Change Log

This page highlights major updates to PharmCAT (starting with v2.10.0).

If you are looking for details on releases, please visit the PharmCAT GitHub Releases page. If you'd like to learn more about how we version PharmCAT, check out our page on versioning and releases. Finally, you can subscribe to PharmCAT release notifications by following these instructions. This method will require a GitHub account.

v3.0.0

Key New Features

• Phase Set Support - Addresses issue [#175], enabling support for phase sets in VCF (the PS genotype field).
• New TSV Reports - Produce focused reports on allele calls that that eliminates the complexity and verbosity of PharmCAT's JSON reports. Learn more in the TSV Reports documentation.
• Allele Frequency Analysis - Leverage the new TSV reports to run frequency analysis, with support for arbitrary sample metadata to enable pivot column analysis as well. Instructions are available in the allele frequence analysis documentation.
• NAT2 Alelle Calling - Enable calling NAT2 alleles with a new mechanism that uses frequency analysis to help call unphased data. See the NAT2 for details. NAT2 allele function, phenotypes, and recommendations will be included when available through CPIC.

⚠ BREAKING CHANGES

• VCF Preprocessor
  • The preprocessor script name has been updated to pharmcat_vcf_preprocessor (.py extension removed).
  • The Python package name has been changed from preprocessor to pcat. If you directly use the PharmCAT Python code in your scripts, update your imports to use the new package name.
• PharmCAT
  • If any reporter output format is requested, all desired formats must be specified. Before 3.0, the PharmCAT reporter would always produce HTML format in addition to any requested formats (e.g. JSON format). Now, if any format is specified, it will only produce the requested formats. To get the same output as before, use the -reporterJson -reporterHtml flags. If no format is specified, the behavior remains the same - the HTML output will be produced by default.
  • JSON data file format has been updated. Many new properties have been added, but the breaking change is renaming the wildtypeAllele property to referenceAllele in both *.phenotype.json and *.report.json files.
  • Combination calls (a research mode flag) will now always return all possible diplotypes

v2.13.0

Added support for FDA drug guidance.

v2.11.0

DPWG removed the recommendation for F5 and hormonal contraceptives for systemic use. The guideline annotation was retired on PharmGKB, and resulted in the removal of F5 from PharmCAT.

v2.10.0

DPYD

DPYD HapB3 is defined by two variants, c.1129-5923C>G (an intronic variant) and c.1236G>A (an exonic variant). PharmVar and CPIC now include and list the variant c.1129-5923C>G separately as this is likely the causal variant leading to a decreased function. CPIC still retains the DPYD HapB3 haplotype definition for cases where only the exonic variant c.1236G>A is tested (e.g. whole-exome sequencing). For more information, see CPIC Guideline for fluoropyrimidines and DPYD.

This change prompted the following PharmCAT updates:

• If c.1236G>A (the exonic defining variant of DPYD HapB3) is missing, PharmCAT will use the intronic variant c.1129-5923C>G.
• If c.1129-5923C>G and c.1236G>A do not agree, PharmCAT will use c.1129-5923C>G and also report the presence of c.1236G>A in the input.
• DPYD HapB3 will be reported if both of its defining variants c.1236G>A and c.1129-5923C>G are present and “in sync” with each other in the input VCF file.

RYR1

In December 2023, CPIC added additional 291 variants that were included in the ClinGen variant curation expert panel (VCEP) recommendations for RYR1 pathogenicity. PharmCAT accommodates these changes by updating the Named Allele Matcher module. The Name Allele Matcher now will report all RYR1 variants found in an individual.

CPIC RYR1 phenotypes are determined based on the function combinations of two RYR1 variants. PharmCAT will prioritize the variants with Malignant Hyperthermia-associated function for individuals with more than two variants. If the input VCF file is not phased, PharmCAT assumes an individual to have two or more Malignant Hyperthermia-associated variants on different chromosomes. PharmCAT prioritizes variants with Malignant Hyperthermia-associated function when determining the RYR1 phenotype for an individual.