CHEERS (Chromatin Element Enrichment Ranking by Specificity) is a method to determine enrichment of annotations in GWAS significant loci. In addition to SNP-peak overlap, CHEERS takes into account peak properties as reflected by quantitative changes in read counts within peaks. Main code by Blagoje Soskic. LD calculation by Lara Bossini-Castillo.
CHEERS is written for Python 2.7. Please see the branch python3 for a Python3.8 version and a script to create test data. It uses the following modules:
os
sys
glob
re
subprocess
time
numpy
pandas
argparse
scipy
math
Description:
For a list of SNPs, it finds all the SNPs in LD (r2>0.8).
Usage:
Create a directory named after the trait. Then move into the directory and run the command.
mkdir trait_name
cd trait_name
python create_LD_blocks.py SNP_LIST OUTPUT_DIR LD_DIR
We uploaded the GRCh38 LD files to ftp://ngs.sanger.ac.uk/production. They are in the trynka/LD_GRCh38/ directory.
Output:
Parent directory is the name of the trait; within that directory there are subdirectories for all the chromosomes (chr1, chr2...) and within each of these there are .txt files named after the lead SNP (for example results_ld_rs9989735.txt). Each file contains all the SNPs in the LD with the lead (python indexing: snp name is at position 3, chr at position 0 and base pair information is at position 4)
Description:
This script is used to normalize read counts within peaks. It :
- loads output of featureCounts (*_ReadsInPeaks.txt - each txt file is a sample that contains 4 tab delimited columns without header: chr, start, end, count )
- scales read counts to the largest library size
- removes the bottom 10th percentile of peaks with the lowest read counts
- quantile normalizes the library size-corrected peak counts
- performs Euclidean normalization to obtain a cell type specificity score
Arguments:
-h, --help show this help message and exit
--input INPUT path to files with read counts per peak (default: None)
--prefix PREFIX file prefix (default: None)
--outdir OUTDIR directory where to output results (default: None)
Outputs:
prefix_normToMax.txt
prefix_normToMax_quantileNorm.txt
prefix_normToMax_quantileNorm_euclideanNorm.txt
Usage:
python CHEERS_normalize.py --input ~/peak/counts/per/sample/ --prefix prefix --outdir ~/output/directory/
Description:
This script computes the disease enrichment of a provided set of SNPs and writes the output to tab-delimited files. It takes 4 inputs to calculate the enrichment p-value:
- Output from CHEERS_normalize.py. This is text file containing peak coordinates and specificity scores for each of the analyzed samples (output_normToMax_quantileNorm_euclideanNorm.txt).
- Output from create_LD_blocks.py - directory with LD information for each SNP. Alternatively provide txt file with fine-mapped SNP set
- trait name that will be used for output prefix
- Directory where to output results
Arguments:
-h, --help show this help message and exit
--input INPUT Text file containing peak coordinates and specificity
scores for each of the analyzed samples (default: None)
--ld LD Directory with LD information for each SNP (default: None)
--snp_list SNP_LIST list of SNPs if CHEERS is used on finemapped set
(default: None)
--trait TRAIT Name of the analyzed trait (default: None)
--outdir OUTDIR Directory where to output results (default: None)
Outputs:
trait_uniquePeaks.txt - list of unique peaks and their ranks per sample
trait _SNPsOverlappingPeaks.txt - list of all overlapping SNPs and peak ranks per sample
trait _disease_enrichment_pValues.txt - enrichment p-values per sample
trait _disease_enrichment_observedMeanRank.txt - observed mean ranks per sample
trait.log - log file containing run information
Usage:
python CHEERS_computeEnrichment.py --input normToMax_quantileNorm_euclideanNorm.txt --ld ~/LD/trait/ --trait trait_name --outdir ~/output/directory/
or
python CHEERS_computeEnrichment.py --input data.txt --snp_list snp_list.txt --trait trait_name --outdir ~/output/directory/