Andy
Assignment for Tuesday: Run a trisomic vs disomic comparison.
Interpreting Data: What do we want to look at? How do we make sense of the numbers? Fold change is important but so is base mean transcription level. The first data set entered will be the numerator of any fold change numbers!
It's being created right now:
Write introduction that conveys understanding of the study we will be conducting. Looking at mice that have been controlled for maternal vs paternal trisomy inheritance. We have the transcription data and are looking for differential expression
Good trisomy info with some genes of interest: http://www.ds-health.com/trisomy.htm
stylizing: human genes are all caps and italicized non-human are only italicized
proteins are the same name but not italicized
PAPER NOTES
“Trisomy 21 Alters DNA Methylation in Parent- of-Origin-Dependent and -Independent Manners” In this article, researchers found a reliable way to distinguish maternal and paternal inheritance of the extra chromosome that produces Down syndrome. This method relies on the gene imprinting in a differentially methylated region named WRB, and specifically in CpG island 2. Because we are working with embryonic stem cells we expect this region to hypomethylated and uninformative as to the Researchers reported a parent-of-origin-dependent methylation status at two genes, RUNX1 and TMEM131. RUNX1 was found to be differentially methylated independent of parent of origin when compared to disomic individuals. This means it could function as a marker by which to check the WRB on was found to be differentially methylated based on parent of origin, but only in mature cells and not in embryonic stem cells. This makes the promise of finding differential expression in our mouse embryonic stem cells unlikely, but we should investigate anyway, to find out if this non-differntial methylation is conserved in our embryonic stem cells. Transcriptome analysis of WRB in embryonic stem cells revealed biallelic expression and so this should be investigated in our experiments as well.
“Domains of genome-wide gene expression dysregulation in Down’s syndrome” Some down syndrome models are based only on the triplication of certain genes (SIM2, DYRK1A). The main differences of expression between discordant twins were clustered in differential gene expression domains. EdgeR used to evaluate the differential expression between the twins’ fibroblast cells. When comparing the T1DS to T2N, 337 GEDDs (Gene expression disregulation domains). When creating iPS cells from the twin fibroblasts, researchers found that the GEDD differential expression was largerly preserved and concluded that “GEDDs are conserved after dedifferentiation and that supernumerary HSA21 has similar effects in the genome-wide dysregulation of gene expression.” GEDDs are also conserved in syntenic regions of the Ts65Dn mouse model. Ie they are chromosome non-specificially dysregulated. “The observed conservation also indi- cates that trisomy 21 has a consistent influence on the transcriptome of iPS cells“
Questions:
Can we combine p-values in this case?
What do you think is the appropriate level of detail for these?
Imprinting vs overview of the genes- audience is class of JAX or both?
