We show that targeted tumor-only sequencing that is commonly used diagnostically (such as Foundation Medicine, Tempus, DFCI OncoPanel) can also be used to impute germline variation using off-target reads. We then apply this approach to ~25,000 clinically sequenced tumors and show accurate inference of variants, germline risk scores, and genetic ancestry. We believe this approach meaningfully broadens the utility of existing tumor studies. The full pipeline and deployable workflow are available in a repository.
Figure | Schematic of the off-target imputation process