Handout for part III of the EpiGenome Browser Workshop
We will demonstrate how to make epigenetic annotation to noncoding SNPs using the Roadmap EpiGenome Browser (http://epigenomegateway.wustl.edu/browser/roadmap). The Roadmap Browser is based on the WashU EpiGenome Browser and has dedicated functions for accessing and analyzing huge volume of epigenomics information.
1. Launching the Roadmap EpiGenome Browser
- Choose reference genome
- Choose view range
- Choose epigenetic mark
2. Navigating the Roadmap EpiGenome Browser
- Position the browser to the promoter region of CHRNA7 gene in the human genome.
- Compare the H3K4me3 profiles (marking accessible gene promoters) of many human samples over the CHRNA7 gene promoter region, especially for brain and blood samples, based on hierarchical data clustering analysis.
- Add H3K27me3 mark (marking repressive chromatins) and compare both histone marks over the CHRNA7 gene promoter in the same set of samples.
3. Epigenetic annotation of a noncoding SNP
- rs756699, located at chr5, 133446575 of the human hg19 genome. Found to be associated with multiple sclerosis by GWAS (Sawcer S. Nature, 2011)
- Show H3K4me1 profiles (marking enhancers) over a 5 kb region surrounding this SNP. Observe that the SNP is located in strong H3K4me1 modified-region specifically in blood cells.
- Show RNA-seq profile for a nearby gene TCF7, and observe the co-occurrence of H3K4me1 profile and high expression of TCF7 gene in blood cells, suggesting a potential regulatory relationship between the enhancer and TCF7.
- Conclusion: this SNP is co-localizing with a potential blood-specific enhancer and may contribute to the disruption of TCF7 gene expression.
- Parallel display of the H3K4me1 profiles of many SNPs, by running gene set view on following SNPs. Remember to select 5 kb region surrounding each SNP:
- chr1 10353111 10353112 rs10492972
chr1 85772008 85772009 rs233100
chr1 93303602 93303603 rs6604026
chr1 101331535 101331536 rs12048904
chr1 101407518 101407519 rs11581062
chr1 117038286 117038287 rs12025416
chr1 117100956 117100957 rs1335532
chr1 117104214 117104215 rs2300747
chr1 179469313 179469314 rs12047808
chr10 6099044 6099045 rs2104286
chr10 6102011 6102012 rs12722489
chr10 6110828 6110829 rs7090512
chr10 43814048 43814049 rs2503875
chr10 81036006 81036007 rs1250540
4. Human-mouse epigenome comparison
- Restart the browser, choose both hg19 and mm9 genomes.
- At the view range selection step, choose a new region for hg19, a homologous region will be automatically shown for mm9. Vice versa.
- Launch the browser to display human and mouse epigenomes in parallel fashion. Use a menu function to keep homology relationship between the human and mouse browser panels, e.g. to show orthologous genes.