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Combinatorial genomics

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https://www.readbyqxmd.com/read/27924040/kdm2a-integrates-dna-and-histone-modification-signals-through-a-cxxc-phd-module-and-direct-interaction-with-hp1
#1
Julie Borgel, Marek Tyl, Karin Schiller, Zsofia Pusztai, Christopher M Dooley, Wen Deng, Carol Wooding, Richard J White, Tobias Warnecke, Heinrich Leonhardt, Elisabeth M Busch-Nentwich, Till Bartke
Functional genomic elements are marked by characteristic DNA and histone modification signatures. How combinatorial chromatin modification states are recognized by epigenetic reader proteins and how this is linked to their biological function is largely unknown. Here we provide a detailed molecular analysis of chromatin recognition by the lysine demethylase KDM2A. Using biochemical approaches we identify a nucleosome interaction module within KDM2A consisting of a CXXC type zinc finger, a PHD domain and a newly identified Heterochromatin Protein 1 (HP1) interaction motif that mediates direct binding between KDM2A and HP1...
October 24, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27921283/choices-have-consequences-the-nexus-between-dna-repair-pathways-and-genomic-instability-in-cancer
#2
REVIEW
Sonali Bhattacharjee, Saikat Nandi
BACKGROUND: The genome is under constant assault from a multitude of sources that can lead to the formation of DNA double-stand breaks (DSBs). DSBs are cytotoxic lesions, which if left unrepaired could lead to genomic instability, cancer and even cell death. However, erroneous repair of DSBs can lead to chromosomal rearrangements and loss of heterozygosity, which in turn can also cause cancer and cell death. Hence, although the repair of DSBs is crucial for the maintenance of genome integrity the process of repair need to be well regulated and closely monitored...
December 2016: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/27913828/engineering-and-evolution-of-saccharomyces-cerevisiae-to-produce-biofuels-and-chemicals
#3
Timothy L Turner, Heejin Kim, In Iok Kong, Jing-Jing Liu, Guo-Chang Zhang, Yong-Su Jin
To mitigate global climate change caused partly by the use of fossil fuels, the production of fuels and chemicals from renewable biomass has been attempted. The conversion of various sugars from renewable biomass into biofuels by engineered baker's yeast (Saccharomyces cerevisiae) is one major direction which has grown dramatically in recent years. As well as shifting away from fossil fuels, the production of commodity chemicals by engineered S. cerevisiae has also increased significantly. The traditional approaches of biochemical and metabolic engineering to develop economic bioconversion processes in laboratory and industrial settings have been accelerated by rapid advancements in the areas of yeast genomics, synthetic biology, and systems biology...
December 3, 2016: Advances in Biochemical Engineering/biotechnology
https://www.readbyqxmd.com/read/27911718/attacking-hiv-1-rna-versus-dna-by-sequence-specific-approaches-rnai-versus-crispr-cas
#4
REVIEW
Elena Herrera-Carrillo, Ben Berkhout
Human immunodeficiency virus type 1 (HIV-1) infection can be effectively controlled by potent antiviral drugs, but this never results in a cure. The patient should therefore take these drugs for the rest of his/her life, which can cause drug-resistance and adverse effects. Therefore, more durable therapeutic strategies should be considered, such as a stable gene therapy to protect the target T cells against HIV-1 infection. The development of potent therapeutic regimens based on the RNA interference (RNAi) and clustered regularly interspaced short palindromic repeats (CRISPR-Cas) mechanisms will be described, which can be delivered by lentiviral vectors...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27897178/functional-exploration-of-colorectal-cancer-genomes-using-drosophila
#5
Erdem Bangi, Claudio Murgia, Alexander G S Teague, Owen J Sansom, Ross L Cagan
The multigenic nature of human tumours presents a fundamental challenge for cancer drug discovery. Here we use Drosophila to generate 32 multigenic models of colon cancer using patient data from The Cancer Genome Atlas. These models recapitulate key features of human cancer, often as emergent properties of multigenic combinations. Multigenic models such as ras p53 pten apc exhibit emergent resistance to a panel of cancer-relevant drugs. Exploring one drug in detail, we identify a mechanism of resistance for the PI3K pathway inhibitor BEZ235...
November 29, 2016: Nature Communications
https://www.readbyqxmd.com/read/27895807/cpas-based-sequencing-on-the-bgiseq-500-to-explore-small-non-coding-rnas
#6
Tobias Fehlmann, Stefanie Reinheimer, Chunyu Geng, Xiaoshan Su, Snezana Drmanac, Andrei Alexeev, Chunyan Zhang, Christina Backes, Nicole Ludwig, Martin Hart, Dan An, Zhenzhen Zhu, Chongjun Xu, Ao Chen, Ming Ni, Jian Liu, Yuxiang Li, Matthew Poulter, Yongping Li, Cord Stähler, Radoje Drmanac, Xun Xu, Eckart Meese, Andreas Keller
BACKGROUND: We present the first sequencing data using the combinatorial probe-anchor synthesis (cPAS)-based BGISEQ-500 sequencer. Applying cPAS, we investigated the repertoire of human small non-coding RNAs and compared it to other techniques. RESULTS: Starting with repeated measurements of different specimens including solid tissues (brain and heart) and blood, we generated a median of 30.1 million reads per sample. 24.1 million mapped to the human genome and 23...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27893398/probabilistic-inference-on-multiple-normalized-genome-wide-signal-profiles-with-model-regularization
#7
Ka-Chun Wong, Chengbin Peng, Shankai Yan, Cheng Liang
Understanding genome-wide protein-DNA interactions forms the basis for further focused studies. In particular, the chromatin immunoprecipitation (ChIP) with sequencing (ChIPSeq) technology can enable us to measure the genome-wide occupancy of DNA-binding protein of interest in vivo. Multiple ChIP-Seq runs thus inherent the potential for us to decipher the combinatorial interactions among multiple DNA-binding proteins. To handle those multiple genome-wide runs, we propose to integrate regularized regression functions (i...
November 21, 2016: IEEE Transactions on Nanobioscience
https://www.readbyqxmd.com/read/27890856/sirna-cell-penetrating-peptides-complexes-as-a-combinatorial-therapy-against-chronic-myeloid-leukemia-using-bv173-cell-line-as-model
#8
João Miguel Freire, Inês Rego de Figueiredo, Javier Valle, Ana Salomé Veiga, David Andreu, Francisco J Enguita, Miguel A R B Castanho
Chronic myeloid leukemia (CML) is a myeloproliferative disorder caused by a single gene mutation, a reciprocal translocation that originates the Bcr-Abl gene with constitutive tyrosine kinase activity. As a monogenic disease, it is an optimum target for RNA silencing therapy. We developed a siRNA-based therapeutic approach in which the siRNA is delivered by pepM or pepR, two cell-penetrating peptides (CPPs) derived from the dengue virus capsid protein. These peptides have a dual role: siRNA delivery into cells and direct action as bioportides, i...
November 24, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27885771/selective-gene-dosage-by-crispr-cas9-genome-editing-in-hexaploid-camelina-sativa
#9
Céline Morineau, Yannick Bellec, Frédérique Tellier, Lionel Gissot, Zsolt Kelemen, Fabien Nogué, Jean-Denis Faure
In many plant species, gene dosage is an important cause of phenotype variation. Selectively engineering gene dosage, particularly in polyploid genomes, would provide an efficient tool for plant breeding. The hexaploid oilseed crop Camelina sativa, which has three closely-related expressed sub-genomes, is an ideal species for investigation of the possibility of creating a large collection of combinatorial mutants. Selective, targeted mutagenesis of the three delta-12-desaturase (FAD2) genes was achieved by CRISPR-Cas9 gene editing, leading to reduced levels of polyunsaturated fatty acids and increased accumulation of oleic acid in the oil...
November 25, 2016: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/27875966/recombinant-approaches-for-microbial-xylanases-recent-advances-and-perspectives
#10
Moumita Basu, Vishal Kumar, Pratyoosh Shukla
Xylanases are crucial enzymes to hydrolyse the xylan of plant hemicellulose in order to complete the carbon cycle. Xylanases have been used widely in a variety of industries ranging from food and feed industry to pulp and paper industry. Most of the industrial processes which using xylanase requires a thermostable and alkali stable enzyme. Therefore it is desired to produce high thermostable and alkali stable xylanase with high activity. In this review a number of molecular techniques are used in this genomic era have been utilized to enhance physiological properties of xylanases for greater commercial application in the industries...
November 22, 2016: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/27865995/g-quadruplex-based-aptamers-against-protein-targets-in-therapy-and-diagnostics
#11
REVIEW
Chiara Platella, Claudia Riccardi, Daniela Montesarchio, Giovanni N Roviello, Domenica Musumeci
Nucleic acid aptamers are single-stranded DNA or RNA molecules identified to recognize with high affinity specific targets including proteins, small molecules, ions, whole cells and even entire organisms, such as viruses or bacteria. They can be identified from combinatorial libraries of DNA or RNA oligonucleotides by SELEX technology, an in vitro iterative selection procedure consisting of binding (capture), partitioning and amplification steps. Remarkably, many of the aptamers selected against biologically relevant protein targets are G-rich sequences that can fold into stable G-quadruplex (G4) structures...
November 16, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27863091/computational-approaches-for-the-identification-of-cancer-genes-and-pathways
#12
REVIEW
Christos M Dimitrakopoulos, Niko Beerenwinkel
High-throughput DNA sequencing techniques enable large-scale measurement of somatic mutations in tumors. Cancer genomics research aims at identifying all cancer-related genes and solid interpretation of their contribution to cancer initiation and development. However, this venture is characterized by various challenges, such as the high number of neutral passenger mutations and the complexity of the biological networks affected by driver mutations. Based on biological pathway and network information, sophisticated computational methods have been developed to facilitate the detection of cancer driver mutations and pathways...
November 11, 2016: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
https://www.readbyqxmd.com/read/27861625/computational-identification-of-tissue-specific-splicing-regulatory-elements-in-human-genes-from-rna-seq-data
#13
Eman Badr, Mahmoud ElHefnawi, Lenwood S Heath
Alternative splicing is a vital process for regulating gene expression and promoting proteomic diversity. It plays a key role in tissue-specific expressed genes. This specificity is mainly regulated by splicing factors that bind to specific sequences called splicing regulatory elements (SREs). Here, we report a genome-wide analysis to study alternative splicing on multiple tissues, including brain, heart, liver, and muscle. We propose a pipeline to identify differential exons across tissues and hence tissue-specific SREs...
2016: PloS One
https://www.readbyqxmd.com/read/27856698/one-cell-doubling-evaluation-by-living-arrays-of-yeast-odelay
#14
Thurston Herricks, David J Dilworth, Fred D Mast, Song Li, Jennifer J Smith, Alexander V Ratushny, John D Aitchison
Cell growth is a complex phenotype widely used in systems biology to gauge the impact of genetic and environmental perturbations. Due to the magnitude of genome-wide studies, resolution is often sacrificed in favor of throughput, creating a demand for scalable, time-resolved, quantitative methods of growth assessment. We present ODELAY (One-cell Doubling Evaluation by Living Arrays of Yeast), an automated and scalable growth analysis platform. High measurement density and single cell resolution provide a powerful tool for large-scale multiparameter growth analysis based on the modeling of microcolony expansion on solid media...
November 16, 2016: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/27852224/novel-approach-for-identification-of-influenza-virus-host-range-and-zoonotic-transmissible-sequences-by-determination-of-host-related-associative-positions-in-viral-genome-segments
#15
Fatemeh Kargarfard, Ashkan Sami, Manijeh Mohammadi-Dehcheshmeh, Esmaeil Ebrahimie
BACKGROUND: Recent (2013 and 2009) zoonotic transmission of avian or porcine influenza to humans highlights an increase in host range by evading species barriers. Gene reassortment or antigenic shift between viruses from two or more hosts can generate a new life-threatening virus when the new shuffled virus is no longer recognized by antibodies existing within human populations. There is no large scale study to help understand the underlying mechanisms of host transmission. Furthermore, there is no clear understanding of how different segments of the influenza genome contribute in the final determination of host range...
November 16, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27834354/gene-expression-profiling-to-predict-responsiveness-to-immunotherapy
#16
REVIEW
N B Jamieson, A V Maker
Recent clinical successes with immunotherapy have resulted in expanding indications for cancer therapy. To enhance antitumor immune responses, and to better choose specific strategies matched to patient and tumor characteristics, genomic-driven precision immunotherapy will be necessary. Herein, we explore the role that tumor gene-expression profiling (GEP) may have in the prediction of an immunotherapeutic response. Genetic markers associated with response to immunotherapy are addressed as they pertain to the tumor genomic landscape, the extent of DNA damage, tumor mutational load and tumor-specific neoantigens...
November 11, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27832531/systematic-discovery-of-chromatin-bound-protein-complexes-from-chip-seq-datasets
#17
Eugenia Giannopoulou, Olivier Elemento
Chromatin immunoprecipitation followed by sequencing is an invaluable assay for identifying the genomic binding sites of transcription factors. However, transcription factors rarely bind chromatin alone but often bind together with other cofactors, forming protein complexes. Here, we describe a computational method that integrates multiple ChIP-seq and RNA-seq datasets to discover protein complexes and determine their role as activators or repressors. This chapter outlines a detailed computational pipeline for discovering and predicting binding partners from ChIP-seq data and inferring their role in regulating gene expression...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27830990/variation-in-arabidopsis-flooding-responses-identifies-numerous-putative-tolerance-genes
#18
Divya Vashisht, Hans van Veen, Melis Akman, Rashmi Sasidharan
Plant survival in flooded environments requires a combinatory response to multiple stress conditions such as limited light availability, reduced gas exchange and nutrient uptake. The ability to fine-tune the molecular response at the transcriptional and/or post-transcriptional level that can eventually lead to metabolic and anatomical adjustments are the underlying requirements to confer tolerance. Previously, we compared the transcriptomic adjustment of submergence tolerant, intolerant accessions and identified a core conserved and genotype-specific response to flooding stress, identifying numerous 'putative' tolerance genes...
November 10, 2016: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/27830751/rapid-construction-of-a-whole-genome-transposon-insertion-collection-for-shewanella-oneidensis-by-knockout-sudoku
#19
Michael Baym, Lev Shaket, Isao A Anzai, Oluwakemi Adesina, Buz Barstow
Whole-genome knockout collections are invaluable for connecting gene sequence to function, yet traditionally, their construction has required an extraordinary technical effort. Here we report a method for the construction and purification of a curated whole-genome collection of single-gene transposon disruption mutants termed Knockout Sudoku. Using simple combinatorial pooling, a highly oversampled collection of mutants is condensed into a next-generation sequencing library in a single day, a 30- to 100-fold improvement over prior methods...
November 10, 2016: Nature Communications
https://www.readbyqxmd.com/read/27812277/a-bioinformatics-approach-for-detecting-repetitive-nested-motifs-using-pattern-matching
#20
José R Romero, Jessica A Carballido, Ingrid Garbus, Viviana C Echenique, Ignacio Ponzoni
The identification of nested motifs in genomic sequences is a complex computational problem. The detection of these patterns is important to allow the discovery of transposable element (TE) insertions, incomplete reverse transcripts, deletions, and/or mutations. In this study, a de novo strategy for detecting patterns that represent nested motifs was designed based on exhaustive searches for pairs of motifs and combinatorial pattern analysis. These patterns can be grouped into three categories, motifs within other motifs, motifs flanked by other motifs, and motifs of large size...
2016: Evolutionary Bioinformatics Online
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