Description

This PR aims to add a post-processing step to TNscope (for standard TGA workflow) to merge SNVs and InDels by their PID to MNVs to be more accurately merged with the VarDict results.

See issue: #1525

The script was taken from Sentieon here: https://github.com/Sentieon/sentieon-scripts/blob/master/merge_mnp/merge_mnp.py

Script has been slightly modified to merge variants despite filters other filters than PASS, this to allow for merging of variants with triallelic-site, and any other future soft-filters we might add. Some refactoring was done as well from the original filter to increase readability. (though it's still very messy)

The TNscope VCF is quality filtered before merging SNVs

To avoid merging of low quality variant to MNVs, the VCF is quality filtered before merging.

Merging SNVs with different filters set

There is an issue about how to consolidate the filters when merging SNVs with different filters set. Such as: germline_risk, in_normal, triallelic_site, and PASS. This was solved with this logic:

1. If all SNVs have the same filter, the final merged MNV gets the common filter from constituent SNVs, such as PASS / in_normal etc
2. If the SNVs have different filters, such as PASS and in_normal, the final merged MNV gets the filter: MNV_CONFLICTING_FILTERS

On top of this, a new INFO field is added called TNSCOPE_MNV_FILTERS which adds the set of all filters from the constituent SNVs and InDels that were merged, which could potentially be displayed in Scout.

Added

• TNscope MNV merge script

Changed

• merge SNVs into MNVs in TNscope TGA
• change raw delivery SNV file for TGA to before any post-processing

Documentation

• N/A
• Updated Balsamic documentation to reflect the changes as needed for this PR.
  • balsamic_filters.rst (updated with TNscope MNV merging)

Tests

Feature Tests

• N/A
• Test that variants are correctly merged, both in terms of stats and positions:
  • See sheet: https://docs.google.com/spreadsheets/d/1pocrlClqrNoDNBAIF_hZMyurMxYe5K649e1iLXPkYhI/edit?gid=1453899946#gid=1453899946

Pipeline Integrity Tests

• Report deliver (generation of the .hk file)
  • N/A
  • Verified
• TGA T/O Workflow
  • N/A
  • Verified
• TGA T/N Workflow
  • N/A
  • Verified
• UMI T/O Workflow
  • N/A
  • Verified
• UMI T/N Workflow
  • N/A
  • Verified
• WGS T/O Workflow
  • N/A
  • Verified
• WGS T/N Workflow
  • N/A
  • Verified
• QC Workflow
  • N/A
  • Verified
• PON Workflow
  • N/A
  • Verified

Clinical Genomics Stockholm

Documentation

• Atlas documentation
  • N/A
  • Updated: [Link]
• Web portal for Clinical Genomics
  • N/A
  • Updated: [Link]

Panel of Normal specific criteria

• The PR includes the addition of a new Panel of Normals
• The samples have been verified to adhere to the sample selection criteria on Atlas PoN creation instructions for Balsamic

User Changes

• N/A
• This PR affects the output files or results.
  • User feedback is considered unnecessary because [Justification].
  • Affected users have been included in the development process and given a chance to provide feedback.

Infrastructure Changes

• Stored files in Housekeeper
  • N/A
  • Updated: [Link]
• CG (CLI and delivered/uploaded files)
  • N/A
  • Updated: [Link]
• Servers (configuration files on Hasta)
  • N/A
  • Updated: [Link]
• Scout interface
  • N/A
  • Updated: [Link]

Validation criteria

Validation criteria to be added to validation report PR: [LINK-TO-VALIDATION-REPORT-PR from the validations repository]

Version specific criteria

• Text here or N/A

• Added version specific validation criteria to validation report
• Changes validated in standard sections: [validation-section]
• Validation criteria not necessary

Checklist

For Developers

• PR Description
  • Provided a comprehensive description of the PR.
  • Linked relevant user stories or issues to the PR.
• Documentation
  • Verified and updated documentation if necessary.
• Validation criteria
  • Completed the validation criteria section of the template.
• Tests
  • Described and tested the functionality addressed in the PR.
  • Ensured integration of the new code with existing workflows.
  • Confirmed that meaningful unit tests were added for the changes introduced.
  • Checked that the PR has successfully passed all relevant code smells and coverage checks.
• Review
  • Addressed and resolved all the feedback provided during the code review process.
  • Obtained final approval from designated reviewers.

For Reviewers

• Code
  • Code implements the intended features or fixes the reported issue.
  • Code follows the project's coding standards and style guide.
• Documentation
  • Pipeline changes are well-documented in the CHANGELOG and relevant documentation.
• Validation criteria
  • The author has completed the validation criteria section of the template
• Tests
  • The author provided a description of their manual testing, including consideration of edge cases and boundary
    conditions where applicable, with satisfactory results.
• Review
  • Confirmed that the developer has addressed all the comments during the code review.