Somatic mutation detection in HLA regions using hg38 alt-aware alignments

Answered

Follow

Elisabetta Manduchi

• April 12, 2022 15:00

Hello, 

I'm interested in identifying somatic mutations (using matched samples) both in the non-HLA and HLA regions.

For the HLA regions, one approach I've used, was to utilize known HLA-typing information about my samples to align to the specific HLA-alleles and then adapting the Mutect2 workflow. My post https://gatk.broadinstitute.org/hc/en-us/community/posts/4417333390619-ApplyBQSR-for-somatic-mutation-detection-in-HLA-regions referred to this approach.

Now, I would instead like to try a different approach, leveraging hg38 and the alt-aware alignments. I found the following (non-production) workflow: https://gatk.broadinstitute.org/hc/en-us/articles/360037498992#6, which has indication on how to call variants on HLA using alt-contigs. I'm wondering if anybody can point me to or can share an analogous workflow, but specific to somatic mutation calls using paired (tumor/normal) samples, aimed at HLA somatic mutation detection.

Thank you. 

 

 

0

• 

  David Benjamin

  • June 13, 2022 17:34

  Hi Elisabetta Manduchi, I'm not aware of anything to point you to for using alt contigs to call somatic variants in the HLA, but a good method along the lines of your first approach is the Polysolver pipeline developed by Sachet Shukla, our friend at MD Anderson Cancer Center.  

  0

  Comment actions Permalink
• 

  Elisabetta Manduchi

  • June 13, 2022 18:26

  Thank you David Benjamin. Indeed my first approach was along the lines of Polysolver. I've also tried to use the Polysolver docker itself as is, which however did not yield any results in my case.

  0

  Comment actions Permalink

Please sign in to leave a comment.