Secure genotype imputation using homomorphic encryption

Genotype imputation estimates missing genotypes from the haplotype or genotype reference panel in individual genetic sequences, which boosts the potential of genome-wide association and is essential in genetic data analysis. However, the genetic sequences involve people’s privacy, confirming an individual’s identification and even disease information. This work proposes a secure genotype imputation model, which uses a linear regression model and the homomorphic encryption scheme over ciphertext to impute missing genotypes. The inference model is trained with float plaintext parameters, which are round into integers to avoid high complexity homomorphic evaluation on float number operations without bootstrapping operations. Even though the rounding parameters in the inference model are not the same as those in the trained model, We find that it will no effect on the outcome of the homomorphic prediction. Thus, a high-efficiency genotype imputation inference model over the ciphertext is obtained while keeping the high-security level. The simulation results indicate that the accuracy of the secure inference model is almost the same as the original model trained on float parameters. The secure inference model’s accuracy is 98.6% for a single genotype

Agile delivery of protein therapeutics to CNS

A variety of therapeutic proteins have shown potential to treat central nervous system (CNS) disorders. Challenge to deliver these protein molecules to the brain is well known. Proteins administered through parenteral routes are often excluded from the brain because of their poor bioavailability and the existence of the blood-brain barrier (BBB). Barriers also exist to proteins administered through non-parenteral routes that bypass the BBB. Several strategies have shown promise in delivering proteins to the brain. This review, first, describes the physiology and pathology of the BBB that underscore the rationale and needs of each strategy to be applied. Second, major classes of protein therapeutics along with some key factors that affect their delivery outcomes are presented. Third, different routes of protein administration (parenteral, central intracerebroventricular and intraparenchymal, intranasal and intrathecal) are discussed along with key barriers to CNS delivery associated with each route. Finally, current delivery strategies involving chemical modification of proteins and use of particle-based carriers are overviewed using examples from literature and our own work. Whereas most of these studies are in the early stage, some provide proof of mechanism of increased protein delivery to the brain in relevant models of CNS diseases, while in few cases proof of concept had been attained in clinical studies. This review will be useful to broad audience of students, academicians and industry professionals who consider critical issues of protein delivery to the brain and aim developing and studying effective brain delivery systems for protein therapeutics