HMZDelFinder_opt

HMZDelFinder_opt is a method to detect homozygous and hemizygous (HMZ) deletions, including partial exon deletions in particular, in typical laboratory cohorts of whole exome sequencing (WES) data that are generated over time under different experimental conditions. Specifically, HMZDelFinder_opt selects the K nearest neighbors of the sample of interest based on a PCA-derived coverage distance in order to select, a priori, a reference control set with a coverage profile similar to that of the WES sample studied. In addition, HMZDelFinder_opt uses a sliding window approach to detect HMZ partial exon deletions (deletions spanning less than an exon) that would otherwise be missed.

Prerequisites

• GNU parallel
• mosdepth (0.2.2 or higher)
• R (v3.4 or higher)
  • R 'data.table' library
  • R 'matrixStats' library
  • R 'coop' library
• Python 3

Usage

Create a database

Create a database from scratch using a list of BAM files.

1. Prepare a text file storing the path to your BAM files, one file per line. Absolute or relative path are accepted.

   Example:

   input_bams.list

   /path/to/1.bam
   ../2.bam
   

2. Create a list of intervals at the BED format. Fourth column is optional.

   intervals.bed

   19      18170418        18170423        IL12RB1
   19      18170704        18170895        IL12RB1
   19      18171932        18172007        IL12RB1
   19      18172991        18173087        IL12RB1
   

3. Run the create_db.sh script.

   ./create_db.sh -i input_bams.list -l intervals.bed -o ref_db.bed

   This will create the ref_db.bed file storing the coverage profile of all samples and a ref_db.RData storing the K nearest neighbors of each sample.

Update an existing database with new samples

Samples can be added to an existing database using:

./create_db.sh -i input_bams.list --update ref_db.bed -o ref_db_new.bed

Find HMZ deletions, including partial exon deletions

HMZDelFinder_opt relies on HMZDelFinder to detect HMZ deletions.

Please download HMZDelFinder separately at https://github.com/BCM-Lupskilab/HMZDelFinder and change the path to HMZDelFinder.R inside scripts/run_hmzdelfinder.R

Find homozygous deletions using an interval list:

find_homdel.sh -i input_bams.list -l intervals.bed --db ref_db.bed

Find homozygous deletions using sliding windows on an interval list:

find_homdel.sh -i input_bams.list -l intervals.bed --sliding-windows 100:50 --db ref_db.bed

Here, intervals will be split in windows of 100bp with 50bp overlap to identify HMZ partial exon deletions.