I curated this 2015 Howard Hughes Medical Institute rodent study of DNA methylation because of the reason driving the researchers’ efforts:
“Epigenomic analyses are limited by averaging of population-wide dynamics and do not inform behavior of single cells.
We observe dynamics at the single-cell level not predicted by epigenomic analysis.”
This rationale was also the driving force behind the Is what’s true for a population what’s true for an individual? study and its companion Changing an individual’s future behavior even before they’re born. The methodology of genome-wide association studies (GWAS) usually:
“Focuses on the average effect of alternative alleles averaged in a population.”
What this methodology often missed was:
“When phenotypic variation results from alleles that modify phenotypic variance rather than the mean, this link between genotype and phenotype will not be detected.”
Population-wide genetic statistics don’t necessarily inform us about the activities and attributes of an individual’s genes, even down at the single-cell level.
http://www.pnas.org/content/112/31/E4216.full “The Xist RNA-PRC2 complex at 20-nm resolution reveals a low Xist stoichiometry and suggests a hit-and-run mechanism in mouse cells”