Running LIRICAL with a Phenopacket file

LIRICAL can be run with clinical data (HPO terms) only or with clinical data and a VCF file representing the results of gene panel, exome, or genome sequencing. The prefered input format is Phenopackets, an open standard for sharing disease and phenotype information. This is a new standard of the Global Alliance for Genomics and Health that links detailed phenotype descriptions with disease, patient, and genetic information (The other allowed input format is YAML. See Running LIRICAL with a YAML file (HPO and VCF data)).

Preparing Phenopacket-formatted data

See the Phenopackets website for details on the format. LIRICAL expects the Phenopacket to be in JSON format. The following example shows a phenopacket representing an individual with Pfeiffer syndrome.

{
    "subject": {
        "id": "example-1"
    },
    "phenotypicFeatures": [{
        "type": {
            "id": "HP:0000244",
            "label": "Turribrachycephaly"
        },
        "classOfOnset": {
            "id": "HP:0003577",
            "label": "Congenital onset"
        }
    }, {
        "type": {
            "id": "HP:0001363",
            "label": "Craniosynostosis"
        },
        "classOfOnset": {
            "id": "HP:0003577",
            "label": "Congenital onset"
         }
    }, {
        "type": {
            "id": "HP:0000453",
            "label": "Choanal atresia"
        },
        "classOfOnset": {
        "id": "HP:0003577",
        "label": "Congenital onset"
         }
    }, {
        "type": {
            "id": "HP:0000327",
        "label": "Hypoplasia of the maxilla"
        },
        "classOfOnset": {
            "id": "HP:0003577",
            "label": "Congenital onset"
        }
    }, {
        "type": {
            "id": "HP:0000238",
            "label": "Hydrocephalus"
    },
        "classOfOnset": {
            "id": "HP:0003577",
            "label": "Congenital onset"
    }
    }],
    "metaData": {
        "createdBy": "Peter R.",
        "resources": [{
            "id": "hp",
            "name": "human phenotype ontology",
            "namespacePrefix": "HP",
            "url": "http://purl.obolibrary.org/obo/hp.owl",
            "version": "2018-03-08",
            "iriPrefix": "http://purl.obolibrary.org/obo/HP_"
        }]
    }
}

Running LIRICAL with clinical data

LIRICAL will perform phenotype-only analysis if the Phenopacket does not contain a htsFiles element. In this case, the only required argument is the phenopacket.

$ java -jar LIRICAL.jar phenopacket -p /path/to/example.json

LIRICAL Options for clinical/genomic analysis

The following options can be use to alter the default behavior of LIRICAL

-d, --data <directory>

By default, LIRICAL downloads several data files to a directory called data that it creates in the current working directory. If you download these files to some other directory, then you will need to indicate that path with this option.

-m, --mindiff <int>

By default, LIRICAL shows all differential diagnoses with a posterior probability of at least 1%, and at least 10 entries regardless of the posterior probability. If you want LIRICAL to show details about more differentials, set this option to the desired number.

-t, --threshold

This option controls the minimum post-test probability to show a differential diagnosis in HTML output. By default, LIRICAL shows all differentials with a posterior probability of 1% or greater.

-x, --prefix

The output file will be either prefix.html or prefix.tsv, whereby prefix can be set with this option (e.g., -x example would cause LIRICAL to output example.html). By default, the prefix is set to “lirical”.

-o, --output-directory

Directory into which to write output file(s).

--tsv

Use TSV instead of HTML output (Default: false).

--orpha

Use annotation data from Orphanet.

Output

See LIRICAL Output for details on the HTML and TSV output files.