Update F5 gene to Pypgx

[NTNguyen13]

Hi, I found that currently Pypgx does not have some genes in PharmGKB guideline, so I want to contribute my effort into this great open-source package. I start with a 'simple' gene first: F5 only have 1 variant in PGKB, and it's a Level 1A.

As I worked on this, I found that this variant is not quite simple. The gene F5 strand has been flipped when moving up from GRCh37 to GRCh38, which makes a quite confusing case. The guideline states that the risk allele is T, but it was the reference allele in GRCh37. This was changed in GRCh38, into C as the reference allele.

I'm afraid that it may lead to some changes in representation of the diplotype: for example, for homozygous of risk allele TT in GRCh37, no variant will be called => Reference/Reference, while in GRCh38, this variant will be called, and represented as c.1601G>A/c.1601G>A diplotype.

What do you think about this case? I'm making this draft pull request so that we can discuss directly on it.

P/s: Do you have any plan to expand to MT-RNR1 gene, it also level 1A and newly published on CPIC: https://cpicpgx.org/guidelines/cpic-guideline-for-aminoglycosides-and-mt-rnr1/

[sbslee]

@NTNguyen13,

Thanks for this PR! Before I do a thorough review, I want to point out few things:

1. It was very wise of you to start with a simple gene :) By the end of this exercise, I hope we can establish some basic expectations when it comes to the addition of a new gene.
2. "The gene F5 strand has been flipped when moving up from GRCh37 to GRCh38" -> I just checked, and please note that this is not the case. The gene is encoded in the minus strand for both GRCh37 and GRCh38. I think what you are referring to is change in reference allele at the SNP level between GRCh37 and GRCh38, which is actually quite common for PGx genes. For example, if you look at the variant-table.csv file, you will find many variants that have different values in the GRCh37Allele and GRCh38Allele columns (e.g. rs1809810 in CYP2A6 where GRCh37 has 19-41350664-A-T while GRCh38 has 19-40844759-T-A).
3. Note that this does NOT affect diplotype representation because star allele definition in PyPGx already accounts for this discrepancy. For example, if you look at the GRCh37Default and GRCh38Default columns in the gene-table.csv file, you will see that GRCh37 is CYP2D6*2 while GRCh38 is CYP2D6*1. This is because the GRCh37 haplotype already contains two variants that define the CYP2D6*2 allele; therefore, if an individual does not have any CYP2D6 variants and the sequence reads were aligned against GRCh37, we know the individual is homozygous for CYP2D6*2/*2. You can also see this in action from the allele-table.csv file:

>>> import pypgx
>>> pypgx.list_variants('CYP2D6', alleles=['*2'], assembly='GRCh37')
[]
>>> pypgx.list_variants('CYP2D6', alleles=['*2'], assembly='GRCh38')
['22-42126611-C-G', '22-42127941-G-A']

4. I didn't have immediate plans for adding new genes for a while, but I'd be more than happy to review any PRs that include addition of new genes. However, there are many moving parts when it comes to the addition of a new gene, so to minimize any potential errors, I will only review one gene at a time.

I will review this PR soon!

[sbslee]

Thanks for the PR! I know how much tedious things can get when adding a new gene to PyPGx, so great job getting this much done already in your first attempt :) Please look at my suggested changes.

Once this PR is merged, there are some additional steps to be taken. For example, we need to add reference haplotype panel from the 1000 Genomes Project for F5 for both GRCh37 and GRCh38. However, these are things that I need to take care because I have the original VCF files downloaded.

[sbslee]

Everything looks good! Merging this PR.

[sbslee]

@NTNguyen13, just letting you know that I added reference haplotype panel for F5 (983abee)! Now you should be able to genotype F5 with PyPGx :)