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Genome Biology

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https://www.readbyqxmd.com/read/28209204/it-s-about-time-studying-gene-regulatory-programs-across-serial-organs
#1
Maayan Baron, Itai Yanai
No abstract text is available yet for this article.
February 16, 2017: Genome Biology
https://www.readbyqxmd.com/read/28209174/mouse-genomic-screen-reveals-novel-host-regulator-of-metastasis
#2
Toni Celià-Terrassa, Yibin Kang
Tumor cells have to overcome challenges in the host tissue microenvironment to metastasize successfully to distant organs. In a recent Nature study, a genome-wide functional screen demonstrated that deficiency of the sphingosine-1-phoshate (S1P) transporter gene Spns2 in endothelium increased immune-mediated cell killing by T cells and natural killer (NK) cells, thereby suppressing metastatic colonization.
February 16, 2017: Genome Biology
https://www.readbyqxmd.com/read/28209164/rnf40-regulates-gene-expression-in-an-epigenetic-context-dependent-manner
#3
Wanhua Xie, Sankari Nagarajan, Simon J Baumgart, Robyn Laura Kosinsky, Zeynab Najafova, Vijayalakshmi Kari, Magali Hennion, Daniela Indenbirken, Stefan Bonn, Adam Grundhoff, Florian Wegwitz, Ahmed Mansouri, Steven A Johnsen
BACKGROUND: Monoubiquitination of H2B (H2Bub1) is a largely enigmatic histone modification that has been linked to transcriptional elongation. Because of this association, it has been commonly assumed that H2Bub1 is an exclusively positively acting histone modification and that increased H2Bub1 occupancy correlates with increased gene expression. In contrast, depletion of the H2B ubiquitin ligases RNF20 or RNF40 alters the expression of only a subset of genes. RESULTS: Using conditional Rnf40 knockout mouse embryo fibroblasts, we show that genes occupied by low to moderate amounts of H2Bub1 are selectively regulated in response to Rnf40 deletion, whereas genes marked by high levels of H2Bub1 are mostly unaffected by Rnf40 loss...
February 16, 2017: Genome Biology
https://www.readbyqxmd.com/read/28202034/transcriptomic-signatures-shaped-by-cell-proportions-shed-light-on-comparative-developmental-biology
#4
Sophie Pantalacci, Laurent Guéguen, Coraline Petit, Anne Lambert, Renata Peterkovà, Marie Sémon
BACKGROUND: Comparative transcriptomics can answer many questions in developmental and evolutionary developmental biology. Most transcriptomic studies start by showing global patterns of variation in transcriptomes that differ between species or organs through developmental time. However, little is known about the kinds of expression differences that shape these patterns. RESULTS: We compared transcriptomes during the development of two morphologically distinct serial organs, the upper and lower first molars of the mouse...
February 15, 2017: Genome Biology
https://www.readbyqxmd.com/read/28196534/comparative-genomics-reveals-high-biological-diversity-and-specific-adaptations-in-the-industrially-and-medically-important-fungal-genus-aspergillus
#5
Ronald P de Vries, Robert Riley, Ad Wiebenga, Guillermo Aguilar-Osorio, Sotiris Amillis, Cristiane Akemi Uchima, Gregor Anderluh, Mojtaba Asadollahi, Marion Askin, Kerrie Barry, Evy Battaglia, Özgür Bayram, Tiziano Benocci, Susanna A Braus-Stromeyer, Camila Caldana, David Cánovas, Gustavo C Cerqueira, Fusheng Chen, Wanping Chen, Cindy Choi, Alicia Clum, Renato Augusto Corrêa Dos Santos, André Ricardo de Lima Damásio, George Diallinas, Tamás Emri, Erzsébet Fekete, Michel Flipphi, Susanne Freyberg, Antonia Gallo, Christos Gournas, Rob Habgood, Matthieu Hainaut, María Laura Harispe, Bernard Henrissat, Kristiina S Hildén, Ryan Hope, Abeer Hossain, Eugenia Karabika, Levente Karaffa, Zsolt Karányi, Nada Kraševec, Alan Kuo, Harald Kusch, Kurt LaButti, Ellen L Lagendijk, Alla Lapidus, Anthony Levasseur, Erika Lindquist, Anna Lipzen, Antonio F Logrieco, Andrew MacCabe, Miia R Mäkelä, Iran Malavazi, Petter Melin, Vera Meyer, Natalia Mielnichuk, Márton Miskei, Ákos P Molnár, Giuseppina Mulé, Chew Yee Ngan, Margarita Orejas, Erzsébet Orosz, Jean Paul Ouedraogo, Karin M Overkamp, Hee-Soo Park, Giancarlo Perrone, Francois Piumi, Peter J Punt, Arthur F J Ram, Ana Ramón, Stefan Rauscher, Eric Record, Diego Mauricio Riaño-Pachón, Vincent Robert, Julian Röhrig, Roberto Ruller, Asaf Salamov, Nadhira S Salih, Rob A Samson, Erzsébet Sándor, Manuel Sanguinetti, Tabea Schütze, Kristina Sepčić, Ekaterina Shelest, Gavin Sherlock, Vicky Sophianopoulou, Fabio M Squina, Hui Sun, Antonia Susca, Richard B Todd, Adrian Tsang, Shiela E Unkles, Nathalie van de Wiele, Diana van Rossen-Uffink, Juliana Velasco de Castro Oliveira, Tammi C Vesth, Jaap Visser, Jae-Hyuk Yu, Miaomiao Zhou, Mikael R Andersen, David B Archer, Scott E Baker, Isabelle Benoit, Axel A Brakhage, Gerhard H Braus, Reinhard Fischer, Jens C Frisvad, Gustavo H Goldman, Jos Houbraken, Berl Oakley, István Pócsi, Claudio Scazzocchio, Bernhard Seiboth, Patricia A vanKuyk, Jennifer Wortman, Paul S Dyer, Igor V Grigoriev
BACKGROUND: The fungal genus Aspergillus is of critical importance to humankind. Species include those with industrial applications, important pathogens of humans, animals and crops, a source of potent carcinogenic contaminants of food, and an important genetic model. The genome sequences of eight aspergilli have already been explored to investigate aspects of fungal biology, raising questions about evolution and specialization within this genus. RESULTS: We have generated genome sequences for ten novel, highly diverse Aspergillus species and compared these in detail to sister and more distant genera...
February 14, 2017: Genome Biology
https://www.readbyqxmd.com/read/28190401/rapid-transcriptional-plasticity-of-duplicated-gene-clusters-enables-a-clonally-reproducing-aphid-to-colonise-diverse-plant-species
#6
Thomas C Mathers, Yazhou Chen, Gemy Kaithakottil, Fabrice Legeai, Sam T Mugford, Patrice Baa-Puyoulet, Anthony Bretaudeau, Bernardo Clavijo, Stefano Colella, Olivier Collin, Tamas Dalmay, Thomas Derrien, Honglin Feng, Toni Gabaldón, Anna Jordan, Irene Julca, Graeme J Kettles, Krissana Kowitwanich, Dominique Lavenier, Paolo Lenzi, Sara Lopez-Gomollon, Damian Loska, Daniel Mapleson, Florian Maumus, Simon Moxon, Daniel R G Price, Akiko Sugio, Manuella van Munster, Marilyne Uzest, Darren Waite, Georg Jander, Denis Tagu, Alex C C Wilson, Cock van Oosterhout, David Swarbreck, Saskia A Hogenhout
BACKGROUND: The prevailing paradigm of host-parasite evolution is that arms races lead to increasing specialisation via genetic adaptation. Insect herbivores are no exception and the majority have evolved to colonise a small number of closely related host species. Remarkably, the green peach aphid, Myzus persicae, colonises plant species across 40 families and single M. persicae clonal lineages can colonise distantly related plants. This remarkable ability makes M. persicae a highly destructive pest of many important crop species...
February 13, 2017: Genome Biology
https://www.readbyqxmd.com/read/28159004/software-tools-for-visualizing-hi-c-data
#7
REVIEW
Galip Gürkan Yardımcı, William Stafford Noble
High-throughput assays for measuring the three-dimensional (3D) configuration of DNA have provided unprecedented insights into the relationship between DNA 3D configuration and function. Data interpretation from assays such as ChIA-PET and Hi-C is challenging because the data is large and cannot be easily rendered using standard genome browsers. An effective Hi-C visualization tool must provide several visualization modes and be capable of viewing the data in conjunction with existing, complementary data. We review five software tools that do not require programming expertise...
February 3, 2017: Genome Biology
https://www.readbyqxmd.com/read/28143571/single-cas9-nickase-induced-generation-of-nramp1-knockin-cattle-with-reduced-off-target-effects
#8
Yuanpeng Gao, Haibo Wu, Yongsheng Wang, Xin Liu, Linlin Chen, Qian Li, Chenchen Cui, Xu Liu, Jingcheng Zhang, Yong Zhang
BACKGROUND: The CRISPR-Cas9 system is a widely utilized platform for transgenic animal production in various species, although its off-target effects should be addressed. Several applications of this tool have been proposed in model animals but remain insufficient for transgenic livestock production. RESULTS: Here, we report the first application of single Cas9 nickase (Cas9n) to induce gene insertion at a selected locus in cattle. We identify the main binding sites of a catalytically inactive Cas9 (dCas9) protein in bovine fetal fibroblast cells (BFFs) with chromatin immunoprecipitation sequencing (ChIP-seq)...
February 1, 2017: Genome Biology
https://www.readbyqxmd.com/read/28137300/discovery-and-functional-prioritization-of-parkinson-s-disease-candidate-genes-from-large-scale-whole-exome-sequencing
#9
Iris E Jansen, Hui Ye, Sasja Heetveld, Marie C Lechler, Helen Michels, Renée I Seinstra, Steven J Lubbe, Valérie Drouet, Suzanne Lesage, Elisa Majounie, J Raphael Gibbs, Mike A Nalls, Mina Ryten, Juan A Botia, Jana Vandrovcova, Javier Simon-Sanchez, Melissa Castillo-Lizardo, Patrizia Rizzu, Cornelis Blauwendraat, Amit K Chouhan, Yarong Li, Puja Yogi, Najaf Amin, Cornelia M van Duijn, Huw R Morris, Alexis Brice, Andrew B Singleton, Della C David, Ellen A Nollen, Shushant Jain, Joshua M Shulman, Peter Heutink
BACKGROUND: Whole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson's disease (PD). However, until now this approach has not been deployed to study large cohorts of unrelated participants. To discover rare PD susceptibility variants, we performed WES in 1148 unrelated cases and 503 control participants. Candidate genes were subsequently validated for functions relevant to PD based on parallel RNA-interference (RNAi) screens in human cell culture and Drosophila and C...
January 30, 2017: Genome Biology
https://www.readbyqxmd.com/read/28137298/human-disease-genomics-from-variants-to-biology
#10
EDITORIAL
Mark I McCarthy, Daniel G MacArthur
We summarize the remarkable progress that has been made in the identification and functional characterization of DNA sequence variants associated with disease.
January 30, 2017: Genome Biology
https://www.readbyqxmd.com/read/28137292/correcting-for-cell-type-effects-in-dna-methylation-studies-reference-based-method-outperforms-latent-variable-approaches-in-empirical-studies
#11
Mohammad W Hattab, Andrey A Shabalin, Shaunna L Clark, Min Zhao, Gaurav Kumar, Robin F Chan, Lin Ying Xie, Rick Jansen, Laura K M Han, Patrik K E Magnusson, Gerard van Grootheest, Christina M Hultman, Brenda W J H Penninx, Karolina A Aberg, Edwin J C G van den Oord
Based on an extensive simulation study, McGregor and colleagues recently recommended the use of surrogate variable analysis (SVA) to control for the confounding effects of cell-type heterogeneity in DNA methylation association studies in scenarios where no cell-type proportions are available. As their recommendation was mainly based on simulated data, we sought to replicate findings in two large-scale empirical studies. In our empirical data, SVA did not fully correct for cell-type effects, its performance was somewhat unstable, and it carried a risk of missing true signals caused by removing variation that might be linked to actual disease processes...
January 30, 2017: Genome Biology
https://www.readbyqxmd.com/read/28137287/response-to-correcting-for-cell-type-effects-in-dna-methylation-studies-reference-based-method-outperforms-latent-variable-approaches-in-empirical-studies
#12
Kevin McGregor, Aurélie Labbe, Celia M T Greenwood
We thank Hattab and colleagues for their correspondence and their investigation of cell-type mixture correction methods in methyl-CG binding domain sequencing. Here, we speculate on why surrogate variable analysis (SVA) performed differently between their two data sets, and poorly in one of them.Please see related Correspondence article: https://genomebiology.biomedcentral.com/articles/10/1186/s13059-017-1148-8 and related Research article: https://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-0935-y...
January 30, 2017: Genome Biology
https://www.readbyqxmd.com/read/28137286/chrom3d-three-dimensional-genome-modeling-from-hi-c-and-nuclear-lamin-genome-contacts
#13
Jonas Paulsen, Monika Sekelja, Anja R Oldenburg, Alice Barateau, Nolwenn Briand, Erwan Delbarre, Akshay Shah, Anita L Sørensen, Corinne Vigouroux, Brigitte Buendia, Philippe Collas
Current three-dimensional (3D) genome modeling platforms are limited by their inability to account for radial placement of loci in the nucleus. We present Chrom3D, a user-friendly whole-genome 3D computational modeling framework that simulates positions of topologically-associated domains (TADs) relative to each other and to the nuclear periphery. Chrom3D integrates chromosome conformation capture (Hi-C) and lamin-associated domain (LAD) datasets to generate structure ensembles that recapitulate radial distributions of TADs detected in single cells...
January 30, 2017: Genome Biology
https://www.readbyqxmd.com/read/28137275/genome-wide-mapping-of-5-hydroxymethyluracil-in-the-eukaryote-parasite-leishmania
#14
Fumiko Kawasaki, Dario Beraldi, Robyn E Hardisty, Gordon R McInroy, Pieter van Delft, Shankar Balasubramanian
BACKGROUND: 5-Hydroxymethyluracil (5hmU) is a thymine base modification found in the genomes of a diverse range of organisms. To explore the functional importance of 5hmU, we develop a method for the genome-wide mapping of 5hmU-modified loci based on a chemical tagging strategy for the hydroxymethyl group. RESULTS: We apply the method to generate genome-wide maps of 5hmU in the parasitic protozoan Leishmania sp. In this genus, another thymine modification, 5-(β-glucopyranosyl) hydroxymethyluracil (base J), plays a key role during transcription...
January 30, 2017: Genome Biology
https://www.readbyqxmd.com/read/28129774/controlling-bias-and-inflation-in-epigenome-and-transcriptome-wide-association-studies-using-the-empirical-null-distribution
#15
Maarten van Iterson, Erik W van Zwet, Bastiaan T Heijmans
We show that epigenome- and transcriptome-wide association studies (EWAS and TWAS) are prone to significant inflation and bias of test statistics, an unrecognized phenomenon introducing spurious findings if left unaddressed. Neither GWAS-based methodology nor state-of-the-art confounder adjustment methods completely remove bias and inflation. We propose a Bayesian method to control bias and inflation in EWAS and TWAS based on estimation of the empirical null distribution. Using simulations and real data, we demonstrate that our method maximizes power while properly controlling the false positive rate...
January 27, 2017: Genome Biology
https://www.readbyqxmd.com/read/28126036/genome-wide-analysis-of-differential-transcriptional-and-epigenetic-variability-across-human-immune-cell-types
#16
Simone Ecker, Lu Chen, Vera Pancaldi, Frederik O Bagger, José María Fernández, Enrique Carrillo de Santa Pau, David Juan, Alice L Mann, Stephen Watt, Francesco Paolo Casale, Nikos Sidiropoulos, Nicolas Rapin, Angelika Merkel, Hendrik G Stunnenberg, Oliver Stegle, Mattia Frontini, Kate Downes, Tomi Pastinen, Taco W Kuijpers, Daniel Rico, Alfonso Valencia, Stephan Beck, Nicole Soranzo, Dirk S Paul
BACKGROUND: A healthy immune system requires immune cells that adapt rapidly to environmental challenges. This phenotypic plasticity can be mediated by transcriptional and epigenetic variability. RESULTS: We apply a novel analytical approach to measure and compare transcriptional and epigenetic variability genome-wide across CD14(+)CD16(-) monocytes, CD66b(+)CD16(+) neutrophils, and CD4(+)CD45RA(+) naïve T cells from the same 125 healthy individuals. We discover substantially increased variability in neutrophils compared to monocytes and T cells...
January 26, 2017: Genome Biology
https://www.readbyqxmd.com/read/28122634/integrated-genome-wide-analysis-of-expression-quantitative-trait-loci-aids-interpretation-of-genomic-association-studies
#17
Roby Joehanes, Xiaoling Zhang, Tianxiao Huan, Chen Yao, Sai-Xia Ying, Quang Tri Nguyen, Cumhur Yusuf Demirkale, Michael L Feolo, Nataliya R Sharopova, Anne Sturcke, Alejandro A Schäffer, Nancy Heard-Costa, Han Chen, Po-Ching Liu, Richard Wang, Kimberly A Woodhouse, Kahraman Tanriverdi, Jane E Freedman, Nalini Raghavachari, Josée Dupuis, Andrew D Johnson, Christopher J O'Donnell, Daniel Levy, Peter J Munson
BACKGROUND: Identification of single nucleotide polymorphisms (SNPs) associated with gene expression levels, known as expression quantitative trait loci (eQTLs), may improve understanding of the functional role of phenotype-associated SNPs in genome-wide association studies (GWAS). The small sample sizes of some previous eQTL studies have limited their statistical power. We conducted an eQTL investigation of microarray-based gene and exon expression levels in whole blood in a cohort of 5257 individuals, exceeding the single cohort size of previous studies by more than a factor of 2...
January 25, 2017: Genome Biology
https://www.readbyqxmd.com/read/28122605/estimating-and-accounting-for-tumor-purity-in-the-analysis-of-dna-methylation-data-from-cancer-studies
#18
Xiaoqi Zheng, Naiqian Zhang, Hua-Jun Wu, Hao Wu
We present a set of statistical methods for the analysis of DNA methylation microarray data, which account for tumor purity. These methods are an extension of our previously developed method for purity estimation; our updated method is flexible, efficient, and does not require data from reference samples or matched normal controls. We also present a method for incorporating purity information for differential methylation analysis. In addition, we propose a control-free differential methylation calling method when normal controls are not available...
January 25, 2017: Genome Biology
https://www.readbyqxmd.com/read/28118853/allele-specific-analysis-of-cell-fusion-mediated-pluripotent-reprograming-reveals-distinct-and-predictive-susceptibilities-of-human-x-linked-genes-to-reactivation
#19
Irene Cantone, Gopuraja Dharmalingam, Yi-Wah Chan, Anne-Celine Kohler, Boris Lenhard, Matthias Merkenschlager, Amanda G Fisher
BACKGROUND: Inactivation of one X chromosome is established early in female mammalian development and can be reversed in vivo and in vitro when pluripotency factors are re-expressed. The extent of reactivation along the inactive X chromosome (Xi) and the determinants of locus susceptibility are, however, poorly understood. Here we use cell fusion-mediated pluripotent reprograming to study human Xi reactivation and allele-specific single nucleotide polymorphisms (SNPs) to identify reactivated loci...
January 25, 2017: Genome Biology
https://www.readbyqxmd.com/read/28118844/single-cell-epigenomic-variability-reveals-functional-cancer-heterogeneity
#20
Ulrike M Litzenburger, Jason D Buenrostro, Beijing Wu, Ying Shen, Nathan C Sheffield, Arwa Kathiria, William J Greenleaf, Howard Y Chang
BACKGROUND: Cell-to-cell heterogeneity is a major driver of cancer evolution, progression, and emergence of drug resistance. Epigenomic variation at the single-cell level can rapidly create cancer heterogeneity but is difficult to detect and assess functionally. RESULTS: We develop a strategy to bridge the gap between measurement and function in single-cell epigenomics. Using single-cell chromatin accessibility and RNA-seq data in K562 leukemic cells, we identify the cell surface marker CD24 as co-varying with chromatin accessibility changes linked to GATA transcription factors in single cells...
January 24, 2017: Genome Biology
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