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Series GSE42409 Query DataSets for GSE42409
Status Public on Mar 04, 2013
Title Additional annotation enhances potential for biologically-relevant analysis of the Illumina Infinium HumanMethylation450 BeadChip array
Organism Homo sapiens
Experiment type Methylation profiling by array
Summary ******************************************************************


Background: Measurement of genome-wide DNA methylation (DNAm) has become an important avenue for investigating potentially functional changes in various pathological conditions. Illumina Infinium is a relatively inexpensive and user-friendly DNAm microarray platform used by many researchers to measure DNAm on a large scale. However it has been suggested that a subset of probes may give rise to misleading results due to issues related to probe design. To facilitate biologically significant data interpretation, we set out to enhance probe annotation of the newest HumanMethylation450 BeadChip array (with >485,000 probes covering 99% of RefSeq genes).
Results: Annotation that was added or expanded on includes 1) SNPs documented in the probe target, 2) probe binding specificity, 3) CpG classification of target sites and 4) gene feature classification of target sites. Probes with documented SNPs within 10bp of the target site and especially those with documented SNPs at the target CpG, were associated with increased within-tissue variation in DNAm. An example of a probe with a SNP at the target CpG was used to demonstrate how sample genotype can confound the measurement of DNAm. 8.6% of probes were identified as non-specific, in other words, these probes map to multiple locations in silico. DNAm measured from these non-specific probes likely represents a combination of DNAm from multiple genomic sites. The expanded biological annotation demonstrated that based on DNAm, grouping probes by alternative CpG classes rather than UCSC islands provides a more distinctive classification system of CpG sites. Finally variable enrichment for tissue-specific differentially methylated probes was noted across CpG classes and gene feature groups, depending on the tissues that were compared.
Conclusion: Probes containing SNPs and non-specific probes may affect the assessment of DNAm using the 450k array. Additionally CpG enrichment classes and to a lesser extent gene feature groups were associated with distinct patterns of DNAm. Thus, we recommend that confounded probes be removed from analyses and that genomic trends be considered in analyses of the Illumina HumanMethylation450 BeadChip. DNAm arrays offer a powerful approach for which thoughtful use of probe content can be utilized to better understand the biological processes affected.
Overall design Bisulfite converted DNA from 4 buccal, 4 blood and 4 chorionic villus samples was hybridized to the Illumina Infinium HumanMethylation450 BeadChip array.
Contributor(s) Price EM, Cotton AM, Lam LL, Farré P, Emberly E, Brown CJ, Robinson WP, Kobor MS
Citation(s) 23452981
Submission date Nov 20, 2012
Last update date May 17, 2016
Contact name Wendy Robinson
Organization name University of British Columbia
Department Medical Genetics
Lab Robinosn
Street address 950 W 28th Ave
City Vancouver
State/province BC
ZIP/Postal code V5Z 4H4
Country Canada
Platforms (1)
GPL16304 Illumina HumanMethylation450 BeadChip [UBC enhanced annotation v1.0]
Samples (12)
GSM1039475 buccal_control_047
GSM1039476 buccal_control_077
GSM1039477 buccal_control_024
BioProject PRJNA181344

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Supplementary file Size Download File type/resource
GSE42409_Control_probes.txt.gz 56.3 Kb (ftp)(http) TXT
GSE42409_RAW.tar 11.1 Mb (http)(custom) TAR
GSE42409_signal_intensities.txt.gz 25.9 Mb (ftp)(http) TXT
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Raw data is available on Series record
Processed data included within Sample table

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