Privacy protection gene sequence alignment method and system based on oblivious transfer protocol

Abstract

The application discloses a privacy protection gene sequence alignment method and system based on a oblivious transfer protocol, and comprises the following steps: setting a shared public random string; adopting one-hot encoding to encode a first gene sequence and a second gene sequence; selecting a first random string and a second random string in valid bits in the first gene sequence base encoding to form a first random ordered pair, wherein the first random string of the valid bits satisfies the public random string, and selecting a second random ordered pair in non-valid bits, so as to obtain a base encoding ordered pair; performing an oblivious transfer protocol according to each bit in the second gene sequence base encoding and the base encoding ordered pair to obtain a matching result of each bit; and judging whether the first gene sequence and the second gene sequence are equal according to the matching result. The method can protect gene sequence information and realize efficient and safe alignment of the gene sequence.

Description

Technical Field

[0001] This invention relates to the field of gene sequence alignment technology, and in particular to a privacy-preserving gene sequence alignment method and system based on the blind transfer protocol. Background Technology

[0002] The statements in this section are merely background information related to the present invention and do not necessarily constitute prior art.

[0003] Due to the inherently sensitive nature of genetic data, the sharing and dissemination of genetic data can lead to privacy leaks. For example, (1) genetic data uniquely identifies human individuals and can be used for identity verification; (2) genetic data contains information about blood relations between families; (3) genetic data is closely related to heredity, phenotype, and susceptibility to diseases; and (4) genetic data contains sensitive information that has not been extracted or obtained.

[0004] Therefore, the leakage of genetic data privacy can have adverse effects. In the early days, the protection of genetic data was mainly achieved through anonymization technology. However, even if the genetic lineage is anonymized, the re-identification of anonymized records is still possible and has a high probability.

[0005] To provide stronger security, research on protecting the privacy of genetic data using cryptographic methods (including homomorphic encryption and obfuscated circuits) has been proposed. Homomorphic encryption allows computation on ciphertext without decryption, but due to technological limitations, its research has not achieved significant breakthroughs. Obfuscated circuits allow two parties holding their own private data to jointly compute a predetermined function without revealing either party's private information, but their practicality is controversial.

[0006] Current research on gene data mostly focuses on improving computational accuracy and operational efficiency, with only a few considering data privacy and security related to gene sequence alignment.

[0007] In addition, gene sequences are composed of four basic nucleotides (adenine A, guanine G, cytosine C, and thymine T). When performing sequence alignment, searching, or similarity calculations on gene data, it is usually necessary to encode the gene sequence, for example, using binary encoding: A-00, G-01, C-10, T-11. However, performing the above operations on gene sequences based on this simple encoding method is not secure and is extremely vulnerable to attacks by malicious adversaries, leading to the leakage of gene data. Summary of the Invention

[0008] To address the aforementioned issues, this invention proposes a privacy-preserving gene sequence alignment method and system based on the blind transfer protocol, which achieves efficient and secure gene sequence alignment while protecting gene sequence information.

[0009] To achieve the above objectives, the present invention adopts the following technical solution:

[0010] In a first aspect, the present invention provides a privacy-preserving gene sequence alignment method based on a blind transmission protocol, comprising:

[0011] Set a public random string shared by the first and second gene sequences;

[0012] One-hot encoding was used to encode the first and second gene sequences respectively;

[0013] For the valid positions in the base encoding of the first gene sequence, select a first random string and a second random string to form a first random ordered pair, and the first random string of all valid positions satisfies the public random string. For the invalid positions, select a second random ordered pair to obtain the base encoding ordered pair.

[0014] Based on each bit in the base encoding of the second gene sequence and the ordered base encoding of the first gene sequence, a random transfer protocol is executed to obtain the matching result of each bit.

[0015] Based on the matching results of all valid bits in the base encoding of the second gene sequence, it is determined whether the public random string is satisfied, thereby obtaining the comparison result of whether the first gene sequence and the second gene sequence are equal.

[0016] As an alternative implementation method, the first random string r i satisfy Where r is a publicly available random string, i is the i-th valid bit in the base encoding of the first gene sequence, and D is the set of valid bits in the base encoding of the first gene sequence.

[0017] As an alternative implementation, the matching result of the bit position where the effective bit j is located in the base encoding of the second gene sequence... In the process of determining whether the publicly available random string is satisfied, the calculation is performed. Where J is the set of valid positions in the base coding of the second gene sequence;

[0018] like Then the first gene sequence and the second gene sequence are not equal;

[0019] like Then the first gene sequence and the second gene sequence are equal.

[0020] As an alternative implementation, the publicly disclosed random string r←{0,1} κ κ is a safety parameter.

[0021] As an alternative implementation, one-hot encoding is used to encode the bases A, G, C, and T in the first and second gene sequences as 00001, 00010, 00100, and 01000 respectively, and to encode the missing bases as 10000.

[0022] As an alternative implementation, the number of valid bits after encoding is consistent with the number of bases in the gene sequence.

[0023] As an alternative implementation, the blind transport protocol employs blind transport extension technology.

[0024] Secondly, the present invention provides a privacy-preserving gene sequence alignment system based on a blind transmission protocol, comprising:

[0025] The initialization module is configured to set a public random string shared by the first and second gene sequences;

[0026] The one-hot encoding module is configured to encode the first gene sequence and the second gene sequence using one-hot encoding respectively;

[0027] The random encoding module is configured to select a first random string and a second random string for the valid positions in the base encoding of the first gene sequence to form a first random ordered pair, and the first random string of all valid positions satisfies the public random string. The second random ordered pair is selected for the invalid positions to obtain the base encoding ordered pair.

[0028] The protocol execution module is configured to execute a random transmission protocol based on each bit in the base encoding of the second gene sequence and the ordered base encoding of the first gene sequence to obtain the matching result of each bit.

[0029] The alignment module is configured to determine whether the public random string is satisfied based on the matching results of the bits where all valid bits are located in the base encoding of the second gene sequence, thereby obtaining the alignment result of whether the first gene sequence and the second gene sequence are equal.

[0030] Thirdly, the present invention provides an electronic device including a memory and a processor, and computer instructions stored in the memory and running on the processor, wherein the computer instructions, when executed by the processor, perform the method described in the first aspect.

[0031] Fourthly, the present invention provides a computer-readable storage medium for storing computer instructions, which, when executed by a processor, perform the method described in the first aspect.

[0032] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0033] This invention proposes a privacy-preserving gene sequence alignment method and system based on the Oblivious Transfer (OT) protocol. Compared with traditional encoding methods, it employs one-hot encoding to encode gene sequences, improving alignment efficiency and preventing gene data leakage. It uses the Oblivious Transfer (OT) protocol for secure string alignment and leverages OT protocol extension technology to reduce the inefficient public-key cryptographic operations introduced by the OT protocol, thereby improving the protocol's operational efficiency. This method offers higher efficiency and security, achieving efficient and secure sequence alignment while protecting gene sequence information.

[0034] Advantages of additional aspects of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. Attached Figure Description

[0035] The accompanying drawings, which form part of this invention, are used to provide a further understanding of the invention. The illustrative embodiments of the invention and their descriptions are used to explain the invention and do not constitute an improper limitation of the invention.

[0036] Figure 1 Here is a flowchart of the privacy-preserving gene sequence alignment method based on the random transmission protocol provided in Embodiment 1 of the present invention;

[0037] Figure 2 A schematic diagram of a gene sequence alignment method including one base provided in Embodiment 1 of the present invention;

[0038] Figure 3 This is a schematic diagram of the gene sequence alignment method provided in Embodiment 1 of the present invention, which includes two bases. Detailed Implementation

[0039] The present invention will be further described below with reference to the accompanying drawings and embodiments.

[0040] It should be noted that the following detailed descriptions are exemplary and intended to provide further illustration of the invention. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0041] It should be noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the exemplary embodiments of the present invention. As used herein, unless the context clearly indicates otherwise, the singular form is also intended to include the plural form. Furthermore, it should be understood that the terms “comprising” and “having”, and any variations thereof, are intended to cover non-exclusive inclusion, for example, a process, method, system, product, or apparatus that comprises a series of steps or units is not necessarily limited to those steps or units explicitly listed, but may include other steps or units not explicitly listed or inherent to such processes, methods, products, or apparatus.

[0042] Where there is no conflict, the embodiments and features in the embodiments of the present invention can be combined with each other.

[0043] Example 1

[0044] This embodiment provides a privacy-preserving gene sequence alignment method based on the blind transfer protocol, which achieves efficient and secure gene sequence alignment while protecting gene sequence information; it is assumed that two mutually distrustful participants, Alice and Bob, each hold gene sequence S. A =a1...a l and S B =b1...b l The two gene sequences are compared without revealing any information.

[0045] This embodiment considers starting from Yao's Millionaire Problem and using secure multi-party computation technology to achieve secure and efficient comparison of gene sequences. Yao's Millionaire Problem is that two millionaires, Alice and Bob, want to know who is richer without revealing any information about their wealth to the other. Yao's Millionaire Problem can be abstracted as a confidential comparison of two numbers, a and b. Considering the case where a = b, the gene sequence alignment problem can be seen as a variation of Yao's Millionaire Problem.

[0046] Therefore, this embodiment proposes an efficient and secure gene sequence alignment method using the random transfer protocol, and the output of the random transfer protocol is the matching result.

[0047] like Figure 1 As shown, it specifically includes:

[0048] Set a public random string shared by the first and second gene sequences;

[0049] One-hot encoding was used to encode the first and second gene sequences respectively;

[0050] For the valid positions in the base encoding of the first gene sequence, select a first random string and a second random string to form a first random ordered pair, and the first random string of all valid positions satisfies the public random string. For the invalid positions, select a second random ordered pair to obtain the base encoding ordered pair.

[0051] Based on each bit in the base encoding of the second gene sequence and the ordered base encoding of the first gene sequence, a random transfer protocol is executed to obtain the matching result of each bit.

[0052] Based on the matching results of all valid bits in the base encoding of the second gene sequence, it is determined whether the public random string is satisfied, thereby obtaining the comparison result of whether the first gene sequence and the second gene sequence are equal.

[0053] In this embodiment, the one-hot encoding method is used to encode the gene sequences S of the first participant (Alice) and the second participant (Bob). A and S B Encoding is performed; after encoding, only one bit is valid, that is, the code for a base has only one bit "1", and the rest are "0". Therefore, the position of the "1" of any two different bases must be different.

[0054] To achieve S A and S B Security comparison to determine S A and S B Whether each corresponding base is equal is crucial to ensuring that each base after one-hot encoding is equal. This embodiment uses a blind transmission protocol to achieve this, specifically:

[0055] The random transmission protocol involves two parties. The first party (Alice) possesses two private strings, x0 and x1. The second party (Bob) selects one of the two strings using its own selection bits b∈{0,1}. After the transmission is complete, Bob will obtain x. b And without knowing another string x 1-b Meanwhile, Alice receives no output and has no way of knowing which string Bob obtained. This process uses a function. describe:

[0056]

[0057] Because different bases result in different positions for the "1" after one-hot encoding, in conventional gene sequence alignment methods, Alice and Bob share a publicly available random number r. Based on the position of the encoded "1", Alice provides 2 lBob receives one input (r if the i-th position is 1; otherwise, a random number s), and selects bit j as his input, where j represents the position of the "1" after the corresponding base encoding. Bob determines whether his character is equal to Alice's based on whether the protocol output is r; if the protocol output is r, it means that Bob's corresponding character is equal to Alice's; otherwise, the conclusion is not valid.

[0058] However, the above method is not secure and poses a risk of information leakage. Specifically, while the method can compare whether two bases at the same position in two gene sequences are equal, Bob will simultaneously know the base information (e.g., non-empty or non-base A) at every position in Alice's gene sequence. This leads to privacy leaks, and Bob could even deduce Alice's gene sequence information based on the additional information he has.

[0059] Therefore, this embodiment makes further modifications to the above solution.

[0060] In this embodiment, the one-hot encoding method is used to encode the bases A, G, C, and T in the gene sequences of the first participant (Alice) and the second participant (Bob) as 00001, 00010, 00100, and 01000, respectively. For the case of base deletion (represented by "—"), it is encoded as 10000.

[0061] Order | S A |=|S B | = n, setting a shared public random string r←{0,1} for Alice and Bob. κ For gene sequence S A and S B Perform one-hot encoding, denoted as t, p∈{0,1} n×l l is the length of the one-hot encoding, each l bits represent the encoding of one base, and n is the number of bases;

[0062] For example: n = 3, S A =ACG, l=5, then the encoded result is: 000010001000100, where 00001 corresponds to base A, 00010 corresponds to base C, and 00100 corresponds to base G.

[0063] Therefore, each base encoding must contain only one "1". Thus, the base encoding t after the first participant's encoding and the base encoding p after the second participant's encoding have a total of n "1"s, and the position of the "1" is the valid bit.

[0064] For 1≤k≤n×l, if the k-th bit of t is 1, that is, t k If k = 1, then add k to the set. middle, And select two random strings r i ←{0,1} κ and s i ←{0,1} κ Random string r i ←{0,1} κ Satisfy XOR operation Then the first random ordered pair (s) is formed. i ,r i ); i refers to the i-th valid bit.

[0065] Otherwise, randomly select two random strings for the invalid bits. Constructing a second random ordered pair

[0066] This yields ordered base-encoded pairs. As execution Input.

[0067] The second input to the random transmission protocol is each bit p in the base encoding of the second participant's gene sequence. k ∈{0,1}, p k This represents the k-th bit of p, which is either "0" or "1".

[0068] After the blind transmission protocol finishes execution, the matching result for each bit is obtained.

[0069] Based on the position j of the "1" in the base encoding of the second gene sequence, construct a set. For the valid positions encoded by the bases in the second gene sequence, the corresponding matching results are obtained, and calculations are performed. Get r';

[0070] If r'≠r, then t≠p, indicating that S A and S B They are not equal;

[0071] If r' = r, then t = p, indicating that S A and S B equal.

[0072] For example, if Then p k =t k =1, then at the k-th bit, S A and S B The two bases are equal; and so on, to obtain all the valid positions. calculate Then t = p, gene sequence SA and S B equal.

[0073] In this embodiment, as Figure 2 As shown, taking n=1 as an example, |S A |=|S B |=1, Alice and Bob share a public random string r←{0,1} κ , for S A and S B Perform one-hot encoding to obtain t,p∈{0,1} l l is the encoding length;

[0074] If the k-th bit of t is t k =1, Alice selects a random string s←{0,1} κ And form the first random ordered pair (s, r); otherwise Alice randomly selects a string. And j≠k, forming a second random ordered pair Obtain ordered base-encoded pairs

[0075] Alice will As Protocol input;

[0076] Bob will p k ∈{0,1} as The input to the protocol is k∈{1,...,l};

[0077] After the protocol is executed, the matching result is obtained.

[0078] if This indicates that during the kth execution... During the protocol, Bob's input p k =1, Alice's input is random strings s and r, therefore t k =1;

[0079] Based on the fact that only the position information of "1" differs after unique thermal encoding of different bases, due to p k =t k =1, therefore t=p, S A and S B Equal bases can be used to safely determine whether two bases are equal.

[0080] In this embodiment, as Figure 3 As shown, taking n=2 as an example, the public random string r←{0,1} is set. κ Gene sequence S A =AG,S B=AT, after one-hot encoding, we get t=0000100100 and p=0000101000. Based on t5=1 and t8=1, we choose r1 and r2, which satisfy...

[0081] Execute the blind transport protocol and construct a set based on the position of "1" in p. calculate If we can see that r'≠r, then it means S A and S B They are not equal.

[0082] The privacy-preserving gene sequence alignment method based on the blind transfer protocol proposed in this embodiment provides a safe and effective encoding method that prevents the leakage of gene data and achieves efficient and secure sequence alignment while protecting gene sequence information.

[0083] In this embodiment, because the OT protocol involves inefficient public-key cryptography operations, it incurs a significant computational cost in OT-based secure computing protocols. For example, in the Yao protocol, the number of OT executions is linearly related to the input size. Considering the massive amount of data involved in gene sequences, which could lead to excessively large input lengths and circuit depths, requiring the use of numerous OT protocols, this embodiment employs an extended OT protocol to improve protocol efficiency.

[0084]

[0085] The OT extension protocol is mainly used to optimize the computational complexity of the participants, so that no matter how long the input of the participants is, the number of public key operations performed by both parties is only related to the security parameter κ.

[0086] Example 2

[0087] This embodiment provides a privacy-preserving gene sequence alignment system based on the blind transfer protocol, including:

[0088] The initialization module is configured to set a public random string shared by the first and second gene sequences;

[0089] The one-hot encoding module is configured to encode the first gene sequence and the second gene sequence using one-hot encoding respectively;

[0090] The random encoding module is configured to select a first random string and a second random string for the valid positions in the base encoding of the first gene sequence to form a first random ordered pair, and the first random string of all valid positions satisfies the public random string. The second random ordered pair is selected for the invalid positions to obtain the base encoding ordered pair.

[0091] The protocol execution module is configured to execute a random transmission protocol based on each bit in the base encoding of the second gene sequence and the ordered base encoding of the first gene sequence to obtain the matching result of each bit.

[0092] The alignment module is configured to determine whether the public random string is satisfied based on the matching results of the bits where all valid bits are located in the base encoding of the second gene sequence, thereby obtaining the alignment result of whether the first gene sequence and the second gene sequence are equal.

[0093] It should be noted that the above modules correspond to the steps described in Embodiment 1, and the examples and application scenarios implemented by the above modules and the corresponding steps are the same, but are not limited to the content disclosed in Embodiment 1. It should also be noted that the above modules, as part of the system, can be executed in a computer system such as a set of computer-executable instructions.

[0094] In further embodiments, the following is also provided:

[0095] An electronic device includes a memory and a processor, as well as computer instructions stored in the memory and running on the processor, wherein the computer instructions, when executed by the processor, perform the method described in Embodiment 1. For brevity, further details are omitted here.

[0096] It should be understood that in this embodiment, the processor can be a central processing unit (CPU), or it can be other general-purpose processors, digital signal processors (DSPs), application-specific integrated circuits (ASICs), programmable gate arrays (FPGAs), or other programmable logic devices, discrete gate or transistor logic devices, discrete hardware components, etc. The general-purpose processor can be a microprocessor or any conventional processor, etc.

[0097] Memory may include read-only memory and random access memory, and provides instructions and data to the processor. A portion of memory may also include non-volatile random access memory. For example, memory may also store information about the device type.

[0098] A computer-readable storage medium for storing computer instructions, which, when executed by a processor, perform the method described in Embodiment 1.

[0099] The method in Example 1 can be directly implemented by a hardware processor, or implemented by a combination of hardware and software modules within the processor. The software modules can reside in readily available storage media in the field, such as random access memory, flash memory, read-only memory, programmable read-only memory, electrically erasable programmable memory, or registers. This storage medium is located in memory, and the processor reads information from the memory and, in conjunction with its hardware, completes the steps of the above method. To avoid repetition, a detailed description is not provided here.

[0100] Those skilled in the art will recognize that the units, i.e., algorithm steps, of the various examples described in connection with this embodiment can be implemented in electronic hardware or a combination of computer software and electronic hardware. Whether these functions are implemented in hardware or software depends on the specific application and design constraints of the technical solution. Those skilled in the art can use different methods to implement the described functions for each specific application, but such implementation should not be considered beyond the scope of this application.

[0101] While the specific embodiments of the present invention have been described above in conjunction with the accompanying drawings, this is not intended to limit the scope of protection of the present invention. Those skilled in the art should understand that various modifications or variations that can be made by those skilled in the art without creative effort based on the technical solutions of the present invention are still within the scope of protection of the present invention.

Claims

1. A privacy preserving sequence alignment method based on the oblivious transfer protocol, characterized in that, The method comprises the following steps: setting a public random string shared by a first gene sequence and a second gene sequence; encoding the first gene sequence and the second gene sequence by using one-hot encoding; encoding bases A, G, C and T in the first gene sequence and the second gene sequence by using one-hot encoding as 00001, 00010, 00100 and 01000 respectively, and encoding a base deletion as 10000; selecting a first random string and a second random string from valid bits in the base encoding of the first gene sequence to form a first random ordered pair, wherein the first random string of all the valid bits meets the public random string, and selecting a second random string from non-valid bits to form a second random ordered pair, thereby obtaining a base encoding ordered pair; performing a blinding transmission protocol according to each bit in the base encoding of the second gene sequence and the base encoding ordered pair of the first gene sequence, and obtaining a matching result of each bit; judging whether the public random string is met according to the matching result of all the valid bits in the base encoding of the second gene sequence, thereby obtaining a comparison result of whether the first gene sequence and the second gene sequence are equal. The first random string Satisfies Wherein, r is a public random string, i is the i-th valid bit in the first gene sequence base code, and D is a set in which the valid bit in the first gene sequence base code is located. The matching result of the bit position where the effective bit j in the base encoding of the second gene sequence is located , whether the process of publishing a random string is satisfied, the calculation , wherein J is a set in which the effective bit in the base encoding of the second gene sequence is located If then the first genetic sequence and the second genetic sequence are not equal; If then the first genetic sequence and the second genetic sequence are equal; The disclosed random string κ is a security parameter.

2. The privacy preserving genetic sequence alignment method based on the oblivious transfer protocol of claim 1, wherein, The number of the encoded valid bits is consistent with the number of bases in the gene sequence.

3. The privacy preserving genetic sequence alignment method based on the oblivious transfer protocol of claim 1, wherein, The blinding transmission protocol adopts a blinding transmission extension technology.

4. A privacy preserving sequence alignment system based on the oblivious transfer protocol, characterized in that, The method comprises the following steps: an initialization module configured to set a public random string shared by a first gene sequence and a second gene sequence; a one-hot encoding module configured to encode the first gene sequence and the second gene sequence by using one-hot encoding; encoding bases A, G, C and T in the first gene sequence and the second gene sequence by using one-hot encoding as 00001, 00010, 00100 and 01000 respectively, and encoding a base deletion as 10000; a random encoding module configured to select a first random string and a second random string from valid bits in the base encoding of the first gene sequence to form a first random ordered pair, wherein the first random string of all the valid bits meets the public random string, and select a second random string from non-valid bits to form a second random ordered pair, thereby obtaining a base encoding ordered pair; a protocol execution module configured to perform a blinding transmission protocol according to each bit in the base encoding of the second gene sequence and the base encoding ordered pair of the first gene sequence, and obtain a matching result of each bit; a comparison module configured to judge whether the public random string is met according to the matching result of all the valid bits in the base encoding of the second gene sequence, thereby obtaining a comparison result of whether the first gene sequence and the second gene sequence are equal. The first random string Satisfies Wherein, r is a public random string, i is the i-th valid bit in the first gene sequence base code, and D is a set in which the valid bit in the first gene sequence base code is located. The matching result of the bit where the effective bit j in the base encoding of the second gene sequence is located , whether the public random string meets the process of judging , wherein J is a set where the effective bit in the base encoding of the second gene sequence is located If then the first genetic sequence and the second genetic sequence are not equal; If then the first genetic sequence and the second genetic sequence are equal; The disclosed random string κ is a security parameter.

5. An electronic device, comprising: A computer device comprises a memory and a processor, and computer instructions stored in the memory and run on the processor, wherein when the computer instructions are run by the processor, the method in any one of claims 1-3 is completed.

6. A computer-readable storage medium, characterized in that, A computer device for storing computer instructions, wherein when the computer instructions are run by the processor, the method in any one of claims 1-3 is completed.

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