besenbacher / dnm_distance

DNM_distance

Requirements

py2bit needs to be installed for the python scripts to work. This can be done using pip:

pip install git+https://github.com/dpryan79/py2bit

For the R plotting script to work the tidyverse and Hmisc packages needs to be installed.

Input files

The de novo mutations should be in a txt file with the following columns: chrom, pos, ref, alt, sample_id. Where sample_id is an identifier of which proband the mutation occured in. The program also requires a bed-file listing which regions are sufficiently covered by the sequencing. Both files needs to be sorted first by chromosome (alphabetically) and then position (numerically).

If no bed-file is available a bed-file listing all chromosomes as covered can be created from a list of chromosome lengths like this:

cat chromSizes_hg38.txt | awk -v OFS="\t" '{print $1,"0",$2}' | sort -k1,1 -k2,2n > all_chromosomes_hg38.bed

The program also requires the a 2bit files with the reference sequence. Such a file can be downloaded from: https://hgdownload.cse.ucsc.edu/goldenpath/{genome}/bigZips/{genome}.2bit where {genome} is a valid UCSC genome assembly name (fx. "hg38").

Example

The DNM_distance script can be run on the example input data from the test_data directory like this:

python src/DNM_distance.py test_data/decode2019_mutations_chr21_chr22_hg38.gor hg38.2bit --bed test_data/all_chromosomes_chr21_chr22_hg38.bed -n100 > test_output_chr21_chr22_n100.txt

Make plot:

./R_scripts/plot_DNM_distances.R test_chr21_chr22_n100.txt test_chr21_chr22_n100_DNM_distances.pdf

To analyse all pairwise mutations:

python src/all_pair_distances.py test_data/decode2019_mutations_chr21_chr22_hg38.gor| gzip > all_pair.txt.gz

Make plot:

./R_scripts/plot_all_pair_results.R all_pair.txt.gz 2976 all_pair_results.pdf

The number is 2976 is the number of probands in the trio data and should be replaced with the right number when the script is run on another dataset.