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John M. Greally

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https://www.readbyqxmd.com/read/30093547/whole-genome-bisulfite-sequencing-with-improved-accuracy-and-cost
#1
Masako Suzuki, Will Liao, Frank Wos, Andrew D Johnston, Justin DeGrazia, Jennifer Ishii, Toby Bloom, Michael C Zody, Soren Germer, John M Greally
DNA methylation patterns in the genome both reflect and help to mediate transcriptional regulatory processes. The digital nature of DNA methylation, present or absent on each allele, makes this assay capable of quantifying events in subpopulations of cells, whereas genome-wide chromatin studies lack the same quantitative capacity. Testing DNA methylation throughout the genome is possible using whole-genome bisulfite sequencing (WGBS), but the high costs associated with the assay have made it impractical for studies involving more than limited numbers of samples...
September 2018: Genome Research
https://www.readbyqxmd.com/read/30061308/mechanisms-of-establishment-and-functional-significance-of-dna-demethylation-during-erythroid-differentiation
#2
Boris Bartholdy, Julien Lajugie, Zi Yan, Shouping Zhang, Rituparna Mukhopadhyay, John M Greally, Masako Suzuki, Eric E Bouhassira
Erythroid differentiation is associated with global DNA demethylation, but a complete methylome was lacking in the erythroid lineage. We have generated allele-specific base resolution methylomes of primary basophilic erythroblasts (BasoEs) and compared these with 8 other cell types. We found that DNA demethylation during differentiation from hematopoietic stem/progenitor cells (HSPCs) to BasoEs occurred predominantly in intergenic sequences and in inactive gene bodies causing the formation of partially methylated domains (PMDs) in 74% of the BasoE methylome...
August 14, 2018: Blood Advances
https://www.readbyqxmd.com/read/30046005/the-runx1-il-34-csf-1r-axis-is-an-autocrinally-regulated-modulator-of-resistance-to-braf-v600e-inhibition-in-melanoma
#3
Orsi Giricz, Yongkai Mo, Kimberly B Dahlman, Xiomaris M Cotto-Rios, Chiara Vardabasso, Hoa Nguyen, Bernice Matusow, Matthias Bartenstein, Veronika Polishchuk, Douglas B Johnson, Tushar D Bhagat, Rafe Shellooe, Elizabeth Burton, James Tsai, Chao Zhang, Gaston Habets, John M Greally, Yiting Yu, Paraic A Kenny, Gregg B Fields, Kith Pradhan, E Richard Stanley, Emily Bernstein, Gideon Bollag, Evripidis Gavathiotis, Brian L West, Jeffrey A Sosman, Amit K Verma
Resistance to current therapies still impacts a significant number of melanoma patients and can be regulated by epigenetic alterations. Analysis of global cytosine methylation in a cohort of primary melanomas revealed a pattern of early demethylation associated with overexpression of oncogenic transcripts. Loss of methylation and associated overexpression of the CSF 1 receptor (CSF1R) was seen in a majority of tumors and was driven by an alternative, endogenous viral promoter in a subset of samples. CSF1R was particularly elevated in melanomas with BRAF and other MAPK activating mutations...
July 25, 2018: JCI Insight
https://www.readbyqxmd.com/read/29766409/where-youth-matters-clinicopathologic-characteristics-and-emerging-trends-in-treatment-and-outcomes-in-young-irish-women-with-breast-cancer
#4
Megan Greally, Jennifer Kielty, Geoffrey A Watson, Geoffrey Das, Christina Malouf, Lynda McSorley, Niamh Coleman, Cecily Quinn, Enda W McDermott, Giuseppe Gullo, John Crown, Ruth S Prichard, Catherine M Kelly, Janice M Walshe
BACKGROUND: Young women with breast cancer (YWBC) represent 7-12% of breast cancer diagnoses and ostensibly have more biologically aggressive subtypes with higher relapse and mortality rates. We studied the clinical and pathological characteristics in YWBC and examined how outcomes and treatment have evolved. METHODS: YWBC were identified from pathology databases at two tertiary centers. Patients were divided into two cohorts: those diagnosed from 2000 to 2005 (C1) and from 2006 to 2015 (C2)...
May 15, 2018: Irish Journal of Medical Science
https://www.readbyqxmd.com/read/29747586/selective-modulation-of-local-linkages-between-active-transcription-and-oxidative-demethylation-activity-shapes-cardiomyocyte-specific-gene-body-epigenetic-status-in-mice
#5
Mayumi Oda, Shunichi Wakabayashi, N Ari Wijetunga, Shinsuke Yuasa, Hirokazu Enomoto, Ruri Kaneda, Sung Han Yoon, Nishant Mittal, Qiang Jing, Masako Suzuki, John M Greally, Keiichi Fukuda, Shinji Makino
BACKGROUND: Cell-type-specific genes exhibit heterogeneity in genomic contexts and may be subject to different epigenetic regulations through different gene transcriptional processes depending on the cell type involved. The gene-body regions (GBRs) of some cardiomyocyte (CM)-specific genes are long and highly hypomethylated in CMs. To explore the cell-type specificities of epigenetic patterns and functions, multiple epigenetic modifications of GBRs were compared among CMs, liver cells and embryonic stem cells (ESCs)...
May 10, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29339796/a-user-s-guide-to-the-ambiguous-word-epigenetics
#6
John M Greally
No abstract text is available yet for this article.
April 2018: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/29224146/the-help-based-dna-methylation-assays
#7
John M Greally
Restriction enzymes have been valuable tools for representing the genome for DNA methylation assays, whether by using methylation-dependent enzymes or by sampling a reduced representation of the genome using a methylation-insensitive enzyme. These survey assays have remained mainstays of genome-wide approaches even with the development of more comprehensive shotgun genome-wide bisulphite sequencing-based assays, as they are significantly more affordable. DNA methylation survey assays are numerous and include reduced representation bisulphite sequencing (RRBS), the Illumina HumanMethylation450K and EPIC microarray system, and our evolving series of HELP-based assays...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28986391/altered-hydroxymethylation-is-seen-at-regulatory-regions-in-pancreatic-cancer-and-regulates-oncogenic-pathways
#8
Sanchari Bhattacharyya, Kith Pradhan, Nathaniel Campbell, Jozef Mazdo, Aparna Vasantkumar, Shahina Maqbool, Tushar D Bhagat, Sonal Gupta, Masako Suzuki, Yiting Yu, John M Greally, Ulrich Steidl, James Bradner, Meelad Dawlaty, Lucy Godley, Anirban Maitra, Amit Verma
Transcriptional deregulation of oncogenic pathways is a hallmark of cancer and can be due to epigenetic alterations. 5-Hydroxymethylcytosine (5-hmC) is an epigenetic modification that has not been studied in pancreatic cancer. Genome-wide analysis of 5-hmC-enriched loci with hmC-seal was conducted in a cohort of low-passage pancreatic cancer cell lines, primary patient-derived xenografts, and pancreatic controls and revealed strikingly altered patterns in neoplastic tissues. Differentially hydroxymethylated regions preferentially affected known regulatory regions of the genome, specifically overlapping with known H3K4me1 enhancers...
November 2017: Genome Research
https://www.readbyqxmd.com/read/28958911/applying-omics-technologies-in-chemicals-risk-assessment-report-of-an-ecetoc-workshop
#9
REVIEW
Roland Buesen, Brian N Chorley, Beatriz da Silva Lima, George Daston, Lize Deferme, Timothy Ebbels, Timothy W Gant, Amber Goetz, John Greally, Laura Gribaldo, Jörg Hackermüller, Bruno Hubesch, Danyel Jennen, Kamin Johnson, Jun Kanno, Hans-Martin Kauffmann, Madeleine Laffont, Patrick McMullen, Richard Meehan, Mark Pemberton, Stefania Perdichizzi, Aldert H Piersma, Ursula G Sauer, Kerstin Schmidt, Hervé Seitz, Kayo Sumida, Knut E Tollefsen, Weida Tong, Tewes Tralau, Ben van Ravenzwaay, Ralf J M Weber, Andrew Worth, Carole Yauk, Alan Poole
Prevailing knowledge gaps in linking specific molecular changes to apical outcomes and methodological uncertainties in the generation, storage, processing, and interpretation of 'omics data limit the application of 'omics technologies in regulatory toxicology. Against this background, the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) convened a workshop Applying 'omics technologies in chemicals risk assessment that is reported herein. Ahead of the workshop, multi-expert teams drafted frameworks on best practices for (i) a Good-Laboratory Practice-like context for collecting, storing and curating 'omics data; (ii) the processing of 'omics data; and (iii) weight-of-evidence approaches for integrating 'omics data...
December 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28911167/in-utero-exposure-to-a-high-fat-diet-programs-hepatic-hypermethylation-and-gene-dysregulation-and-development-of-metabolic-syndrome-in-male-mice
#10
Yoshinori Seki, Masako Suzuki, Xingyi Guo, Alan Scott Glenn, Patricia M Vuguin, Ariana Fiallo, Quan Du, Yi-An Ko, Yiting Yu, Katalin Susztak, Deyou Zheng, John M Greally, Ellen B Katz, Maureen J Charron
Exposure to a high-fat (HF) diet in utero is associated with increased incidence of cardiovascular disease, diabetes, and metabolic syndrome later in life. However, the molecular basis of this enhanced susceptibility for metabolic disease is poorly understood. Gene expression microarray and genome-wide DNA methylation analyses of mouse liver revealed that exposure to a maternal HF milieu activated genes of immune response, inflammation, and hepatic dysfunction. DNA methylation analysis revealed 3360 differentially methylated loci, most of which (76%) were hypermethylated and distributed preferentially to hotspots on chromosomes 4 [atherosclerosis susceptibility quantitative trait loci (QTLs) 1] and 18 (insulin-dependent susceptibility QTLs 21)...
September 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28684528/epigenetically-aberrant-stroma-in-mds-propagates-disease-via-wnt-%C3%AE-catenin-activation
#11
Tushar D Bhagat, Si Chen, Matthias Bartenstein, A Trevor Barlowe, Dagny Von Ahrens, Gaurav S Choudhary, Patrick Tivnan, Elianna Amin, A Mario Marcondes, Mathijs A Sanders, Remco M Hoogenboezem, Suman Kambhampati, Nandini Ramachandra, Iaonnis Mantzaris, Vineeth Sukrithan, Remi Laurence, Robert Lopez, Prafullla Bhagat, Orsi Giricz, Davendra Sohal, Amittha Wickrema, Cecilia Yeung, Kira Gritsman, Peter Aplan, Konrad Hochedlinger, Yiting Yu, Kith Pradhan, Jinghang Zhang, John M Greally, Siddhartha Mukherjee, Andrea Pellagatti, Jacqueline Boultwood, Britta Will, Ulrich Steidl, Marc H G P Raaijmakers, H Joachim Deeg, Michael G Kharas, Amit Verma
The bone marrow microenvironment influences malignant hematopoiesis, but how it promotes leukemogenesis has not been elucidated. In addition, the role of the bone marrow stroma in regulating clinical responses to DNA methyltransferase inhibitors (DNMTi) is also poorly understood. In this study, we conducted a DNA methylome analysis of bone marrow-derived stromal cells from myelodysplastic syndrome (MDS) patients and observed widespread aberrant cytosine hypermethylation occurring preferentially outside CpG islands...
September 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28629478/genetic-epigenetic-interactions-in-cis-a-major-focus-in-the-post-gwas-era
#12
REVIEW
Catherine Do, Alyssa Shearer, Masako Suzuki, Mary Beth Terry, Joel Gelernter, John M Greally, Benjamin Tycko
Studies on genetic-epigenetic interactions, including the mapping of methylation quantitative trait loci (mQTLs) and haplotype-dependent allele-specific DNA methylation (hap-ASM), have become a major focus in the post-genome-wide-association-study (GWAS) era. Such maps can nominate regulatory sequence variants that underlie GWAS signals for common diseases, ranging from neuropsychiatric disorders to cancers. Conversely, mQTLs need to be filtered out when searching for non-genetic effects in epigenome-wide association studies (EWAS)...
June 19, 2017: Genome Biology
https://www.readbyqxmd.com/read/28557546/inflammation-associated-dna-methylation-patterns-in-epithelium-of-ulcerative-colitis
#13
Alan Barnicle, Cathal Seoighe, John M Greally, Aaron Golden, Laurence J Egan
Aberrant DNA methylation patterns have been reported in inflamed tissues and may play a role in disease. We studied DNA methylation and gene expression profiles of purified intestinal epithelial cells from ulcerative colitis patients, comparing inflamed and non-inflamed areas of the colon. We identified 577 differentially methylated sites (false discovery rate <0.2) mapping to 210 genes. From gene expression data from the same epithelial cells, we identified 62 differentially expressed genes with increased expression in the presence of inflammation at prostate cancer susceptibility genes PRAC1 and PRAC2...
August 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28555657/associating-cellular-epigenetic-models-with-human-phenotypes
#14
REVIEW
Tuuli Lappalainen, John M Greally
Epigenetic association studies have been carried out to test the hypothesis that environmental perturbations trigger cellular reprogramming, with downstream effects on cellular function and phenotypes. There have now been numerous studies of the potential molecular mediators of epigenetic changes by epigenome-wide association studies (EWAS). However, a challenge for the field is the interpretation of the results obtained. We describe a second-generation EWAS approach, which focuses on the possible cellular models of epigenetic perturbations, studied by rigorous analysis and interpretation of genomic data...
July 2017: Nature Reviews. Genetics
https://www.readbyqxmd.com/read/28479334/cdc42-related-genes-are-upregulated-in-helper-t-cells-from-obese-asthmatic-children
#15
Deepa Rastogi, John Nico, Andrew D Johnston, Toni Adrianne M Tobias, Yurydia Jorge, Fernando Macian, John M Greally
BACKGROUND: Pediatric obesity-related asthma is more severe and less responsive to medications than asthma in normal-weight children. Obese asthmatic children have nonatopic TH 1-polarized systemic inflammation that correlates with pulmonary function deficits, but the pathways underlying TH 1-polarized inflammation are not well understood. OBJECTIVE: We compared the CD4+ T-cell transcriptome in obese children with asthma with that in normal-weight children with asthma to identify key differentially expressed genes associated with TH 1-polarized inflammation...
February 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28367533/population-epigenetics
#16
John M Greally
The field of epigenetics is maturing, with increased interest in understanding the normal regulation of the genome and the possibility that it becomes reprogrammed aberrantly as part of the cause of disease phenotypes. Applying the current technologies and insights to the study of human populations is potentially a way of understanding mechanisms and consequences of these diseases. When extended to encompass health care disparities, understanding why certain populations are unusually prone to specific conditions, there is certainly some potential for gaining new and valuable insights, but these studies are likely to be unusually prone to the effects of confounding influences and need to be designed, executed and interpreted with extra care...
February 2017: Current Opinion in Systems Biology
https://www.readbyqxmd.com/read/28100166/smite-an-r-bioconductor-package-that-identifies-network-modules-by-integrating-genomic-and-epigenomic-information
#17
N Ari Wijetunga, Andrew D Johnston, Ryo Maekawa, Fabien Delahaye, Netha Ulahannan, Kami Kim, John M Greally
BACKGROUND: The molecular assays that test gene expression, transcriptional, and epigenetic regulation are increasingly diverse and numerous. The information generated by each type of assay individually gives an insight into the state of the cells tested. What should be possible is to add the information derived from separate, complementary assays to gain higher-confidence insights into cellular states. At present, the analysis of multi-dimensional, massive genome-wide data requires an initial pruning step to create manageable subsets of observations that are then used for integration, which decreases the sizes of the intersecting data sets and the potential for biological insights...
January 18, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/27956497/non-cpg-methylation-by-dnmt3b-facilitates-rest-binding-and-gene-silencing-in-developing-mouse-hearts
#18
Donghong Zhang, Bingruo Wu, Ping Wang, Yidong Wang, Pengfei Lu, Tamilla Nechiporuk, Thomas Floss, John M Greally, Deyou Zheng, Bin Zhou
The dynamic interaction of DNA methylation and transcription factor binding in regulating spatiotemporal gene expression is essential for embryogenesis, but the underlying mechanisms remain understudied. In this study, using mouse models and integration of in vitro and in vivo genetic and epigenetic analyses, we show that the binding of REST (repressor element 1 (RE1) silencing transcription factor; also known as NRSF) to its cognate RE1 sequences is temporally regulated by non-CpG methylation. This process is dependent on DNA methyltransferase 3B (DNMT3B) and leads to suppression of adult cardiac genes in developing hearts...
April 7, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/27918756/the-current-state-of-epigenetic-research-in-humans-promise-and-reality
#19
John M Greally, Amanda J Drake
No abstract text is available yet for this article.
February 1, 2017: JAMA Pediatrics
https://www.readbyqxmd.com/read/27909050/notch-pathway-is-activated-via-genetic-and-epigenetic-alterations-and-is-a-therapeutic-target-in-clear-cell-renal-cancer
#20
Tushar D Bhagat, Yiyu Zou, Shizheng Huang, Jihwan Park, Matthew B Palmer, Caroline Hu, Weijuan Li, Niraj Shenoy, Orsolya Giricz, Gaurav Choudhary, Yiting Yu, Yi-An Ko, María C Izquierdo, Ae Seo Deok Park, Nishanth Vallumsetla, Remi Laurence, Robert Lopez, Masako Suzuki, James Pullman, Justin Kaner, Benjamin Gartrell, A Ari Hakimi, John M Greally, Bharvin Patel, Karim Benhadji, Kith Pradhan, Amit Verma, Katalin Susztak
Clear cell renal cell carcinoma (CCRCC) is an incurable malignancy in advanced stages and needs newer therapeutic targets. Transcriptomic analysis of CCRCCs and matched microdissected renal tubular controls revealed overexpression of NOTCH ligands and receptors in tumor tissues. Examination of the TCGA RNA-seq data set also revealed widespread activation of NOTCH pathway in a large cohort of CCRCC samples. Samples with NOTCH pathway activation were also clinically distinct and were associated with better overall survival...
January 20, 2017: Journal of Biological Chemistry
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