A long-term, reliable, low-cost, and accurate storage technology for genomic information

By generating genomic error correction code (ECC) information and encoding it into DNA sequences, the accuracy, reliability and cost issues of genomic information storage in existing technologies are solved, low-cost genome modification information storage and accurate reading are achieved, and sequencing coverage requirements are reduced.

CN119380821BActive Publication Date: 2025-09-30TIANJIN INST OF IND BIOTECH CHINESE ACADEMY OF SCI
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Patent Information

Application Number
CN202310933643.0
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2023-07-27
Publication Date
2025-09-30
Estimated Expiration
2043-07-27

AI Technical Summary

Technical Problem

Existing technologies cannot simultaneously guarantee the accuracy, reliability and low cost of genomic information storage, and cannot preserve genomic modification information.

Method used

The genome error correction code (ECC) information method is adopted. By dividing the genome sequence into blocks and Block fragments, the error correction code information is embedded and encoded into a DNA sequence. It is stored in combination with fountain code and CRC16 check code, and Reed-Solomon code is used for erasure coding to achieve accurate reading of information and long-term reliability.

Benefits of technology

It achieves accurate and reliable storage of genomic information, reduces storage costs, supports research related to genomic DNA molecules, reduces sequencing coverage requirements, and ensures accurate reading and long-term reliability of information.

✦ Generated by Eureka AI based on patent content.

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Abstract

The present invention discloses a long-term, reliable, low-cost, and precise storage technology for genomic information. The specific solution is to generate a small amount of ECC information based on the sequenced and assembled DNA sequence information, and then synthesize and encode these ECC information into a large number of small DNA fragments through DNA information storage technology. These small DNA fragments can be mixed with the extracted genomic DNA, or stored separately, thereby realizing the storage process of genomic information. During the reading process, the stored samples need to be mixed or sequenced separately. After sequencing, the ECC information is first decoded, and then the genomic sequence is accurately assembled under the guidance of the ECC information. Compared with directly storing genomic DNA molecules, the solution of the present invention can achieve accurate reading and assembly of genomic information and significantly enhance the reliability of long-term storage, and can reduce the coverage requirements of sequencing in the reading process; compared with directly encoding and storing genomic sequence information through DNA information storage technology, the solution of the present invention has significant cost advantages, and can store information on genomic modifications, thereby supporting related research on the genomic DNA molecules themselves.
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Description

Technical Field

[0001] The present invention belongs to the fields of bioinformatics and synthetic biology, and specifically relates to the long-term storage and precise reading of genomic DNA information. Background Art

[0002] With global climate change and the continued development of human activities, many species of microorganisms, animals, and plants are facing extinction. Therefore, protecting and preserving the vital information of these species is extremely important. Preserving vital information can help us understand and preserve a species' genetic information, including genome sequences, biological characteristics, and population history. This information can provide important scientific support and guidance for species conservation efforts and promote research and development in basic biology. Furthermore, preserving vital information can provide valuable resources for future research and applications. For example, preserving species genetic information can provide the foundation for the development and breeding of new varieties and offer new ideas and approaches for medical research and biotechnology. Therefore, species protection and the preservation of vital information are crucial for maintaining ecological balance and safeguarding human well-being. Currently, there are two different approaches to preserving vital information, or genomic information. The first involves using DNA information storage technology to recode and synthesize genomic information, generating DNA fragments that are completely different from genomic DNA. These fragments are then synthesized using DNA synthesis technology, and the resulting large numbers of short DNA fragments are cryopreserved. The second approach involves directly extracting the genomic DNA of a species and cryopreserving it.

[0003] The first approach involves recoding and synthesizing genomic information using DNA information storage technology, generating DNA fragments that are completely different from genomic DNA and synthesizing them using DNA synthesis technology. This method can ensure accurate information reading and long-term reliability. However, writing is expensive and cannot preserve information about modifications carried on the original genome. The second approach involves directly extracting the genomic DNA of the species for storage. This approach is low-cost and can preserve information about modifications on the genomic DNA, but it cannot support accurate reading and long-term reliability. Summary of the Invention

[0004] Compared to directly storing genomic information through DNA information storage technology, the present invention's solution significantly reduces costs while ensuring accurate and reliable information storage. Furthermore, it can store information about genome modifications and directly support research related to the genomic DNA molecules themselves. Compared to directly storing genomic DNA molecules, this technology enables accurate information reading and long-term reliability. Specific aspects of the present invention include:

[0005] The first aspect of the present invention provides a method for generating genome error correction code (ECC) information based on a species genome sequence,

[0006] The genome error correction code (ECC) information includes header information and error correction code (ECC) information of each chromosome of the species genome;

[0007] The header information includes the number of chromosomes, the length and hash value of each chromosome sequence, the block length, the block segment length, the number of redundancies of the block segments, and remarks;

[0008] The chromosome error correction code (ECC) information consists of block ECC information and block segment erasure coding. The block ECC information consists of block anchor bit information and block segment ECC information. The block anchor bit information is obtained by converting the block anchor sequence according to the base-bit correspondence. The block anchor sequence is a small sequence at the beginning of the block sequence, with a length of 10 to 60 bp. The block segment ECC information is obtained by converting the base sequence of the block segment DNA sequence into a bit sequence according to the base-bit correspondence, and then calculating the segment ECC information based on the error correction coding algorithm;

[0009] The method comprises:

[0010] S1) Divide the genome sequence into m blocks of fixed length, and further divide each block into n fixed-length block segments;

[0011] S2) calculating header information based on the genome sequence and the settings of S1);

[0012] S3) calculating the ECC codes of all blocks based on the genome sequence and the settings of S1);

[0013] S4) Perform erasure coding on all Block fragments.

[0014] In a specific embodiment of the present invention, the base-bit correspondence is:

[0015]

[0016] or

[0017]

[0018] Or any other combination among the 24 base bit combination correspondences.

[0019] In a specific embodiment of the present invention, the length of the block is between 400-10000 bp, and the preferred block length is 3000 bp; the length of the Block fragment is between 100-1000 bp, and the preferred Block fragment length is 400 bp.

[0020] In a specific embodiment of the present invention, the length of the block anchor sequence is between 10-60 bp, and the preferred length is 24 bp.

[0021] In a specific embodiment of the present invention, the Block sequence ECC error correction coding algorithm includes CRC16 algorithm, CRC32 algorithm, Reed-Solomon (RS) coding, and LDPC coding; preferably, CRC16 algorithm.

[0022] In a specific embodiment of the present invention, a Reed-Solomon (RS) coding scheme is used for erasure coding between blocks, and the redundancy rate range is generally set to be less than or equal to 10%. Preferably, the redundancy rate is set to 5%.

[0023] In a specific embodiment of the present invention, the hash value algorithm includes MD5, SHA, CRC32, Blake2, HMAC, MurmurHash, CityHash, etc. Preferably, the MD5 algorithm is adopted.

[0024] A second aspect of the present invention provides a method for encoding the genomic ECC information of the first aspect into a DNA sequence, comprising:

[0025] S1) determining the length of the DNA sequence fragment to be synthesized;

[0026] S2) Encode the DNA sequence fragment using a coding scheme.

[0027] In a specific embodiment of the present invention, the length of the DNA sequence fragment is 200 bp.

[0028] In a specific embodiment of the present invention, the adopted coding scheme is a scheme combining the fountain code outer code and the CRC16 check code inner code.

[0029] In a specific embodiment of the present invention, the structure of each short DNA fragment is a primer region at both ends for amplification of the DNA fragment, and primer 1 is followed by an index region, a data carrying region, an ECC check code region and primer 2 in sequence.

[0030] In a specific embodiment of the present invention, the length of the index region is 16 bp, the length of the data carrying region is 140 bp, the length of the ECC check code region is 8 bp, and the length of the primer region is 18 bp.

[0031] The third aspect of the present invention provides a DNA sequence library carrying ECC information encoded by the method of the second aspect.

[0032] A fourth aspect of the present invention provides a sample that can store species genome information for a long period of time, wherein the sample comprises a separated or mixed species genome sample and the above-mentioned DNA sequence library carrying ECC information.

[0033] A fifth aspect of the present invention provides a method for accurately assembling a genome sequence under the guidance of ECC information, comprising the following steps:

[0034] Step S0, sequencing the species genome sample and obtaining a De Blaine map (DBG map), and simultaneously sequencing the DNA sequence library carrying the ECC information to obtain the ECC information; or simultaneously sequencing the mixed sample to obtain the corresponding information;

[0035] Step S1, calculate the initial k-mer of the current block sequence to be assembled according to the anchor point information of the block in the ECC information;

[0036] Step S2: Search for the k-mer connected to the k-mer in the DBG graph; if no k-mer is found, the assembly of the current block fails; since the anchor sequence of the next block is connected to the end of the current block, a similar search and assembly process can be performed in reverse through the anchor sequence of the next block to assemble the block sequence of the current block as much as possible;

[0037] Step S3: If connected k-mers are found in the DBG graph, these k-mers are placed at the end of the search path; each k-mer found forms an independent terminal k-mer node;

[0038] Step S4: Determine the node. If the path length does not match the length of the Block sequence, repeat steps S2-S4 until the path length matches the Block length.

[0039] Step S5: When the path length matches the length of the block sequence, read the ECC information of the block sequence related to the path and perform ECC verification;

[0040] Step S6, judgment node, determines the number of paths that meet the ECC check; if the number of paths is zero, the block sequence assembly process in this direction fails, and a similar search and assembly process can be attempted in the reverse direction through the anchor sequence of the next block to assemble the block sequence of the current block as much as possible; if the number of paths is 1, the relevant block sequence is output; if the number of paths is greater than or equal to 1, enter the judgment node S8;

[0041] Step S7: If the number of paths that meet the ECC check is 1, then output the blocks contained in the path (the number of blocks may be greater than 1);

[0042] Step S8, judging the node, if the number of blocks assembled is less than the set number of blocks, then continue the block assembly process of the current block, otherwise, enter the next block assembly process.

[0043] In a specific embodiment of the present invention, after all blocks of the block are assembled, if a small number of blocks are missing due to unsuccessful assembly, the block erasure code embedded in the genome ECC information is further used to repair the missing blocks.

[0044] In a specific embodiment of the present invention, after all blocks are repaired, they are sequentially arranged and concatenated to generate a bit sequence for the entire genome. A hash value of the genome bit sequence is then calculated and compared with the hash value stored in the genome ECC information to confirm that the genome bit sequence was successfully decoded.

[0045] In a specific embodiment of the present invention, the final genome base sequence is obtained through the base-bit correspondence relationship.

[0046] The sixth aspect of the present invention provides a computer module, which runs the method for generating genomic error correction code (ECC) information described in the first aspect of the present invention, the method for encoding genomic ECC information into a DNA sequence described in the second aspect, or the method for accurately assembling a genomic sequence under the guidance of ECC information described in the fifth aspect, or a combination of the methods.

[0047] Beneficial technical effects

[0048] Compared with directly storing genomic information through DNA information storage technology, the solution of the present invention can greatly reduce costs while ensuring the accuracy and reliability of information storage, and can also store information on genome modification, thereby supporting related research on the genomic DNA molecule itself.

[0049] Compared with directly storing genomic DNA molecules, this technology can achieve accurate reading of information and long-term reliability.

[0050] In addition, the technology of the present invention can reduce the coverage requirement for sequencing during the reading process. Conventional genome sequencing coverage is generally above 100X. Using the technology of the present invention, a coverage of ≥15% can ensure accurate and complete reading of genomic information. BRIEF DESCRIPTION OF THE DRAWINGS

[0051] Figure 1: Left: Basic principle diagram of the genome information storage and reading process of the present invention; Right: Schematic diagram of the principle of generating ECC information from genome sequence;

[0052] Figure 2 : Block fragment assembly process under the guidance of ECC information;

[0053] Figure 3 :The impact of different sequencing coverage on block loss rate;

[0054] Figure 4 :The impact of block length on block assembly recovery rate and total number of ECC information bytes DETAILED DESCRIPTION

[0055] the term

[0056] DBG method and DBG diagram

[0057] The de Bruijn Graph (DBG) is an anti-intuition algorithm for assembling sequencing data. It is primarily used for assembling short, high-abundance fragments, particularly second-generation sequencing data. The DBG algorithm transforms the assembly process into the problem of finding an Eulerian path in the DBG graph (starting from a certain point and traversing all edges exactly once). An Eulerian path is a P-type problem, meaning that there are reliable necessary and sufficient conditions to prove the existence of an Eulerian path and that it can be solved within a certain timeframe. The method is as follows:

[0058] ① Split the reads into shorter k-mers of uniform length (reads shorter than k will be discarded);

[0059] ② Find the overlapping relationship between k-mers and build a DBG graph. That is, for any two k-mers u and w, if the last k-1 base sequences of u are the same as the first k-1 base sequences of w, then build a directed edge from u to w.

[0060] ③Find the Euler path in the DBG graph to obtain the assembly sequence.

[0061] Because second-generation sequencing produces shorter reads and contains less information, genome assembly requires higher coverage, and accurate genome assembly typically requires the use of third-generation long-fragment sequencing. This invention, through the introduction of genomic ECC information, effectively addresses the problem of achieving accurate genome assembly using second-generation sequencing information with low sequence coverage.

[0062] Implementation of the present invention:

[0063] like Figure 1 As shown in the figure (left), the present invention generates a small amount of ECC information based on the sequence information of the sequenced and assembled DNA. This ECC information is then synthesized and encoded into a large number of small DNA fragments using DNA information storage technology. These small DNA fragments can be mixed with the extracted genomic DNA or stored separately, thereby realizing the storage process of genomic information. During the reading process, the stored samples need to be mixed or sequenced separately. After sequencing, the ECC information is first decoded, and then the genomic sequence is accurately assembled under the guidance of the ECC information.

[0064] Example

[0065] Example 1

[0066] This technology solution uses wild-type Corynebacterium glutamicum ATCC13032 as an example to provide long-term and reliable storage of genomic information. The genomic information stored in this technology solution can be obtained through NCBI (https: / / www.ncbi.nlm.nih.gov / assembly / GCF_000011325.1).

[0067] like Figure 1 As shown in (right), the present invention divides the DNA sequence into blocks and then embeds error correction code information into the blocks. The specific steps are described as follows: First, the genome sequence is divided into m blocks of fixed length, and the block length is recommended to be between 1000-10000bp. Each block is further divided into n fixed-length Block fragments, and the fragment length is recommended to be between 100-1000bp. The block length used in the embodiment of this technical solution is 3000bp, and the length of the Block fragment is 300bp. Each block contains 10 Block fragments. As shown in FIG. Figure 1As shown in (right), the genome sequence verification information consists of header information and verification information. The header information contains information such as the number of chromosomes in the genome, the length of each chromosome, the hash value of each chromosome sequence, and the settings of block and fragment lengths. Then comes the ECC information of each chromosome. The ECC information of each chromosome sequence consists of block ECC information. For each block, the ECC information consists of block anchor bit information and block fragment ECC information within the block. The block anchor sequence is a small sequence at the beginning of the block sequence, and the length can be set to 10 to 60bp. The block anchor sequence used in this technical solution is 24bp long. The block anchor bit information is obtained by converting the block anchor sequence according to the base-bit correspondence shown in Table 1. The generation of block fragment ECC information first converts the base sequence of the block fragment DNA sequence into a bit sequence according to the base-bit correspondence shown in Table 1. The ECC code is then calculated based on a specific error correction coding algorithm. This technical solution uses the CRC16 algorithm to calculate the ECC check value of the bit sequence, that is, the ECC code of the block fragment. Other error correction coding schemes, such as CRC32, Reed-Solomon (RS), LDPC coding, etc., can be used as alternative ECC coding schemes for block segments.

[0068] After all blocks have been ECC-encoded, they need to be erasure-encoded. This is to prevent partial damage to part of the block sequence during the reading process. This technical solution uses the Reed-Solomon (RS) encoding scheme to perform erasure coding on the block sequence. The redundancy rate of RS encoding is recommended to be set in the range of 1%-10%. A fixed number of redundancies, such as 200, can also be set according to actual conditions. This setting can tolerate the random loss of 200 or fewer blocks without affecting the integrity of the block information. A higher block redundancy setting can tolerate a higher block loss rate, thereby further improving storage reliability.

[0069] Table 1 Base bit correspondence table used in technical solution 1

[0070]

[0071] Note: Any other base-bit correspondence can achieve similar technical effects.

[0072] After calculating the complete ECC information of the genome, all ECC information can be encoded into DNA sequences using a specific DNA information storage encoding scheme. Depending on the specific DNA information storage encoding scheme, these DNA sequences can be long or short DNA fragments. The technical solution of this embodiment adopts a short sequence DNA storage scheme. The sequence length of the short sequence storage scheme is multiple short DNA sequences with a length of 100 to 300bp. The length of the short DNA sequence can be set according to the synthesis capacity of the DNA synthesis technology used. The short DNA sequence length used in this technical solution is 200bp. The encoding scheme used is a scheme that combines the outer code of the fountain code and the inner code of the CRC16 check code. In this encoding scheme, the structure of each short DNA fragment is composed of primer regions (18bp) at both ends for amplification of the short DNA fragment. Primer 1 is followed by an index region (16bp), a data carrier region (140bp), a CRC check code region (8bp), and primer 2. The order and length of the index region, data carrier region, and CRC code region are variable parameters and can be adjusted according to actual conditions. The sequences of primer 1 and primer 2 are: primer 1-CCTGCAGAGTAGCATGTC, primer 2-CTGACACTGATGCATCCG.

[0073] The encoding method of the index area, data area, and CRC check code area and the decoding and reading of ECC information can be referred to:

[0074] Patent document: CN110190858B - A polymer molecular information storage and error correction encoding and decoding system;

[0075] Non-patent literature: Robust data storage in DNA by de Bruijn graph-based denovo strand assembly, Song et al., Nature Communications, 13:5361 (2022).

[0076] The precise ECC-guided genome sequence assembly process of this invention is achieved by reading the ECC header information and then assembling each chromosome separately based on the chromosome data and other information contained in the header. The assembly process for each chromosome is achieved by assembling the block sequence within each block of the chromosome and subsequently repairing any failed blocks using the embedded block erasure code. Figure 2 The core steps of the block sequence assembly process within each block are shown. The process starts with the anchor point information of the block to be processed and includes the following six core steps:

[0077] Step S1, calculate the initial k-mer of the current block sequence to be assembled according to the anchor point information;

[0078] Step S2: Search for the k-mer connected to the k-mer in the DBG graph; if not found, the assembly of the current block fails; since the anchor sequence of the next block is connected to the end of the current block, a similar reverse search and assembly process can be performed through the anchor sequence of the next block to assemble the block sequence of the current block as much as possible;

[0079] Step S3: If connected k-mers are found in the DBG graph, these k-mers are placed at the end of the search path; each k-mer found forms an independent terminal k-mer node;

[0080] Step S4: If the path length does not reach the length of the block sequence, repeat steps S2-S4 until the path length meets the block length.

[0081] Step S5: When the path length reaches the length of the block sequence, read the CRC value of the block sequence related to the path and perform a CRC check. It should be noted that there may be multiple block sequences at this node. This is because the CRC check node of the previous block sequence found more than one path that meets the CRC check.

[0082] Step S6, judgment node, determines the number of paths that meet the CRC check; if the number of paths is zero, the block sequence assembly process in this direction fails, and a similar reverse search assembly process can be attempted through the anchor sequence of the next block to assemble the block sequence of the current block as much as possible; if the number of paths is 1, the relevant block sequence is output; if the number of paths is greater than or equal to 1, enter the S8 judgment node.

[0083] Step S7: If the number of paths that meet the CRC check is 1, then the blocks included in the path are output (the number of blocks may be greater than 1).

[0084] Step S8: If the number of blocks assembled is less than the set number of blocks, the block assembly process of the current block will continue. Otherwise, the block assembly process of the next block will be entered.

[0085] After all blocks have been assembled, a small number of blocks may be missing due to unsuccessful assembly. In this case, the block erasure code embedded in the chromosome's ECC can be used to repair the missing blocks. After all blocks have been repaired, they can be sequentially arranged and concatenated to generate the bit sequence of the entire chromosome. The MD5 value of this chromosome bit sequence is then calculated and compared with the MD5 value stored in the chromosome's ECC. If the two values ​​are identical, the chromosome bit sequence is successfully decoded. The final chromosome DNA sequence can be generated using the base-bit correspondence shown in Table 1. A similar assembly process is performed for each chromosome, completing the precise assembly of all chromosome sequences, and ultimately, the complete genome sequence of the entire species.

[0086] Figure 3 The figure shows the effect of different sequencing coverage on the block loss rate when the block length is fixed at 400bp. The figure reveals that as the sequencing coverage increases, the loss rate decreases rapidly. In particular, when the sequencing coverage reaches 13, the loss rate has dropped to below 5%, which can effectively support accurate genome decoding. On the other hand, Figure 4 The figure shows the effects of different block lengths on the block assembly recovery rate and the total number of ECC information bytes under a fixed 20x coverage of sequencing data. This figure clearly shows that as the block length increases, the total ECC byte length decreases, but the block recovery rate also decreases. Therefore, the selection of block length requires finding a suitable balance between ECC byte length and recovery rate. However, it should be noted that when the block length reaches 1000bp, the block loss rate begins to exceed 5%, and the effect of ECC byte reduction begins to weaken. Therefore, it is recommended that the block length should be kept at 1000bp or less. At the same time, too low a block length will lead to a significant increase in the ECC byte length, so the block length should be controlled at 100bp or above.

Claims

1. A method for generating genome error correction code (ECC) information based on the genome sequence of a species. The genome error correction code ECC information includes header information and error correction code ECC information of each chromosome of the species genome; The header information includes the number of chromosomes, the length and hash value of each chromosome sequence, the block length, the block segment length, the number of redundancies of the block segments, and remarks; The chromosome error correction code ECC information consists of block ECC information and block segment erasure code, the block ECC information consists of block anchor bit information and block segment ECC information, the block anchor bit information is obtained by converting the block anchor sequence according to the base-bit correspondence relationship, the block anchor sequence is the sequence at the beginning of the block sequence, and the length is 10 to 60bp, the block segment ECC information is obtained by converting the base sequence of the block segment DNA sequence into a bit sequence according to the base-bit correspondence relationship, and then calculating the segment ECC information based on the error correction coding algorithm; The method comprises: S1) Divide the genome sequence into fixed-length m blocks, and further divide each block n Block segments of fixed length, m and n is any integer; S2) Calculate header information based on the genome sequence and the settings of S1); S3) calculating ECC codes for all blocks based on the genome sequence and the settings of S1), wherein the error correction coding algorithm used for calculating the ECC information of the block segments in the block ECC codes is selected from the group consisting of CRC16 algorithm, CRC32 algorithm, Reed-Solomon code, or LDPC code; S4) Perform inter-block erasure coding on all block fragments to obtain block fragment erasure coding, wherein the Reed-Solomon coding scheme is used for block fragment erasure coding.

2. The method of claim 1, wherein the species is selected from prokaryotic microorganisms, eukaryotic microorganisms, plants, animals or humans.

3. The method according to claim 1, The base-bit correspondence is: or Or any other combination among the 24 base-bit combination correspondences; and / or The length of the block is between 400-10000 bp, and the length of the Block fragment is between 100-1000 bp; and / or The block anchor sequence length is between 10-60 bp; and / or The Block sequence ECC error correction coding algorithm is the CRC16 algorithm; and / or The Reed-Solomon coding scheme is used for erasure coding between blocks, and the redundancy rate range is set to <= 10%; and / or The hash value algorithm is selected from MD5, SHA, CRC32, Blake2, HMAC, MurmurHash or CityHash.

4. A method for accurately and reliably storing genome sequence information by additionally storing redundant error correction information (ECC). The redundant error correction information ECC is generated by the method according to claim 1.

5. A method for encoding the genomic ECC information of claim 1 into a DNA sequence, comprising: S1) Determine the length of the DNA sequence fragment to be synthesized; S2) Use an encoding scheme to encode genomic ECC information into short DNA sequences.

6. The method of claim 5, comprising: The DNA sequence fragment is 200 bp in length; and / or The coding scheme in step S2) is a scheme combining a fountain code outer code or a Reed-Solomon outer code with a CRC check code or an RS inner code.

7. A DNA sequence library carrying ECC information encoded by the method of any one of claims 5-6.

8. A sample that can store species genome information for a long time, the sample comprising a separated or mixed species genome sample and one or more DNA sequence libraries carrying ECC information as described in claim 7, each representing a genome sequence assembly version.

9. A method for accurately assembling a genome sequence under the guidance of ECC information, comprising the following steps: Step S0, sequencing the species genome sample and obtaining a De Blaine map (DBG map), and simultaneously sequencing the DNA sequence library carrying ECC information as described in claim 7 to obtain ECC information; or simultaneously sequencing the mixed sample as described in claim 8 to obtain corresponding information; Step S1: Calculate the initial block sequence to be assembled based on the anchor point information of the block in the ECC information. k -mer; Step S2, search the DBG graph for the k -mer connected k -mer; if not found, the assembly of the current block fails; since the anchor sequence of the next block is connected to the end of the current block, a similar search and assembly process can be performed in reverse through the anchor sequence of the next block to assemble the block sequence of the current block as much as possible; Step S3, if a connected k -mer, these k -mer is put at the end of the search path; each found k -mer forms an independent end k -mer node; Step S4: Determine the node. If the path length does not match the length of the Block sequence, repeat steps S2-S4 until the path length matches the Block length. Step S5: When the path length matches the length of the block sequence, read the ECC information of the block sequence related to the path and perform ECC verification; Step S6, determining the node and the number of paths that meet the ECC check; If the number of paths is zero, the block sequence assembly process in that direction fails. You can try to perform a similar search and assembly process in the reverse direction through the anchor sequence of the next block to assemble the block sequence of the current block as much as possible. If the number of paths is 1, the relevant Block sequence is output; if the number of paths is greater than or equal to 1, enter the S8 judgment node; Step S7: If the number of paths that meet the ECC check is 1, then output the blocks contained in the path; Step S8, judging the node, if the number of blocks assembled is less than the set number of blocks, then continue the block assembly process of the current block, otherwise, enter the next block assembly process.

10. The method for accurately assembling a genome sequence according to claim 9, wherein: When all blocks are assembled, if a small number of blocks are missing due to unsuccessful assembly, the block erasure code embedded in the genome ECC information is further used to repair the missing blocks; and / or, After all blocks are repaired, all blocks are sequentially connected to generate the bit sequence of the entire genome, and then the hash value of the genome bit sequence is calculated and compared with the hash value stored in the genome ECC information to determine whether the genome bit sequence is successfully decoded; and / or, The final genome base sequence is obtained through the base-bit correspondence.

11. A computer module, wherein the module runs the method for generating genomic error correction code (ECC) information according to claim 1, the method for encoding genomic ECC information into a DNA sequence according to claim 5 or 6, or the method for accurately assembling a genomic sequence under the guidance of ECC information according to claim 9, or a combination of these methods.

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