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https://www.readbyqxmd.com/read/28625481/chromatin-accessibility-landscape-of-cutaneous-t-cell-lymphoma-and-dynamic-response-to-hdac-inhibitors
#1
Kun Qu, Lisa C Zaba, Ansuman T Satpathy, Paul G Giresi, Rui Li, Yonghao Jin, Randall Armstrong, Chen Jin, Nathalie Schmitt, Ziba Rahbar, Hideki Ueno, William J Greenleaf, Youn H Kim, Howard Y Chang
Here, we define the landscape and dynamics of active regulatory DNA in cutaneous T cell lymphoma (CTCL) by ATAC-seq. Analysis of 111 human CTCL and control samples revealed extensive chromatin signatures that distinguished leukemic, host, and normal CD4(+) T cells. We identify three dominant patterns of transcription factor (TF) activation that drive leukemia regulomes, as well as TF deactivations that alter host T cells in CTCL patients. Clinical response to histone deacetylase inhibitors (HDACi) is strongly associated with a concurrent gain in chromatin accessibility...
June 1, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28572580/uropa-a-tool-for-universal-robust-peak-annotation
#2
Maria Kondili, Annika Fust, Jens Preussner, Carsten Kuenne, Thomas Braun, Mario Looso
The annotation of genomic ranges of interest represents a recurring task for bioinformatics analyses. These ranges can originate from various sources, including peaks called for transcription factor binding sites (TFBS) or histone modification ChIP-seq experiments, chromatin structure and accessibility experiments (such as ATAC-seq), but also from other types of predictions that result in genomic ranges. While peak annotation primarily driven by ChiP-seq was extensively explored, many approaches remain simplistic ("most closely located TSS"), rely on fixed pre-built references, or require complex scripting tasks on behalf of the user...
June 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28555639/clonally-stable-v%C3%AE%C2%BA-allelic-choice-instructs-ig%C3%AE%C2%BA-repertoire
#3
Rena Levin-Klein, Shira Fraenkel, Michal Lichtenstein, Louise S Matheson, Osnat Bartok, Yuval Nevo, Sebastian Kadener, Anne E Corcoran, Howard Cedar, Yehudit Bergman
Although much has been done to understand how rearrangement of the Igκ locus is regulated during B-cell development, little is known about the way the variable (V) segments themselves are selected. Here we show, using B6/Cast hybrid pre-B-cell clones, that a limited number of V segments on each allele is stochastically activated as characterized by the appearance of non-coding RNA and histone modifications. The activation states are clonally distinct, stable across cell division and developmentally important in directing the Ig repertoire upon differentiation...
May 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/28550296/reducing-mitochondrial-reads-in-atac-seq-using-crispr-cas9
#4
Lindsey Montefiori, Liana Hernandez, Zijie Zhang, Yoav Gilad, Carole Ober, Gregory Crawford, Marcelo Nobrega, Noboru Jo Sakabe
ATAC-seq is a high-throughput sequencing technique that identifies open chromatin. Depending on the cell type, ATAC-seq samples may contain ~20-80% of mitochondrial sequencing reads. As the regions of open chromatin of interest are usually located in the nuclear genome, mitochondrial reads are typically discarded from the analysis. We tested two approaches to decrease wasted sequencing in ATAC-seq libraries generated from lymphoblastoid cell lines: targeted cleavage of mitochondrial DNA fragments using CRISPR technology and removal of detergent from the cell lysis buffer...
May 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28538187/bivariate-genomic-footprinting-detects-changes-in-transcription-factor-activity
#5
Songjoon Baek, Ido Goldstein, Gordon L Hager
In response to activating signals, transcription factors (TFs) bind DNA and regulate gene expression. TF binding can be measured by protection of the bound sequence from DNase digestion (i.e., footprint). Here, we report that 80% of TF binding motifs do not show a measurable footprint, partly because of a variable cleavage pattern within the motif sequence. To more faithfully portray the effect of TFs on chromatin, we developed an algorithm that captures two TF-dependent effects on chromatin accessibility: footprinting and motif-flanking accessibility...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28505247/single-cell-regulome-data-analysis-by-scrat
#6
Zhicheng Ji, Weiqiang Zhou, Hongkai Ji
Summary: Emerging single-cell technologies (e.g., single-cell ATAC-seq, DNase-seq or ChIP-seq) have made it possible to assay regulome of individual cells. Single-cell regulome data are highly sparse and discrete. Analyzing such data is challenging. User-friendly software tools are still lacking. We present SCRAT, a Single-Cell Regulome Analysis Toolbox with a graphical user interface, for studying cell heterogeneity using single-cell regulome data. SCRAT can be used to conveniently summarize regulatory activities according to different features (e...
May 12, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28498703/realization-of-a-cascaded-quantum-system-heralded-absorption-of-a-single-photon-qubit-by-a-single-electron-charged-quantum-dot
#7
Aymeric Delteil, Zhe Sun, Stefan Fält, Atac Imamoğlu
Photonic losses pose a major limitation for the implementation of a quantum state transfer between nodes of a quantum network. A measurement that heralds a successful transfer without revealing any information about the qubit may alleviate this limitation. Here, we demonstrate the heralded absorption of a single photonic qubit, generated by a single neutral quantum dot, by a single-electron charged quantum dot that is located 5 m away. The transfer of quantum information to the spin degree of freedom takes place upon the emission of a photon; for a properly chosen or prepared quantum dot, the detection of this photon yields no information about the qubit...
April 28, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/28494403/her2-status-predicts-for-upfront-ai-benefit-a%C3%A2-trans-aiog-meta-analysis-of-12-129-patients-from%C3%A2-atac-big-1-98-and-team-with-centrally-determined-her2
#8
John M S Bartlett, Ikhlaaq Ahmed, Meredith M Regan, Ivana Sestak, Elizabeth A Mallon, Patrizia Dell'Orto, Beat Thürlimann, Caroline Seynaeve, Hein Putter, Cornelis J H Van de Velde, Cassandra L Brookes, John F Forbes, Giuseppe Viale, Jack Cuzick, Mitchell Dowsett, Daniel W Rea
BACKGROUND: A meta-analysis of the effects of HER2 status, specifically within the first 2-3 years of adjuvant endocrine therapy, has the potential to inform patient selection for upfront aromatase inhibitor (AI) therapy or switching strategy tamoxifen followed by AI. The pre-existing standardisation of methodology for HER2 (immunohistochemistry/fluorescence in situ hybridization) facilitates analysis of existing data for this key marker. METHODS: Following a prospectively designed statistical analysis plan, patient data from 3 phase III trials Arimidex, Tamoxifen, Alone or in Combination Trial (ATAC), Breast International Group (BIG) 1-98 and Tamoxifen Exemestane Adjuvant Multicentre Trial (TEAM)] comparing an AI to tamoxifen during the first 2-3 years of adjuvant endocrine treatment were collected and a treatment-by-marker analysis of distant recurrence-free interval-censored at 2-3 years treatment - for HER2 status × AI versus tamoxifen treatment was performed to address the clinical question relating to efficacy of 'upfront' versus 'switch' strategies for AIs...
May 8, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28473594/evaluation-of-sinus-edge-corrected-zte-based-attenuation-correction-in-brain-pet-mri
#9
Jaewon Yang, Florian Wiesinger, Sandeep Kaushik, Dattesh Shanbhag, Thomas A Hope, Peder E Z Larson, Youngho Seo
Purpose: In brain positron emission tomography/magnetic resonance imaging (PET/MRI), the major challenge of zero-echo-time (ZTE)-based attenuation correction (ZTAC) is the misclassification of air/tissue/bone mixtures or their boundaries. Our study aimed to evaluate a sinus/edge corrected (SEC) ZTAC (ZTACSEC), relative to an "uncorrected (UC)" ZTAC (ZTACUC) and a computed tomography (CT) atlas-based attenuation correction (ATAC). Materials and Methods: Whole-body fluorodeoxyglucose PET/MRI scans were performed for twelve patients, following PET/CT scans...
May 4, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28472346/a-c-myb-mutant-causes-deregulated-differentiation-due-to-impaired-histone-binding-and-abrogated-pioneer-factor-function
#10
Bettina M Fuglerud, Roza B Lemma, Pimthanya Wanichawan, Arvind Y M Sundaram, Ragnhild Eskeland, Odd S Gabrielsen
The transcription factor c-Myb is involved in early differentiation and proliferation of haematopoietic cells, where it operates as a regulator of self-renewal and multi-lineage differentiation. Deregulated c-Myb plays critical roles in leukaemias and other human cancers. Due to its role as a master regulator, we hypothesized it might function as a pioneer transcription factor. Our approach to test this was to analyse a mutant of c-Myb, D152V, previously reported to cause haematopoietic defects in mice by an unknown mechanism...
May 2, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28459457/conserved-roles-of-mouse-dux-and-human-dux4-in-activating-cleavage-stage-genes-and-mervl-hervl-retrotransposons
#11
Peter G Hendrickson, Jessie A Doráis, Edward J Grow, Jennifer L Whiddon, Jong-Won Lim, Candice L Wike, Bradley D Weaver, Christian Pflueger, Benjamin R Emery, Aaron L Wilcox, David A Nix, C Matthew Peterson, Stephen J Tapscott, Douglas T Carrell, Bradley R Cairns
To better understand transcriptional regulation during human oogenesis and preimplantation development, we defined stage-specific transcription, which highlighted the cleavage stage as being highly distinctive. Here, we present multiple lines of evidence that a eutherian-specific multicopy retrogene, DUX4, encodes a transcription factor that activates hundreds of endogenous genes (for example, ZSCAN4, KDM4E and PRAMEF-family genes) and retroviral elements (MERVL/HERVL family) that define the cleavage-specific transcriptional programs in humans and mice...
June 2017: Nature Genetics
https://www.readbyqxmd.com/read/28439570/epigenomics-of-human-cd8-t-cell-differentiation-and-aging
#12
David M Moskowitz, David W Zhang, Bin Hu, Sabine Le Saux, Rolando E Yanes, Zhongde Ye, Jason D Buenrostro, Cornelia M Weyand, William J Greenleaf, Jörg J Goronzy
The efficacy of the adaptive immune response declines dramatically with age, but the cell-intrinsic mechanisms driving immune aging in humans remain poorly understood. Immune aging is characterized by a loss of self-renewing naïve cells and the accumulation of differentiated but dysfunctional cells within the CD8 T cell compartment. Using ATAC-seq, we inferred the transcription factor binding activities correlated with naive and central and effector memory CD8 T cell states in young adults. Integrating our results with RNA-seq, we identified transcription networks associated with CD8 T cell differentiation, with prominent roles implicated for BATF, ETS1, Eomes, and Sp1...
February 2017: Science Immunology
https://www.readbyqxmd.com/read/28381412/the-ddr-at-telomeres-lacking-intact-shelterin-does-not-require-substantial-chromatin-decompaction
#13
Leonid A Timashev, Hazen Babcock, Xiaowei Zhuang, Titia de Lange
Telomeres are protected by shelterin, a six-subunit protein complex that represses the DNA damage response (DDR) at chromosome ends. Extensive data suggest that TRF2 in shelterin remodels telomeres into the t-loop structure, thereby hiding telomere ends from double-stranded break repair and ATM signaling, whereas POT1 represses ATR signaling by excluding RPA. An alternative protection mechanism was suggested recently by which shelterin subunits TRF1, TRF2, and TIN2 mediate telomeric chromatin compaction, which was proposed to minimize access of DDR factors...
March 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28369967/a-simulation-study-to-compare-the-treatment-effect-of-tamoxifen-by-cyp2d6-genotypes-and-third-generation-aromatase-inhibitors
#14
Gwan Cheol Park, Jin-A Jung, Kyun-Seop Bae, Hyeong-Seok Lim
Some prospective, randomized clinical trials, including ATAC and BIG 1-98, demonstrated superior treatment effect of third-generation aromatase inhibitors (AIs) versus tamoxifen in postoperative therapy for patients with breast cancer. In retrospective genotyping analyses of the 2 studies using tumor samples, no difference in the treatment effect of tamoxifen was observed by CYP2D6 genotypes. However, those analyses did not consider loss of heterozygosity that could have occurred when genotyping using tumor tissue...
April 3, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28365152/dynamic-gene-regulatory-networks-of-human-myeloid-differentiation
#15
Ricardo N Ramirez, Nicole C El-Ali, Mikayla Anne Mager, Dana Wyman, Ana Conesa, Ali Mortazavi
The reconstruction of gene regulatory networks underlying cell differentiation from high-throughput gene expression and chromatin data remains a challenge. Here, we derive dynamic gene regulatory networks for human myeloid differentiation using a 5-day time series of RNA-seq and ATAC-seq data. We profile HL-60 promyelocytes differentiating into macrophages, neutrophils, monocytes, and monocyte-derived macrophages. We find a rapid response in the expression of key transcription factors and lineage markers that only regulate a subset of their targets at a given time, which is followed by chromatin accessibility changes that occur later along with further gene expression changes...
April 26, 2017: Cell Systems
https://www.readbyqxmd.com/read/28360229/aortic-calcification-onset-and-progression-association-with-the-development-of-coronary-atherosclerosis
#16
Hagen Kälsch, Nils Lehmann, Susanne Moebus, Barbara Hoffmann, Andreas Stang, Karl-Heinz Jöckel, Raimund Erbel, Amir A Mahabadi
BACKGROUND: Thoracic aortic calcification (TAC) and coronary artery calcification (CAC) are markers of subclinical atherosclerosis and are associated with incident major cardiovascular events. We investigated major determinants for incidence and progression of TAC and the association between TAC and CAC incidence and progression. METHODS AND RESULTS: In a population-based cohort study, 3270 participants (aged 45-74 years, 53.1% women) received cardiac computed tomography at baseline and after a mean follow-up of 5...
March 30, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28356342/widespread-changes-in-nucleosome-accessibility-without-changes-in-nucleosome-occupancy-during-a-rapid-transcriptional-induction
#17
Britta Mueller, Jakub Mieczkowski, Sharmistha Kundu, Peggy Wang, Ruslan Sadreyev, Michael Y Tolstorukov, Robert E Kingston
Activation of transcription requires alteration of chromatin by complexes that increase the accessibility of nucleosomal DNA. Removing nucleosomes from regulatory sequences has been proposed to play a significant role in activation. We tested whether changes in nucleosome occupancy occurred on the set of genes that is activated by the unfolded protein response (UPR). We observed no decrease in occupancy on most promoters, gene bodies, and enhancers. Instead, there was an increase in the accessibility of nucleosomes, as measured by micrococcal nuclease (MNase) digestion and ATAC-seq (assay for transposase-accessible chromatin [ATAC] using sequencing), that did not result from removal of the nucleosome...
March 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28350380/transcriptomic-profiling-of-39-commonly-used-neuroblastoma-cell-lines
#18
Jo Lynne Harenza, Maura A Diamond, Rebecca N Adams, Michael M Song, Heather L Davidson, Lori S Hart, Maiah H Dent, Paolo Fortina, C Patrick Reynolds, John M Maris
Neuroblastoma cell lines are an important and cost-effective model used to study oncogenic drivers of the disease. While many of these cell lines have been previously characterized with SNP, methylation, and/or mRNA expression microarrays, there has not been an effort to comprehensively sequence these cell lines. Here, we present raw whole transcriptome data generated by RNA sequencing of 39 commonly-used neuroblastoma cell lines. These data can be used to perform differential expression analysis based on a genetic aberration or phenotype in neuroblastoma (e...
March 28, 2017: Scientific Data
https://www.readbyqxmd.com/read/28335009/open-chromatin-profiling-of-human-postmortem-brain-infers-functional-roles-for-non-coding-schizophrenia-loci
#19
John F Fullard, Claudia Giambartolomei, Mads E Hauberg, Ke Xu, Georgios Voloudakis, Zhiping Shao, Christopher Bare, Joel T Dudley, Manuel Mattheisen, Nikolaos K Robakis, Vahram Haroutunian, Panos Roussos
Open chromatin provides access to DNA-binding proteins for the correct spatiotemporal regulation of gene expression. Mapping chromatin accessibility has been widely used to identify the location of cis regulatory elements (CREs) including promoters and enhancers. CREs show tissue- and cell-type specificity and disease-associated variants are often enriched for CREs in the tissues and cells that pertain to a given disease. To better understand the role of CREs in neuropsychiatric disorders we applied the Assay for Transposase Accessible Chromatin followed by sequencing (ATAC-seq) to neuronal and non-neuronal nuclei isolated from frozen postmortem human brain by fluorescence-activated nuclear sorting (FANS)...
May 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28279124/effect-of-maternal-and-neonatal-interleukin-6-174%C3%A2-g-c-polymorphism-on-preterm-birth-and-neonatal-morbidity
#20
N M Karakaş, A Ecevit, Y Yalçın, B Özdemir, H Verdi, M A Tekindal, N Y Özbek, A Tarcan, F B Ataç, A Haberal
OBJECTIVE: The aim of this study was to analyze maternal and neonatal interleukin 6 (IL-6) (-174 G/C) polymorphism and to determine effect on preterm birth and neonatal morbidity. STUDY DESIGN: 164 mothers (100 term births, 64 preterm births) and 183 newborn infants who were 100 healthy term and 83 preterm babies followed in newborn intensive care units were evaluated. PCR-RFLP was performed for IL-6 (-174 G/C) genotyping. RESULTS: The rate of GG genotype in mothers of term and preterm infants were 54% (n = 54/100), 75% (n = 48/64), respectively (p> 0...
March 9, 2017: Journal of Maternal-fetal & Neonatal Medicine
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