Upon review of these recent technologies for assessing effects of ethanol on the methylome, it is clear that specific advances have been made. Whole-genome sequencing or at least CpG-region-targeted sequencing of bisulfite-treated DNA should now be considered to be the norm. Bioinformatic workflows have been established for analyzing such genome-wide datasets, such as the Bismark package (Krueger, Andrews 2011) that was used as an example. Validation methods provide not only precise measurements of selected regulatory regions, but they also verify that choices made during data filtering were appropriate. It seems clear that with the current state of technology, whole genome bisulfite sequencing, or at least sequencing of selected genomic regions, should be used for future studies to obtain the highest-resolution, most reliable data. Biological models of alcohol exposure in fetal brain precursors should consider the validity of the model (cells vs. tissue; monolayer cultures vs. organoids, for example) and the dosage and exposure schedule for alcohol treatment. Understanding the role of ethanol in the etiology of disorders such as AUD and FAS is important and therefore the techniques used to investigate specific mechanisms must be acceptable by the scientific community.
