Epigenetic differences at the  HTR2A  locus in progressive multiple sclerosis patients

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

The pathology of progressive multiple sclerosis (MS) is poorly understood. We have previously assessed DNA methylation in the CD4 ⁺ T cells of relapsing–remitting (RR) MS patients compared to healthy controls and identified differentially methylated regions (DMRs) in HLA-DRB1 and RNF39. This study aimed to investigate the DNA methylation profiles of the CD4 ⁺ T cells of progressive MS patients. DNA methylation was measured in two separate case/control cohorts using the Illumina 450K/EPIC arrays and data was analysed with the Chip Analysis Methylation Pipeline (ChAMP). Single nucleotide polymorphisms (SNPs) were assessed using the Illumina Human OmniExpress24 arrays and analysed using PLINK. Expression was assessed using the Illumina HT12 array and analysed in R using a combination of Limma and Illuminaio. We identified three DMRs at HTR2A, SLC17A9 and HDAC4 that were consistent across both cohorts. The DMR at HTR2A is located within the bounds of a haplotype block; however, the DMR remained significant after accounting for SNPs in the region. No expression changes were detected in any DMRs. HTR2A is differentially methylated in progressive MS independent of genotype. This differential methylation is not evident in RRMS, making it a potential biomarker of progressive disease.

Related collections

Most cited references 40

Record: found
Abstract: found
Article: found

Is Open Access

limma powers differential expression analyses for RNA-sequencing and microarray studies

Matthew E. Ritchie, Belinda Phipson, Di Wu … (2015)

limma is an R/Bioconductor software package that provides an integrated solution for analysing data from gene expression experiments. It contains rich features for handling complex experimental designs and for information borrowing to overcome the problem of small sample sizes. Over the past decade, limma has been a popular choice for gene discovery through differential expression analyses of microarray and high-throughput PCR data. The package contains particularly strong facilities for reading, normalizing and exploring such data. Recently, the capabilities of limma have been significantly expanded in two important directions. First, the package can now perform both differential expression and differential splicing analyses of RNA sequencing (RNA-seq) data. All the downstream analysis tools previously restricted to microarray data are now available for RNA-seq as well. These capabilities allow users to analyse both RNA-seq and microarray data with very similar pipelines. Second, the package is now able to go past the traditional gene-wise expression analyses in a variety of ways, analysing expression profiles in terms of co-regulated sets of genes or in terms of higher-order expression signatures. This provides enhanced possibilities for biological interpretation of gene expression differences. This article reviews the philosophy and design of the limma package, summarizing both new and historical features, with an emphasis on recent enhancements and features that have not been previously described.

0 comments Cited 10755 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria

Alan Thompson, Brenda Banwell, Frederik Barkhof … (2018)

The 2010 McDonald criteria for the diagnosis of multiple sclerosis are widely used in research and clinical practice. Scientific advances in the past 7 years suggest that they might no longer provide the most up-to-date guidance for clinicians and researchers. The International Panel on Diagnosis of Multiple Sclerosis reviewed the 2010 McDonald criteria and recommended revisions. The 2017 McDonald criteria continue to apply primarily to patients experiencing a typical clinically isolated syndrome, define what is needed to fulfil dissemination in time and space of lesions in the CNS, and stress the need for no better explanation for the presentation. The following changes were made: in patients with a typical clinically isolated syndrome and clinical or MRI demonstration of dissemination in space, the presence of CSF-specific oligoclonal bands allows a diagnosis of multiple sclerosis; symptomatic lesions can be used to demonstrate dissemination in space or time in patients with supratentorial, infratentorial, or spinal cord syndrome; and cortical lesions can be used to demonstrate dissemination in space. Research to further refine the criteria should focus on optic nerve involvement, validation in diverse populations, and incorporation of advanced imaging, neurophysiological, and body fluid markers.

0 comments Cited 1681 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays.

Martin Aryee, Andrew E Jaffe, Héctor Corrada Bravo … (2014)

The recently released Infinium HumanMethylation450 array (the '450k' array) provides a high-throughput assay to quantify DNA methylation (DNAm) at ∼450 000 loci across a range of genomic features. Although less comprehensive than high-throughput sequencing-based techniques, this product is more cost-effective and promises to be the most widely used DNAm high-throughput measurement technology over the next several years. Here we describe a suite of computational tools that incorporate state-of-the-art statistical techniques for the analysis of DNAm data. The software is structured to easily adapt to future versions of the technology. We include methods for preprocessing, quality assessment and detection of differentially methylated regions from the kilobase to the megabase scale. We show how our software provides a powerful and flexible development platform for future methods. We also illustrate how our methods empower the technology to make discoveries previously thought to be possible only with sequencing-based methods. http://bioconductor.org/packages/release/bioc/html/minfi.html. khansen@jhsph.edu; rafa@jimmy.harvard.edu Supplementary data are available at Bioinformatics online.

0 comments Cited 1109 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Jeannette Lechner-Scott: Jeannette.lechner-scott@hnehealth.nsw.gov.au

Journal

Journal ID (nlm-ta): Sci Rep

Journal ID (iso-abbrev): Sci Rep

Title: Scientific Reports

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2045-2322

Publication date (Electronic): 17 December 2020

Publication date PMC-release: 17 December 2020

Publication date Collection: 2020

Volume: 10

Electronic Location Identifier: 22217

Affiliations

[1 ]GRID grid.266842.c, ISNI 0000 0000 8831 109X, School of Medicine and Public Health, , University of Newcastle, ; Callaghan, NSW 2308 Australia

[2 ]GRID grid.413648.c, Centre for Brain and Mental Health, , Hunter Medical Research Institute, ; New Lambton Heights, NSW 2305 Australia

[3 ]GRID grid.1024.7, ISNI 0000000089150953, Institute of Health and Biomedical Innovations, Genomics Research Centre, , Queensland University of Technology, ; Kelvin Grove, QLD 4059 Australia

[4 ]GRID grid.266842.c, ISNI 0000 0000 8831 109X, School of Biomedical Sciences and Pharmacy, , University of Newcastle, ; Callaghan, NSW 2308 Australia

[5 ]GRID grid.413631.2, ISNI 0000 0000 9468 0801, Centre for Anatomical and Human Sciences, , Hull York Medical School, ; Hull, UK

[6 ]GRID grid.266842.c, ISNI 0000 0000 8831 109X, School of Environmental and Life Sciences, , University of Newcastle, ; Callaghan, NSW 2308 Australia

[7 ]GRID grid.1008.9, ISNI 0000 0001 2179 088X, Department of Medicine, , University of Melbourne, ; Melbourne, VIC Australia

[8 ]GRID grid.416153.4, ISNI 0000 0004 0624 1200, Royal Melbourne Hospital, ; Melbourne, VIC Australia

[9 ]GRID grid.1623.6, ISNI 0000 0004 0432 511X, Alfred Hospital, ; Melbourne, VIC Australia

[10 ]GRID grid.1002.3, ISNI 0000 0004 1936 7857, MS and Neuroimmunology Unit, Central Clinical School, , Monash University, ; Melbourne, VIC Australia

[11 ]GRID grid.414724.0, ISNI 0000 0004 0577 6676, Division of Molecular Genetics, Pathology North, , John Hunter Hospital, ; New Lambton Heights, NSW 2305 Australia

[12 ]GRID grid.413648.c, Centre for Cancer Research, , Hunter Medical Research Institute, ; New Lambton Heights, NSW 2305 Australia

[13 ]GRID grid.414724.0, ISNI 0000 0004 0577 6676, Department of Neurology, , John Hunter Hospital, ; New Lambton Heights, NSW 2305 Australia

Author information

Vicki E. Maltby http://orcid.org/0000-0002-3785-4742

Sean Burnard http://orcid.org/0000-0003-2149-3556

Alexandre Xavier http://orcid.org/0000-0002-6397-051X

Rebecca Seeto http://orcid.org/0000-0002-6807-9638

Article

Publisher ID: 78809

DOI: 10.1038/s41598-020-78809-x

PMC ID: 7747721

PubMed ID: 33335118

SO-VID: 69f62a69-3614-4e02-9378-70213b47bf02

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 1 March 2019

Date accepted : 22 November 2020

Funding

Funded by: Multiple Sclerosis Research Australia (MSRA)

Award ID: 13-037

Award ID: 14-027

Funded by: Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)

Award ID: 320577

Award Recipient : Vicki E. Maltby

Custom metadata

ScienceOpen disciplines: Uncategorized

Keywords: medical research,multiple sclerosis

Data availability:

ScienceOpen disciplines: Uncategorized

Keywords: medical research, multiple sclerosis

Comments

Comment on this article

scite_

Cited by 5

See all cited by

Most referenced authors 989

See all reference authors

Epigenetic differences at the HTR2A locus in progressive multiple sclerosis patients

Read this article at

Abstract

Related collections

International Journal of Medicine and Medical Research

Most cited references 40

limma powers differential expression analyses for RNA-sequencing and microarray studies

Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria

Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays.

Author and article information

Contributors

Journal

Affiliations

Author information

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 170

Cited by 5

Most referenced authors 989