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Article ; Online: A user's guide to the ambiguous word 'epigenetics'.

Greally, John M

2018 Volume 19, Issue 4, Page(s) 207–208

MeSH term(s)	Animals ; Epigenesis, Genetic ; Epigenomics ; Humans ; Terminology as Topic
Language	English
Publishing date	2018-01-17
Publishing country	England
Document type	Journal Article
ZDB-ID	2031313-5
ISSN	1471-0080 ; 1471-0072
ISSN (online)	1471-0080
ISSN	1471-0072
DOI	10.1038/nrm.2017.135
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Article ; Online: The HELP-Based DNA Methylation Assays.

Greally, John M

Methods in molecular biology (Clifton, N.J.)

2017 Volume 1708, Page(s) 191–207

Abstract: 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 ...

Abstract	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. The HELP (HpaII tiny fragment Enrichment by Ligation-mediated PCR) assays initially involved microarray-based reporting of DNA methylation, but have now migrated to the use of massively parallel sequencing. In this chapter, we describe the latest HELP-tagging assay that uses Illumina Tru-Seq adapters, and mention the extension of the HELP-tagging assay to quantify 5-hydroxymethylation using the HELP-GT assay.
MeSH term(s)	CpG Islands ; DNA Methylation ; DNA Restriction Enzymes/metabolism ; Gene Library ; Genome, Human ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Polymerase Chain Reaction ; Sequence Analysis, DNA/methods
Chemical Substances	DNA Restriction Enzymes (EC 3.1.21.-)
Language	English
Publishing date	2017-12-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-7481-8_11
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Article ; Online: Using epigenomics to understand cellular responses to environmental influences in diseases.

Wattacheril, Julia J / Raj, Srilakshmi / Knowles, David A / Greally, John M

PLoS genetics

2023 Volume 19, Issue 1, Page(s) e1010567

Abstract: It is a generally accepted model that environmental influences can exert their effects, at least in part, by changing the molecular regulators of transcription that are described as epigenetic. As there is biochemical evidence that some epigenetic ... ...

Abstract	It is a generally accepted model that environmental influences can exert their effects, at least in part, by changing the molecular regulators of transcription that are described as epigenetic. As there is biochemical evidence that some epigenetic regulators of transcription can maintain their states long term and through cell division, an epigenetic model encompasses the idea of maintenance of the effect of an exposure long after it is no longer present. The evidence supporting this model is mostly from the observation of alterations of molecular regulators of transcription following exposures. With the understanding that the interpretation of these associations is more complex than originally recognised, this model may be oversimplistic; therefore, adopting novel perspectives and experimental approaches when examining how environmental exposures are linked to phenotypes may prove worthwhile. In this review, we have chosen to use the example of nonalcoholic fatty liver disease (NAFLD), a common, complex human disease with strong environmental and genetic influences. We describe how epigenomic approaches combined with emerging functional genetic and single-cell genomic techniques are poised to generate new insights into the pathogenesis of environmentally influenced human disease phenotypes exemplified by NAFLD.
MeSH term(s)	Humans ; Non-alcoholic Fatty Liver Disease/genetics ; Epigenesis, Genetic ; Epigenomics ; Environmental Exposure/adverse effects ; Phenotype
Language	English
Publishing date	2023-01-19
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	2186725-2
ISSN	1553-7404 ; 1553-7390
ISSN (online)	1553-7404
ISSN	1553-7390
DOI	10.1371/journal.pgen.1010567
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Article: Population Epigenetics.

Greally, John M

Current opinion in systems biology

2017 Volume 1, Page(s) 84–89

Abstract: 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 ... ...

Abstract	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.
Language	English
Publishing date	2017-01-27
Publishing country	England
Document type	Journal Article
ISSN	2452-3100
ISSN	2452-3100
DOI	10.1016/j.coisb.2017.01.004
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Article ; Online: Umbilical cord blood: an undervalued and underutilized resource in allogeneic hematopoietic stem cell transplant and novel cell therapy applications.

Shi, Patricia A / Luchsinger, Larry L / Greally, John M / Delaney, Colleen S

Current opinion in hematology

2022 Volume 29, Issue 6, Page(s) 317–326

Abstract: Purpose of review: The purpose of this review is to primarily discuss the unwarranted decline in the use of umbilical cord blood (UCB) as a source of donor hematopoietic stem cells (HSC) for hematopoietic cell transplantation (HCT) and the resulting ... ...

Abstract	Purpose of review: The purpose of this review is to primarily discuss the unwarranted decline in the use of umbilical cord blood (UCB) as a source of donor hematopoietic stem cells (HSC) for hematopoietic cell transplantation (HCT) and the resulting important implications in addressing healthcare inequities, and secondly to highlight the incredible potential of UCB and related birthing tissues for the development of a broad range of therapies to treat human disease including but not limited to oncology, neurologic, cardiac, orthopedic and immunologic conditions. Recent findings: When current best practices are followed, unrelated donor umbilical cord blood transplant (CBT) can provide superior quality of life-related survival compared to other allogeneic HSC donor sources (sibling, matched or mismatched unrelated, and haploidentical) through decreased risks of relapse and chronic graft vs. host disease. Current best practices include improved UCB donor selection criteria with consideration of higher resolution human leukocyte antigen (HLA) typing and CD34+ cell dose, availability of newer myeloablative but reduced toxicity conditioning regimens, and rigorous supportive care in the early posttransplant period with monitoring for known complications, especially related to viral and other infections that may require intervention. Emerging best practice may include the use of ex vivo expanded single-unit CBT rather than double-unit CBT (dCBT) or 'haplo-cord' transplant, and the incorporation of posttransplant cyclophosphamide as with haploidentical transplant and/or incorporation of novel posttransplant therapies to reduce the risk of relapse, such as NK cell adoptive transfer. Novel, non-HCT uses of UCB and birthing tissue include the production of UCB-derived immune effector cell therapies such as unmodified NK cells, chimeric antigen receptor-natural killer cells and immune T-cell populations, the isolation of mesenchymal stem cells for immune modulatory treatments and derivation of induced pluripotent stem cells haplobanks for regenerative medicine development and population studies to facilitate exploration of drug development through functional genomics. Summary: The potential of allogeneic UCB for HCT and novel cell-based therapies is undervalued and underutilized. The inventory of high-quality UCB units available from public cord blood banks (CBB) should be expanding rather than contracting in order to address ongoing healthcare inequities and to maintain a valuable source of cellular starting material for cell and gene therapies and regenerative medicine approaches. The expertise in Good Manufacturing Practice-grade manufacturing provided by CBB should be supported to effectively partner with groups developing UCB for novel cell-based therapies.
MeSH term(s)	Cell- and Tissue-Based Therapy ; Cord Blood Stem Cell Transplantation ; Cyclophosphamide ; Fetal Blood ; Graft vs Host Disease ; HLA Antigens/genetics ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Quality of Life ; Receptors, Chimeric Antigen ; Recurrence ; Unrelated Donors
Chemical Substances	HLA Antigens ; Receptors, Chimeric Antigen ; Cyclophosphamide (8N3DW7272P)
Language	English
Publishing date	2022-08-29
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	1153887-9
ISSN	1531-7048 ; 1065-6251
ISSN (online)	1531-7048
ISSN	1065-6251
DOI	10.1097/MOH.0000000000000732
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Article: Egr1 is a sex-specific regulator of neuronal chromatin, synaptic plasticity, and behaviour.

Rocks, Devin / Purisic, Eric / Gallo, Eduardo F / Greally, John M / Suzuki, Masako / Kundakovic, Marija

bioRxiv : the preprint server for biology

2023

Abstract: Sex differences are found in brain structure and function across species, and across brain disorders in ... ...

Abstract	Sex differences are found in brain structure and function across species, and across brain disorders in humans
Language	English
Publishing date	2023-12-21
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.12.20.572697
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Article ; Online: Regulatory landscape enrichment analysis (RLEA): a computational toolkit for non-coding variant enrichment and cell type prioritization.

Rosean, Samuel / Sosa, Eric A / O'Shea, Dónal / Raj, Srilakshmi M / Seoighe, Cathal / Greally, John M

BMC bioinformatics

2024 Volume 25, Issue 1, Page(s) 179

Abstract: Background: As genomic studies continue to implicate non-coding sequences in disease, testing the roles of these variants requires insights into the cell type(s) in which they are likely to be mediating their effects. Prior methods for associating non- ... ...

Abstract	Background: As genomic studies continue to implicate non-coding sequences in disease, testing the roles of these variants requires insights into the cell type(s) in which they are likely to be mediating their effects. Prior methods for associating non-coding variants with cell types have involved approaches using linkage disequilibrium or ontological associations, incurring significant processing requirements. GaiaAssociation is a freely available, open-source software that enables thousands of genomic loci implicated in a phenotype to be tested for enrichment at regulatory loci of multiple cell types in minutes, permitting insights into the cell type(s) mediating the studied phenotype. Results: In this work, we present Regulatory Landscape Enrichment Analysis (RLEA) by GaiaAssociation and demonstrate its capability to test the enrichment of 12,133 variants across the cis-regulatory regions of 44 cell types. This analysis was completed in 134.0 ± 2.3 s, highlighting the efficient processing provided by GaiaAssociation. The intuitive interface requires only four inputs, offers a collection of customizable functions, and visualizes variant enrichment in cell-type regulatory regions through a heatmap matrix. GaiaAssociation is available on PyPi for download as a command line tool or Python package and the source code can also be installed from GitHub at https://github.com/GreallyLab/gaiaAssociation . Conclusions: GaiaAssociation is a novel package that provides an intuitive and efficient resource to understand the enrichment of non-coding variants across the cis-regulatory regions of different cells, empowering studies seeking to identify disease-mediating cell types.
MeSH term(s)	Software ; Genetic Variation ; Humans ; Genomics/methods ; Computational Biology/methods ; Phenotype ; Regulatory Sequences, Nucleic Acid/genetics ; Linkage Disequilibrium
Language	English
Publishing date	2024-05-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2041484-5
ISSN	1471-2105 ; 1471-2105
ISSN (online)	1471-2105
ISSN	1471-2105
DOI	10.1186/s12859-024-05794-7
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Article ; Online: Quantitative Kinetic Analyses of Histone Turnover Using Imaging and Flow Cytometry.

Sato, Hanae / Singer, Robert H / Greally, John M

Bio-protocol

2020 Volume 10, Issue 17

Abstract: Dynamic histone changes occur as a central part of chromatin regulation. Deposition of histone variants and post-translational modifications of histones are strongly associated with properties of chromatin status. Characterizing the kinetics of histone ... ...

Abstract	Dynamic histone changes occur as a central part of chromatin regulation. Deposition of histone variants and post-translational modifications of histones are strongly associated with properties of chromatin status. Characterizing the kinetics of histone variants allows important insights into transcription regulation, chromatin maintenance and other chromatin properties. Here we provide a protocol of quantitative and sensitive approaches to test the timing of incorporation and dissociation of histones using a two-color SNAP-labeling system, labelling pre-existing and newly-incorporated histones distinctly. Together with cell cycle synchronization methods and cell cycle markers, this approach enables a pulse-chase analysis to determine the turnover of histone variants during the cell cycle, detected using imaging or flow cytometry methods at single cell resolution. As well as testing global histone turnover, cell cycle-dependent cellular localization of histone variants can be also addressed using imaging approaches.
Language	English
Publishing date	2020-09-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	2833269-6
ISSN	2331-8325 ; 2331-8325
ISSN (online)	2331-8325
ISSN	2331-8325
DOI	10.21769/bioprotoc.3738
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Article ; Online: Identification of a novel subgroup of endometrial cancer patients with loss of thyroid hormone receptor beta expression and improved survival.

Piqué, Daniel G / Greally, John M / Mar, Jessica C

BMC cancer

2020 Volume 20, Issue 1, Page(s) 857

Abstract: Background: Endometrial cancer (EC) is the most common gynecologic cancer in women, and the incidence of EC has increased by about 1% per year in the U. S over the last 10 years. Although 5-year survival rates for early-stage EC are around 80%, certain ... ...

Abstract	Background: Endometrial cancer (EC) is the most common gynecologic cancer in women, and the incidence of EC has increased by about 1% per year in the U. S over the last 10 years. Although 5-year survival rates for early-stage EC are around 80%, certain subtypes of EC that lose nuclear hormone receptor (NHR) expression are associated with poor survival rates. For example, estrogen receptor (ER)-negative EC typically harbors a worse prognosis compared to ER-positive EC. The molecular basis for the loss of NHR expression in endometrial tumors and its contribution to poor survival is largely unknown. Furthermore, there are no tools to systematically identify tumors that lose NHR mRNA expression relative to normal tissue. The development of such an approach could identify sets of NHR-based biomarkers for classifying patients into subgroups with poor survival outcomes. Methods: Here, a new computational method, termed receptLoss, was developed for identifying NHR expression loss in endometrial cancer relative to adjacent normal tissue. When applied to gene expression data from The Cancer Genome Atlas (TCGA), receptLoss identified 6 NHRs that were highly expressed in normal tissue and exhibited expression loss in a subset of endometrial tumors. Results: Three of the six identified NHRs - estrogen, progesterone, and androgen receptors - that are known to lose expression in ECs were correctly identified by receptLoss. Additionally, a novel association was found between thyroid hormone receptor beta (THRB) expression loss, increased expression of miRNA-146a, and increased rates of 5-year survival in the EC TCGA patient cohort. THRB expression loss occurs independently of estrogen and progesterone expression loss, suggesting the discovery of a distinct, clinically-relevant molecular subgroup. Conclusion: ReceptLoss is a novel, open-source software tool to systematically identify NHR expression loss in cancer. The application of receptLoss to endometrial cancer gene expression data identified THRB, a previously undescribed biomarker of survival in endometrial cancer. Applying receptLoss to expression data from additional cancer types could lead to the development of biomarkers of disease progression for patients with any other tumor type. ReceptLoss can be applied to expression data from additional cancer types with the goal of identifying biomarkers of differential survival.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics ; Disease-Free Survival ; Endometrial Neoplasms/epidemiology ; Endometrial Neoplasms/genetics ; Endometrial Neoplasms/pathology ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Kaplan-Meier Estimate ; MicroRNAs/genetics ; Middle Aged ; Prognosis ; Receptors, Estrogen/genetics ; Thyroid Hormone Receptors beta/genetics
Chemical Substances	Biomarkers, Tumor ; MIRN146 microRNA, human ; MicroRNAs ; Receptors, Estrogen ; Thyroid Hormone Receptors beta
Keywords	covid19
Language	English
Publishing date	2020-09-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2041352-X
ISSN	1471-2407 ; 1471-2407
ISSN (online)	1471-2407
ISSN	1471-2407
DOI	10.1186/s12885-020-07325-y
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Article ; Online: Preleukemic and leukemic evolution at the stem cell level.

Stauber, Jacob / Greally, John M / Steidl, Ulrich

Blood

2020 Volume 137, Issue 8, Page(s) 1013–1018

Abstract: Hematological malignancies are an aggregate of diverse populations of cells that arise following a complex process of clonal evolution and selection. Recent approaches have facilitated the study of clonal populations and their evolution over time across ... ...

Abstract	Hematological malignancies are an aggregate of diverse populations of cells that arise following a complex process of clonal evolution and selection. Recent approaches have facilitated the study of clonal populations and their evolution over time across multiple phenotypic cell populations. In this review, we present current concepts on the role of clonal evolution in leukemic initiation, disease progression, and relapse. We highlight recent advances and unanswered questions about the contribution of the hematopoietic stem cell population to these processes.
MeSH term(s)	Animals ; Carcinogenesis/genetics ; Carcinogenesis/pathology ; Clonal Evolution ; Disease Progression ; Hematopoietic Stem Cells/metabolism ; Hematopoietic Stem Cells/pathology ; Humans ; Leukemia/genetics ; Leukemia/pathology ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology
Language	English
Publishing date	2020-12-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2019004397
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Zs.MO 364: Show issues

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