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A statistical method for single sample analysis of HumanMethylation450 array data: genome-wide methylation analysis of patients with imprinting disorders

A statistical method for single sample analysis of HumanMethylation450 array data: genome-wide methylation analysis of patients with imprinting disorders
A statistical method for single sample analysis of HumanMethylation450 array data: genome-wide methylation analysis of patients with imprinting disorders
Background
The Illumina Infinium HumanMethylation450 BeadChip is an array-based technology for analysing DNA methylation at approximately 475,000 differentially methylated cytosines across the human genome. Hitherto, the array has been used for case-control studies, where sample numbers can be sufficient to yield statistically robust data on a genome-wide basis. We recently reported an informatic pipeline capable of yielding statistically and biologically significant results using only five cases, which expanded the use of this technology to rare disease studies. However, the clinical application of these technologies requires the ability to perform robust analysis of individual patients.

Results
Here we report a novel informatic approach for methylation array analysis of single samples, using the Crawford-Howell t-test. We tested our approach on patients with ultra-rare imprinting disorders with aberrant DNA methylation at multiple locations across the genome, which was previously detected by targeted testing. However, array analysis outperformed targeted assays in three ways: it detected loci not normally analysed by targeted testing, detected methylation changes too subtle to detect by the targeted testing and reported broad and consistent methylation changes across genetic loci not captured by point testing.

Conclusions
This method has potential clinical utility for human disorders where DNA methylation change may be a biomarker of disease.
1868-7075
1-11
Rezwan, Faisal I.
203f8f38-1f5d-485b-ab11-c546b4276338
Docherty, Louise E.
4accb565-e53b-400f-8d62-83935e2ae410
Poole, Rebecca L.
d8fe00fa-9deb-4a34-a7d8-4b7f57ce82fa
Lockett, Gabrielle A.
4d92a28c-f54c-431b-81f6-e82ad9057d7a
Arshad, S. Hasan
917e246d-2e60-472f-8d30-94b01ef28958
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Temple, I. Karen
d63e7c66-9fb0-46c8-855d-ee2607e6c226
Mackay, Deborah J.G.
588a653e-9785-4a00-be71-4e547850ee4a
Rezwan, Faisal I.
203f8f38-1f5d-485b-ab11-c546b4276338
Docherty, Louise E.
4accb565-e53b-400f-8d62-83935e2ae410
Poole, Rebecca L.
d8fe00fa-9deb-4a34-a7d8-4b7f57ce82fa
Lockett, Gabrielle A.
4d92a28c-f54c-431b-81f6-e82ad9057d7a
Arshad, S. Hasan
917e246d-2e60-472f-8d30-94b01ef28958
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Temple, I. Karen
d63e7c66-9fb0-46c8-855d-ee2607e6c226
Mackay, Deborah J.G.
588a653e-9785-4a00-be71-4e547850ee4a

Rezwan, Faisal I., Docherty, Louise E., Poole, Rebecca L., Lockett, Gabrielle A., Arshad, S. Hasan, Holloway, John W., Temple, I. Karen and Mackay, Deborah J.G. (2015) A statistical method for single sample analysis of HumanMethylation450 array data: genome-wide methylation analysis of patients with imprinting disorders. Clinical Epigenetics, 7 (1), 1-11, [48]. (doi:10.1186/s13148-015-0081-5).

Record type: Article

Abstract

Background
The Illumina Infinium HumanMethylation450 BeadChip is an array-based technology for analysing DNA methylation at approximately 475,000 differentially methylated cytosines across the human genome. Hitherto, the array has been used for case-control studies, where sample numbers can be sufficient to yield statistically robust data on a genome-wide basis. We recently reported an informatic pipeline capable of yielding statistically and biologically significant results using only five cases, which expanded the use of this technology to rare disease studies. However, the clinical application of these technologies requires the ability to perform robust analysis of individual patients.

Results
Here we report a novel informatic approach for methylation array analysis of single samples, using the Crawford-Howell t-test. We tested our approach on patients with ultra-rare imprinting disorders with aberrant DNA methylation at multiple locations across the genome, which was previously detected by targeted testing. However, array analysis outperformed targeted assays in three ways: it detected loci not normally analysed by targeted testing, detected methylation changes too subtle to detect by the targeted testing and reported broad and consistent methylation changes across genetic loci not captured by point testing.

Conclusions
This method has potential clinical utility for human disorders where DNA methylation change may be a biomarker of disease.

Full text not available from this repository.

More information

Accepted/In Press date: 6 April 2015
e-pub ahead of print date: 21 April 2015
Published date: 21 April 2015
Organisations: Human Development & Health, Clinical & Experimental Sciences
Learn more about Institute for Life Sciences research

Identifiers

Local EPrints ID: 376628
URI: http://eprints.soton.ac.uk/id/eprint/376628
DOI: doi:10.1186/s13148-015-0081-5
ISSN: 1868-7075
PURE UUID: a0e67b32-d9bf-4b04-96af-2ede9ab22d04
ORCID for Faisal I. Rezwan: ORCID iD orcid.org/0000-0001-9921-222X
ORCID for John W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464
ORCID for I. Karen Temple: ORCID iD orcid.org/0000-0002-6045-1781
ORCID for Deborah J.G. Mackay: ORCID iD orcid.org/0000-0003-3088-4401

Catalogue record

Date deposited: 06 May 2015 11:25
Last modified: 18 Feb 2021 16:52

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Contributors

Author: Faisal I. Rezwan ORCID iD
Author: Louise E. Docherty
Author: Rebecca L. Poole
Author: Gabrielle A. Lockett
Author: S. Hasan Arshad
Author: John W. Holloway ORCID iD
Author: I. Karen Temple ORCID iD
Author: Deborah J.G. Mackay ORCID iD

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