Installation

Installation#

Installation process has been tested for python 3.9 and 3.10. Python dev version is needed.

Install HerediClassify#

1. Install general dependencies:#

sudo apt install libpg-dev

2. Install python packages#

pip install -r requirements.txt

3. Install pyensembl database#

bash install_dependencies/install_pyensembl.sh

4. Install non-python dependencies#

The versions indicated have been tested with the tool

bash install_dependencies/install_bedtools.sh -p PATH -v 2.29.1
bash install_dependencies/install_htslib.sh -p PATH -v 1.18
bash install_dependencies/install_samtools.sh -p PATH -v 1.11

Download additional data#

1. Download and format databases#

The script will create a database folder with different subfolders per database. The scripts expects the python dependencies installed above to be available.

bash install_dependencies/download_data.sh -p PATH

2. Annotate ClinVar with SpliceAI#

A ClinVar file annotated with SpliceAI scores is needed for the application of PS1 and PM5. In order to obtain this file manual steps and additional dependencies need to be resolved.

1. Download SpliceAI scores from Illumina

The SpliceAI scores can be found here. Please download the masked indel ans snv file for GRCh38:

  • spliceai_scores.masked.indel.hg38.vcf.gz

  • spliceai_scores.masked.indel.hg38.vcf.gz.tbi

  • spliceai_scores.masked.snv.hg38.vcf.gz

  • spliceai_scores.masked.snv.hg38.vcf.gz.tbi

2. Install ngs-bits

See the ngs-bits github for install instructions.

3. Perform annotation

Use the merge_clinvar_spliceai.sh script to annotate the ClinVar download with the SpliceAI annotations. Make sure to change the paths at the top of the script to match paths on your system.

4. Filtering

Filter the ClinVar file annotated with SpliceAI by using the data_filter_clinvar.py script.

python ../HerediClassify/install_dependencies/data_filter_clinvar.py -i path_to/clinvar_spliceai_all_sorted.vcf.gz

Testing#

Tests are implemented using pytest. To test general functionality execute:

pytest test/