Journal:

Article Title: Mapping Allele-Specific DNA Methylation: A New Tool for Maximizing Information from GWAS

doi: 10.1016/j.ajhg.2010.01.021

Figure Lengend Snippet: Sequence-Dependent ASM as a Tool for Extracting Maximum Information from GWAS

Article Snippet: Also, microarray-based methods are limited by the annoying fact that only a subset of all SNPs is “chipable.” Microarrays, particularly those with custom designs, will still be very useful for high sample throughput, but Nextgen bisulfite sequencing will inevitably become the way to go for analyzing fewer samples at definitive single-base-pair resolution, ultimately eliminating false negatives from incomplete genomic coverage.

Techniques: Sequencing

Journal: Nature biotechnology

Article Title: Genome-wide mapping of DNA methylation: a quantitative technology comparison

doi: 10.1038/nbt.1681

Figure Lengend Snippet: Genomic coverage was quantified by the number of DNA methylation measurements that overlap with CpG islands (top row), gene promoters (center row) and a 1-kilobase tiling of the genome (bottom row). For MeDIP and MethylCap, the number of measurements is equal to the number of unique sequencing reads that fall inside each region. For RRBS, it refers to the number of valid DNA methylation measurements at CpGs within each region (one RRBS sequencing read typically yields one measurement, but can also give rise to more than one measurement if it contains several CpGs). For Infinium, the number of measurements is equal to the number of CpGs within each region that are present on the HumanMethylation27 microarray. CpG islands were calculated using CgiHunter ( http://cgihunter.bioinf.mpi-inf.mpg.de/ ), requiring a minimum CpG observed vs. expected ratio of 0.6, a minimum GC content of 0.5 and a minimum length of 700 basepairs . Promoter regions were calculated based on Ensembl gene annotations, such that the region starts one kilo-base upstream of the annotated transcription start site (TSS) and extends to one kilobase downstream of the TSS. The genomic tiling was obtained by sliding a 1-kilobase window through the genome such that each tile starts at the position where the previous tile ends. No repeat-masking was performed for any of the three types of genomic regions. Data are shown for the HUES6 human ES cell line.

Article Snippet: We selected MeDIP-seq , MethylCap-seq , RRBS and the Infinium HumanMethylation27 assay for inclusion in this comparison, based on the following considerations: (i) All four methods are relatively easy to set up because detailed protocols have been published and / or commercial kits are available. (ii) We chose RRBS rather than genome-wide bisulfite sequencing because its per-sample cost are comparable to the other methods and realistic for large sample sizes. (iii) The Infinium HumanMethylation27 assay was included because of its wide use and easy integration with existing genotyping pipelines; it is the only microarray-based method in our comparison. (iv) Methods that utilize tiling microarrays were excluded because they have been benchmarked previously and because next-generation sequencing enables higher resolution and/or higher genomic coverage at competitive cost. (v) Methylation-specific digestion was excluded because no algorithm exists that could accurately infer quantitative DNA methylation data from digested read frequencies .

Techniques: DNA Methylation Assay, Methylated DNA Immunoprecipitation, Sequencing, Microarray