regulatory elements (CREs) control spatially specific stress response has yet to emerge. Using Arabidopsis thaliana as a model, we identified a set of 1,894 putative CREs (pCREs) that are associated with high salinity (salt) up-regulated genes in the root or the shoot...
April 3, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28369193/sequential-computation-of-elementary-modes-and-minimal-cut-sets-in-genome-scale-metabolic-networks-using-alternate-integer-linear-programming
#9
Hyun-Seob Song, Noam Goldberg, Ashutosh Mahajan, Doraiswami Ramkrishna
Motivation: Elementary (flux) modes (EMs) have served as a valuable tool for investigating structural and functional properties of metabolic networks. Identification of the full set of EMs in genome-scale networks remains challenging due to combinatorial explosion of EMs in complex networks. It is often, however, that only a small subset of relevant EMs needs to be known, for which optimization-based sequential computation is a useful alternative. Most of the currently available methods along this line are based on the iterative use of mixed integer linear programming (MILP), the effectiveness of which significantly deteriorates as the number of iterations builds up...
March 27, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28361242/optimal-resource-allocation-enables-mathematical-exploration-of-microbial-metabolic-configurations
#10
Laurent Tournier, Anne Goelzer, Vincent Fromion
Central to the functioning of any living cell, the metabolic network is a complex network of biochemical reactions. It may also be viewed as an elaborate production system, integrating a diversity of internal and external signals in order to efficiently produce the energy and the biochemical precursors to ensure all cellular functions. Even in simple organisms like bacteria, it shows a striking level of coordination, adapting to very different growth media. Constraint-based models constitute an efficient mathematical framework to compute optimal metabolic configurations, at the scale of a whole genome...
March 30, 2017: Journal of Mathematical Biology
https://www.readbyqxmd.com/read/28361034/combinatorial-ranking-of-gene-sets-to-predict-disease-relapse-the-retinoic-acid-pathway-in-early-prostate-cancer
#11
Hieu T Nim, Milena B Furtado, Mirana Ramialison, Sarah E Boyd
BACKGROUND: Quantitative high-throughput data deposited in consortia such as International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) present opportunities and challenges for computational analyses. METHODS: We present a computational strategy to systematically rank and investigate a large number (2(10)-2(20)) of clinically testable gene sets, using combinatorial gene subset generation and disease-free survival (DFS) analyses. This approach integrates protein-protein interaction networks, gene expression, DNA methylation, and copy number data, in association with DFS profiles from patient clinical records...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28357345/what-s-old-is-new-again-yeast-mutant-screens-in-the-era-of-pooled-segregant-analysis-by-genome-sequencing
#12
EDITORIAL
Chris Curtin, Cordente Toni
While once de-rigueur for identification of genes involved in biological processes, screening of chemically induced mutant populations is an approach that has largely been superseded for model organisms such as Saccharomyces cerevisiae. Availability of single gene deletion/overexpression libraries and combinatorial synthetic genetic arrays provide yeast researchers more structured ways to probe genetic networks. Furthermore, in the age of inexpensive DNA sequencing, methodologies such as mapping of quantitative trait loci (QTL) by pooled segregant analysis and genome-wide association enable the identification of multiple naturally occurring allelic variants that contribute to polygenic phenotypes of interest...
April 4, 2016: Microbial Cell
https://www.readbyqxmd.com/read/28349863/structural-perspective-of-cooperative-transcription-factor-binding
#13
REVIEW
Ekaterina Morgunova, Jussi Taipale
In prokaryotes, individual transcription factors (TFs) can recognize long DNA motifs that are alone sufficient to define the genes that they induce or repress. In contrast, in higher organisms that have larger genomes, TFs recognize sequences that are too short to define unique genomic positions. In addition, development of multicellular organisms requires molecular systems that are capable of executing combinatorial logical operations. Co-operative recognition of DNA by multiple TFs allows both definition of unique genomic positions in large genomes, and complex information processing at the level of individual regulatory elements...
March 24, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28348165/combinatorial-dna-methylation-codes-at-repetitive-elements
#14
Christophe Papin, Abdulkhaleg Ibrahim, Stephanie Le Gras, Amandine Velt, Bernard Jost, Isabelle Stoll, Hervé Menoni, Christian Bronner, Stefan Dimitrov, Ali Hamiche
DNA methylation is an essential epigenetic modification, present in both unique DNA sequences and repetitive elements, but its exact function in repetitive elements remains obscure. Here, we describe the genome-wide comparative analysis of the 5mC, 5hmC, 5fC and 5caC profiles of repetitive elements in mouse embryonic fibroblasts and mouse embryonic stem cells. We provide evidence for distinct and highly specific DNA methylation/oxidation patterns of the repetitive elements in both cell types, which mainly affect CA repeats and evolutionary conserved mouse-specific transposable elements including IAP-LTRs, SINEs B1m/B2m and L1Md-LINEs...
March 27, 2017: Genome Research
https://www.readbyqxmd.com/read/28348045/stratification-of-pancreatic-ductal-adenocarcinoma-combinatorial-genetic-stromal-and-immunological-markers
#15
Erik Knudsen, Paris Vail, Uthra Balaji, Hoai Ngo, Ihab W Botros, Vladimir Makarov, Nadeem Riaz, Vinod P Balachandran, Steven D Leach, Debrah M Thompson, Timothy A Chan, Agnieszka K Witkiewicz
PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is associated with an immunosuppressive milieu that supports immune system evasion and disease progression. Here, we interrogated genetic, stromal, and immunological features of PDAC to delineate impact on prognosis and to more effectively employ immunotherapy. EXPERIMENTAL DESIGN: A cohort of 109 PDAC cases annotated for overall survival was utilized as a primary discovery cohort. Gene expression analysis defined immunological subtypes of PDAC that were confirmed in the Cancer Genome Atlas data set...
March 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28344190/an-artificial-intelligence-approach-fit-for-trna-gene-studies-in-the-era-of-big-sequence-data
#16
Yuki Iwasaki, Takashi Abe, Kennosuke Wada, Yoshiko Wada, Toshimichi Ikemura
Unsupervised data mining capable of extracting a wide range of knowledge from big data without prior knowledge or particular models is a timely application in the era of big sequence data accumulation in genome research. By handling oligonucleotide compositions as high-dimensional data, we have previously modified the conventional self-organizing map (SOM) for genome informatics and established BLSOM, which can analyze more than ten million sequences simultaneously. Here, we develop BLSOM specialized for tRNA genes (tDNAs) that can cluster (self-organize) more than one million microbial tDNAs according to their cognate amino acid solely depending on tetra- and pentanucleotide compositions...
March 24, 2017: Genes & Genetic Systems
https://www.readbyqxmd.com/read/28332231/development-of-humanized-mice-in-the-age-of-genome-editing
#17
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
#18
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
#19
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
#20
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
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