Threshold labeled private set intersection protocol for human genetic testing

Abstract Recent breakthroughs in genome sequencing have revolutionized genetic diagnostics, yet secure sharing of sensitive genomic data remains a critical barrier to clinical collaboration.We address this challenge through Threshold Labeled Private Set Intersection (TLPSI), a novel cryptographic protocol without using computation-heavy homomorphic encryption. enabling confidential diagnostic label exchange between a client with private variants and a server hosting pathogenic variant databases–disclosing labels only when matched variants surpass clinical threshold t . TLPSI integrates three key innovations: threshold-bound label recovery via ( t ,  n )-Shamir sharing, genomic marker protection through VOLE-based oblivious polynomial evaluation, and optimized O ( n ) complexity operations. Provably secure under the Decisional Diffie–Hellman assumption in semi-honest settings, TLPSI guarantees no leakage of unmatched variants or labels. In BRCA1/2