北京生物醫(yī)學(xué)工程

基于密碼學(xué)的致病基因安全定位方案

Secure location scheme of pathogenic genes based on cryptography

作者：黃秀珍周潭平李寧波

單位：中國人民武裝警察部隊陜西省總隊醫(yī)院(西安 710000) 中國人民武裝警察部隊工程大學(xué)密碼工程學(xué)院(西安 710086)

關(guān)鍵詞：致病基因；隱私保護(hù)；致病基因定位；多基因疾病；多密鑰全同態(tài)加密

分類號：R318.04

出版年·卷·期（頁碼）：2021·40·2（151-159）

摘要：

目的基因中發(fā)生的一些惡性突變可能會導(dǎo)致癌癥、白化病等疾病。醫(yī)院的研究人員希望定位某個疾病的致病基因的位置信息，但單個醫(yī)院的基因數(shù)據(jù)樣本都太少，無法進(jìn)行有效的統(tǒng)計分析。如何在保護(hù)患者基因數(shù)據(jù)隱私的前提下，對不同醫(yī)院的患者基因數(shù)據(jù)進(jìn)行統(tǒng)計與分析，從而定位致病基因的位置，是對這些疾病開展針對性治療的重要前提。本文在有效保護(hù)患者基因數(shù)據(jù)隱私的前提下，提出一種對不同患者基因數(shù)據(jù)的密文進(jìn)行致病基因定位的方法，以在一定程度上解決了基因數(shù)據(jù)的共享和個人隱私保護(hù)的矛盾。方法首先，結(jié)合密碼學(xué)中基于格的多密鑰全同態(tài)加密技術(shù)和基于頻率的臨床遺傳學(xué)相關(guān)內(nèi)容，提出了一個致病基因安全定位方案，各醫(yī)院利用同態(tài)加密方案加密患者基因數(shù)據(jù)，將產(chǎn)生的密文上傳到云端，云端密態(tài)計算基于頻率的致病基因定位算法，得到最終統(tǒng)計結(jié)果的密文，該密文由各醫(yī)院聯(lián)合解密。其次并設(shè)計了針對多基因疾病的定位電路ITH-intersection、ITop-k，該電路能夠?qū)λ袇⑴c者中變異次數(shù)較多的多個基因位置進(jìn)行輸出，使其具備定位多基因疾病的能力。最后根據(jù)上述算法，本文實現(xiàn)了致病基因安全定位整體過程，對兩方參與的Intersection電路、SET DIFF電路，每個用戶輸入48比特的信息進(jìn)行了測試；對三方參與的ITH-intersection電路，每個用戶輸入48比特的信息進(jìn)行了測試。結(jié)果相比JWB+17方案，本方案能夠?qū)崿F(xiàn)多基因疾病的致病基因的安全定位，且參與者只需要將各自的基因數(shù)據(jù)加密和上傳一次即可，數(shù)據(jù)通信量降低了一到兩個數(shù)量級，且不需要參與者實時在線，但本方案運(yùn)行的時間更長。結(jié)論支持對多方來源的數(shù)據(jù)進(jìn)行密態(tài)處理的致病基因安全定位方案一定程度上解決了不同機(jī)構(gòu)間基因數(shù)據(jù)的分享和個人隱私保護(hù)的矛盾，能夠大幅降低各醫(yī)療機(jī)構(gòu)自身基因數(shù)據(jù)被泄露的風(fēng)險，適用于多基因疾病的致病基因的安全定位。

Objective Genes are of great significance for the prevention and treatment of some diseases, such as cancer and albinism. These diseases are usually caused by some malignant mutations in genes. How to locate the pathogenic genes by analyzing the genetic data of different medical institutions while protecting the gene privacy of patients’ genetic data is very important. Our scheme can locate pathogenic genes by homomorphically analyzing the ciphertexts of multiple different medical institutions, which can significantly reduce the risk of leaking genetic data. Methods We combined a cryptography tool, Multi-key fully homomorphic encryption (MKHE) and frequency-based pathogenic genes locating function, and propose a secure location scheme of disease-causing genes. Medical institutions encrypt patient’s genetic data using homomorphic encryption schemes, then upload them to the cloud, where cloud calculate frequency-based pathogenic gene location algorithms, and output the ciphertext of result, which will be decrypted by the Medical institutions jointly. What’s more, we propose two location circuits (ITH-intersection & ITop-k), which can be used for diagnosis of polygenic diseases. Results We implemented the secure locating pathogenic genes protocol for Intersection circuit and SET DIFF circuit involving two parties, and ITH-intersection circuit involving three parties, and each party input 48-bits genetic data. Experimental results show that our scheme can be used to diagnose polygenic diseases, our communication traffic was reduced by an order of magnitude or two compared to JWB+17, published in Science, but the running time of our scheme is longer because of the complicated homomorphic evaluation process. Conclusions Our scheme can be used to diagnose polygenic diseases safely, solves the contradiction between the sharing of genetic data and personal privacy protection among different institutions, can reduce the risk of leakage of gene data of various medical institutions.

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