Running LIRICAL with a YAML file (HPO and VCF data)

YAML

Before running LIRICAL, download and built it and set it up according to the instructions on the Setting up LIRICAL page. LIRICAL uses default values for many configuration options (see below), and a simple YAML configuration file would include the following information.

## LIRICAL Analysis Template.
# These are all the possible options for running LIRICAL. Use this as a template for
# your own set-up.
---
analysis:
# hg19 or hg38 is supported
    genomeAssembly: hg19
    vcf: /path/to/example.vcf
    exomiser: /path/to/1811_hg19/
hpoIds: ['HP:0001156', 'HP:0001363', 'HP:0011304', 'HP:0010055']
prefix: example

This file can be found at src/test/resources/yaml/hpo_and_vcf.yml.

In YAML, lines that begin with # are comments, and the three dashes indicate the start of the contents of the file. The analysis element is used to hold a dictionary with options for running the program. The items in analysis refer to the genome assembly and to the paths of files required to run LIRICAL. Users must provide values for genomeAssembly, vcf, and exomiser. Default values will be use for the other three entries if the user does not proviude values.

  1. vcf is the path to the file we want to analyze (required).
  2. exomiser is the path to the Exomiser data directory (see Exomiser database files for details) (required)
  3. genomeAssembly This should be either hg19 (or hg37, which is synonymous) or hg38 (required)
  4. datadir The path with LIRICAL data that should be downloaded before running LIRICAL (see Setting up LIRICAL for details). This option should not be used if the default data location (data) is used.
  5. background_freq Most users will want to use the precomputed background files provided by LIRICAL. In this case, the correct background file (for hg19 or hg38) is determined automatically on the basis of the genomeAssembly. This option should be used to have LIRICAL ingest a custom background file
  6. transcriptdb. This determines the set of transcripts used to call variants. Valid values are UCSC or RefSeq, and the default is UCSC (optional)
  7. global. If the YAML file contains the line global: true then it will not discard candidate diseases with no known disease gene or candidates for which no predicted pathogenic variant was found in the VCF.

Any of the options described in Running LIRICAL with a YAML file (HPO data) can also be used here.

Additionally, hpoIds is a list of HPO term representing the clinical manifestations observed in the individual being analyzed. Finally, prefix is the prefix of the output file (optional, default: lirical) For instance, if the prefix is example1, then the HTML output file will be example1.html. prefix is not used to represent the path to the outfile.

The following YAML file contains values for all of the options.

## LIRICAL Analysis Template.
# These are all the possible options for running LIRICAL. Use this as a template for
# your own set-up.
---
analysis:
# hg19 or hg38 is supported
    genomeAssembly: hg19
    vcf: /Users/peterrobinson/Documents/data/Pfeiffer.vcf
    exomiser: /Users/peterrobinson/Documents/data/exomiser/1802_hg19/
    datadir: /path/to/custom_location1/
    background: /path/to/custom_location2/background-hg38.txt
    transcriptdb: refseq
hpoIds: [ 'HP:0001363', 'HP:0011304', 'HP:0010055']
negatedHpoIds: ['HP:0001328']
prefix: example2
outdir: /path/to/output/directory

This file can be found at src/test/resources/yaml/hpo_and_vcf_mult.yml. This YAML file additionally has a list of HPO terms that represent abnormalities that were excluded in the proband (negatedHpoIds).

You can use either example file as a starting point for your own configuration file.

Running LIRICAL

A typical command that runs LIRICAL using settings shown in the YAML file with the default data directory would be simply

$ java -jar LIRICAL.jar yaml -y example.yml