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Measuring the methylome in clinical samples: improved processing of the Infinium Human Methylation 450 BeadChip Array

Measuring the methylome in clinical samples: improved processing of the Infinium Human Methylation 450 BeadChip Array
Measuring the methylome in clinical samples: improved processing of the Infinium Human Methylation 450 BeadChip Array
The Infinium Human Methylation450 BeadChip ArrayTM (Infinium 450K) is an important tool for studying epigenetic patterns associated with disease. This array offers a high-throughput, low cost alternative to more comprehensive sequencing-based methodologies. Here we compare data generated by interrogation of the same seven clinical samples by Infinium 450K and reduced representation bisulfite sequencing (RRBS). This is the largest data set comparing Infinium 450K array to the comprehensive RRBS methodology reported so far. We show good agreement between the two methodologies. A read depth of four or more reads in the RRBS data was sufficient to achieve good agreement with Infinium 450K. However, we observe that intermediate methylation values (20–80%) are more variable between technologies than values at the extremes of the bimodal methylation distribution. We describe careful processing of Infinium 450K data to correct for known limitations and batch effects. Using methodologies proposed by others and newly implemented and combined in this report, agreement of Infinium 450K data with independent techniques can be vastly improved.
1559-2294
1173-1187
Pan, H.
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Chen, L.
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Dogra, S.
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Teh, A.L.
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Tan, J.H.
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Lim, Y.I.
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Jin, S.
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Lee, Y.K.
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Ng, P.Y.
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Ong, M.L.
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Barton, S.
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Chong, Y.S.
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Meaney, M.J.
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Gluckman, P.D.
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Stunkel, W.
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Ding, C.
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Holbrook, J.D.
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Pan, H.
c3e588e4-072e-4f05-802a-ab6d47d7358a
Chen, L.
586c0d55-dc72-49c0-a4fa-31df7000ce18
Dogra, S.
31aee96e-9fe2-4830-ad6f-66229b61db0f
Teh, A.L.
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Tan, J.H.
a15e2edf-4053-4887-90ea-563cced6c2eb
Lim, Y.I.
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Jin, S.
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Lee, Y.K.
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Ng, P.Y.
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Ong, M.L.
c673bb86-6e5c-401e-a3e8-5af16f575332
Barton, S.
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Chong, Y.S.
b50c99c9-4d83-46c5-a1c7-23f9a553ab8a
Meaney, M.J.
cb875853-8497-4382-9aff-739714aa49f9
Gluckman, P.D.
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Stunkel, W.
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Ding, C.
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Holbrook, J.D.
070ac5b7-0f42-4425-994a-8135218212d7

Pan, H., Chen, L., Dogra, S., Teh, A.L., Tan, J.H., Lim, Y.I., Jin, S., Lee, Y.K., Ng, P.Y., Ong, M.L., Barton, S., Chong, Y.S., Meaney, M.J., Gluckman, P.D., Stunkel, W., Ding, C. and Holbrook, J.D. (2012) Measuring the methylome in clinical samples: improved processing of the Infinium Human Methylation 450 BeadChip Array. Epigenetics, 7 (10), 1173-1187. (doi:10.4161/epi.22102). (PMID:22964528)

Record type: Article

Abstract

The Infinium Human Methylation450 BeadChip ArrayTM (Infinium 450K) is an important tool for studying epigenetic patterns associated with disease. This array offers a high-throughput, low cost alternative to more comprehensive sequencing-based methodologies. Here we compare data generated by interrogation of the same seven clinical samples by Infinium 450K and reduced representation bisulfite sequencing (RRBS). This is the largest data set comparing Infinium 450K array to the comprehensive RRBS methodology reported so far. We show good agreement between the two methodologies. A read depth of four or more reads in the RRBS data was sufficient to achieve good agreement with Infinium 450K. However, we observe that intermediate methylation values (20–80%) are more variable between technologies than values at the extremes of the bimodal methylation distribution. We describe careful processing of Infinium 450K data to correct for known limitations and batch effects. Using methodologies proposed by others and newly implemented and combined in this report, agreement of Infinium 450K data with independent techniques can be vastly improved.

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Published date: October 2012
Organisations: Faculty of Medicine

Identifiers

Local EPrints ID: 359483
URI: http://eprints.soton.ac.uk/id/eprint/359483
ISSN: 1559-2294
PURE UUID: bae28524-9281-468c-b900-fa08eac3903c
ORCID for S. Barton: ORCID iD orcid.org/0000-0003-4963-4242

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Date deposited: 04 Nov 2013 15:19
Last modified: 09 Jul 2020 00:28

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Contributors

Author: H. Pan
Author: L. Chen
Author: S. Dogra
Author: A.L. Teh
Author: J.H. Tan
Author: Y.I. Lim
Author: S. Jin
Author: Y.K. Lee
Author: P.Y. Ng
Author: M.L. Ong
Author: S. Barton ORCID iD
Author: Y.S. Chong
Author: M.J. Meaney
Author: P.D. Gluckman
Author: W. Stunkel
Author: C. Ding
Author: J.D. Holbrook

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