SVAT: Secure outsourcing of variant annotation and genotype aggregation

BACKGROUND: Sequencing of thousands of samples provides genetic variants with allele frequencies spanning a very large spectrum and gives invaluable insight into genetic determinants of diseases. Protecting the genetic privacy of participants is challenging as only a few rare variants can easily re-identify an individual among millions. In certain cases, there are policy barriers against sharing genetic data from indigenous populations and stigmatizing conditions. RESULTS: We present SVAT, a method for secure outsourcing of variant annotation and aggregation, which are two basic steps in variant interpretation and detection of causal variants. SVAT uses homomorphic encryption to encrypt the data at the client-side. The data always stays encrypted while it is stored, in-transit, and most importantly while it is analyzed. SVAT makes use of a vectorized data representation to convert annotation and aggregation into efficient vectorized operations in a single framework. Also, SVAT utilizes a secure re-encryption approach so that multiple disparate genotype datasets can be combined for federated aggregation and secure computation of allele frequencies on the aggregated dataset. CONCLUSIONS: Overall, SVAT provides a secure, flexible, and practical framework for privacy-aware outsourcing of annotation, filtering, and aggregation of genetic variants. SVAT is publicly available for download from https://github.com/harmancilab/SVAT. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12859-022-04959-6.