MTHFR.vcf 1kgp pypgx bundle

[nbiesot]

Hi,

First of all, thanks for this tool! I want to add the MTHFR gene and I was wondering where I could find the MTHFR.vcf or how to create it for the 1kgp folder in the pypgx bundle.
Adding the gene to all .csv files was already successful.

Thank you in advance.

[sbslee]

@nbiesot,

Thanks for reaching out! It's exciting to hear that you're planning to add a new gene to PyPGx. As for obtaining the reference haplotype panel VCF file for MTHFR, it needs to be created from the following resources: GRCh37 and GRCh38. If you're unsure how to do this, please let me know. I'd be more than happy to help. If you'd like, I could also review what you have done with the CSV files because things can be tricky.

Best,
Steven

[nbiesot]

Hi Steven,

I would appreciate it if you could provide instructions on how to create the MTHFR VCF file.

Currently, I have only checked whether the tool can identify the variants mentioned on PharmGKB (https://www.pharmgkb.org/gene/PA245/variantAnnotation), not the phenotype.
allele-table.csv
gene-table.csv
phenotype-table.csv
variant-table.csv

Best,
Nienke

[sbslee]

@nbiesot,

Thanks for your patience! I've looked at your files and they all look fantastic. Thanks so much for your contribution. Here's my response:

1. allele-table.csv: You nailed this one.
2. gene-table.csv: This was mostly fine, but I had to make some changes with genomic coordinates. For PyPGx, I use Table Browser from UCSC Genome Browser to get the start/end positions of the transcript and exons for each gene (Group: Genes and Gene Predictions; track: NCBI RefSeq; table: RefSeq All (ncbiRefSeq)).
3. phenotype-table.csv: This is not needed. Indeterminate is the default for genes that don't have any phenotypes.
4. variant-table.csv: You also nailed this one, but I just sorted them by chromosome position.

I uploaded these changes to the 0.23.0-dev branch of pypgx.

As for adding reference haplotype panel in pypgx-bundle, I uploaded it for both GRCh37 and GRCh38 in the 0.23.0-dev branch.

I tested the dev version and confirmed that everything works as expected. I'd greatly appreciate it if you could test it from your end.

Best regards,
Steven

[nbiesot]

Hi Steven,

Thank you for reviewing the files and for uploading the MTHFR reference haplotype panel! I was wondering if you could still provide the steps for making the reference panel?

I have tested the dev version and it works for my samples!

Best,
Nienke

[sbslee]

@nbiesot,

No problem. I used the fuc package's CLI to create the panels for GRCh37 and GRCh38:

$ fuc vcf-slice chr1.1kg.phase3.v5a.vcf.gz 1:11842779-11869021 | fuc fuc-bgzip > MTHFR.vcf.gz
$ fuc vcf-slice CCDG_14151_B01_GRM_WGS_2020-08-05_chr1.filtered.shapeit2-duohmm-phased.vcf.gz 1:11782722-11808964 | fuc fuc-bgzip > MTHFR.vcf.gz

Note that fuc is another Python program I wrote.

I will update the Read the Docs soon to reflect the new gene addition. Please let me know if you have further questions.

[sbslee]

P.S. The fuc package is one of the dependencies for pypgx, so you don't need to install fuc separately.

[nbiesot]

Thank you for the help.

I also want to add the COMT gene. If this was successful and you are interested, I can share the files when it is finished.

[sbslee]

@nbiesot,

That sounds awesome! I'd be more than happy to help.

[nbiesot]

Hi Steven,

Here are the files. I would appreciate it if you could take a look at them. Again, I used the variants described on PharmGKB
allele-table.csv
gene-table.csv
variant-table.csv

[sbslee]

@nbiesot,

Thanks for your contribution! I've only made slight changes to the files and uploaded them to the 0.23.0-dev branch. I'd greatly appreciate if you can test the latest version.

[nbiesot]

Thank you for reviewing the files. I have tested the dev version and it works for my samples!

[sbslee]

@nbiesot, FYI, I just released the official 0.23.0 version to PyPI and Anaconda. Please use this version going forward. Thanks!