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https://www.readbyqxmd.com/read/28445466/human-pluripotent-stem-cells-recurrently-acquire-and-expand-dominant-negative-p53-mutations
#1
Florian T Merkle, Sulagna Ghosh, Nolan Kamitaki, Jana Mitchell, Yishai Avior, Curtis Mello, Seva Kashin, Shila Mekhoubad, Dusko Ilic, Maura Charlton, Genevieve Saphier, Robert E Handsaker, Giulio Genovese, Shiran Bar, Nissim Benvenisty, Steven A McCarroll, Kevin Eggan
Human pluripotent stem cells (hPS cells) can self-renew indefinitely, making them an attractive source for regenerative therapies. This expansion potential has been linked with the acquisition of large copy number variants that provide mutated cells with a growth advantage in culture. The nature, extent and functional effects of other acquired genome sequence mutations in cultured hPS cells are not known. Here we sequence the protein-coding genes (exomes) of 140 independent human embryonic stem cell (hES cell) lines, including 26 lines prepared for potential clinical use...
April 26, 2017: Nature
https://www.readbyqxmd.com/read/28443113/barcode-system-for-genetic-identification-of-soybean-glycine-max-l-merrill-cultivars-using-indel-markers-specific-to-dense-variation-blocks
#2
Hwang-Bae Sohn, Su-Jeong Kim, Tae-Young Hwang, Hyang-Mi Park, Yu-Young Lee, Kesavan Markkandan, Dongwoo Lee, Sunghoon Lee, Su-Young Hong, Yun-Ho Song, Bon-Cheol Koo, Yul-Ho Kim
For genetic identification of soybean [Glycine max (L.) Merrill] cultivars, insertions/deletions (InDel) markers have been preferred currently because they are easy to use, co-dominant and relatively abundant. Despite their biological importance, the investigation of InDels with proven quality and reproducibility has been limited. In this study, we described soybean barcode system approach based on InDel makers, each of which is specific to a dense variation block (dVB) with non-random recombination due to many variations...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28439259/increased-biological-activity-of-aneurinibacillus-migulanus-strains-correlates-with-the-production-of-new-gramicidin-secondary-metabolites
#3
Faizah N Alenezi, Imen Rekik, Ali Chenari Bouket, Lenka Luptakova, Hedda J Weitz, Mostafa E Rateb, Marcel Jaspars, Stephen Woodward, Lassaad Belbahri
The soil-borne gram-positive bacteria Aneurinibacillus migulanus strain Nagano shows considerable potential as a biocontrol agent against plant diseases. In contrast, A. migulanus NCTC 7096 proved less effective for inhibition of plant pathogens. Nagano strain exerts biocontrol activity against some gram-positive and gram-negative bacteria, fungi and oomycetes through the production of gramicidin S (GS). Apart from the antibiotic effects, GS increases the rate of evaporation from the plant surface, reducing periods of surface wetness and thereby indirectly inhibiting spore germination...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28431213/genome-mining-unearths-a-hybrid-nonribosomal-peptide-synthetase-like-pteridine-synthase-biosynthetic-gene-cluster
#4
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/28430977/deep-mining-heterogeneous-networks-of-biomedical-linked-data-to-predict-novel-drug-target-associations
#5
Nansu Zong, Hyeoneui Kim, Victoria Ngo, Olivier Harismendy
Motivation: A heterogeneous network topology possessing abundant interactions between biomedical entities has yet to be utilized in similarity-based methods for predicting drug-target associations based on the array of varying features of drugs and their targets. Deep learning reveals features of vertices of a large network that can be adapted in accommodating the similarity-based solutions to provide a flexible method of drug-target prediction. Results: We propose a similarity-based drug-target prediction method that enhances existing association discovery methods by using a topology-based similarity measure...
April 18, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28429721/a-mouse-tissue-transcription-factor-atlas
#6
Quan Zhou, Mingwei Liu, Xia Xia, Tongqing Gong, Jinwen Feng, Wanlin Liu, Yang Liu, Bei Zhen, Yi Wang, Chen Ding, Jun Qin
Transcription factors (TFs) drive various biological processes ranging from embryonic development to carcinogenesis. Here, we employ a recently developed concatenated tandem array of consensus TF response elements (catTFRE) approach to profile the activated TFs in 24 adult and 8 fetal mouse tissues on proteome scale. A total of 941 TFs are quantitatively identified, representing over 60% of the TFs in the mouse genome. Using an integrated omics approach, we present a TF network in the major organs of the mouse, allowing data mining and generating knowledge to elucidate the roles of TFs in various biological processes, including tissue type maintenance and determining the general features of a physiological system...
April 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28423633/novel-lincrna-slinky-is-a-prognostic-biomarker-in-kidney-cancer
#7
Xue Gong, Zurab Siprashvili, Okyaz Eminaga, Zhewei Shen, Yusuke Sato, Haruki Kume, Yukio Homma, Seishi Ogawa, Paul A Khavari, Jonathan R Pollack, James D Brooks
Clear cell renal cell carcinomas (ccRCC) show a broad range of clinical behavior, and prognostic biomarkers are needed to stratify patients for appropriate management. We sought to determine whether long intergenic non-coding RNAs (lincRNAs) might predict patient survival. Candidate prognostic lincRNAs were identified by mining The Cancer Genome Atlas (TCGA) transcriptome (RNA-seq) data on 466 ccRCC cases (randomized into discovery and validation sets) annotated for ~21,000 lncRNAs. A previously uncharacterized lincRNA, SLINKY (Survival-predictive LINcRNA in KidneY cancer), was the top-ranked prognostic lincRNA, and validated in an independent University of Tokyo cohort (P=0...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423339/germ-cell-specific-inflammasome-component-nlrp14-negatively-regulates-cytosolic-nucleic-acid-sensing-to-promote-fertilization
#8
Takayuki Abe, Albert Lee, Ramaswami Sitharam, Jordan Kesner, Raul Rabadan, Sagi D Shapira
Cytosolic sensing of nucleic acids initiates tightly regulated programs to limit infection. Oocyte fertilization represents a scenario wherein inappropriate responses to exogenous yet non-pathogen-derived nucleic acids would have negative consequences. We hypothesized that germ cells express negative regulators of nucleic acid sensing (NAS) in steady state and applied an integrated data-mining and functional genomics approach to identify a rheostat of DNA and RNA sensing-the inflammasome component NLRP14. We demonstrated that NLRP14 interacted physically with the nucleic acid sensing pathway and targeted TBK1 (TANK binding kinase 1) for ubiquitination and degradation...
April 18, 2017: Immunity
https://www.readbyqxmd.com/read/28415613/promoter-dna-methylation-analysis-reveals-a-combined-diagnosis-of-cpg-based-biomarker-for-prostate-cancer
#9
Yuanyuan Tang, Shusuan Jiang, Yinmin Gu, Weidong Li, Zengnan Mo, Yuanjie Huang, Tianyu Li, Yanling Hu
BACKGROUND: Prostate cancer (PCa) is the most common tumor in elderly men. However, the specificity and sensitivity of serum prostate-specific antigen levels in PCa diagnosis are controversial. This study aims to reveal a novel diagnosis biomarker in PCa. MATERIALS AND METHODS: The differential methylated CpG sites between 423 primary PCa and 39 adjacent samples from The Cancer Genome Atlas (TCGA) on Illumina HumanMethylation 450 platform were analyzed. The diagnostic methylation markers were mined using the Prediction Analysis of Microarrays package in Bioconductor...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28407145/gepia-a-web-server-for-cancer-and-normal-gene-expression-profiling-and-interactive-analyses
#10
Zefang Tang, Chenwei Li, Boxi Kang, Ge Gao, Cheng Li, Zemin Zhang
Tremendous amount of RNA sequencing data have been produced by large consortium projects such as TCGA and GTEx, creating new opportunities for data mining and deeper understanding of gene functions. While certain existing web servers are valuable and widely used, many expression analysis functions needed by experimental biologists are still not adequately addressed by these tools. We introduce GEPIA (Gene Expression Profiling Interactive Analysis), a web-based tool to deliver fast and customizable functionalities based on TCGA and GTEx data...
April 12, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28406289/phylogenomic-analysis-of-the-microviridin-biosynthetic-pathway-coupled-with-targeted-chemo-enzymatic-synthesis-yields-potent-protease-inhibitors
#11
Muhammad N Ahmed, Emmanuel Reyna-González, Bianca Schmid, Vincent Wiebach, Roderich D Süssmuth, Elke Dittmann, David P Fewer
Natural products and their semisynthetic derivatives are an important source of drugs for the pharmaceutical industry. Bacteria are prolific producers of natural products and encode a vast diversity of natural product biosynthetic gene clusters. However, much of this diversity is inaccessible to natural product discovery. Here, we use a combination of phylogenomic analysis of the microviridin biosynthetic pathway and chemo-enzymatic synthesis of bioinformatically predicted microviridins to yield new protease inhibitors...
April 26, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28404948/germline-whole-exome-sequencing-and-large-scale-replication-identifies-fancm-as-a-likely-high-grade-serous-ovarian-cancer-susceptibility-gene
#12
Ed Dicks, Honglin Song, Susan J Ramus, Elke Van Oudenhove, Jonathan P Tyrer, Maria P Intermaggio, Siddhartha Kar, Patricia Harrington, David D Bowtell, Aocs Study Group, Mine S Cicek, Julie M Cunningham, Brooke L Fridley, Jennifer Alsop, Mercedes Jimenez-Linan, Anna Piskorz, Teodora Goranova, Emma Kent, Nadeem Siddiqui, James Paul, Robin Crawford, Samantha Poblete, Shashi Lele, Lara Sucheston-Campbell, Kirsten B Moysich, Weiva Sieh, Valerie McGuire, Jenny Lester, Kunle Odunsi, Alice S Whittemore, Natalia Bogdanova, Matthias Dürst, Peter Hillemanns, Beth Y Karlan, Aleksandra Gentry-Maharaj, Usha Menon, Marc Tischkowitz, Douglas Levine, James D Brenton, Thilo Dörk, Ellen L Goode, Simon A Gayther, Paul D P Pharoah
We analyzed whole exome sequencing data in germline DNA from 412 high grade serous ovarian cancer (HGSOC) cases from The Cancer Genome Atlas Project and identified 5,517 genes harboring a predicted deleterious germline coding mutation in at least one HGSOC case. Gene-set enrichment analysis showed enrichment for genes involved in DNA repair (p = 1.8x10-3). Twelve DNA repair genes - APEX1, APLF, ATX, EME1, FANCL, FANCM, MAD2L2, PARP2, PARP3, POLN, RAD54L and SMUG1 - were prioritized for targeted sequencing in up to 3,107 HGSOC cases, 1,491 cases of other epithelial ovarian cancer (EOC) subtypes and 3,368 unaffected controls of European origin...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28403818/srnas-as-possible-regulators-of-retrotransposon-activity-in-cryptococcus-gattii-vgii
#13
Patrícia Aline Gröhs Ferrareze, Rodrigo Silva Araujo Streit, Francine Melise Dos Santos, Augusto Schrank, Livia Kmetzsch, Marilene Henning Vainstein, Charley Christian Staats
BACKGROUND: The absence of Argonaute genes in the fungal pathogen Cryptococcus gattii R265 and other VGII strains indicates that yeasts of this genotype cannot have a functional RNAi pathway, an evolutionarily conserved gene silencing mechanism performed by small RNAs. The success of the R265 strain as a pathogen that caused the Pacific Northwest and Vancouver Island outbreaks may imply that RNAi machinery loss could be beneficial under certain circumstances during evolution. As a result, a hypermutant phenotype would be created with high rates of genome retrotransposition, for instance...
April 12, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28402441/mining-prokaryotes-for-antimicrobial-compounds-from-diversity-to-function
#14
Vittorio Tracanna, Anne de Jong, Marnix H Medema, Oscar P Kuipers
The bacterial kingdom provides a major source of antimicrobials that can either be directly applied or used as scaffolds to further improve their functionality in the host. The rapidly increasing amount of bacterial genomic, metabolomic and transcriptomic data offers unique opportunities to apply a variety of approaches to mine for existing and novel antimicrobials. Here, we discuss several powerful mining approaches to identify novel molecules with antimicrobial activity across structurally diverse natural products, including ribosomally synthesized and posttranslationally modified peptides, nonribosomal peptides and polyketides...
April 11, 2017: FEMS Microbiology Reviews
https://www.readbyqxmd.com/read/28401470/streptomyces-artemisiae-mccb-248-isolated-from-arctic-fjord-sediments-has-unique-pks-and-nrps-biosynthetic-genes-and-produces-potential-new-anticancer-natural-products
#15
M Dhaneesha, C Benjamin Naman, K P Krishnan, Rupesh Kumar Sinha, P Jayesh, Valsamma Joseph, I S Bright Singh, William H Gerwick, T P Sajeevan
After screening marine actinomycetes isolated from sediment samples collected from the Arctic fjord Kongsfjorden for potential anticancer activity, an isolate identified as Streptomyces artemisiae MCCB 248 exhibited promising results against the NCI-H460 human lung cancer cell line. H460 cells treated with the ethyl acetate extract of strain MCCB 248 and stained with Hoechst 33342 showed clear signs of apoptosis, including shrinkage of the cell nucleus, DNA fragmentation and chromatin condensation. Further to this treated cells showed indications of early apoptotic cell death, including a significant proportion of Annexin V positive staining and evidence of DNA damage as observed in the TUNEL assay...
May 2017: 3 Biotech
https://www.readbyqxmd.com/read/28401336/genome-wide-identification-and-characterization-of-nb-arc-resistant-genes-in-wheat-triticum-aestivum-l-and-their-expression-during-leaf-rust-infection
#16
Saket Chandra, Andaleeb Z Kazmi, Zainab Ahmed, Gargi Roychowdhury, Veena Kumari, Manish Kumar, Kunal Mukhopadhyay
NB-ARC domain-containing resistance genes from the wheat genome were identified, characterized and localized on chromosome arms that displayed differential yet positive response during incompatible and compatible leaf rust interactions. Wheat (Triticum aestivum L.) is an important cereal crop; however, its production is affected severely by numerous diseases including rusts. An efficient, cost-effective and ecologically viable approach to control pathogens is through host resistance. In wheat, high numbers of resistance loci are present but only few have been identified and cloned...
April 11, 2017: Plant Cell Reports
https://www.readbyqxmd.com/read/28399820/multi-scale-structural-community-organisation-of-the-human-genome
#17
Rasha E Boulos, Nicolas Tremblay, Alain Arneodo, Pierre Borgnat, Benjamin Audit
BACKGROUND: Structural interaction frequency matrices between all genome loci are now experimentally achievable thanks to high-throughput chromosome conformation capture technologies. This ensues a new methodological challenge for computational biology which consists in objectively extracting from these data the structural motifs characteristic of genome organisation. RESULTS: We deployed the fast multi-scale community mining algorithm based on spectral graph wavelets to characterise the networks of intra-chromosomal interactions in human cell lines...
April 11, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28397319/damold-a-data-mining-platform-for-variant-annotation-and-visualization-in-molecular-diagnostics-research
#18
Ram Vinay Pandey, Stephan Pabinger, Albert Kriegner, Andreas Weinhäusel
Next-Generation Sequencing (NGS) has become a powerful and efficient tool for routine mutation screening in clinical research. As each NGS test yields hundreds of variants, the current challenge is to meaningfully interpret the data and select potential candidates. Analyzing each variant while manually investigating several relevant databases to collect specific information is a cumbersome and time-consuming process, and it requires expertise and familiarity with these databases. Thus, a tool that can seamlessly annotate variants with clinically relevant databases under one common interface would be of great help for variant annotation, cross-referencing, and visualization...
April 11, 2017: Human Mutation
https://www.readbyqxmd.com/read/28394353/genomic-analyses-of-primitive-wild-and-cultivated-citrus-provide-insights-into-asexual-reproduction
#19
Xia Wang, Yuantao Xu, Siqi Zhang, Li Cao, Yue Huang, Junfeng Cheng, Guizhi Wu, Shilin Tian, Chunli Chen, Yan Liu, Huiwen Yu, Xiaoming Yang, Hong Lan, Nan Wang, Lun Wang, Jidi Xu, Xiaolin Jiang, Zongzhou Xie, Meilian Tan, Robert M Larkin, Ling-Ling Chen, Bin-Guang Ma, Yijun Ruan, Xiuxin Deng, Qiang Xu
The emergence of apomixis-the transition from sexual to asexual reproduction-is a prominent feature of modern citrus. Here we de novo sequenced and comprehensively studied the genomes of four representative citrus species. Additionally, we sequenced 100 accessions of primitive, wild and cultivated citrus. Comparative population analysis suggested that genomic regions harboring energy- and reproduction-associated genes are probably under selection in cultivated citrus. We also narrowed the genetic locus responsible for citrus polyembryony, a form of apomixis, to an 80-kb region containing 11 candidate genes...
April 10, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28389555/targeting-of-microbe-derived-metabolites-to-improve-human-health-the-next-frontier-for-drug-discovery
#20
J Mark Brown, Stanley L Hazen
Recent advances in metabolomic and genome mining approaches have uncovered a poorly understood metabolome that originates solely or in part from bacterial enzyme sources. Whether living on exposed surfaces or within our intestinal tract, our microbial inhabitants produce a remarkably diverse set of natural products and small molecule metabolites that can impact human health and disease. Highlighted here, the gut microbe-derived metabolite trimethylamine N-oxide (TMAO) has been causally linked to the development of cardiovascular diseases...
April 7, 2017: Journal of Biological Chemistry
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