Epigenetic Signatures Discriminate Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis From Patients With Ulcerative Colitis.
850k methylation array
DNA methylation/methylome
mass cytometry
peripheral blood
primary sclerosing cholangitis
ulcerative colitis
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2022
2022
Historique:
received:
21
12
2021
accepted:
14
02
2022
entrez:
4
4
2022
pubmed:
5
4
2022
medline:
9
4
2022
Statut:
epublish
Résumé
Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease affecting the intra- and extrahepatic bile ducts, and is strongly associated with ulcerative colitis (UC). In this study, we explored the peripheral blood DNA methylome and its immune cell composition in patients with PSC-UC, UC, and healthy controls (HC) with the aim to develop a predictive assay in distinguishing patients with PSC-UC from those with UC alone. The peripheral blood DNA methylome of male patients with PSC and concomitant UC, UC and HCs was profiled using the Illumina HumanMethylation Infinium EPIC BeadChip (850K) array. Differentially methylated CpG position (DMP) and region (DMR) analyses were performed alongside gradient boosting classification analyses to discern PSC-UC from UC patients. As observed differences in the DNA methylome could be the result of differences in cellular populations, we additionally employed mass cytometry (CyTOF) to characterize the immune cell compositions. Genome wide methylation analysis did not reveal large differences between PSC-UC and UC patients nor HCs. Nonetheless, using gradient boosting we were capable of discerning PSC-UC from UC with an area under the receiver operator curve (AUROC) of 0.80. Four CpG sites annotated to the DNA methylation enables discerning PSC-UC from UC patients, with a potential for biomarker development.
Sections du résumé
Background
Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease affecting the intra- and extrahepatic bile ducts, and is strongly associated with ulcerative colitis (UC). In this study, we explored the peripheral blood DNA methylome and its immune cell composition in patients with PSC-UC, UC, and healthy controls (HC) with the aim to develop a predictive assay in distinguishing patients with PSC-UC from those with UC alone.
Methods
The peripheral blood DNA methylome of male patients with PSC and concomitant UC, UC and HCs was profiled using the Illumina HumanMethylation Infinium EPIC BeadChip (850K) array. Differentially methylated CpG position (DMP) and region (DMR) analyses were performed alongside gradient boosting classification analyses to discern PSC-UC from UC patients. As observed differences in the DNA methylome could be the result of differences in cellular populations, we additionally employed mass cytometry (CyTOF) to characterize the immune cell compositions.
Results
Genome wide methylation analysis did not reveal large differences between PSC-UC and UC patients nor HCs. Nonetheless, using gradient boosting we were capable of discerning PSC-UC from UC with an area under the receiver operator curve (AUROC) of 0.80. Four CpG sites annotated to the
Conclusion
DNA methylation enables discerning PSC-UC from UC patients, with a potential for biomarker development.
Identifiants
pubmed: 35371111
doi: 10.3389/fimmu.2022.840935
pmc: PMC8965896
doi:
Substances chimiques
Biomarkers
0
Cell Adhesion Molecules, Neuronal
0
NINJ2 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
840935Informations de copyright
Copyright © 2022 de Krijger, Hageman, Li Yim, Verhoeff, Garcia Vallejo, van Hamersveld, Levin, Hakvoort, Wildenberg, Henneman, Ponsioen and de Jonge.
Déclaration de conflit d'intérêts
Author EL was employed by Horaizon BV. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Aging (Albany NY). 2019 Oct 9;11(19):8526-8541
pubmed: 31597121
Bioinformatics. 2002 Nov;18(11):1427-31
pubmed: 12424112
Gut Microbes. 2021 Jan-Dec;13(1):1993513
pubmed: 34747338
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
Gut. 2021 Jan;70(1):92-105
pubmed: 33106354
Scand J Gastroenterol. 2012 Jul;47(7):820-6
pubmed: 22554193
Semin Liver Dis. 2016 Feb;36(1):5-14
pubmed: 26870928
BMC Genomics. 2015 Nov 09;16:911
pubmed: 26553366
F1000Res. 2014 Jul 30;3:175
pubmed: 25285208
Genome Biol. 2013;14(10):R115
pubmed: 24138928
Genome Biol. 2016 Mar 31;17:61
pubmed: 27036880
PLoS One. 2014 Apr 03;9(4):e93933
pubmed: 24699908
Genome Biol. 2012 Aug 31;13(8):R77
pubmed: 22937822
Am J Hum Genet. 2010 Mar 12;86(3):411-9
pubmed: 20215007
Genome Biol. 2002 Jun 18;3(7):RESEARCH0034
pubmed: 12184808
Lancet. 2014 Jun 7;383(9933):1952-4
pubmed: 24630775
BMC Bioinformatics. 2012 May 08;13:86
pubmed: 22568884
Bioinformatics. 2014 May 15;30(10):1363-9
pubmed: 24478339
J Crohns Colitis. 2016 Jan;10(1):77-86
pubmed: 26419460
Epigenomics. 2009 Oct;1(1):177-200
pubmed: 22122642
Epigenomics. 2020 Aug;12(16):1363-1375
pubmed: 32914644
J Neurosci. 2000 Jan 1;20(1):187-95
pubmed: 10627596
Cancer Res. 2018 Aug 1;78(15):4150-4162
pubmed: 29844124
Nat Biotechnol. 2013 Jun;31(6):545-52
pubmed: 23685480
Liver Int. 2018 Mar;38(3):532-541
pubmed: 28796371
Clin Epigenetics. 2018 Oct 16;10(1):123
pubmed: 30326963
Nat Genet. 2017 Feb;49(2):269-273
pubmed: 27992413
BMC Genomics. 2015 Nov 25;16:1003
pubmed: 26607064
NPJ Genom Med. 2020 Sep 24;5:41
pubmed: 33062306
Nat Genet. 2011 Oct 09;43(11):1066-73
pubmed: 21983784
Anticancer Res. 2019 Nov;39(11):6063-6066
pubmed: 31704833
Genes Dev. 2011 May 15;25(10):1010-22
pubmed: 21576262
J Hepatol. 2012 Aug;57(2):366-75
pubmed: 22521342
Semin Liver Dis. 2017 May;37(2):159-174
pubmed: 28564724
Cancer Epidemiol. 2013 Oct;37(5):732-6
pubmed: 23731550
Hepatology. 2013 Sep;58(3):1074-83
pubmed: 22821403
Cell. 2018 Oct 4;175(2):372-386.e17
pubmed: 30270042
Clin Epigenetics. 2016 Jun 08;8:65
pubmed: 27279921
Gastroenterology. 2017 Jun;152(8):1975-1984.e8
pubmed: 28274849
J Hepatol. 2019 Sep;71(3):603-615
pubmed: 31108158
Nat Rev Immunol. 2006 Mar;6(3):244-51
pubmed: 16498453
Nucleic Acids Res. 2013 Apr;41(7):e90
pubmed: 23476028
Cytometry A. 2020 Feb;97(2):184-198
pubmed: 31737997
Nat Genet. 2013 Jun;45(6):670-5
pubmed: 23603763
Hepatology. 2020 Oct;72(4):1310-1326
pubmed: 33090557
PLoS One. 2018 Oct 31;13(10):e0206511
pubmed: 30379917
Aging (Albany NY). 2016 Sep 28;8(9):1844-1865
pubmed: 27690265
Hepatology. 2013 Dec;58(6):2045-55
pubmed: 23775876
Cytometry A. 2015 Jul;87(7):636-45
pubmed: 25573116
EBioMedicine. 2020 Nov;61:103079
pubmed: 33096472
Cell Signal. 2017 Jul;35:231-241
pubmed: 28431986
Curr Protoc Cytom. 2010 Jul;Chapter 10:Unit10.17
pubmed: 20578106
Clin Dev Immunol. 2006 Jun-Dec;13(2-4):265-71
pubmed: 17162367
Int J Gen Med. 2021 Jan 13;14:89-102
pubmed: 33469348
Blood. 2012 Jan 12;119(2):422-33
pubmed: 22086415
JHEP Rep. 2019 Dec 05;2(1):100060
pubmed: 32039401
Genome Biol. 2018 May 29;19(1):64
pubmed: 29843789
Bioinformatics. 2011 Jun 1;27(11):1571-2
pubmed: 21493656
Forensic Sci Int Genet. 2016 Jan;20:89-100
pubmed: 26520215
Genom Data. 2016 May 26;9:22-4
pubmed: 27330998
Bioinformatics. 2014 Dec 1;30(23):3435-7
pubmed: 25147358
Biochem Biophys Res Commun. 2009 Sep 18;387(2):321-5
pubmed: 19595672
Genome Biol. 2014 Feb 04;15(2):R31
pubmed: 24495553
Microbiol Rev. 1991 Sep;55(3):451-8
pubmed: 1943996
BMC Genomics. 2013 May 01;14:293
pubmed: 23631413
Nucleic Acids Res. 2009 Apr;37(6):e45
pubmed: 19237396
Nat Genet. 2016 May;48(5):510-8
pubmed: 26974007
Nucleic Acids Res. 2017 Feb 28;45(4):e22
pubmed: 27924034
Nat Genet. 2011 Jan;43(1):17-9
pubmed: 21151127
Gut. 2018 Aug;67(8):1517-1524
pubmed: 28779025