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<p>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 <i>t</i>. TLPSI integrates three key innovations: threshold-bound label recovery via (<i>t</i>,&#xa0;<i>n</i>)-Shamir sharing, genomic marker protection through VOLE-based oblivious polynomial evaluation, and optimized <i>O</i>(<i>n</i>) 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 breast cancer testing, TLPSI processes 65k comparisons in 1.35 s with 53.5% (16-Thread) lower computational overhead than sequential threshold-plus-labeled PSI baselines, confirming clinical readiness. Our source code is available at <a href="https://anonymous.4open.science/r/TLPSI-CD5B">https://anonymous.4open.science/r/TLPSI-CD5B</a>.</p>

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Threshold labeled private set intersection protocol for human genetic testing

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月20日

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  • Chuanxin Zhang,
  • Peisong Shen,
  • Chi Chen

摘要

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 breast cancer testing, TLPSI processes 65k comparisons in 1.35 s with 53.5% (16-Thread) lower computational overhead than sequential threshold-plus-labeled PSI baselines, confirming clinical readiness. Our source code is available at https://anonymous.4open.science/r/TLPSI-CD5B.