Running the PharmCAT Tool

This document teaches you how to use the core PharmCAT tool.

Prerequisites

This assumes that you are either using Docker or have already set up PharmCAT.

Prepare Your VCF Files

PharmCAT takes VCF files as input.

Please make sure you have read and understand PharmCAT's VCF requirements.

If you are not preparing your VCF files yourself, we highly recommend you run your VCF file through PharmCAT's VCF Preprocessor.

Running PharmCAT

This is the basic command, which will take your VCF file and produce the PharmCAT report:

# java -jar <path_to_pharmcat_jar_file> -vcf <vcf_file>

Where:

-jar <path_to_jar_file>

The compiled PharmCAT Jar file

-vcf <vcf_file>

Input VCF file (must comply with PharmCAT's VCF requirements)

By default, the output will be saved to the same directory as the input VCF file and will use the same base file name. For example:

# java -jar pharmcat.jar -vcf /tmp/sample1.vcf
Saving named allele matcher JSON results to /tmp/sample1.match.json
Saving phenotyper JSON results to /tmp/sample1.phenotype.json
Saving reporter HTML results to /tmp/sample1.report.html

Notice that all intermediary files will be kept.

To control this behavior, provide:

-o <dir>
or --output-dir <dir>

Directory to save files to

-bf <name>
or --base-filename <name>

The base name (without file extensions) used for output files

-del
or --delete-intermediary-files

Delete intermediary output files

Example:

# java -jar pharmcat.jar -vcf /tmp/input.vcf -o /tmp/results -bf sample
Saving named allele matcher JSON results to /tmp/results/sample.match.json
Saving phenotyper JSON results to /tmp/results/sample.phenotype.json
Saving reporter HTML results to /tmp/results/sample.report.html

# java -jar pharmcat.jar -vcf /tmp/input.vcf --output-dir /tmp/results -del
Saving reporter HTML results to /tmp/results/input.report.html

If the provided VCF file contains multiple samples, you can limit which samples get processed with either:

-S <txt_file>
or --sample-file <txt_file>

The list of samples to be processed and prepared for PharmCAT. The file should contain one sample per line.

-s <samples>
or --samples <samples>

A comma-separated list of sample IDs.

Outside Calls

If you need to provide diplotypes directly to PharmCAT, you can do so using an "outside calls" file. You might want to do this for genes that PharmCAT does not call directly, or to override PharmCAT's call.

To do so, provide:

-po <tsv_file>
or --phenotyper-outside-call-file <tsv_file>

Path to an outside call file (TSV)

Example:

# java -jar pharmcat.jar -vcf /tmp/sample.vcf -po /tmp/outside_calls.tsv
Saving named allele matcher JSON results to /tmp/results/sample.match.json
Saving phenotyper JSON results to /tmp/results/sample.phenotype.json
Saving reporter HTML results to /tmp/results/sample.report.html

Advanced Usage

Remember that the PharmCAT tool is composed of 3 modules: the Named Allele Matcher, the Phenotyper, and the Reporter.

graph LR;
  MI{{vcf file}} --> M[Named Allele Matcher];
  M --> P[Phenotyper];
  PI{{"outside call file"}} -. optional .-> P;
  P --> R[Reporter];
  R --> RO([HTML report]);
  class M,P,R module;
  class PI optional;

Each module has its own arguments to customize its behavior.

Named Allele Matcher

-matcher

run Named Allele Matcher

-ma
or --matcher-all-results

return all possible diplotypes, not just top hits

-matcherHtml
or --matcher-save-html

save named allele matcher results as HTML

Phenotyper

-phenotyper

run Phenotyper

-pi <json_file>
or --phenotyper-input <json_file>

JSON results from named allele matcher

-po <tsv_file>
or --phenotyper-outside-call-file <tsv_file>

path to an outside call file (TSV)

Reporter

-reporter

run Reporter

-ri <json_file>
or --reporter-input <json_file>

JSON results from phenotyper

-rt <title>
or --reporter-title <title>

text to add to the report title

-rs <CPIC, DPWG or FDA>
or --reporter-sources <CPIC, DPWG or FDA>

comma-separated list of sources to limit recommendations to (defaults to all)

-re
or --reporter-extended

write an extended report (includes all possible genes and drugs, even if no data is available)

-reporterJson

save reporter results as JSON

Running Individual Modules

Just the Named Allele Matcher

This will call the diplotypes for the input VCF file.

Examples:

# java -jar pharmcat.jar -matcher -vcf /tmp/sample.vcf
Saving named allele matcher JSON results to /tmp/sample.match.json

Just the Phenotyper

This will take matcher and/or call data and output function and phenotype information for them.

Examples:

# java -jar pharmcat.jar -phenotyper -pi /tmp/sample1.match.json
Saving phenotyper JSON results to /tmp/results/sample1.phenotype.json

# java -jar pharmcat.jar -phenotyper -pi /tmp/sample2.match.json -po /tmp/outside_calls.tsv
Saving phenotyper JSON results to /tmp/results/sample2.phenotype.json

# java -jar pharmcat.jar -phenotyper -po /tmp/outside_calls.tsv
Saving phenotyper JSON results to /tmp/results/outside_calls.phenotype.json

Just the Reporter

This will take the phenotyper data and output the relevant drug annotations in a comprehensive HTML report.

Examples:

# java -jar pharmcat.jar -reporter -ri /tmp/sample1.phenotype.json
Saving reporter HTML results to /tmp/results/sample1.report.html

# java -jar pharmcat.jar -reporter -ri /tmp/sample2.phenotype.json -rt "Awesome Report" -reporterJson
Saving reporter JSON results to /tmp/results/sample1.report.json
Saving reporter HTML results to /tmp/results/sample1.report.html

Combinations

Run Named Allele Matcher and Phenotyper:

# java -jar pharmcat.jar -matcher -vcf /tmp/sample1.vcf -phenotyper
Saving named allele matcher JSON results to /tmp/sample1.match.json
Saving phenotyper JSON results to /tmp/results/sample1.phenotype.json

# java -jar pharmcat.jar -matcher -vcf /tmp/sample2.vcf -phenotyper -po /tmp/outside_calls.tsv
Saving named allele matcher JSON results to /tmp/sample2.match.json
Saving phenotyper JSON results to /tmp/results/sample2.phenotype.json

Run Phenotyper and Reporter:

# java -jar pharmcat.jar -phenotyper -pi /tmp/sample1.phenotype.json -po /tmp/outside_calls.tsv -reporter
Saving phenotyper JSON results to /tmp/results/sample1.phenotype.json
Saving reporter HTML results to /tmp/results/sample1.report.html

# java -jar pharmcat.jar -phenotyper -po /tmp/outside_calls.tsv -reporter
Saving phenotyper JSON results to /tmp/results/outside_calls.phenotype.json
Saving reporter HTML results to /tmp/results/outside_calls.report.html

Research Mode Options

PharmCAT has functionality meant for research use only. You can read about these features on the Research Mode page.

Custom Definition Files

Advanced users can provide PharmCAT with custom allele definitions:

-def <dir>
or --definitions-dir <dir>

directory containing named allele definitions (JSON files)

This can be used to get PharmCAT to call diplotypes for genes that PharmCAT does not support by default. Unless these are genes that PharmCAT supports through outside calls, PharmCAT will NOT be able to match them to any recommendations.