Can we correlate RNA expression and DNase hypersensitivity sites in DNA domains? David John Haan...
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Transcript of Can we correlate RNA expression and DNase hypersensitivity sites in DNA domains? David John Haan...
![Page 1: Can we correlate RNA expression and DNase hypersensitivity sites in DNA domains? David John Haan Stuart’s Lab Nov 20, 2014 UCSC.](https://reader030.fdocuments.in/reader030/viewer/2022032723/56649d1a5503460f949ef40d/html5/thumbnails/1.jpg)
Can we correlate RNA expression and DNase hypersensitivity sites in DNA domains?
David John HaanStuart’s Lab
Nov 20, 2014UCSC
![Page 2: Can we correlate RNA expression and DNase hypersensitivity sites in DNA domains? David John Haan Stuart’s Lab Nov 20, 2014 UCSC.](https://reader030.fdocuments.in/reader030/viewer/2022032723/56649d1a5503460f949ef40d/html5/thumbnails/2.jpg)
Topological Associated Domains (TAD)
• Megabase-sized local chromatin interaction domains
• Determined thru HiC Assay
![Page 3: Can we correlate RNA expression and DNase hypersensitivity sites in DNA domains? David John Haan Stuart’s Lab Nov 20, 2014 UCSC.](https://reader030.fdocuments.in/reader030/viewer/2022032723/56649d1a5503460f949ef40d/html5/thumbnails/3.jpg)
GTEX Portal RNAseq Data2,921 samples
![Page 4: Can we correlate RNA expression and DNase hypersensitivity sites in DNA domains? David John Haan Stuart’s Lab Nov 20, 2014 UCSC.](https://reader030.fdocuments.in/reader030/viewer/2022032723/56649d1a5503460f949ef40d/html5/thumbnails/4.jpg)
“Wrangle” the Data!• HiC Assay Domain data:
• GTEX RNAseq Data in RPKMs:
• Take the mean of each domain and each tissue type
Gene Pancreas1 Pancreas2 Heart1CMA1 61.305 44.22 17.085CTSG 100.5 21.105 53.265GZMH 4.02 86.43 89.445GZMB 64.32 85.425 39.195STXBP6 14.07 97.485 8.04
chr14_24960000_26280000 CMA1 CTSG GZMH GZMB STXBP6
chr14_26560000_28200000 MIR4307 NOVA1
chr14_29080000_30080000 FOXG1 C14orf23 MIR548AI PRKD1
chr14_30160000_30920000 MIR548AI PRKD1
![Page 5: Can we correlate RNA expression and DNase hypersensitivity sites in DNA domains? David John Haan Stuart’s Lab Nov 20, 2014 UCSC.](https://reader030.fdocuments.in/reader030/viewer/2022032723/56649d1a5503460f949ef40d/html5/thumbnails/5.jpg)
GTEX RNAseq expression in 150 most variable domains
Tissue Type
High Expression
Low Expression
DN
A D
omai
ns
![Page 6: Can we correlate RNA expression and DNase hypersensitivity sites in DNA domains? David John Haan Stuart’s Lab Nov 20, 2014 UCSC.](https://reader030.fdocuments.in/reader030/viewer/2022032723/56649d1a5503460f949ef40d/html5/thumbnails/6.jpg)
DNase Hypersensitivity Sites
These 5 tissue samples are from the Human Epigenome Atlas
DNase HS assay is an adequate assay to determine if a domain is open for transcription
![Page 7: Can we correlate RNA expression and DNase hypersensitivity sites in DNA domains? David John Haan Stuart’s Lab Nov 20, 2014 UCSC.](https://reader030.fdocuments.in/reader030/viewer/2022032723/56649d1a5503460f949ef40d/html5/thumbnails/7.jpg)
Pancreas DNase coverage Vs RNA level
Points in red are significantly (p<.05) more expressed in Pancreas than other tissues determined by a right sided t-test.
![Page 8: Can we correlate RNA expression and DNase hypersensitivity sites in DNA domains? David John Haan Stuart’s Lab Nov 20, 2014 UCSC.](https://reader030.fdocuments.in/reader030/viewer/2022032723/56649d1a5503460f949ef40d/html5/thumbnails/8.jpg)
How does pancreas HS coverage in DNA domains differ from other tissue types?
![Page 9: Can we correlate RNA expression and DNase hypersensitivity sites in DNA domains? David John Haan Stuart’s Lab Nov 20, 2014 UCSC.](https://reader030.fdocuments.in/reader030/viewer/2022032723/56649d1a5503460f949ef40d/html5/thumbnails/9.jpg)
Pancreas HS differential insignificantly expressed Domains
SOX9 – progenitor geneREG Family
![Page 10: Can we correlate RNA expression and DNase hypersensitivity sites in DNA domains? David John Haan Stuart’s Lab Nov 20, 2014 UCSC.](https://reader030.fdocuments.in/reader030/viewer/2022032723/56649d1a5503460f949ef40d/html5/thumbnails/10.jpg)
More tests: Heart and Ovary
![Page 11: Can we correlate RNA expression and DNase hypersensitivity sites in DNA domains? David John Haan Stuart’s Lab Nov 20, 2014 UCSC.](https://reader030.fdocuments.in/reader030/viewer/2022032723/56649d1a5503460f949ef40d/html5/thumbnails/11.jpg)
Future direction
• Use more DNase hypersensitivity data
• Gene-specific analysis
• Analyze tissue specific “closed” domains
• Compare domains among tissue types including cancer
• Integrating domains into pathway models
![Page 12: Can we correlate RNA expression and DNase hypersensitivity sites in DNA domains? David John Haan Stuart’s Lab Nov 20, 2014 UCSC.](https://reader030.fdocuments.in/reader030/viewer/2022032723/56649d1a5503460f949ef40d/html5/thumbnails/12.jpg)
Thank you
• Josh’s lab specifically Josh Stuart, Dan Carlin, Kiley Graim, and Evan Paull
• Charles Markello for helping create the t-test
• Evan for helping determine what I need (or don’t need) on my bike to get up the hill faster
![Page 13: Can we correlate RNA expression and DNase hypersensitivity sites in DNA domains? David John Haan Stuart’s Lab Nov 20, 2014 UCSC.](https://reader030.fdocuments.in/reader030/viewer/2022032723/56649d1a5503460f949ef40d/html5/thumbnails/13.jpg)
Pancreas HS differential VSsignificantly expressed Breast domains
*No Correlation!!!
In black is the Dnase HS coverage differential plot
In red/blue is a density plot of significant expression levels