Handout for part V of the Roadmap Epigenomic Workshop

0. Introduction

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

• RECOVER session: H3K4me3 profile over default region in the human genome http://epigenomegateway.wustl.edu/browser/roadmap/?pin=http://epigenomegateway.wustl.edu/browser/roadmap/t/2105449020.json 

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.

• RECOVER session: covariation of H3K4me3 and H3K27me3 over CHRNA7 gene promoter in the human genome http://epigenomegateway.wustl.edu/browser/roadmap/?pin=http://epigenomegateway.wustl.edu/browser/roadmap/t/569628616.json 

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.

• RECOVER session: H3K4me1 profile over 10 kb region surrounding SNP rs756699 http://epigenomegateway.wustl.edu/browser/roadmap/?pin=http://epigenomegateway.wustl.edu/browser/roadmap/t/937810367.json 

• 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.

• RECOVER session: covariation of H3K4me1 profile over the SNP, and RNA-seq profile for TCF7 gene http://epigenomegateway.wustl.edu/browser/roadmap/?pin=http://epigenomegateway.wustl.edu/browser/roadmap/t/1981500908.json 

• 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

• RECOVER session: H3K4me1 profile over 14 SNPs http://epigenomegateway.wustl.edu/browser/roadmap/?pin=http://epigenomegateway.wustl.edu/browser/roadmap/t/681261629.json