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  1. Article ; Online: Cell Type-Specific Signal Analysis in Epigenome-Wide Association Studies.

    Breeze, Charles E

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

    2022  Volume 2432, Page(s) 57–71

    Abstract: Hundreds of epigenome-wide association studies (EWAS) have been performed, successfully identifying replicated epigenomic signals in processes such as aging and smoking. Despite this progress, it remains a major challenge in EWAS to detect both cell type- ...

    Abstract Hundreds of epigenome-wide association studies (EWAS) have been performed, successfully identifying replicated epigenomic signals in processes such as aging and smoking. Despite this progress, it remains a major challenge in EWAS to detect both cell type-specific and cell type confounding effects impacting study results. One way to identify these effects is through eFORGE (experimentally derived Functional element Overlap analysis of ReGions from EWAS), a published tool that uses 815 datasets from large-scale mapping studies to detect enriched tissues, cell types, and genomic regions. Here, I show that eFORGE analysis can be extended to EWAS differentially variable positions (DVPs), identifying target cell types and tissues. In addition, I also show that eFORGE tissue-specific enrichment can be detected for sites below EWAS significance threshold. I develop on these and other analysis examples, extending our knowledge of eFORGE cell type- and tissue-specific enrichment results for different EWAS.
    MeSH term(s) DNA Methylation ; Epigenesis, Genetic ; Epigenome ; Epigenomics ; Genome-Wide Association Study/methods
    Language English
    Publishing date 2022-05-03
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-1994-0_5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The missing diversity in human epigenomic studies.

    Breeze, Charles E / Beck, Stephan / Berndt, Sonja I / Franceschini, Nora

    Nature genetics

    2022  Volume 54, Issue 6, Page(s) 737–739

    MeSH term(s) Epigenesis, Genetic ; Epigenomics ; Humans
    Language English
    Publishing date 2022-05-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
    ZDB-ID 1108734-1
    ISSN 1546-1718 ; 1061-4036
    ISSN (online) 1546-1718
    ISSN 1061-4036
    DOI 10.1038/s41588-022-01081-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Diversity in EWAS: current state, challenges, and solutions.

    Breeze, Charles E / Wong, Jason Y Y / Beck, Stephan / Berndt, Sonja I / Franceschini, Nora

    Genome medicine

    2022  Volume 14, Issue 1, Page(s) 71

    Abstract: Here, we report a lack of diversity in epigenome-wide association studies (EWAS) and DNA methylation (DNAm) data, discuss current challenges, and propose solutions for EWAS and DNAm research in diverse populations. The strategies we propose include ... ...

    Abstract Here, we report a lack of diversity in epigenome-wide association studies (EWAS) and DNA methylation (DNAm) data, discuss current challenges, and propose solutions for EWAS and DNAm research in diverse populations. The strategies we propose include fostering community involvement, new data generation, and cost-effective approaches such as locus-specific analysis and ancestry variable region analysis.
    MeSH term(s) DNA Methylation ; Epigenesis, Genetic ; Epigenome ; Humans
    Language English
    Publishing date 2022-07-06
    Publishing country England
    Document type Letter ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
    ZDB-ID 2484394-5
    ISSN 1756-994X ; 1756-994X
    ISSN (online) 1756-994X
    ISSN 1756-994X
    DOI 10.1186/s13073-022-01065-3
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  4. Article ; Online: The RNA editing landscape in acute myeloid leukemia reveals associations with disease mutations and clinical outcome.

    Meduri, Eshwar / Breeze, Charles / Marando, Ludovica / Richardson, Simon E / Huntly, Brian J P

    iScience

    2022  Volume 25, Issue 12, Page(s) 105622

    Abstract: Several studies have documented aberrant RNA editing patterns across multiple tumors across large patient cohorts from The Cancer Genome Atlas (TCGA). However, studies on understanding the role of RNA editing in acute myeloid leukemia (AML) have been ... ...

    Abstract Several studies have documented aberrant RNA editing patterns across multiple tumors across large patient cohorts from The Cancer Genome Atlas (TCGA). However, studies on understanding the role of RNA editing in acute myeloid leukemia (AML) have been limited to smaller sample sizes. Using high throughput transcriptomic data from the TCGA, we demonstrated higher levels of editing as a predictor of poor outcome within the AML patient samples. Moreover, differential editing patterns were observed across individual AML genotypes. We also could demonstrate a negative association between the degree of editing and mRNA abundance for some transcripts, identifying the potential regulatory potential of RNA-editing in altering gene expression in AML. Further edQTL analysis suggests potential
    Language English
    Publishing date 2022-11-17
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2022.105622
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  5. Article ; Online: FORGEdb: a tool for identifying candidate functional variants and uncovering target genes and mechanisms for complex diseases.

    Breeze, Charles E / Haugen, Eric / Gutierrez-Arcelus, María / Yao, Xiaozheng / Teschendorff, Andrew / Beck, Stephan / Dunham, Ian / Stamatoyannopoulos, John / Franceschini, Nora / Machiela, Mitchell J / Berndt, Sonja I

    Genome biology

    2024  Volume 25, Issue 1, Page(s) 3

    Abstract: The majority of disease-associated variants identified through genome-wide association studies are located outside of protein-coding regions. Prioritizing candidate regulatory variants and gene targets to identify potential biological mechanisms for ... ...

    Abstract The majority of disease-associated variants identified through genome-wide association studies are located outside of protein-coding regions. Prioritizing candidate regulatory variants and gene targets to identify potential biological mechanisms for further functional experiments can be challenging. To address this challenge, we developed FORGEdb ( https://forgedb.cancer.gov/

    https://forge2.altiusinstitute.org/files/forgedb.html

    and https://doi.org/10.5281/zenodo.10067458 ), a standalone and web-based tool that integrates multiple datasets, delivering information on associated regulatory elements, transcription factor binding sites, and target genes for over 37 million variants. FORGEdb scores provide researchers with a quantitative assessment of the relative importance of each variant for targeted functional experiments.
    MeSH term(s) Genome-Wide Association Study ; Regulatory Sequences, Nucleic Acid ; Protein Binding ; Polymorphism, Single Nucleotide
    Language English
    Publishing date 2024-01-02
    Publishing country England
    Document type Journal Article
    ZDB-ID 2040529-7
    ISSN 1474-760X ; 1474-760X
    ISSN (online) 1474-760X
    ISSN 1474-760X
    DOI 10.1186/s13059-023-03126-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: EPISCORE: cell type deconvolution of bulk tissue DNA methylomes from single-cell RNA-Seq data.

    Teschendorff, Andrew E / Zhu, Tianyu / Breeze, Charles E / Beck, Stephan

    Genome biology

    2020  Volume 21, Issue 1, Page(s) 221

    Abstract: Cell type heterogeneity presents a challenge to the interpretation of epigenome data, compounded by the difficulty in generating reliable single-cell DNA methylomes for large numbers of cells and samples. We present EPISCORE, a computational algorithm ... ...

    Abstract Cell type heterogeneity presents a challenge to the interpretation of epigenome data, compounded by the difficulty in generating reliable single-cell DNA methylomes for large numbers of cells and samples. We present EPISCORE, a computational algorithm that performs virtual microdissection of bulk tissue DNA methylation data at single cell-type resolution for any solid tissue. EPISCORE applies a probabilistic epigenetic model of gene regulation to a single-cell RNA-seq tissue atlas to generate a tissue-specific DNA methylation reference matrix, allowing quantification of cell-type proportions and cell-type-specific differential methylation signals in bulk tissue data. We validate EPISCORE in multiple epigenome studies and tissue types.
    MeSH term(s) Algorithms ; DNA Methylation ; Endothelial Cells ; Epigenesis, Genetic ; Epigenome ; Epigenomics ; Humans ; Lung ; Lung Neoplasms/genetics ; RNA, Messenger ; RNA-Seq/methods ; Single-Cell Analysis/methods
    Chemical Substances RNA, Messenger
    Language English
    Publishing date 2020-09-04
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2040529-7
    ISSN 1474-760X ; 1474-760X
    ISSN (online) 1474-760X
    ISSN 1474-760X
    DOI 10.1186/s13059-020-02126-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: A pan-tissue DNA methylation atlas enables in silico decomposition of human tissue methylomes at cell-type resolution.

    Zhu, Tianyu / Liu, Jacklyn / Beck, Stephan / Pan, Sun / Capper, David / Lechner, Matt / Thirlwell, Chrissie / Breeze, Charles E / Teschendorff, Andrew E

    Nature methods

    2022  Volume 19, Issue 3, Page(s) 296–306

    Abstract: Bulk-tissue DNA methylomes represent an average over many different cell types, hampering our understanding of cell-type-specific contributions to disease development. As single-cell methylomics is not scalable to large cohorts of individuals, cost- ... ...

    Abstract Bulk-tissue DNA methylomes represent an average over many different cell types, hampering our understanding of cell-type-specific contributions to disease development. As single-cell methylomics is not scalable to large cohorts of individuals, cost-effective computational solutions are needed, yet current methods are limited to tissues such as blood. Here we leverage the high-resolution nature of tissue-specific single-cell RNA-sequencing datasets to construct a DNA methylation atlas defined for 13 solid tissue types and 40 cell types. We comprehensively validate this atlas in independent bulk and single-nucleus DNA methylation datasets. We demonstrate that it correctly predicts the cell of origin of diverse cancer types and discovers new prognostic associations in olfactory neuroblastoma and stage 2 melanoma. In brain, the atlas predicts a neuronal origin for schizophrenia, with neuron-specific differential DNA methylation enriched for corresponding genome-wide association study risk loci. In summary, the DNA methylation atlas enables the decomposition of 13 different human tissue types at a high cellular resolution, paving the way for an improved interpretation of epigenetic data.
    MeSH term(s) CpG Islands ; DNA Methylation ; Epigenesis, Genetic ; Epigenome ; Epigenomics ; Genome-Wide Association Study ; Humans ; Neurons/metabolism
    Language English
    Publishing date 2022-03-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2169522-2
    ISSN 1548-7105 ; 1548-7091
    ISSN (online) 1548-7105
    ISSN 1548-7091
    DOI 10.1038/s41592-022-01412-7
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  8. Article ; Online: Early detection of HPV-associated oropharyngeal cancer.

    Lechner, Matt / Breeze, Charles E / O'Mahony, James F / Masterson, Liam

    Lancet (London, England)

    2019  Volume 393, Issue 10186, Page(s) 2123

    MeSH term(s) Early Detection of Cancer ; Human papillomavirus 16 ; Humans ; Oropharyngeal Neoplasms/virology ; Papillomavirus Infections ; Vaccination
    Language English
    Publishing date 2019-06-24
    Publishing country England
    Document type Letter ; Comment
    ZDB-ID 3306-6
    ISSN 1474-547X ; 0023-7507 ; 0140-6736
    ISSN (online) 1474-547X
    ISSN 0023-7507 ; 0140-6736
    DOI 10.1016/S0140-6736(19)30227-2
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  9. Article ; Online: Will the COVID-19 pandemic boost access to personal health care records? Smartphone data access to tackle the modern pandemic

    Breeze, Charles Edmund / Murkin, Charlotte / Lechner, Matt

    BMJ Innovations

    2020  , Page(s) bmjinnov–2020–000561

    Keywords General Medicine ; covid19
    Language English
    Publisher BMJ
    Publishing country uk
    Document type Article ; Online
    ISSN 2055-8074
    DOI 10.1136/bmjinnov-2020-000561
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Gender-neutral HPV vaccination in the UK, rising male oropharyngeal cancer rates, and lack of HPV awareness.

    Lechner, Matt / Jones, Oliver S / Breeze, Charles E / Gilson, Richard

    The Lancet. Infectious diseases

    2019  Volume 19, Issue 2, Page(s) 131–132

    MeSH term(s) Adolescent ; Adult ; Awareness ; Child ; Female ; Health Knowledge, Attitudes, Practice ; Humans ; Incidence ; Male ; Neoplasms, Squamous Cell/epidemiology ; Neoplasms, Squamous Cell/etiology ; Oropharyngeal Neoplasms/epidemiology ; Oropharyngeal Neoplasms/etiology ; Papillomaviridae/immunology ; Papillomavirus Infections/complications ; Papillomavirus Infections/prevention & control ; Papillomavirus Infections/virology ; Papillomavirus Vaccines ; United Kingdom/epidemiology ; Vaccination
    Chemical Substances Papillomavirus Vaccines
    Language English
    Publishing date 2019-01-30
    Publishing country United States
    Document type Letter
    ZDB-ID 2061641-7
    ISSN 1474-4457 ; 1473-3099
    ISSN (online) 1474-4457
    ISSN 1473-3099
    DOI 10.1016/S1473-3099(18)30802-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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