MbShea@PWP@English@UMCP

ABSTRACT: DNA methylation is a significant mechanism in many biological phenomena including gene transcription and complex disease. However, it is often difficult to draw conclusive links between methylation or differential methylation and biological functions. We thus introduce a novel technique that isolates significant differentially methylated positions and maps the results to histone modification regions of the same cell type. We mapped these overlapping DMPs to genes and use functional annotation tools to test the significance of our results. We tested our method on data from peripheral blood samples of 51 healthy children before and after pubertal onset, and we found that differential methylation was most significant in the TRIP6 and KCNAB3 genes. We also found 4209 significant differentially methylated positions that overlapped with histone modification regions. We functionally annotated the genes that corresponded with the 4209 DMPs and we found that our results corresponded to transcription factor binding with a p-value less that 0.0001% (p<0.0000001). We tested our method using random samples of 4209 DMPs and histone modification data from different cell types and got insignificant results. We thus conclude that our method is able to compare methylation data and data from regulatory regions in order to focus on differentially methylated genes that correspond to a regulatory event in a significant way. These results do not conclusively draw biological links, but the method gives us a streamlined way to isolate genes that are worth further studying.

WC = 238
READER’S PROFILE: I imagine a reader may be skeptical of the results because they have not been used to make biological conclusions.

READER’S RESPONSE: I find the results a little too abstract. I wish the researchers would have elaborated more on the biological significance of the results and not just the methodological implications.

V -- that difficult reader may be reflecting some discomfort with the complexity of bioinformatics. Most life scientists are new to this vetting of information or -- as you note -- a kind of method. This will improve eventually.

How long is this document now?