WO2024125260A1 - Dna information storage method based on natural and non-natural bases - Google Patents

Abstract

The present invention relates to a DNA information storage method based on natural and non-natural bases, comprising the following steps: extracting data information to be stored; designing a coding table, wherein the coding table is formed by mapping DNA information and data information units; according to split data information, sequentially confirming, in the coding table, DNA information corresponding to the split data information; sequentially arranging the DNA information in hole sites of a physical medium according to a sequence to obtain a DNA information storage carrier; and during reading, reading the DNA information in a mass spectrum mode and decoding the DNA information. According to the storage and reading methods, natural and non-natural bases can be fully utilized, q-ary coding is implemented, and the density is expected to be greater than 8 bits/nt; furthermore, a trouble that DNA needs to be synthesized from the beginning for information storage is avoided; additionally, the method of identifying recorded information by using a sequencer is further discarded, the type of the base is innovatively read by using a mass spectrometer, and errors and limitations caused by a sequencing process are overcome.

Description

A DNA information storage method based on natural and unnatural bases Technical Field

The present invention belongs to the technical field of data storage, and in particular relates to a DNA information storage method based on natural and non-natural bases.

Background technique

With the advancement of network technology, the exchange and generation of information have exploded. For such a huge amount of information, how to store it will become an urgent problem. The existing silicon-based storage technology can no longer meet the growth of demand, and researchers have focused their attention on other substances, among which the research on deoxyribonucleic acid (DNA) as a storage medium is a hot topic. As an information storage medium, DNA has the advantages of high storage density, long and stable storage time, and low energy consumption. However, at the same time, there are still some problems that need to be solved in the early stage of DNA research. For example, the current method does not make full use of the characteristics of bases, especially non-natural bases, and the coding density is limited to 2 bits/nt; at the same time, based on the current method, when storing information, each time the information is stored, the base needs to be synthesized from scratch, which is costly.

In addition, DNA information storage technology is severely limited by DNA synthesis and sequencing technology, and it is difficult to eliminate errors caused by the synthesis and sequencing process. Therefore, how to skip or reduce the errors caused by DNA synthesis and sequencing has gradually become one of the research hotspots in the field of DNA information storage. Patent CN113066534A proposes to use quaternary encoding encoded by four ATCG bases to read data on a biochip, and use a method of sequencing while synthesizing. This method measures the DNA sequence on the chip to read information. The biochip can be stored for a long time at low temperatures, but it still cannot solve the error problem caused by sequencing.

Existing DNA information storage technology mainly relies on DNA synthesis and sequencing technology, and some errors are often introduced during the synthesis and sequencing process, which makes it difficult to decode the information. At the same time, synthesis and sequencing also have certain restrictions on DNA sequences, such as the sequence to be synthesized cannot contain continuous repeated bases (i.e., homopolymer length ≤ 4), the GC content is controlled at 40% to 60%, and the sequences cannot complement each other to form secondary structures.

Summary of the invention

In the existing DNA information storage technology, both the writing and reading of information are subject to various technical limitations. For example, the current writing of information still remains in the mode of using only natural DNA encoding, and the characteristics of non-natural bases are not fully utilized, and the encoding density is limited; in the process of oligo synthesis, the length of the synthesis is limited to 200bp and there cannot be more than 3bp of homopolymers in the synthesized sequence, and there are more restrictions in the sequencing process, and a large number of repeated sequences cannot appear. The sequencer itself has a large sequencing error; and the cost of synthesizing DNA from scratch is high. The above problems not only limit the randomness of information encoding, but also distort the results, resulting in a situation where decoding cannot be performed. In order to solve the above problems, the present invention is based on natural and non-natural bases, and utilizes the advantages of mass spectrometry sequencing analysis to establish a set of DNA information storage methods. This storage process does not require the step of synthesis, so there are no various restrictions on sequence synthesis. It can not only meet the needs of information storage, but also break the inherent framework of existing DNA information storage. At the same time, based on natural and non-natural base storage, the encoding density is high, providing a new direction for the development of DNA information storage technology.

One aspect of the present invention provides a DNA storage method based on natural and unnatural bases, the DNA storage method comprising the following steps:

S11): extracting data information of computer data information to be stored;

S12): Designing a coding table, wherein the coding table is formed by one-to-one mapping of DNA information and data information units;

S13) splitting the data information in step S11) into data information units, and confirming the DNA information corresponding to the split data information units in the coding table obtained in step S12);

S14) obtaining the deoxyribonucleotides or polynucleotide sequences consisting of two or more deoxyribonucleotides corresponding to the DNA information confirmed in step S13), and arranging them in sequence in different wells of the chip to obtain a DNA information storage carrier;

The DNA information is a deoxyribonucleotide or a polynucleotide sequence consisting of two or more deoxyribonucleotides, or a combination of any two of the deoxyribonucleotides or the polynucleotide sequence consisting of two or more deoxyribonucleotides;

In the coding table, the molecular weight of each DNA information is different, and the molecular weight difference between each is no less than 10.

Furthermore, in step S11), the computer data information is text, numbers, pictures, videos, programs, and audio.

Further, in step S11), the data information is character information, RGB information, binary data information, octal data information, hexadecimal data information, or decimal data information.

Furthermore, in the coding table, the molecular weight of each DNA information is different, and the difference in molecular weight between each pair is no less than 10.

Furthermore, the deoxyribonucleotide is a natural deoxyribonucleotide or a non-natural deoxyribonucleotide, and the non-natural deoxyribonucleotide is a base-modified deoxyribonucleotide.

Furthermore, the deoxyribonucleotides in the polynucleotide sequence composed of two or more deoxyribonucleotides are natural deoxyribonucleotides or non-natural deoxyribonucleotides.

Furthermore, the polynucleotide sequence composed of two or more deoxyribonucleotides has different molecular weights by adjusting the combination of the types and quantities of deoxyribonucleotides in the polynucleotide sequence.

Furthermore, the 32-1024 mapping relationships formed in the coding table are, for example, 32, 64, 128, 256, 512, and 1024.

Furthermore, the data information unit is to divide the data information into different units for recording information. In some examples, the data information unit is RGB pixel information that can correspond to a 4-bit or 8-bit binary number, a single character, or a single pixel.

Furthermore, the bases in the nucleic acid sequence are modified or unmodified. Furthermore, the modified bases are at least one of DBCO modification, AMCA modification, thio modification, amino modification, biotin modification, digoxigenin modification, phosphate group, and sulfhydryl group.

Furthermore, there are 32 types of polynucleotide sequences in the coding table, and 128 different combined polynucleotide sequences are formed by combining two polynucleotide sequences.

Furthermore, the coding table maps DNA information to 4-bit or 8-bit binary numbers one by one.

Furthermore, the coding table maps DNA information to the ASCII code table one by one.

Furthermore, the coding table maps DNA information to 128 characters one by one.

Furthermore, the coding table maps DNA information to RGB pixel information one by one.

In some specific embodiments, the DNA information in the coding table is 128 or 256 different nucleotides with modified bases, and 32 or 64 different types of modifications are performed on A, T, C, and G, respectively, to obtain a total of 128 or 256 different nucleotides with modified bases.

Furthermore, in the coding table, one type of DNA information is mapped one-to-one with the color information in the RGB pixel information, namely R\G\B, and the other type of DNA information is mapped one-to-one with the numbers 0-255 in the color information of the RGB pixel information, and the combination of the two types of DNA information forms a one-to-one mapping relationship with the RGB pixel information.

In an embodiment comprising only four natural bases, the coding table comprises 128 combined polynucleotide sequences, the lengths of the polynucleotide sequences are divided into 8 groups, the lengths of the 8 groups of polynucleotide sequences are successively extended, each comprising 10-24 base nucleotides, and each group comprises 4 polynucleotide sequences, and the types and or quantities of bases in the 4 polynucleotide sequences in each group are different.

Another aspect of the present invention provides a method for reading information from a DNA information storage carrier obtained by the above DNA storage method, the information reading method comprising the following steps:

S21) performing mass spectrometry on the sequences to be tested at different wells in the DNA information storage carrier to obtain molecular weight information of the DNA information in each well;

S22) analyzing the base combination information according to the molecular weight information of the DNA information to confirm the DNA information corresponding to the different pore positions;

S23) interpreting the data information unit according to the DNA information obtained in step S22) and the coding table in step S12);

S24) splicing the data information units obtained in S23) and decoding the data information to obtain the stored computer data information.

Furthermore, in step S21), the mass spectrometry detection method is MALDI mass spectrometry sequencing.

Further, in step S21), the method of mass spectrometry detection comprises the following steps:

S211) digesting and/or purifying the sequence to be tested;

S212) The purified fragments are subjected to mass spectrometry to obtain molecular weight.

Furthermore, the purification method in step S211) is ethanol precipitation, microdialysis or MillporeZiptip microlayer Analysis.

Furthermore, computer data information is data information that can exist on a computer, preferably selected from pictures, texts, programs, audio, and video.

Another aspect of the present invention provides a method for storing and decoding DNA information based on natural and unnatural bases, the method comprising:

The DNA storage method based on natural and unnatural bases as described above comprises the following steps:

S11): extracting binary information of computer data information to be stored;

S12): Designing a coding table, wherein the coding table is formed by one-to-one mapping of DNA information and data information units;

S13): splitting the data information in step S11) into data information units, and confirming the DNA information corresponding to the split data information units in the coding table obtained in step S12);

S14) obtaining the deoxyribonucleotides or polynucleotide sequences consisting of two or more deoxyribonucleotides corresponding to the DNA information confirmed in step S13), and arranging them in sequence in different wells of the chip to obtain a DNA information storage carrier;

The DNA information is a deoxyribonucleotide or a polynucleotide sequence consisting of two or more deoxyribonucleotides, or a combination of any two of the deoxyribonucleotides or the polynucleotide sequence consisting of two or more deoxyribonucleotides;

In the coding table, the molecular weight of each DNA information is different, and the molecular weight difference between each is no less than 10;

And a method for reading information from a DNA information storage carrier obtained by the DNA storage method as described above, the information reading method comprising the following steps:

S21) performing mass spectrometry on the sequences to be tested at different wells in the DNA information storage carrier to obtain molecular weight information of the DNA information in each well;

S22) analyzing the base combination information according to the molecular weight information of the DNA information to confirm the DNA information corresponding to the different pore positions;

S23) interpreting the data information unit according to the DNA information obtained in step S22) and the coding table in step S12);

S24) splicing the data information units obtained in S23) and decoding the data information to obtain the stored computer data information.

Another aspect of the present invention provides a DNA information storage device based on natural and unnatural bases, the device comprising:

A data information extraction unit, used for extracting the computer data to be stored and converting the computer data to be stored into data information corresponding to the information;

A data information and DNA information conversion unit, used to split or assemble the data information sequence and convert it into DNA information according to a preset mapping relationship;

A synthesis and storage unit, used to synthesize the data information and the nucleic acid sequence converted by the DNA information conversion unit, and store the deoxyribonucleotides corresponding to the DNA information, a polynucleotide sequence consisting of two or more deoxyribonucleotides, or a combination thereof in order on different wells of the storage unit chip;

The mapping relationship is a one-to-one mapping relationship between DNA information and data information units;

The DNA information is a deoxyribonucleotide or a polynucleotide sequence consisting of two or more deoxyribonucleotides, or a combination of any two of the deoxyribonucleotides or the polynucleotide sequence consisting of two or more deoxyribonucleotides;

In the mapping relationship, the molecular weight of each DNA information is different, and the molecular weight difference between each pair is no less than 10.

The data information and DNA information conversion unit may include a DNA information encoding unit, a DNA information and data information matching unit, and a DNA information information conversion unit. The DNA information encoding unit is used to record the combination of base types and quantities corresponding to each type of DNA information. The DNA information and data information matching unit is used to call different DNA information in the DNA information encoding unit to match and correspond to the data information units one by one. The DNA information conversion unit is used to convert the digital information in the data information extraction unit into DNA information one by one according to the information of the DNA information and data information matching unit.

Another aspect of the present invention provides a decoding device based on natural and non-natural base nucleic acid storage, the device include:

A reading unit, used to detect the sequence to be tested stored in the synthesis and storage unit by a mass spectrometer, and confirm its DNA information according to the molecular weight;

A DNA information and data information conversion unit, used to convert the DNA information obtained by the reading unit into data information according to a preset mapping relationship, that is, the same data information and DNA information mapping relationship in the DNA information storage device;

A computer data output unit, used to convert the DNA information and the data information obtained by the data information conversion unit into stored computer data;

The reading module includes a mass spectrometer for performing mass spectrometry detection on the nucleic acid sequence in each well position in the chip for detecting stored information, and may also include a unit for purifying and/or enzymatically hydrolyzing the nucleic acid sequence in each well position.

In yet another aspect, the present invention provides a computer-readable storage medium having a computer program stored thereon, wherein when the computer program is executed by a processor, the steps of implementing the above-mentioned DNA storage method based on natural and non-natural bases or the information reading method of obtaining a DNA information storage carrier using the above-mentioned storage method are implemented.

In another aspect, the present invention provides a computer device, including a memory and a processor, wherein the memory stores a computer program that can be run on the processor, and when the processor executes the computer program, it implements the steps of the above-mentioned DNA storage method based on natural and non-natural bases or the above-mentioned DNA storage method to obtain the information reading method of the DNA information storage carrier.

Beneficial Effects

1) The scheme of the present invention can use any modified base or unmodified base and unnatural base pairs. And as the number of available bases increases, the efficiency of DNA storage is also enhanced. By using a variety of unnatural bases, each base can encode 8-bit binary code, so the logical encoding capacity of the present invention can reach 8bit/nt, which has broken through the theoretical limit of 2bit/nt of 4-base encoding.

2) The encoding method of the present invention is designed according to the type and number of bases, without considering issues such as repetition and secondary structure in the sequence.

3) The present invention solves a series of problems caused by synthesis and sequencing from the source, directly abandons these two technologies, and instead adopts a method of fixed-point base storage and mass spectrometer detection.

4) The prior art uses four natural bases to directly map to quaternary codes, but the coding efficiency is still low. The present invention can encode any natural and non-natural bases, and base combinations of different numbers and lengths can also be encoded as a variable of the code, which solves the limitations of the coding efficiency and coding method. At the same time, by introducing a large number of non-natural bases, the coding efficiency and the degree of freedom of coding are greatly improved. Since there are many types of commercially available non-natural bases and they are highly commercialized, they can fully meet the coding requirements.

5) Due to the special way of information reading and encoding, there is no need to synthesize DNA sequences. Instead, grid storage combined with microfluidic technology is used. Only short sequences need to be synthesized, and no long sequences need to be synthesized, thus breaking the shackles brought by synthesis.

6) The storage and reading method of the present invention abandons the practice of using a sequencer to identify the nucleic acid sequence of the recorded information in the prior art, and innovatively uses a mass spectrometer to read the type of base, overcoming the errors and limitations brought by the sequencing process. Different molecular weight chain types can be formed by combining different bases in different ratios.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic diagram of a DNA storage method based on natural and unnatural base matrix spectrum decoding according to the present invention.

2 is a schematic diagram of a direct-encoded DNA storage method based on natural and unnatural base matrix spectrum decoding according to Example 1 of a specific embodiment of the present invention.

FIG. 3 is a schematic diagram of an information reading method of a DNA information storage carrier of the present invention.

FIG4 is a schematic diagram of mass spectrometry detection according to the present invention.

FIG5 is a schematic diagram of the structure of an encoding device provided in Embodiment 4 of the present invention.

FIG6 is a schematic diagram of the structure of a decoding device provided in Embodiment 4 of the present invention.

FIG. 7 is a schematic diagram of the structure of a terminal device provided in Embodiment 4 of the present invention.

FIG8 is an overall technical flow chart of the present invention.

FIG. 9 is a schematic diagram of a picture to be encoded according to the present invention.

Detailed ways

In order to make the above-mentioned objects, features and advantages of the present invention more obvious and understandable, the specific implementation modes of the present invention are described in detail below, but it should not be understood as limiting the applicable scope of the present invention.

It should be understood that when used in the present specification and the appended claims, the term "comprising" indicates the presence of described features, integers, steps, operations, elements and/or components, but does not exclude the presence or addition of one or more other features, integers, steps, operations, elements, components and/or combinations thereof.

It should also be understood that the term “and/or” used in the specification and appended claims refers to and includes any and all possible combinations of one or more of the associated listed items.

In addition, in the description of the present application specification and the appended claims, the terms "first", "second", "third", etc. are only used to distinguish the descriptions and cannot be understood as indicating or implying relative importance.

References to "one embodiment" or "some embodiments" etc. described in the specification of this application mean that one or more embodiments of the present application include specific features, structures or characteristics described in conjunction with the embodiment. Therefore, the statements "in one embodiment", "in some embodiments", "in some other embodiments", "in some other embodiments", etc. that appear in different places in this specification do not necessarily refer to the same embodiment, but mean "one or more but not all embodiments", unless otherwise specifically emphasized in other ways. The terms "including", "comprising", "having" and their variations all mean "including but not limited to", unless otherwise specifically emphasized in other ways. Some specific implementation plans of the present invention are described below in conjunction with the accompanying drawings.

In the existing DNA information storage technology, both the writing and reading of information are subject to various technical limitations, especially based on sequencing technology, which greatly limits information storage. To solve the above problems, the present invention innovatively establishes a DNA storage method based on natural and non-natural bases, replaces the sequencing method with a mass spectrometry method, and subverts the traditional information storage and decoding method. Moreover, the storage process of the present invention does not require too much synthesis, or even the steps of synthesis, so there are no various limitations on sequence synthesis. The method of the present invention is described in the form of an embodiment in conjunction with the accompanying drawings.

Example 1 DNA storage method based on natural and unnatural base matrix spectrum decoding:

S11) extracting data information of computer data information to be stored;

The computer data information to be stored may be data in any format, such as text, numbers, pictures, videos, programs, audio, etc. In a specific embodiment of the present invention, the data information may be RGB information, binary data information, octal data information, hexadecimal data information, decimal data information, or character information.

In some specific embodiments, the computer data information to be stored is converted into digital information by any method known in the art.

In some other specific implementation schemes, the image information can be converted into RGD information. The RGD information is RGD pixel information, and the image information is converted into RGD pixel information of different pixel points. The RGD pixel information consists of color types, namely R\G\D information and color intensity 0-255.

In some specific implementation schemes, if the information to be stored is character information, it is also possible not to perform conversion, and directly use the character information as data information for subsequent conversion and encoding.

S12) designing a coding table, wherein the coding table is formed by one-to-one mapping of DNA information and data information units;

The DNA information is a deoxyribonucleotide or a polynucleotide sequence consisting of two or more deoxyribonucleotides, or a combination of any two of the deoxyribonucleotides or the polynucleotide sequence consisting of two or more deoxyribonucleotides;

In the coding table, the molecular weight of each DNA information is different, and the molecular weight difference between each is no less than 5.

In some specific embodiments, illustratively, the molecular weight difference between two DNA information is greater than 10, for example, any number between 10-100.

In some specific technical solutions, the 32-1024 mapping relationships in the coding table are, for example, 32, 64, 128, 256, 512, and 1024.

In some specific technical solutions, the data information in the DNA information and data information coding table is exemplarily 4-bit binary data or 8-bit binary data, and is the same as the number of DNA information in the coding table, forming a one-to-one mapping relationship.

In some specific technical solutions, the DNA information and the data information in the data information coding table are exemplarily character information, and the number is the same as the DNA information in the coding table, forming a one-to-one mapping relationship.

In some specific technical solutions, the data information in the DNA information and data information coding table is illustratively RGB pixel information, and forms a one-to-one mapping relationship with the DNA information in the coding table.

In some specific technical solutions, the DNA information may be natural deoxyribonucleotides or non-natural deoxyribonucleotides, and the non-natural deoxyribonucleotides are base-modified deoxyribonucleotides.

In some specific technical solutions, the modified base refers to at least one or a combination of two or more of DBCO modification, AMCA modification, thio modification, amino modification, biotin modification, digoxigenin modification, phosphate group, sulfhydryl group, amino group, NHBOC modification, Fmoc modification, carboxylic acid modification, Mal modification, NHS modification, azide modification, Cy3/Cy5/Cy7 modification, THP modification, benzyl modification, propynyl modification, bromine modification, tert-butyl propionate modification, tert-butyl acetate modification, methyl modification, biotin modification, pentafluorophenol modification, and sulfonate modification. There are some commercial modified bases now, and those skilled in the art can choose according to the molecular weight requirements. The detailed modification types can be queried on the official website of the commercial company.

Exemplarily, the unnatural base is selected from 2-aminoadenin-9-yl, 2-aminoadenine, 2-F-adenine, 2-thiouracil, 2-thiothymine, 2-thiocytosine, 2-propyl and alkyl derivatives of adenine and guanine, 2-amino-adenine, 2-amino-propyl-adenine, 2-aminopyridine, 2-pyridone, 2'-deoxyuridine, 2-amino-2'-deoxyadenosine, 3-deazaguanine, 3-deazaadenine, 4-thio Uracil, 4-thiothymine, uracil-5-yl, hypoxanthine-9-yl (I), 5-methyl-cytosine, 5-hydroxymethylcytosine, xanthine, hypoxanthine, 5-bromo- and 5-trifluoromethyl-uracil and cytosine; 5-halouracil, 5-halocytosine, 5-propynyl-uracil, 5-propynylcytosine, 5-uracil, 5-substituted, 5-halogenated, 5-substituted pyrimidines, 5-hydroxycytosine, 5-bromocytosine, 5-bromouracil, 5-chlorocytosine Pyrimidine, chlorinated cytosine, cyclocytosine, cytosine arabinoside, 5-fluorocytosine, fluoropyrimidine, fluorouracil, 5,6-dihydrocytosine, 5-iodocytosine, hydroxyurea, iodouracil, 5-nitrocytosine, 5-bromouracil, 5-chlorouracil, 5-fluorouracil and 5-iodouracil, 6-alkyl derivatives of adenine and guanine, 6-azapyrimidine, 6-azo-uracil, 6-azocytosine, azacytosine, 6-azo-thymine, 6-thioguanine guanine, 7-methylguanine, 7-methyladenine, 7-deazaguanine, 7-deazaguanosine, 7-deaza-adenine, 7-deaza-8-azaguanine, 8-azaguanine, 8-azaadenine, 8-halogen, 8-amino, 8-thiol, 8-thioalkyl and 8-hydroxy substituted adenine and guanine; N4-ethylcytosine, N-2 substituted purine, N-6 substituted purine, O-6 substituted purine, those that increase the stability of duplex formation , Universal Nucleic Acid, Hydrophobic Nucleic Acid, Hybrid Nucleic Acid, Size-Extended Nucleic Acid, Fluorinated Nucleic Acid, Tricyclic Pyrimidine, Phenoxazine Cytidine ([5,4-b][1,4]benzoxazin-2(3H)-one), Phenothiazine Cytidine (1H-pyrimido[5,4-b][1,4]benzothiazin-2(3H)-one), G-clamp, Phenoxazine Cytidine (9-(2-aminoethoxy)-H-pyrimido[5,4-b][1,4]benzoxazin-2(3H)-one), Carbazole Cytidine (2H-pyrimido[4,5-b]indol-2-one), pyridoindolecytidine (H-pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-2-one), 5-fluorouracil, 5-bromouracil, 5-chlorouracil, 5-iodouracil, hypoxanthine, xanthine, 4-acetylcytosine, 5-(carboxyhydroxymethyl)uracil, 5-carboxymethylaminomethyl-2-thiouridine, 5-carboxymethylaminomethyluracil, dihydrouracil, β-D-galactocyanate Glycosyl quercetin, inosine, N6-isopentenyl adenine, 1-methylguanine, 1-methylinosine, 2,2-dimethylguanine, 2-methyladenine, 2-methylguanine, 3-methylcytosine, 5-methylcytosine, N6-adenine, 7-methylguanine, 5-methylaminomethyluracil, 5-methoxyaminomethyl-2-thiouracil, β-D-mannosyl quercetin, 5'-methoxycarboxymethyluracil, 5-methoxyuracil, 2-methylthio-N6-iso Pentenyl adenine, uracil-5-oxoacetic acid, whibutoxoside, pseudouracil, braided uracil, 2-thiocytosine, 5-methyl-2-thiouracil, 2-thiouracil, 4-thiouracil, 5-methyluracil, uracil-5-oxoacetic acid methyl ester, uracil-5-oxoacetic acid, 5-methyl-2-thiouracil, 3-(3-amino-3-N-2-carboxypropyl)uracil, (acp3)w and 2,6-diaminopurine as well as purine or pyrimidine bases are replaced by heterocycles.

In some specific embodiments, the deoxyribonucleotides in the polynucleotide sequence composed of two or more deoxyribonucleotides in the DNA information are natural deoxyribonucleotides or non-natural deoxyribonucleotides. The polynucleotide sequence composed of two or more deoxyribonucleotides is made to have different molecular weights by adjusting the combination of the types and quantities of deoxyribonucleotides in the polynucleotide sequence. For example, a combination encoding containing four natural bases is used; or a mixed encoding of natural and non-natural bases is used.

Since the present invention does not require sequencing during the decoding process but adopts mass spectrometry for determination, the different masses of the chain types composed of ribonucleotides or deoxyribonucleotides in the chain types can be distinguished by mass spectrometry data.

Exemplarily, the coding table contains 128 combined polynucleotide sequences, the lengths of the polynucleotide sequences are divided into 8 groups, the lengths of the 8 groups of polynucleotide sequences are successively extended, each containing 10-24 base nucleotides, 4 chain types in each group, and the base types and or quantities in the 4 chain types in each group are different.

For example, four deoxyribonucleotides can be modified with different modification groups. Under the action of different modification groups, for example, 32 modifications are performed on each deoxyribonucleotide, and 128 different deoxyribonucleotides can be obtained, while 64 modifications can be used to obtain 256 different deoxyribonucleotides. If the number of nucleotides is increased, the number of encoded types can be doubled on the basis of the above.

In some specific embodiments, a combination of two polynucleotides, a combination of two non-natural deoxyribonucleotides, or a combination of a polynucleotide and a non-natural deoxyribonucleotide may also be used.

Exemplarily, the types of DNA information in the coding table can be increased in the form of combinations, thereby improving coding efficiency. For example, by preparing 32 different nucleotide sequences and combining them two by two, a maximum of 1024 combinations can be obtained, of which 128 or 256 can be selected for designing the coding table.

In a specific embodiment, the DNA information in the coding table can be confirmed by the following method. First, in this embodiment, only polynucleotides composed of natural nucleotides are used, that is, polynucleotide sequences with a length of 10 to 24 composed of deoxyribonucleic acid of A, T, C, and G, and a total of 8 length gradients are set, and each length gradient is set with four different base contents. The four chains of the same length can be arbitrarily combined into 16 different combinations (as shown in Table 1, for example, the 16 combinations in the first length gradient are a1a1, a1a2, a1a3, a1a4, a2a1, a2a2, a2a3, a2a4, a3a1, a3a2, a3a3, a3a4, a4a1, a4a2, a4a3, a4a4), so there are a total of 8×16=128 types. For example, a1a1 corresponds to A4T2C2G2.

Table 1 Comparison table of polynucleotide length gradient and base composition

They correspond to the 128 elements of the ASCII code table, and each element is represented by an 8-bit binary number.

It is understandable that the number of nucleotides in a polynucleotide sequence can be adjusted, and if the upper limit of the number range selected for the number of polynucleotide sequences is smaller, the number of bases required will be less. The above exemplary scheme selects 4 bases, and if the types of bases involved in coding are increased, the number of bases required will also be sharply reduced.

The polynucleotide sequence is mapped to the data information one by one, and a coding table is formed. For example, the polynucleotide sequence described in Table 1 above, i.e., DNA information and 8-bit binary information are mapped one by one to form a DNA information and binary data coding table encoding 128 kinds of information. Four vertical digits and four horizontal digits of binary numbers together form 8-bit binary numbers. Each group of 8-bit binary numbers corresponds to a group of DNA information, as shown in Table 2:

Table 2 DNA information and data information coding table

For example: 00000000 corresponds to a1a1, and the polynucleotide sequence combination corresponding to a1a1 is a sequence composed of A8T4C4G4.

In another specific embodiment, four deoxyribonucleotides can be modified with different modification groups. Under the action of different modification groups, for example, 32 modifications are performed on each deoxyribonucleotide, then 128 different deoxyribonucleotides can be obtained, and 64 modifications can be used to obtain 256 different deoxyribonucleotides.

The nucleotides with modified bases are matched with the data information and a coding table is formed.

Specifically, taking the above 256 nucleotides with modified bases as an example, matching them with 8-bit binary information can be A matching table of 256 nucleotides with modified bases and binary data is obtained, as shown in Table 3:

Table 3 Matching table of nucleotides with modified bases and data information

In Table 3, A1 represents the first modified deoxyadenine nucleotide, and so on, A, T, C, G+numbers represent the Nth modified deoxyribonucleotides.

Exemplarily, 32 ribonucleotides with different modified bases can also be selected, with a total of 128 different modified bases, which are directly matched with the characters, and the encoding table is shown in Table 4 below:

Table 4

In some specific implementation schemes, direct coding can also be used to directly map each combination with a character, so as to achieve direct conversion of a text file into a DNA information file. For example, the DNA information in the coding table of Table 4 is used, and it is mapped one by one with the 128 types of character information in the ASII table to form a coding table, and the character information in the text can be directly converted into DNA information using the coding table.

S13) splitting the data information in step S11), and confirming the DNA information corresponding to the split data information in sequence with the DNA information obtained in step S12) and the data information coding table.

Exemplarily, when the data information mapped in the above DNA information and data information encoding table is an 8-bit binary number, the data information in step S11) is split into 8-bit binary numbers and mapped in the above DNA information and data information encoding table in sequence. Find the DNA information corresponding to 8-bit binary data.

S14) obtaining the chain types confirmed in step S13) and sequentially arranging different wells of the chip to obtain a DNA information storage carrier;

According to the DNA information confirmed in step S13), the method for obtaining nucleotide or polynucleotide sequence can be directly using commercially available nucleotides or synthesizing for different polynucleotide sequence types. It can also be synthesized and stored on a large scale according to the types in the coding table in step S12), and extracted during storage.

The confirmed nucleotide or polynucleotide sequences can be directly arranged in order in different wells of the chip without further connection, which can reduce the number of synthesis steps.

The method of the present invention is demonstrated below with several specific data to be stored. The first specific implementation case is storing English words and characters: Hello world!

The information to be stored is the string "Hello world!". First, the 12 characters in the string are converted into 12 8-bit binary numbers in sequence, and then these binary numbers are converted into different polynucleotide sequence combinations according to the coding tables in Table 1 and Table 2. The chain types corresponding to different characters are synthesized and placed in different wells of the chip in sequence. The chip containing all the information is the storage medium for the above information.

In addition, the above characters can also be encoded in the form of direct encoding, as shown in Figure 2, by mapping the characters with different DNA sequences or ribonucleotides of non-natural bases with different modification groups, as shown in Table 4 above, and encoded and stored.

In a second specific implementation scheme, the information to be stored is the text file "wssnt10.txt" encoded in Goldman's 2012 article "Towards practical, high-capacity, low-maintenance information storage in synthesized DNA".

The wssnt10.txt is as follows:

First, the above 107,738-byte text is directly encoded and converted into a base combination information file. For example, the polynucleotide combination corresponding to "!" is e1e2, that is, the base sequence is "4A4T4C6G4A4T4C6G". After conversion into DNA information, an exemplary fragment is as follows:

Further converted to chain types displayed in terms of base types and numbers, an example fragment is shown below:

Based on the obtained DNA information, a biochip is prepared for DNA information storage.

In a third specific implementation manner, the information to be stored is a picture.

First, convert the image information into binary data. The sample snippet is as follows:

The generated binary file is encoded according to the encoding tables in Tables 1 and 2 above. For example, the polynucleotide combination corresponding to "0100 0001" is e1e2, that is, the base sequence is "4A4T4C6G4A4T4C6G".

An exemplary fragment after conversion to polynucleotides is shown below:

Further converted to DNA information displayed in terms of base types and numbers, an example fragment is shown below:

As for the base encoding method, the first three specific implementation cases selected four natural bases ATCG for demonstration, but those skilled in the art can choose as needed when using the method of the present invention for encoding, which can be a polynucleotide sequence, or even a combination thereof, or a single non-natural base deoxyribonucleotide, not limited to natural base deoxyribonucleotides. This is because the present invention innovatively uses mass spectrometry as a detection method, which can not only distinguish natural bases but also identify non-natural bases, achieving a function that DNA sequencing cannot achieve.

The following provides several specific implementation plans using non-natural base amino deoxyribonucleic acid as an example.

The fourth specific implementation case is demonstrated by storing the first chapter of the original version of Pride and Prejudice. The text file size is 4,501 bytes. The binary file size generated by the binary-encoded text conversion is 36,008 bytes, as shown in the following excerpt:

In this embodiment, the above text is first converted into binary data, and some excerpts of binary data information are shown below:

2. Convert the binary data into a polybase sequence file with a size of 13,478 bytes according to the above encoding table, i.e., Table 3. The excerpt of the encoded sequence information is as follows:

The nucleotides corresponding to the encoded DNA information are stored in different wells of the biochip according to their sequence.

It can be seen from this embodiment that each nucleotide can encode an 8-bit binary code, so the logical encoding capacity of the present invention can reach 8 bits/nt, which has broken through the theoretical limit of the existing four-base encoding.

The information to be stored in the fifth embodiment is still the text of Chapter 1 of Pride and Prejudice, but unlike the fourth embodiment, in this embodiment, the text information is not converted into binary data, but the characters in the text information are directly used as the information data to be encoded.

Using the above coding table, the corresponding DNA information can be directly obtained after encoding Table 4, as shown below:

By comparing the coding efficiency of the above two specific embodiments, it can be seen that although the coding density of direct coding (fifth embodiment) and indirect coding (fourth embodiment) is 8bit/nt, direct coding uses fewer types of modified bases and is simpler.

The encoded nucleotides are sequentially stored in different wells of the chip to obtain a storage medium.

In the sixth implementation scheme, the information to be stored is a picture file. The picture information to be stored is shown in FIG9 . The original picture in FIG9 is a color picture. Its RGB information is as follows:

RGB format information:

The image information is directly encoded and converted into nucleotide information. The encoded sequence information is as follows:

The nucleotides are sequentially stored in different wells of the chip to obtain a storage medium.

The image information can also be divided into different pixel points according to the pixels, and the RGB pixel information of different pixel points is used as the data information. A coding table is further designed, which contains DNA information corresponding to different colors, namely RGB, at a depth of 0-255, and is encoded and stored in this way.

Example 2 DNA information decoding method based on natural and non-natural base matrix spectrum decoding

S21) performing mass spectrometry on the sequences to be tested at different wells in the DNA information storage carrier to obtain molecular weight information of the DNA information in each well;

Different from the prior art which uses a sequencer and needs to sequence the order of bases, the present invention uses MALDI mass spectrometry sequencing to read out the base combination in the chain type at each position on the chip.

During the information recording process, different nucleotide or polynucleotide sequences or their combinations are placed in different chip wells, and mass spectrometry detection is performed on the sequences to be tested in different wells, and the peaks of the substances are ejected in the order of different wells.

The mass spectrometry results show the molecular weight of the sequence to be tested and its fragment peaks after bombardment. Based on these data, the type of DNA information to be sequenced in the coding table can be confirmed.

Before mass spectrometry sequencing, the following may also be included:

S211) performing enzyme digestion and purification on the sequence to be tested;

S212) The purified fragments are subjected to mass spectrometry to obtain molecular weight.

In step S211), the purification method is ethanol precipitation, microdialysis or MillporeZiptip microchromatography.

In step S21), the mass spectrometry sequencing method is MALDI mass spectrometry sequencing.

S22) analyzing the base combination information according to the molecular weight information of the DNA information to confirm the DNA information corresponding to the different pore positions;

MALDI mass spectrometry sequencing can display RNA or DNA with different bases as peaks of different flight time sequences, identify the base combinations contained in these time sequence peaks, and directly translate these base combinations into Into their corresponding different nucleic acid sequences.

S23) interpreting the data information unit according to the DNA information obtained in step S22) and the coding table in step S12);

The chain type and data information coding table in step S23) is the chain type and data information coding table obtained in step S12) in the above-mentioned DNA storage method based on natural and non-natural bases.

In a specific embodiment, according to the chain type obtained in step S22), the corresponding binary number is confirmed in Table 2. Since every two chain types in Table 2 correspond to 8-bit binary numbers, the conversion is performed in a manner that every two serial chains correspond to one ASCII character to obtain all binary data;

S24) splicing the data information units obtained in S23) and decoding the data information to obtain the stored computer data information.

According to the six specific implementation plans of the data to be stored shown in Example 1, the steps in the decoding process are respectively given:

First, for the chip storing English words and characters: Hello world!, the polynucleotide sequence combinations in the 12 different wells in the chip are first digested and purified, and then the specific nucleotide types and quantities in the chain types are obtained by MALDI mass spectrometry. According to the MALDI mass spectrometry results, the type of polynucleotide sequence corresponding to each well can be confirmed, and the corresponding binary number can be confirmed according to the correspondence between the DNA information used in the encoding process and the data information encoding table. The binary number is directly converted into the corresponding character, that is, the original data information, that is, the string Hello world!, is obtained.

In the second specific embodiment, the stored information is the text file "wssnt10.txt" encoded in Goldman's 2012 article "Towards practical, high-capacity, low-maintenance information storage in synthesized DNA".

First, the polynucleotide sequences in different wells in the chip are digested and purified respectively, and then the specific nucleotide types and quantities in the chain types are obtained by MALDI mass spectrometry. According to the MALDI mass spectrometry results, the type of DNA information corresponding to each well can be confirmed, and according to the corresponding relationship between the DNA information used in the encoding process and the data information encoding table, the different coding bases are converted into corresponding characters, that is, the original data information, that is, the text file "wssnt10.txt" is obtained.

In the third specific embodiment, the stored information is picture information. The difference from the first two specific embodiments is that the obtained binary data is converted into picture information.

In a fourth specific implementation scheme, for the stored Pride and Prejudice Chapter 1: first purify the nucleotides with modified bases in different wells in the chip, and then obtain the specific types and quantities of nucleotides in the nucleotides with modified bases by MALDI mass spectrometry. According to the MALDI mass spectrometry results, the type of nucleotides with modified bases corresponding to each well can be confirmed, and according to the correspondence between the nucleotides with modified bases used in the encoding process and the data information matching table, the corresponding binary number can be confirmed, and the binary number is directly converted into the corresponding character, that is, the original data information, namely Pride and Prejudice Chapter 1, can be obtained.

In the fifth specific implementation scheme, the stored information is Chapter 1 of Pride and Prejudice.

First, the nucleotides with modified bases in different wells in the chip are purified separately, and then the specific nucleotide types in the nucleotides with modified bases are obtained by MALDI mass spectrometry. The type of nucleotides with modified bases corresponding to each well can be confirmed according to the MALDI mass spectrometry results, and the corresponding characters can be directly confirmed according to the correspondence between the nucleotides with modified bases and the data information matching table used in the encoding process, and spliced according to the characters to obtain the original computer data information.

In the sixth specific embodiment, the stored information is picture information. It is similar to the fourth and fifth specific embodiments, except that the obtained binary data is converted into picture information.

Example 3 Encoding device for decoding DNA storage based on natural and unnatural base matrix spectra

Corresponding to the encoding method described in the above embodiment 1, FIG5 shows a structural block diagram of the encoding device provided by embodiment 3 of the present invention. For the sake of ease of explanation, FIG5 only shows the part related to embodiment 3 of the present invention.

Referring to FIG5 , the encoding device may include:

A data information extraction unit, used for extracting the computer data to be stored and converting the computer data to be stored into data information corresponding to the information;

A data information and DNA information conversion unit, used to split or assemble the data information sequence and convert it into DNA information according to a preset mapping relationship;

The synthesis and storage unit is used to synthesize the DNA sequence obtained by converting the data information with the DNA information conversion unit, and The DNA sequences are stored in different wells of the memory cell chip in sequence.

The data information extraction unit may include an information storage unit and a conversion unit, wherein the information storage unit can be used to store and call computer information to be stored, such as text, numbers, pictures, audio, video, etc. The conversion unit can convert computer information into any digital information in a conventional way, such as characters, binary data information, octal data information, hexadecimal data information, decimal data information, RGB pixel information, etc.

The data information and DNA information conversion unit may include a DNA information encoding unit, a DNA information and data information matching unit, and a DNA information information conversion unit. The DNA information encoding unit is used to record the combination of base types and quantities corresponding to each type of DNA information. The DNA information and data information matching unit is used to call different DNA information in the DNA information encoding unit to match and correspond to the data information units one by one. The DNA information conversion unit is used to convert the digital information in the data information extraction unit into DNA information one by one according to the information of the DNA information and data information matching unit.

In a specific technical solution, only 4 deoxyribonucleotides with different bases can be selected to form at least 128 different chain types. That is, different numbers of deoxyribonucleic acids with different bases are combined. The length of the chain type is between 10 and 24, and a total of 8 length gradients are set. Each length gradient is set with four DNA chains with different base contents. The four chains of the same length can be arbitrarily combined into 16 different combinations. There are 8 length gradients, so there are a total of 8×16=128 types. The number of chain types can be enlarged or reduced by increasing the number of nucleotide types or adjusting the length of the chain types to meet the information storage requirements of different needs.

In another specific technical solution, only 4 deoxyribonucleotides can be selected, and each deoxyribonucleotide is subjected to 32 or 64 different modifications, so as to form at least 128 or 256 different nucleotides with modified bases. By increasing the number of nucleotides or adjusting the type and number of modifications of the nucleotides with modified bases, the number of nucleotides with modified bases can be enlarged or reduced to meet the information storage capacity of different requirements.

The synthesis and storage unit includes a synthesis unit and a storage unit, and the synthesis can obtain the DNA information for the storage information confirmed by the data information and the DNA information conversion unit. The storage unit can store the DNA sequence that records the data information. The storage unit is a chip with multiple wells, and each well accommodates a sequence. In other words, each well corresponds to one type of DNA information. The wells on the chip are arranged in order.

Example 4 Decoding device for decoding nucleic acid storage based on natural and unnatural base matrix spectra

Corresponding to the decoding method described in the above embodiment 2, FIG6 shows a structural block diagram of a decoding device provided in embodiment 4 of the present invention. For ease of explanation, FIG6 only shows the part related to embodiment 4 of the present invention.

6, the decoding device may include:

A reading unit, used to detect the sequence to be tested stored in the synthesis and storage unit by a mass spectrometer, and confirm its DNA information according to the molecular weight;

A DNA information and data information conversion unit, used to convert the DNA information obtained by the reading unit into data information according to a preset mapping relationship, that is, the same data information and DNA information mapping relationship in the DNA information storage device;

The reading module includes a mass spectrometer for performing mass spectrometry detection on the nucleic acid sequence in each well position in the chip for detecting stored information, and may also include pre-treatment such as purification and/or enzymatic hydrolysis of the nucleic acid sequence in each well position.

A computer data output unit, used to convert the DNA information and the data information obtained by the data information conversion unit into stored computer data;

It should be noted that the information interaction, execution process, etc. between the above-mentioned devices/units are based on the same concept as the method embodiment of the present invention. Their specific functions and technical effects can be found in the method embodiment part and will not be repeated here.

Fig. 7 is a schematic diagram of the structure of a computer device provided by an embodiment of the present invention. As shown in Fig. 7, the computer device of this embodiment includes: at least one processor (only one is shown in Fig. 7), storage, and a computer program stored in the memory and executable on the at least one processor, and when the processor executes the computer program, any storage method and decoding method of the present invention are implemented.

The computer device may be a computing device such as a laptop computer, a desktop computer, a tablet computer, a mobile phone, etc. The computer device includes at least a processor and a memory. Those skilled in the art will appreciate that FIG. 7 is only a schematic diagram of a computer device and does not constitute a limitation on the computer device, and may also include other components, such as information input or output components.

An embodiment of the present application further provides a computer-readable storage medium, wherein the computer-readable storage medium stores a computer program, and when the computer program is executed by a processor, the steps in the above-mentioned method embodiments can be implemented.

The computer-readable storage medium may also be any available medium or data storage device that can be accessed by a computer, such as a server or data center integrated with the medium. The available medium may be a magnetic medium, a DVD, or a semiconductor medium.

An embodiment of the present invention provides a computer program product. When the computer program product is run on a terminal device, the terminal device can implement the steps in the above-mentioned method embodiments when executing the computer program product.

The terminal device may be a general-purpose computer, a handheld computer, a mobile phone, a special-purpose computer, a computer network, or other programmable devices, or storage devices with programming functions. The computer program may be stored in a computer-readable storage medium, or transmitted to another computer-readable storage medium via a network.

In addition, each functional unit in each embodiment of the present application may be integrated into one processing unit, or each unit may exist physically separately, or two or more units may be integrated into one unit.

In the above embodiments, all or part of the above embodiments may be implemented by software, hardware, firmware or any combination thereof. When the computer program instructions are loaded and executed on the computer, all or part of the steps and methods described in the embodiments of the present invention are generated.

It is to be understood that the systems, devices and methods described in the present application may also be implemented in other ways. For example, the device embodiments described above are merely illustrative, and for example, the division of the functional units may be re-divided according to actual needs without affecting the satisfaction or completion of the above-mentioned functions and steps of the present invention. For example, multiple units or components may be combined or integrated into another system, or some features may be ignored or not executed. The units of the above-mentioned devices may be merged or re-divided according to the storage and decoding methods, and additional functional units may be added according to actual needs to meet the requirements of the above-mentioned steps and methods.

The embodiments described above are only used to illustrate the technical solutions of the present application, rather than to limit them. Although the present application has been described in detail with reference to the aforementioned embodiments, a person skilled in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some of the technical features may be replaced by equivalents. Such modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present application, and should all be included in the protection scope of the present application.

Claims (17)

The method for storing DNA information based on natural and non-natural bases is characterized in that the method for storing DNA information comprises the following steps: S11): extracting data information of computer data information to be stored; S12): Designing a coding table, wherein the coding table is formed by one-to-one mapping of DNA information and data information units; S13) splitting the data information in step S11) into data information units, and confirming the DNA information corresponding to the split data information units in the coding table obtained in step S12); S14) obtaining the deoxyribonucleotides or polynucleotide sequences consisting of two or more deoxyribonucleotides corresponding to the DNA information confirmed in step S13), and arranging them in sequence in different wells of the chip to obtain a DNA information storage carrier; The DNA information is a deoxyribonucleotide or a polynucleotide sequence consisting of two or more deoxyribonucleotides, or a combination of any two of the deoxyribonucleotides or the polynucleotide sequence consisting of two or more deoxyribonucleotides; In the coding table, the molecular weight of each DNA information is different, and the molecular weight difference between each is no less than 10. The DNA storage method according to claim 1, characterized in that the deoxyribonucleotide is a natural deoxyribonucleotide or a non-natural deoxyribonucleotide, and the non-natural deoxyribonucleotide is a base-modified deoxyribonucleotide. The DNA storage method according to claim 1, characterized in that the deoxyribonucleotides in the polynucleotide sequence composed of two or more deoxyribonucleotides are natural deoxyribonucleotides or non-natural deoxyribonucleotides; Preferably, the polynucleotide sequence composed of two or more deoxyribonucleotides has different molecular weights by adjusting the combination of the types and quantities of deoxyribonucleotides in the polynucleotide sequence. The DNA storage method according to claim 1 is characterized in that the 32 to 1024 mapping relationships are formed in the coding table. The DNA storage method according to claim 1 is characterized in that, in step S11), the data information is character information, RGB information, binary data information, octal data information, hexadecimal data information, or decimal data information. The DNA storage method according to claim 1 is characterized in that, in the coding table, the molecular weight of each DNA information is different, and the difference in molecular weight between each two is not less than 10. The DNA storage method according to claim 1, characterized in that the coding table maps DNA information to 4-bit or 8-bit binary numbers one by one; or The coding table maps DNA information to the ASCII code table one by one; or The coding table maps DNA information to 128 characters one by one; or The coding table maps DNA information to RGB pixel information one by one; or The DNA information in the coding table is 128 or 256 different nucleotides with modified bases, and 32 or 64 different types of modifications are performed on A, T, C, and G, respectively, to obtain a total of 128 or 256 different nucleotides with modified bases; or In the coding table, one of the DNA information is mapped one by one with the color information in the RGB pixel information, i.e., R\G\B, and the other of the DNA information is mapped one by one with the numbers 0-255 in the color information of the RGB pixel information, and the combination of the two DNA information forms a one-to-one mapping relationship with the RGB pixel information; or The coding table contains 128 combined polynucleotide sequences, the lengths of the polynucleotide sequences are divided into 8 groups, the lengths of the 8 groups of polynucleotide sequences are successively extended, each containing 10-24 base nucleotides, each group has 4 polynucleotide sequences, and the types and or quantities of bases in the 4 polynucleotide sequences in each group are different. The method for reading information from a DNA information storage carrier obtained by the DNA storage method according to any one of claims 1 to 7, characterized in that the information reading method comprises the following steps: S21) performing mass spectrometry on the sequences to be tested at different wells in the DNA information storage carrier to obtain molecular weight information of the DNA information in each well; S22) analyzing the base combination information according to the molecular weight information of the DNA information to confirm the DNA information corresponding to the different pore positions; S23) interpreting the data information unit according to the DNA information obtained in step S22) and the coding table in step S12); S24) splicing the data information units obtained in S23) and decoding the data information to obtain the stored computer data information. The information reading method according to claim 8 is characterized in that the mass spectrometry sequencing method in step S21) is MALDI mass spectrometry sequencing. The information reading method according to claim 8, characterized in that in step S21), the mass spectrometry sequencing method comprises the following steps: S211) digesting and/or purifying the sequence to be tested; S212) The purified fragments are subjected to mass spectrometry to obtain molecular weight. The information reading method according to claim 8 is characterized in that the purification method in step S211) is ethanol precipitation, microdialysis or MillporeZiptip microchromatography. A coding device based on natural and unnatural base DNA information storage, characterized in that the DNA information storage device comprises: A data information extraction unit, used for extracting the computer data to be stored and converting the computer data to be stored into data information corresponding to the information; A data information and DNA information conversion unit, used to split or assemble the data information sequence and convert it into DNA information according to a preset mapping relationship; A synthesis and storage unit, used to synthesize the data information and the nucleic acid sequence converted by the DNA information conversion unit, and store the deoxyribonucleotides corresponding to the DNA information, a polynucleotide sequence consisting of two or more deoxyribonucleotides, or a combination thereof in order on different wells of the storage unit chip; The mapping relationship is a one-to-one mapping relationship between DNA information and data information units; The DNA information is a deoxyribonucleotide or a polynucleotide sequence consisting of two or more deoxyribonucleotides, or a combination of any two of the deoxyribonucleotides or the polynucleotide sequence consisting of two or more deoxyribonucleotides; In the mapping relationship, the molecular weight of each DNA information is different, and the molecular weight difference between each pair is no less than 10. The DNA information storage device according to claim 12 is characterized in that the data information and DNA information conversion unit may include a DNA information encoding unit, a DNA information and data information matching unit, and a DNA information conversion unit. The DNA information encoding unit is used to record the combination of base types and quantities corresponding to each type of DNA information. The DNA information and data information matching unit is used to call different DNA information and data information units in the DNA information encoding unit for one-to-one matching and correspondence. The DNA information conversion unit is used to convert the digital information in the data information extraction unit into DNA information one-to-one according to the information of the DNA information and data information matching unit. A decoding device for DNA information storage based on natural and unnatural bases, characterized in that the decoding device comprises: A reading unit, used to detect the sequence to be tested synthesized and stored in the storage unit of the DNA information storage device of claim 12 or 13 by a mass spectrometer, and confirm its DNA information according to the molecular weight; A DNA information and data information conversion unit, used to convert the DNA information obtained by the reading unit into data information according to a preset mapping relationship, that is, the same data information and DNA information mapping relationship in the DNA information storage device; A computer data output unit, used to convert the DNA information and the data information obtained by the data information conversion unit into stored computer data; The reading module comprises a mass spectrometer for performing mass spectrometry detection on the nucleic acid sequence in each well in the chip for detecting the stored information. The decoding device according to claim 14 is characterized in that the reading module includes a mass spectrometer for performing mass spectrometry detection on the nucleic acid sequence in each well position in the chip for detecting the stored information, and may also include a unit for preprocessing the sequence to be detected in each well position. A computer-readable storage medium, characterized in that a computer program is stored thereon, wherein when the computer program is executed by a processor, the method for storing DNA information based on natural and non-natural bases according to any one of claims 1 to 7 or the method for reading information from a DNA information storage carrier obtained by the DNA storage method according to any one of claims 8 to 11 is implemented. step. A computer device, characterized in that it comprises a memory and a processor, wherein a computer program that can be run on the processor is stored in the memory, and when the processor executes the computer program, the steps of the method for reading information of a DNA information storage carrier obtained by the DNA storage method based on natural and non-natural bases as described in any one of claims 1 to 7 or the DNA storage method as described in any one of claims 8 to 11 are implemented.