This repository contains scripts involved in our workflow for detecting CNVs from WGS data using read depth-based methods.

If you use any of these scripts, please cite:

B. Trost, S. Walker, Z. Wang, B. Thiruvahindrapuram, J.R. MacDonald, W.W.L. Sung, S.L. Pereira, J. Whitney, A.J.S. Chan, G. Pellecchia, M.S. Reuter, S. Lok, R.K.C. Yuen, C.R. Marshall, D. Merico, and S.W. Scherer. A comprehensive workflow for read depth-based identification of copy-number variation from whole-genome sequence data. American Journal of Human Genetics 102(1):142-155, 2018.

This README file lists, and explains the purpose of, each script. The scripts are divided into three categories:

1. "main scripts", which are designed to be called directly;
2. "accessory scripts", which are only meant to be called by/used by the main scripts; and
3. "commands", which are not meant to be called as scripts, but rather contain commands (for running, e.g., BWA, GATK, the CNV detection algorithms) that the user can copy-and-paste, replace placeholder filenames with their own, and then execute sequentially on their system/cluster.

For instructions on each script, as well as example usage, please refer to the comments at the beginning of each one.

• benchmark_overlap_counts.py: Output counts summarizing how CNVs in different categories overlap with the benchmark.
• CNV_overlap.py: Finding overlapping CNV calls from either the CNV-detection algorithms, or different benchmark methods, or both.
• CNV_read_depth_checker.sh: Calculate the ratio between the read depth of a CNV and the read depth of the same-size surrounding regions.
• compare_CNVs_to_benchmark.py: Compare CNVs output from the CNV-detection algorithms to a CNV benchmark.
• compare_with_RLCR_definition.py: Compare CNV calls that have been converted to the common format with the RLCR definition. Requires the "intervaltree" Python module to be installed.
• convert_CNV_calls_to_common_format.py: Convert CNV calls to common format.
• IQR_samtools_depth.sh: Calculates IQR from a BAM file.
• merge_Genome_STRiP.py: Use this script on a Genome STRiP file that has already been converted to the common format using convert_CNV_calls_to_common_format.py in order to merge overlapping calls.
• process_cnvs.erds+.sh: Use this script to perform the CNVnator-ERDS merging that was used in Stage 3 of the study (the analysis of rare, genic CNVs in the Autism Speaks MSSNG cohort).
• reproduce_results.sh: A script that runs all the other main scripts in an appropriate sequence.
• split_HuRef_benchmark.sh: Split the file containing the HuRef benchmark CNVs into separate files, one for each benchmark technology.

• add_features.py: Used by process_cnvs.erds+.sh.
• Canvas.py: Custom library for converting Canvas output to common format.
• cnMOPS.py: Custom library for converting cn.MOPS output to common format.
• CNVnator.py: Custom library for converting CNVnator output to common format.
• CNVworkflowlib.py: Custom library of python functions used by other python scripts.
• ERDS.py: Custom library for converting ERDS output to common format.
• format_cnvnator_results.py: Used by process_cnvs.erds+.sh.
• format_erds_results.py: Used by process_cnvs.erds+.sh.
• functions.py: Used by process_cnvs.erds+.sh.
• Genome_STRiP.py: Custom library for converting Genome_STRiP output to common format.
• get_normalized_depth.py: Used by CNV_read_depth_checker.sh to actually calculate the normalized depth of a CNV.
• index_samtools_depth.py: Used by CNV_read_depth_checker.sh to index a "samtools depth" file for fast use of get_normalized_depth.py.
• IQR_samtools_depth.py: Does most of the work involved in calculating IQR from a BAM file.
• merge_cnvnator_results.py: Used by process_cnvs.erds+.sh.
• merge_erds_results.py: Used by process_cnvs.erds+.sh.
• myvcf.py: Custom library of python functions for dealing with VCF files.
• RDXplorer.py: Custom library for converting RDXplorer output to common format.
• SV.py: Custom library of python functions for representing SVs/CNVs.

• hg19_gap.bed: Used by process_cnvs.erds+.sh

• commands.sh: a list of commands for running BWA and the CNV-detection algorithms