Epigenetic analysis of Paget’s disease of bone identifies differentially methylated loci that predict disease status
<p dir="ltr">Paget’s disease of bone (PDB) is characterized by focal increases in disorganized bone remodeling. This study aims to characterize PDB-associated changes in DNA methylation profiles in patients’ blood. Meta-analysis of data from the discovery and cross-validation set, ea...
محفوظ في:
| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , , |
| منشور في: |
2021
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| الموضوعات: | |
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| _version_ | 1864513516148359168 |
|---|---|
| author | Ilhame Diboun (3522413) |
| author2 | Sachin Wani (11704868) Stuart H Ralston (9771312) Omar ME Albagha (18456732) |
| author2_role | author author author |
| author_facet | Ilhame Diboun (3522413) Sachin Wani (11704868) Stuart H Ralston (9771312) Omar ME Albagha (18456732) |
| author_role | author |
| dc.creator.none.fl_str_mv | Ilhame Diboun (3522413) Sachin Wani (11704868) Stuart H Ralston (9771312) Omar ME Albagha (18456732) |
| dc.date.none.fl_str_mv | 2021-04-30T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.7554/elife.65715 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Epigenetic_analysis_of_Paget_s_disease_of_bone_identifies_differentially_methylated_loci_that_predict_disease_status/25779786 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Paget’s disease of bone (PDB) Bone remodeling DNA methylation Epigenetics Blood samples Meta-analysis CpG sites |
| dc.title.none.fl_str_mv | Epigenetic analysis of Paget’s disease of bone identifies differentially methylated loci that predict disease status |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Paget’s disease of bone (PDB) is characterized by focal increases in disorganized bone remodeling. This study aims to characterize PDB-associated changes in DNA methylation profiles in patients’ blood. Meta-analysis of data from the discovery and cross-validation set, each comprising 116 PDB cases and 130 controls, revealed significant differences in DNA methylation at 14 CpG sites, 4 CpG islands, and 6 gene-body regions. These loci, including two characterized as functional through expression quantitative trait-methylation analysis, were associated with functions related to osteoclast differentiation, mechanical loading, immune function, and viral infection. A multivariate classifier based on discovery samples was found to discriminate PDB cases and controls from the cross-validation with a sensitivity of 0.84, specificity of 0.81, and an area under curve of 92.8%. In conclusion, this study has shown for the first time that epigenetic factors contribute to the pathogenesis of PDB and may offer diagnostic markers for prediction of the disease.</p><h2>Other Information</h2><p dir="ltr">Published in: eLife<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.7554/elife.65715" target="_blank">https://dx.doi.org/10.7554/elife.65715</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_be531d3e3b84609c3b4f7c812cb0802f |
| identifier_str_mv | 10.7554/elife.65715 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25779786 |
| publishDate | 2021 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Epigenetic analysis of Paget’s disease of bone identifies differentially methylated loci that predict disease statusIlhame Diboun (3522413)Sachin Wani (11704868)Stuart H Ralston (9771312)Omar ME Albagha (18456732)Biological sciencesGeneticsBiomedical and clinical sciencesClinical sciencesPaget’s disease of bone (PDB)Bone remodelingDNA methylationEpigeneticsBlood samplesMeta-analysisCpG sites<p dir="ltr">Paget’s disease of bone (PDB) is characterized by focal increases in disorganized bone remodeling. This study aims to characterize PDB-associated changes in DNA methylation profiles in patients’ blood. Meta-analysis of data from the discovery and cross-validation set, each comprising 116 PDB cases and 130 controls, revealed significant differences in DNA methylation at 14 CpG sites, 4 CpG islands, and 6 gene-body regions. These loci, including two characterized as functional through expression quantitative trait-methylation analysis, were associated with functions related to osteoclast differentiation, mechanical loading, immune function, and viral infection. A multivariate classifier based on discovery samples was found to discriminate PDB cases and controls from the cross-validation with a sensitivity of 0.84, specificity of 0.81, and an area under curve of 92.8%. In conclusion, this study has shown for the first time that epigenetic factors contribute to the pathogenesis of PDB and may offer diagnostic markers for prediction of the disease.</p><h2>Other Information</h2><p dir="ltr">Published in: eLife<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.7554/elife.65715" target="_blank">https://dx.doi.org/10.7554/elife.65715</a></p>2021-04-30T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.7554/elife.65715https://figshare.com/articles/journal_contribution/Epigenetic_analysis_of_Paget_s_disease_of_bone_identifies_differentially_methylated_loci_that_predict_disease_status/25779786CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/257797862021-04-30T03:00:00Z |
| spellingShingle | Epigenetic analysis of Paget’s disease of bone identifies differentially methylated loci that predict disease status Ilhame Diboun (3522413) Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Paget’s disease of bone (PDB) Bone remodeling DNA methylation Epigenetics Blood samples Meta-analysis CpG sites |
| status_str | publishedVersion |
| title | Epigenetic analysis of Paget’s disease of bone identifies differentially methylated loci that predict disease status |
| title_full | Epigenetic analysis of Paget’s disease of bone identifies differentially methylated loci that predict disease status |
| title_fullStr | Epigenetic analysis of Paget’s disease of bone identifies differentially methylated loci that predict disease status |
| title_full_unstemmed | Epigenetic analysis of Paget’s disease of bone identifies differentially methylated loci that predict disease status |
| title_short | Epigenetic analysis of Paget’s disease of bone identifies differentially methylated loci that predict disease status |
| title_sort | Epigenetic analysis of Paget’s disease of bone identifies differentially methylated loci that predict disease status |
| topic | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Paget’s disease of bone (PDB) Bone remodeling DNA methylation Epigenetics Blood samples Meta-analysis CpG sites |