This repo contains pipelines and scripts for phenotype-driven analysis of rare disease cases.

LIRICAL

LIkelihood Ratio Interpretation of Clinical AbnormaLities (LIRICAL) is a tool "... that calculates the likelihood ratio of each observed or excluded phenotypic abnormality. If genomic data is available, likelihood ratios are additionally calculated for genotypes. In contrast to previous approaches based on semantic similarity, LIRICAL provides an estimate of the posttest probability of candidate diagnoses." [Robinson 2020]

LIRICAL Tool Details

Inputs:

• Exomiser reference data directory
• Single-sample VCF
• Phenopacket JSON file that contains:
  • Patient phenotype as a list of HPO terms
  • Path of the single-sample VCF

Outputs:

• HTML file containing user-friendly descriptions and visualizations of top hits
• TSV file containing the full set of results, including ones below the post-test probability threshold.

Example command:

java -jar LIRICAL.jar P -p sample1.phenopacket.json -e /ref_data/exomiser-cli-13.0.0/2109_hg38

Additional Info:

• Phenopacket docs
• LIRICIAL docs

docker

./lirical/docker directory contains files for building a docker image with LIRICAL installed. To build the image, run:

cd docker; make

lirical_pipeline.py

./lirical/lirical_pipeline.py script contains a Hail Batch pipeline for running LIRICAL in parallel on any number of phenopackets. The script uses the step-pipeline library, which is a wrapper around Hail Batch that further simplifies some common aspects of pipeline development.

Requirements:

To install required python libraries, run: python3 -m pip install -r requirements.txt

Example command:

python3 lirical/lirical_pipeline.py \
  -d gs://lirical-reference-data/LIRICAL/data \
  -e gs://lirical-reference-data/exomiser-cli-13.0.0/2109_hg38 \
  --vcf gs://lirical-reference-data/example_inputs/project.NIST.hc.snps.indels.vcf \
  -o gs://your-bucket/LIRICAL_output/ \
  gs://lirical-reference-data/example_inputs/example1.phenopacket.json  

Other Scripts

single_sample_vcf_pipeline.py

single_sample_vcf_pipeline.py is a Hail Batch pipeline that takes a Hail Matrix Table and exports single sample VCF(s) from it.

Example command:

python3 single_sample_vcf_pipeline.py gs://bucket/input.mt -s sample_id1 -s sample_id2 -o gs://output-bucket/path/