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adding script to create a dummy proband for the ravenscroft-rpl project - #55

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SamBryen wants to merge 21 commits into
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dummy-gvcf
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SamBryen wants to merge 21 commits into
mainfrom
dummy-gvcf

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Purpose

Synthesize a 'dummy' male proband gVCF from a pair of parental gVCFs (RD-1168).

The ravenscroft-rpl cohort contains only unaffected parental duos (no probands), so to enable
trio analysis in seqr we create a synthetic proband that inherits, at worst case, every variant
its parents carry:

autosomes / chrX PAR : maternal allele = ALT iff mother carries any ALT
                       paternal allele = ALT iff father carries any ALT
                       e.g. 0/1 + 0/1 -> 1/1 ; 0/0 + 0/1 -> 0/1 ; 0/0 + 0/0 -> 0/0
non-PAR chrX (male)  : hemizygous, maternal-only -> haploid 1 iff mother carries ALT
chrY                 : copy the father's records verbatim (already hemizygous)
chrM                 : copy the mother's records verbatim (maternal inheritance)

The output is a spec-valid GATK-style gVCF with <NON_REF> reference blocks, so that once it is
combined with the real samples it reads as confident hom-ref (0/0) - not missing - at sites that
are variant only in other families. The dummy's reference blocks are the intersection of the two
parents' hom-ref bands, split at the union of their variant sites.

This phase is gVCF synthesis only. Metamist registration (participant/sample/SG creation,
pedigree import, gvcf analysis linking) and the VDS/seqr workflow wiring are handled separately.

Proposed Changes

  • NEW src/cpg_seqr_loader/scripts/synthesize_dummy_probands.py
  • EDIT pyproject.toml (add pysam), Dockerfile (install pysam)

Checklist

  • Version Bump!
  • Related GitHub Issue created
  • Tests covering new change
  • Linting checks pass

Comment thread Dockerfile Outdated
Co-authored-by: Matt Welland <mattwellie@gmail.com>
… reads them as variants, not reference blocks
Comment thread src/cpg_seqr_loader/scripts/synthesize_dummy_probands.py Outdated
…ll copy the alt values when there is only 1 alt between the two parents. Also added better logic for inheriting multiallelic sites where it will check for matching alts, rather than taking the first value
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3 participants