[User Story] Replace alt_allele_in_normal filter in TNscope

[mathiasbio]

Need

As a clinician I want to be able to detect somatic variants using a matched normal sample to filter out germline-variants, but I want the filtering-strategy to be appropriately set so that true somatic variants with some minor presence in the normal sample (due to Tumor In Normal Contamination, or artefacts) are not filtered out.

It has been observed specifically for TNscope an issue with the "alt_allele_in_normal filter" for this, and which seems to be way too stringent.

Suggested approach

Remove alt_allele_in_normal filter, and add a bcftools command which we have more control over. Something like this:

bcftools filter -s high_normal_frac -e '(FORMAT/AF[1] / FORMAT/AF[0]) >= 0.5' -m

Where we would set this filter if the normal AF is present at 50% or more of the tumor AF. For example: IF T_AF = 100% N_AF = 100% filter N_AF = 70% filter N_AF = 50% filter N_AF = 49% keep

Perhaps it could be more stringent. But we already have a lot of germline filtering applied.

Considered alternatives

No response

Deviation

No response

System requirements assessed

• [ ] Yes, I have reviewed the system requirements

Requirements affected by this story

No response

Risk assessment needed

• [ ] Needed
• [ ] Not needed

Risk assessment

No response

Can be closed when

The "alt_allele_in_normal filter" from TNscope has removed / replaced.

Blockers

No response

Anything else?

SEE ORIGINAL FEATURE ISSUE FOR MORE INFO! https://github.com/Clinical-Genomics/BALSAMIC/issues/1254

Example: Out of 1511 variants in a matched WGS TN case with only "alt_allele_in_normal" filter se, 1002 of them had a total number of reads supporting the variant = 1

[mathiasbio]

Closing original issue.

[ivadym]

The PR has been merged, should we close it @mathiasbio?

[mathiasbio]

Ah si! :D 🌟