ABSTRACT
The recent advances in genome sequencing technologies provide unprecedented opportunities to understand the relationship between human genetic variation and diseases. However, genotyping whole genomes from a large cohort of individuals is still cost prohibitive. Imputation methods to predict genotypes of missing genetic variants are widely used, especially for genome-wide association studies. Accurate genotype imputation requires complex statistical methods. Due to the data and computing-intensive nature of the problem, imputation is increasingly outsourced, raising serious privacy concerns. In this work, we investigate solutions for fast, scalable, and accurate privacy-preserving genotype imputation using Machine Learning (ML) and a standardized homomorphic encryption scheme, Paillier cryptosystem. ML-based privacy-preserving inference has been largely optimized for computation-heavy non-linear functions in a single-output multi-class classification setting. However, having a large number of multi-class outputs per genome per individual calls for further optimizations and/or approximations specific to this application. Here we explore the effectiveness of linear models for genotype imputation to convert them to privacy-preserving equivalents using standardized homomorphic encryption schemes. Our results show that performance of our privacy-preserving genotype imputation method is equivalent to the state-of-the-art plaintext solutions, achieving up to 99% micro area under curve score, even on real-world large-scale datasets up to 80,000 targets.
