A secure system for genomics clinical decision support

[Display omitted] •A secure remote repository and computation for genomic data is proposed.•A numerical representation of genomic data has been defined.•Homomorphic encryptionenables secure computations for decision support. We developed a prototype genomic archiving and communications system to securely store genome data and provide clinical decision support (CDS). This system operates on a client-server model. The client encrypts the data, and the server stores data and performs the computations necessary for CDS. Computations are directly performed on encrypted data, and the client decrypts results. The server cannot decrypt inputs or outputs, which provides strong guarantees of security. We have validated our system with three genomics-based CDS applications. The results demonstrate that it is possible to resolve a long-standing dilemma in genomic data privacy and accessibility, by using a principled cryptographical framework and a mathematical representation of genome data and CDS questions.