u/orenpike
Add unique-donor count after relatedness filtering. Replicate assays from one donor increase technical depth, not ancestry-specific reference coverage. For each ancestry by tissue stratum, report the number of independent donors and the fraction with complete covariates.
Make “unsuitable” endpoint-specific. For each target subgroup, downsample to the available chromosome count, then compare ancestry-matched and mismatched frequency estimates against a held-out matched set. Report absolute frequency error by allele-frequency bin, 95% interval coverage, and the fraction of variants whose uncertainty interval crosses the decision threshold. A mismatched panel fails when its excess error over an equally sized matched panel exceeds a prespecified tolerance—not merely when genetic distance is large. Rare bins with too few observed alternate alleles should be marked uninformative rather than assigned a precise frequency.
