How to manage a phased vcf input?

[ManuRodriguezCano]

I have a vcf file with phases and I want to use it as input in Pharmcat, however when using it I see no differences with the file without phases. Do I need to manage it somehow or is there a specific parameter?

• Please tell us about your environment:

  • PharmCAT Version: 2.15.5
  • Environment: [ Linux | Docker ]

[markwoon]

It's really hard help you without more details.

What's the difference between the file with phases and the file without phases? Sample VCF with data on just one chromosome would be enough to help debug. Just make sure the data is de-identified.

[ManuRodriguezCano]

Sorry for the time!
The main difference is that I used the WhatsHap tool, which is responsible for genotype phasing, i.e. assigning the correct alleles to each of the two homologous chromosomes in a sample, using information about the phases of genetic variants. WhatsHap focuses on reconstructing the haplotypes of the variants in a genome, which is particularly useful for complex variants or genes with multiple alleles. This allows for a more accurate representation of genetic variants and is essential in pharmacogenomic analysis.
The main difference between the phased and unphased files is that the phased file includes the | separator in the genotypes, indicating haplotype phasing.
Phased example:

#CHROM POS ID REF ALT QUAL FILTER INFO FORMAT SAMPLE
1 12345 rs123 A G . PASS . GT:DP 0|1:35
1 67890 rs456 C T . PASS . GT:DP 1|0:40

Unphased example:

#CHROM POS ID REF ALT QUAL FILTER INFO FORMAT SAMPLE
1 12345 rs123 A G . PASS . GT:DP 0/1:35
1 67890 rs456 C T . PASS . GT:DP 1/0:40

[markwoon]

OK, but without seeing your actual data, it's hard to see if there actually is a problem.

If the sample is "effectively phased" (i.e. homozygous at all positions or all but 1 position), the result would be the same. Depending on your actual data, what you're seeing may be entirely reasonable.