This repository contains the code for the paper "Non-coding variants impact cis-regulatory coordination in a cell type-specific manner".

Note

Chromatin modules (CMs) represent sub-TAD hubs encompassing interactions between cis-regulatory elements, such as promoters and enhancers. CMs are charachterized by

• interaction of active promoters with one or more active enhancers simultaneously (median of two-four enhancers),
• preferential scaling at a sub-TAD level and therefore often being <100 kb in size (with median sizes ranging from 32 to 70 kb),
• physical proximity of interacting elements within modules that show enrichment in 3D contacts,
• deposition of histone modifications and binding of TFs in such regions in a coordinated fashion with transcriptional activity being a strong predictor of module formation. For more details, please refer to this review.

Explore CMs online!

This repository contains:

1. Input data used for CM mapping
2. Scripts for CM mapping with VCMtools, Clomics and PHM

Data preparation and CM mapping

I. Preparation steps:

1. Clone the Chromatin modules repository
2. Data preparation
   1. Download test data for LCLs, chr22, or use your own data
   2. Make sure to have ChIP-seq data (used in all methods) in the following format:

#Chr	start	end	pid	did	strand	sample_id_1	sample_id_2	...
22	16192326	16192745	chr22:16192326:16192745	chr22:16192326:16192745	+	-0.212	-0.175	...
22	16204838	16205246	chr22:16204838:16205246	chr22:16204838:16205246	+	-0.221	0.339	...
22	16293852	16294075	chr22:16293852:16294075	chr22:16293852:16294075	+	-0.038	0.0989	...

3. Genotype data in VCF files (used in PHM), see section 3 of this notebook on PHM-specific data preparation

II. CM mapping:

1. Clomics
   1. Install Clomics-2.0.
   2. Adjust paths and parameters in the clomics_example.sh file.
   3. Run the script.
2. VCMtools
   1. Adjust paths and parameters in the vcmtools_example.sh file.
   2. Run the script.
3. PHM
   1. Install PHM.
   2. Prepare data in a PHM-specific format, following the steps explained in this notebook.
   3. Adjust paths and parameters in the 1.phm_example.sh file.
   4. Run the script.

III. CM exploration:

1. Explore CMs from [...]CM.tracks.bed in IGV. Information on CM content, namely CM peak IDs, can be found in [...]CM.content.txt

Upcoming updates

1. Methods for CM reproducibility/similarity scoring
2. CM simulation strategy