title: Measuring the methylome in clinical samples: improved processing of the Infinium Human Methylation450 BeadChip Array.
abstract: The Infinium Human Methylation450 BeadChip Array (TM)  (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.
authors.affiliation: Singapore Institute for Clinical Sciences, Agency for Science Technology and Research, Singapore, Singapore.
authors.forename: Hong
authors.initials: H
authors.lastname: Pan
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Shaillay
authors.initials: S
authors.lastname: Dogra
authors.forename: Ai Ling
authors.initials: AL
authors.lastname: Teh
authors.forename: Jun Hao
authors.initials: JH
authors.lastname: Tan
authors.forename: Yubin I
authors.initials: YI
authors.lastname: Lim
authors.forename: Yen Ching
authors.initials: YC
authors.lastname: Lim
authors.forename: Shengnan
authors.initials: S
authors.lastname: Jin
authors.forename: Yew Kok
authors.initials: YK
authors.lastname: Lee
authors.forename: Poh Yong
authors.initials: PY
authors.lastname: Ng
authors.forename: Mei Lyn
authors.initials: ML
authors.lastname: Ong
authors.forename: Shelia
authors.initials: S
authors.lastname: Barton
authors.forename: Yap-Seng
authors.initials: YS
authors.lastname: Chong
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Meaney
authors.forename: Peter D
authors.initials: PD
authors.lastname: Gluckman
authors.forename: Walter
authors.initials: W
authors.lastname: Stunkel
authors.forename: Chunming
authors.initials: C
authors.lastname: Ding
authors.forename: Joanna D
authors.initials: JD
authors.lastname: Holbrook
mesh_terms: D018899:CpG Islands; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic; D015894:Genome, Human; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D017422:Sequence Analysis, DNA / Q000379:methods*