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Demo1-captureHiC_promoter_contacts

README.md

Long-range promoter contacts with capture Hi-C

This genome browser demo presents 4 datasets of long-range genome interactions along with human genome assembly GRCh37 (hg19) for comparative studies. These datasets were generated from a Nature Genetics paper Borbala Mifsud et al., Nature Genetics 47, 598-606 (2015). They used Capture Hi-C (CHi-C), an adapted genome conformation assay, to examine the long-range interactions of almost 22,000 promoters in 2 human blood cell types, GM12878 and CD34+. The promoter-promoter and promoter-other interactions were separated as different tracks in the genome browser.

fig

Data preparation for GIVE

The processed significant long-range promoter contacts data in that paper can be downloaded from E-MTAB-2323 of ArrayExpress.

## run these commands in linux shell
wget http://www.ebi.ac.uk/arrayexpress/files/E-MTAB-2323/E-MTAB-2323.additional.1.zip
unzip E-MTAB-2323.additional.1.zip

After unzipping the downloaded file, we got four datasets,

  • TS5_CD34_promoter-promoter_significant_interactions.txt,
  • TS5_GM12878_promoter-promoter_significant_interactions.txt,
  • TS5_CD34_promoter-other_significant_interactions.txt,
  • TS5_GM12878_promoter-other_significant_interactions.txt.

Following table shows the format of the datasets. Columns 1-3 and 7-9 show the coordinates of two genome regions with interactions. The last column can be treated as interaction score. These datasets are based on GRCh37 (hg19) human genome assembly.

chr start end Symbol Ensembl Gene ID expresssion quartile chr start end Symbol Ensembl Gene ID expresssion quartile raw count log(observed/expected)
chr5 140556909 140558389 PCDHB8-001 ENSG00000120322 2 chr5 140558467 140562101 PCDHB16-201 ENSG00000196963 2 338 16.7349171319745
chr3 183266196 183267882 KLHL6-AS1-001 ENSG00000242522 1 chr3 183269400 183277960 KLHL6-001 ENSG00000172578 5 249 16.4555995112416
chr6 26238741 26244133 HIST1H4F-201 ENSG00000198327 5 chr6 26244367 26249842 HIST1H4G-201 ENSG00000124578 1 443 16.2749178680534

We need to convert the datasets to the GIVE supported interaction bed format (the format definition can be found in GIVE Manual). Using simple scripts chic2give.sh and chic2give_directed.sh, we can easily convert them to GIVE interaction bed files, which are named with a prefix give_x_. chic2give_directed.sh is used for promoter-other interactions to assign interaction direction using dirFlag column (see detail in GIVE Manual).

## run these commands in linux shell
# the first two command lines are used for undirected promoter-promoter interactions
bash chic2give.sh TS5_CD34_promoter-promoter_significant_interactions.txt ./
bash chic2give.sh TS5_GM12878_promoter-promoter_significant_interactions.txt ./

# following two command lines are used for directed promoter-other interactions
bash chic2give_directed.sh TS5_CD34_promoter-other_significant_interactions.txt ./
bash chic2give_directed.sh TS5_GM12878_promoter-other_significant_interactions.txt ./

Finally, we got four GIVE interaction bed files,

  • give_x_TS5_CD34_promoter-promoter_significant_interactions.txt,
  • give_x_TS5_CD34_promoter-other_significant_interactions.txt,
  • give_x_TS5_GM12878_promoter-promoter_significant_interactions.txt,
  • give_x_TS5_GM12878_promoter-other_significant_interactions.txt.

The following table shows the GIVE interaction bed format. These datasets can be loaded to GIVE MySQL server.

ID chrom Start End linkID value dirFlag
1 chr20 47889560 47895795 1 16.026310742063 0
2 chr20 47896527 47898203 1 16.026310742063 1
3 chr17 79827812 79838989 2 15.548584214411 0
4 chr17 79848037 79871266 2 15.548584214411 1
5 chr17 27046828 27048611 3 15.5357777367182 0
6 chr17 27048612 27049990 3 15.5357777367182 1

Build track in MariaDB

You need a server to build a genome browser with GIVE. Please read the prerequisites and configuration of GIVE server. In that tutorial page, you will also learn how to prepare MariaDB database and the GIVE Toolbox has information on how to build a reference genome for GIVE. When you have prepared MariaDB and build a hg19 database, you can use GIVE_chicTrack.sql file and following command template to load all the datasets to MariaDB and build the tracks.

## run these commands in linux shell
# change `<your user name>` to your user name of MariaDB
mysql -u `<your user name>` -p <./GIVE_chicTrack.sql

Build genome browser

When you have built tracks in MariaDB, it's very easy to build a genome browser. The following code is what we used to build our demo. You can just copy and paste it in jsfiddle and then you can get the genome browser supported by our GIVE server. If you have built the tracks on your own GIVE server, you only need to replace the url in the code with your own server's url.

<!-- change the url to your own server path -->
<script src="https://www.givengine.org/libWC/webcomponents-lite.min.js"></script> 
<!-- change the url to your own server path-->
<link rel="import" href="https://www.givengine.org/lib/chart-controller/chart-controller.html">
<!-- Embed the browser in your web page -->
<chart-controller title-text="long-range promoter contacts with capture Hi-C" 
    ref="hg19" num-of-subs="2" 
    coordinate='["chr18:19140000-19450000", "chr18:19140000-19450000"]' 
    group-id-list='["genes", "CHi-C_promoter", "customTracks"]'>
</chart-controller>

You can read this tutorial to learn how to simply tweak the genome browser. Our demo is based on the tweaked give_chic.html html file.