Method and device for recommending concentration of nucleic acid molecule solution, and computer equipment

Abstract

The present disclosure provides a method and device for recommending the concentration of a nucleic acid molecule solution, and a computer device. The method includes: obtaining multiple nucleic acid molecule configurations and parameters to be recommended, wherein the multiple nucleic acid molecule configurations to be recommended are multiple nucleic acid molecule configurations designed for the same genetic disease based on different chemical modification methods, and the parameters of the nucleic acid molecule configurations include nucleic acid molecule chemical modification, the stability of the nucleic acid molecule configuration under a first environment, and the long-term effectiveness and long-term specificity of nucleic acid molecule solutions of different concentrations under the first environment, wherein the first environment includes at least one of the following: a plasma environment and a physiological saline environment; inputting the multiple nucleic acid molecule configurations and parameters into a recommendation model, and obtaining the nucleic acid molecule configurations and nucleic acid molecule solution concentrations recommended by the recommendation model.

Description

Technical Field

[0001] The present disclosure relates to the field of biotechnology, and in particular to a method and device for recommending the concentration of a nucleic acid molecule solution, and a computer device. Background Art

[0002] Nucleic acid is one of the basic substances in cells, and determining the properties of nucleic acid molecular structure will help study their functions.

[0003] In related technologies, nucleic acids can be used as targeted drugs to treat some gene defects in the human body. Usually, after the gene defect is determined, a variety of nucleic acid molecular configurations with different chemical modifications are designed based on drug development experience and chemical physics knowledge. Clinical trials are conducted on these nucleic acid molecular configurations with different chemical modifications, and the best chemical modification and concentration are determined to obtain the final nucleic acid molecular configuration and its concentration.

[0004] However, the above method completes screening through clinical trials, which has a long experimental cycle and is time-consuming and labor-intensive. Summary of the invention

[0005] The disclosed embodiment provides a method and device for recommending the concentration of a nucleic acid molecule solution, and a computer device, which can improve the cycle of determining the concentration of nucleic acid molecules and reduce the time consumption. The technical solution is as follows:

[0006] At least one embodiment of the present disclosure provides a method for recommending the concentration of a nucleic acid molecule solution, the method comprising:

[0007] Acquiring multiple nucleic acid molecule configurations to be recommended and parameters thereof, wherein the multiple nucleic acid molecule configurations to be recommended are multiple nucleic acid molecule configurations designed for the same genetic disease based on different chemical modification methods, the parameters of the nucleic acid molecule configurations include nucleic acid molecule chemical modification, stability of the nucleic acid molecule configuration under a first environment, and long-term effectiveness and long-term specificity of nucleic acid molecule solutions of different concentrations under the first environment, wherein the first environment includes at least one of the following: a plasma environment and a physiological saline environment;

[0008] The multiple nucleic acid molecule configurations and their parameters are input into a recommendation model to obtain the nucleic acid molecule configurations and nucleic acid molecule solution concentrations recommended by the recommendation model, wherein the recommendation model is used to quantify the chemical modification of the nucleic acid molecules, the stability of the nucleic acid molecule configurations, and the long-term effectiveness and long-term specificity of the nucleic acid molecule solutions of different concentrations, and the recommendation degree of the nucleic acid molecule configuration is calculated using the quantified chemical modification of the nucleic acid molecules, the stability of the nucleic acid molecule configurations, and the long-term effectiveness and long-term specificity of the nucleic acid molecule solutions of different concentrations, and the nucleic acid molecule configuration and the nucleic acid molecule solution concentration are selected for recommendation based on the recommendation degree.

[0009] Optionally, the method further comprises:

[0010] Acquire a training set, wherein the training set includes a plurality of training samples, each of the plurality of training samples includes a plurality of nucleic acid molecule configurations and parameters thereof designed for the same genetic disease;

[0011] The recommendation model is trained using the multiple training samples.

[0012] Optionally, the using the multiple training samples to train the recommendation model includes:

[0013] Inputting the training samples into the recommendation model;

[0014] Obtaining the nucleic acid molecule configuration and nucleic acid molecule solution concentration output by the recommended model;

[0015] The parameters of the recommendation model are updated using the known nucleic acid molecule configuration and nucleic acid molecule solution concentration for the genetic disease as feedback.

[0016] Optionally, the parameters of the nucleic acid molecule configuration further include: production line cost corresponding to the nucleic acid molecule configuration;

[0017] The recommendation model is used to quantify the chemical modification of the nucleic acid molecules, the stability of the nucleic acid molecule configuration, the long-term effectiveness and long-term specificity of the nucleic acid molecule solutions of different concentrations, and the production line cost corresponding to the nucleic acid molecule configuration, and calculate the recommendation degree of the nucleic acid molecule configuration using the quantified chemical modification of the nucleic acid molecules, the stability of the nucleic acid molecule configuration, the long-term effectiveness and long-term specificity of the nucleic acid molecule solutions of different concentrations, and the production line cost corresponding to the nucleic acid molecule configuration, and select the nucleic acid molecule configuration and the nucleic acid molecule solution concentration for recommendation based on the recommendation degree.

[0018] Optionally, the method comprises:

[0019] The long-term effectiveness and long-term specificity of the nucleic acid molecule configuration in nucleic acid molecule solutions of different concentrations under the first environment are determined.

[0020] Optionally, the determining of the long-term effectiveness and long-term specificity of the nucleic acid molecule configuration in nucleic acid molecule solutions of different concentrations under the first environment comprises:

[0021] Obtaining a nucleic acid molecule configuration to be tested, wherein the stability of the nucleic acid molecule configuration to be tested in an aqueous solution environment meets a condition;

[0022] Performing a physical simulation test on the nucleic acid molecule configuration to be tested to simulate the stability of the nucleic acid molecule configuration to be tested in a first environment, wherein the first environment includes at least one of the following: a plasma environment and a physiological saline environment;

[0023] Obtaining the short-term effectiveness and short-term specificity of nucleic acid molecule solutions of different concentrations obtained through experiments under the first environment for the nucleic acid molecule configuration to be tested;

[0024] According to the stability of the nucleic acid molecule configuration to be tested in the first environment and the short-term effectiveness and short-term specificity in the first environment, the long-term effectiveness and long-term specificity of the nucleic acid molecule solution of different concentrations of the nucleic acid molecule configuration to be tested in the first environment are determined.

[0025] At least one embodiment of the present disclosure provides a nucleic acid molecule solution concentration recommendation device, the device comprising:

[0026] an acquisition module, for acquiring a plurality of nucleic acid molecule configurations to be recommended and parameters thereof, wherein the plurality of nucleic acid molecule configurations to be recommended are a plurality of nucleic acid molecule configurations designed for the same genetic disease based on different chemical modification methods, wherein the parameters of the nucleic acid molecule configurations include chemical modification of nucleic acid molecules, stability of the nucleic acid molecule configurations under a first environment, and long-term effectiveness and long-term specificity of nucleic acid molecule solutions of different concentrations under the first environment, wherein the first environment includes at least one of the following: a plasma environment and a physiological saline environment;

[0027] A recommendation module is used to input the multiple nucleic acid molecule configurations and their parameters into a recommendation model, and obtain the nucleic acid molecule configurations and nucleic acid molecule solution concentrations recommended by the recommendation model, wherein the recommendation model is used to quantify the chemical modification of the nucleic acid molecule, the stability of the nucleic acid molecule configuration, and the long-term effectiveness and long-term specificity of the nucleic acid molecule solutions of different concentrations, and calculate the recommendation degree of the nucleic acid molecule configuration using the quantified chemical modification of the nucleic acid molecule, the stability of the nucleic acid molecule configuration, and the long-term effectiveness and long-term specificity of the nucleic acid molecule solutions of different concentrations, and select the nucleic acid molecule configuration and the nucleic acid molecule solution concentration for recommendation based on the recommendation degree.

[0028] Optionally, the parameters of the nucleic acid molecule configuration further include: production line cost corresponding to the nucleic acid molecule configuration;

[0029] The recommendation model is used to quantify the chemical modification of the nucleic acid molecules, the stability of the nucleic acid molecule configuration, the long-term effectiveness and long-term specificity of the nucleic acid molecule solutions of different concentrations, and the production line cost corresponding to the nucleic acid molecule configuration, and calculate the recommendation degree of the nucleic acid molecule configuration using the quantified chemical modification of the nucleic acid molecules, the stability of the nucleic acid molecule configuration, the long-term effectiveness and long-term specificity of the nucleic acid molecule solutions of different concentrations, and the production line cost corresponding to the nucleic acid molecule configuration, and select the nucleic acid molecule configuration and the nucleic acid molecule solution concentration for recommendation based on the recommendation degree.

[0030] At least one embodiment of the present disclosure provides a computer device, which includes a processor and a memory, wherein the memory stores at least one program code, and the program code is loaded and executed by the processor to implement the method for recommending the concentration of a nucleic acid molecule solution as described above.

[0031] At least one embodiment of the present disclosure provides a computer-readable storage medium, wherein at least one program code is stored in the computer-readable storage medium, and the program code is loaded and executed by a processor to implement the method for recommending the concentration of a nucleic acid molecule solution as described in any of the preceding items.

[0032] The technical solution provided by the embodiments of the present disclosure brings the following beneficial effects:

[0033] In the disclosed embodiments, the stability of the nucleic acid molecule configuration, and the long-term effectiveness and long-term specificity of the nucleic acid molecule solutions of different concentrations are digitized by using a recommendation model, and then the recommendation degree of different nucleic acid molecule configurations and concentrations is calculated using the digitized chemical modification of the nucleic acid molecules, the stability of the nucleic acid molecule configuration, and the long-term effectiveness and long-term specificity of the nucleic acid molecule solutions of different concentrations, and then the concentration of the nucleic acid molecule solution is recommended according to the recommendation degree. The recommendation model can be trained based on a large amount of known nucleic acid molecule data in the nucleic acid library, so the use of the recommendation model can ensure the accuracy of the recommendation, and no long-term clinical experiments are required, which shortens the cycle of determining the nucleic acid molecule configuration and concentration, saving time and effort. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] In order to more clearly illustrate the technical solutions in the embodiments of the present disclosure, the drawings required for use in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present disclosure. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0035] Figure 1 is a flow chart of a method for recommending the concentration of a nucleic acid molecule solution provided by an embodiment of the present disclosure;

[0036] Figure 2 is a flow chart of a method for recommending the concentration of a nucleic acid molecule solution provided by an embodiment of the present disclosure;

[0037] Figure 3 is a flow chart of a method for determining the structural properties of a nucleic acid molecule provided by an embodiment of the present disclosure;

[0038] Figure 4 is a flow chart of a method for determining the structural properties of a nucleic acid molecule provided by an embodiment of the present disclosure;

[0039] Figure 5 is a flow chart of a method for screening nucleic acid molecular structures provided by an embodiment of the present disclosure;

[0040] Figure 6 is a flow chart of a method for screening nucleic acid molecular structures provided by an embodiment of the present disclosure;

[0041] Figure 7 It is a schematic diagram of the structure of a nucleic acid molecule solution concentration recommendation device provided by an embodiment of the present disclosure;

[0042] Figure 8 It is a structural block diagram of a computer device provided by an embodiment of the present disclosure. DETAILED DESCRIPTION

[0043] In order to make the objectives, technical solutions and advantages of the present disclosure more clear, the embodiments of the present disclosure will be further described in detail below with reference to the accompanying drawings.

[0044] Unless otherwise defined, the technical or scientific terms used herein shall have the usual meanings understood by persons of ordinary skill in the field to which the present disclosure belongs. The words "first", "second", "third" and similar words used in the patent application specification and claims of the present disclosure do not indicate any order, quantity or importance, but are only used to distinguish different components. Similarly, words such as "one" or "one" do not indicate a quantitative limitation, but rather indicate the presence of at least one. Words such as "include" or "comprise" and similar words mean that the elements or objects appearing before "include" or "comprises" cover the elements or objects listed after "include" or "comprises" and their equivalents, and do not exclude other elements or objects.

[0045] Figure 1 is a flow chart of a method for recommending the concentration of a nucleic acid molecule solution provided by an embodiment of the present disclosure. Figure 1 , the method comprising:

[0046] 101: Obtain multiple nucleic acid molecule configurations to be recommended and their parameters.

[0047] Among them, the multiple nucleic acid molecule configurations to be recommended are multiple nucleic acid molecule configurations designed for the same genetic disease based on different chemical modification methods, and the parameters of the nucleic acid molecule configuration include chemical modification of the nucleic acid molecule, the stability of the nucleic acid molecule configuration under a first environment, and the long-term effectiveness and long-term specificity of nucleic acid molecule solutions of different concentrations under the first environment, and the first environment includes at least one of the following: plasma environment, physiological saline environment.

[0048] Among them, multiple nucleic acid molecular configurations designed for the same genetic disease based on different chemical modification methods refer to multiple nucleic acid molecular configurations designed specifically for a nucleic acid base sequence based on different chemical modification methods in order to achieve nucleic acid molecular drug properties that are effective for the aforementioned genetic disease.

[0049] It should be noted that how to design multiple nucleic acid molecule configurations for genetic diseases is not the content of this disclosure, and this disclosure is to further screen on the basis of having designed multiple nucleic acid molecule configurations. The involvement of these multiple nucleic acid molecule configurations can be completed manually in advance, for example, first, bioinformatics experts determine the target site (such as a certain effective target gene) based on genetic diseases, then, for the determined target site, select the strategy (increase or decrease) of nucleic acid molecule regulation gene expression, again, carry out molecular bias design, such as biased drug delivery ability or drug enrichment or drug half-life and other performances to design molecules, finally, determine the modification strategy of nucleic acid molecules, based on the demand / bias of the design, select suitable chemical synthesis and modification methods. By designing multiple groups, multiple nucleic acid molecule configurations to be recommended are obtained.

[0050] Among them, chemical modification refers to the modification of the base, middle, pentose, two ends, phosphate backbone, etc. of the nucleic acid molecule. Different modification methods include different modification positions and different modification methods.

[0051] Stability refers to the fact that the structural configuration of the nucleic acid molecule will not change or will have a very small probability of changing under certain conditions. The very small probability here may refer to a probability less than a certain threshold, such as less than 2% or 1%.

[0052] Among them, effectiveness refers to the effect of nucleic acid molecular configuration acting on genes under a specific target, for example, the effect of reducing fat when nucleic acid molecular configuration acts on genes, or the effect of increasing protein when nucleic acid molecular configuration acts on genes, etc. Here, reducing fat and increasing protein are both the aforementioned specific targets. Specificity refers to the tissue enrichment of nucleic acid molecular configuration for a specific organ under a specific target, as well as the effect on a specific organ. Therefore, effectiveness and specificity are the effects of nucleic acid molecular configuration acting on genes under a specific target for a specific organ.

[0053] In the embodiments of the present disclosure, the concentration of the nucleic acid molecule solution can be expressed in a variety of ways, for example, as a mass percentage concentration, which refers to the ratio of the mass of the nucleic acid molecule to the mass of the entire solution when the nucleic acid molecule (nucleic acid molecule configuration) is used as the solute. The solvent of the solution is usually water, blood or physiological saline.

[0054] The concentration of the nucleic acid molecule solution can also be the mass of the solute per unit of solution, for example, the mass of the solute per 100 grams of solution.

[0055] The concentration of the nucleic acid molecule solution may also be a concentration calculated by volume.

[0056] Before recommendation, multiple concentrations may be preset, for example, multiple mass percentage concentrations may be set according to fixed differences, such as 20%, 30%, 40%, ... 70%, etc.

[0057] 102: Input the multiple nucleic acid molecule configurations and their parameters into a recommendation model to obtain the nucleic acid molecule configurations and nucleic acid molecule solution concentrations recommended by the recommendation model.

[0058] The recommendation model is used to quantify the chemical modification of the nucleic acid molecules, the stability of the nucleic acid molecule configuration, and the long-term effectiveness and long-term specificity of the nucleic acid molecule solutions of different concentrations, and calculate the recommendation degree of the nucleic acid molecule configuration using the quantified chemical modification of the nucleic acid molecules, the stability of the nucleic acid molecule configuration, and the long-term effectiveness and long-term specificity of the nucleic acid molecule solutions of different concentrations, and select the nucleic acid molecule configuration and the nucleic acid molecule solution concentration for recommendation based on the recommendation degree.

[0059] In the disclosed embodiments, the stability of the nucleic acid molecule configuration, and the long-term effectiveness and long-term specificity of the nucleic acid molecule solutions of different concentrations are digitized by using a recommendation model, and then the recommendation degree of different nucleic acid molecule configurations and concentrations is calculated using the digitized chemical modification of the nucleic acid molecules, the stability of the nucleic acid molecule configuration, and the long-term effectiveness and long-term specificity of the nucleic acid molecule solutions of different concentrations, and then the concentration of the nucleic acid molecule solution is recommended according to the recommendation degree. The recommendation model can be trained based on a large amount of known nucleic acid molecule data in the nucleic acid library, so the use of the recommendation model can ensure the accuracy of the recommendation, and no long-term clinical experiments are required, which shortens the cycle of determining the nucleic acid molecule configuration and concentration, saving time and effort.

[0060] Figure 2 is a flow chart of a method for recommending the concentration of a nucleic acid molecule solution provided by an embodiment of the present disclosure. Figure 2 , the method comprising:

[0061] 201: Get the training set.

[0062] The training set includes a plurality of training samples, and each of the plurality of training samples includes a plurality of nucleic acid molecule configurations and parameters thereof designed for the same genetic disease.

[0063] The training set can be obtained from a nucleic acid library, which includes known nucleic acid molecular configurations and parameters thereof, and the above-mentioned sample is formed by screening out multiple nucleic acid molecular configurations and parameters thereof designed for the same genetic disease.

[0064] 202: Train the recommendation model using the multiple training samples.

[0065] Exemplarily, the using the multiple training samples to train the recommendation model includes:

[0066] Inputting the training samples into the recommendation model;

[0067] Obtaining the nucleic acid molecule configuration and nucleic acid molecule solution concentration output by the recommended model;

[0068] The parameters of the recommendation model are updated using the known nucleic acid molecule configuration and nucleic acid molecule solution concentration for the genetic disease as feedback.

[0069] In the disclosed embodiment, the recommendation model is used to digitize the chemical modification of the nucleic acid molecule, the stability of the nucleic acid molecule configuration, and the long-term effectiveness and long-term specificity of the nucleic acid molecule solutions of different concentrations, and the recommendation degree of the nucleic acid molecule configuration is calculated using the digitized chemical modification of the nucleic acid molecule, the stability of the nucleic acid molecule configuration, and the long-term effectiveness and long-term specificity of the nucleic acid molecule solutions of different concentrations, and the nucleic acid molecule configuration and the concentration of the nucleic acid molecule solution are selected for recommendation based on the recommendation degree. Therefore, what is updated here may be the parameters for digitizing the stability of the nucleic acid molecule configuration, and the long-term effectiveness and long-term specificity at different concentrations, and / or the parameters for calculating the recommendation degree of the nucleic acid molecule configuration using the digitized stability of the nucleic acid molecule configuration, and the long-term effectiveness and long-term specificity at different concentrations.

[0070] The recommendation model is trained with known samples, and finally a stable recommendation model is obtained.

[0071] 203: Obtain multiple nucleic acid molecule configurations to be recommended and their parameters, wherein the multiple nucleic acid molecule configurations to be recommended are multiple nucleic acid molecule configurations designed for the same genetic disease based on different chemical modification methods, and the parameters of the nucleic acid molecule configurations include chemical modification of the nucleic acid molecule, stability of the nucleic acid molecule configuration under a first environment, and long-term effectiveness and long-term specificity of nucleic acid molecule solutions of different concentrations under the first environment, wherein the first environment includes at least one of the following: plasma environment, physiological saline environment.

[0072] The stability of the nucleic acid molecule configuration under the first environment, and the long-term effectiveness and long-term specificity of nucleic acid molecule solutions of different concentrations under the first environment can be measured by Figure 3 or Figure 4 The method flow shown is obtained.

[0073] 204: Input the multiple nucleic acid molecule configurations and their parameters into a recommendation model to obtain the nucleic acid molecule configurations and nucleic acid molecule solution concentrations recommended by the recommendation model.

[0074] Optionally, the parameters of the nucleic acid molecule configuration further include: production line cost corresponding to the nucleic acid molecule configuration;

[0075] The recommendation model is used to quantify the chemical modification of the nucleic acid molecules, the stability of the nucleic acid molecule configuration, the long-term effectiveness and long-term specificity of the nucleic acid molecule solutions of different concentrations, and the production line cost corresponding to the nucleic acid molecule configuration, and calculate the recommendation degree of the nucleic acid molecule configuration using the quantified chemical modification of the nucleic acid molecules, the stability of the nucleic acid molecule configuration, the long-term effectiveness and long-term specificity of the nucleic acid molecule solutions of different concentrations, and the production line cost corresponding to the nucleic acid molecule configuration, and select the nucleic acid molecule configuration and the nucleic acid molecule solution concentration for recommendation based on the recommendation degree.

[0076] Among them, the production line cost corresponding to the nucleic acid molecule configuration can be calculated manually and then input into the computer device that executes the method.

[0077] For example, nucleic acid researchers divide nucleic acid molecule development into multiple stages, such as molecular design and R&D stage, molecular cell experiment design and R&D stage, animal experiment stage, clinical registration application stage, pharmaceutical factory / synthetic manufacturing stage, etc. Then, based on experience, the cost corresponding to each nucleic acid molecule configuration at each stage is evaluated, and then the production line cost corresponding to the nucleic acid molecule configuration is comprehensively derived.

[0078] The following provides a method for determining the structural properties of nucleic acid molecules to determine the long-term effectiveness and long-term specificity of the nucleic acid molecule configuration.

[0079] Figure 3is a flow chart of a method for determining the structural properties of a nucleic acid molecule provided by an embodiment of the present disclosure. Figure 3 , the method comprising:

[0080] 301: Obtain a nucleic acid molecule configuration to be tested, wherein the stability of the nucleic acid molecule configuration to be tested in an aqueous solution environment meets a condition.

[0081] In the aqueous solution referred to in this step, the solute is the nucleic acid molecule (nucleic acid molecule configuration) and the solvent is water.

[0082] Here, there may be multiple nucleic acid molecule configurations to be tested, and these multiple nucleic acid molecule configurations are multiple nucleic acid molecule configurations designed for the same genetic disease. For example, a nucleic acid molecule is designed for the same genetic disease, and then predicted based on the nucleic acid molecule parameters of the nucleic acid molecule.

[0083] The nucleic acid molecule parameters include: nucleic acid molecule sequence, length of nucleic acid molecule sequence, chemical modification of nucleic acid molecule, and multiple nucleic acid molecule configurations to be screened and corresponding energy and experimental data obtained by computational simulation based on quantum mechanics and molecular dynamics.

[0084] Among them, the sequence of a nucleic acid molecule refers to the base sequence of a nucleic acid molecule. The length of a sequence refers to the number or length of bases in a nucleic acid molecule. The data obtained by computational simulation based on quantum mechanics and molecular dynamics can also be referred to as computational physics result data, which is the data such as the configuration of nucleic acid molecules (mainly including configuration coordinates, molecular size), energy size, etc. obtained by computational physics simulation of nucleic acid molecules. Experimental data include at least one of the experimental environment, half-life, annealing temperature, drug enrichment, membrane permeability, and water absorption rate.

[0085] Among the above parameters, multiple nucleic acid molecular configurations to be screened and corresponding energies obtained by computational simulation based on quantum mechanics and molecular dynamics can be obtained through quantum mechanics and molecular dynamics simulation experiments. Experimental data are obtained by conducting biomolecular experiments and animal experiments on the nucleic acid molecular configurations to be screened. Nucleic acid molecule sequence, the length of nucleic acid molecule sequence, and chemical modification of nucleic acid molecules are the basic parameters of nucleic acid molecules processed in this application.

[0086] Stability refers to the fact that the structural configuration of the nucleic acid molecule will not change or will have a very small probability of changing under certain conditions. The very small probability here may refer to a probability less than a certain threshold, such as less than 2% or 1%.

[0087] Here, the stability meeting the condition may mean that the stability exceeds a threshold, such as 60%, or the stability ranking among all configurations of the nucleic acid molecule meets the condition, such as being among the top 5.

[0088] 302: Performing a physical simulation test on the nucleic acid molecule configuration to be tested, simulating the stability of the nucleic acid molecule configuration to be tested in a first environment, wherein the first environment includes at least one of the following: a plasma environment and a physiological saline environment.

[0089] Here, the physics simulation can be a quantum mechanics simulation. The quantum mechanics implementation is based on the ab initio algorithm (the most original input molecular initial configuration coordinates), using density functional theory or Hartree-Fock theory to solve the Schrödinger equation and obtain the wave function of the system, and with the continuous convergence of energy and gradient descent, the configuration of the nucleic acid molecule after energy convergence is found.

[0090] Exemplarily, the physics simulation is implemented by physics simulation software. The above-mentioned computational physics simulation software includes but is not limited to VASP, Gaussian, GAMESS, NWchem, Q-chem, Spartan, openMM, Amber, NAMD, Lammps, Gromacs, CHARMM, etc.

[0091] 303: Obtaining the short-term effectiveness and short-term specificity of nucleic acid molecule solutions of different concentrations obtained through experiments under the first environment for the nucleic acid molecule configuration to be tested.

[0092] Among them, effectiveness refers to the effect of nucleic acid molecular configuration acting on genes under a specific target, for example, the effect of reducing fat when nucleic acid molecular configuration acts on genes, or the effect of increasing protein when nucleic acid molecular configuration acts on genes, etc. Here, reducing fat and increasing protein are both the aforementioned specific targets. Specificity refers to the tissue enrichment of nucleic acid molecular configuration for a specific organ under a specific target, as well as the effect on a specific organ. Therefore, effectiveness and specificity are the effects of nucleic acid molecular configuration acting on genes under a specific target for a specific organ.

[0093] Short-term effectiveness and short-term specificity refer to the effects of nucleic acid molecule configurations acting on genes within a shorter period of time, targeting a specific organ and under a specific target.

[0094] Exemplarily, the short-term effectiveness and the short-term specificity are obtained through experiments, and therefore, the short-term effectiveness and the short-term specificity also belong to the experimental data mentioned in step 301 .

[0095] Optionally, when determining the long-term effectiveness and long-term specificity of the nucleic acid molecule configuration in the first environment in step 304, in addition to using the short-term effectiveness and short-term specificity in the experimental data, other data in the experimental data, such as half-life, annealing temperature, and drug enrichment, may also be used.

[0096] In step 302 and step 303, specific parameters of the plasma environment and the physiological saline environment may be preset, such as concentration, volume, etc., and the present disclosure does not impose any limitation on the specific parameters.

[0097] Here, during the experiment, the short-term effectiveness and short-term specificity of solutions of different concentrations of the same nucleic acid molecule configuration can be tested.

[0098] 304: Determine the long-term effectiveness and long-term specificity of nucleic acid molecule solutions of different concentrations of the nucleic acid molecule configuration to be tested under the first environment according to the stability of the nucleic acid molecule configuration to be tested under the first environment and the short-term effectiveness and short-term specificity under the first environment.

[0099] Long-term effectiveness and long-term specificity refer to the effects of nucleic acid molecule configurations acting on genes under a specific target in a specific organ over a longer period of time.

[0100] In the disclosed embodiment, by conducting a physical simulation test on the nucleic acid molecule configuration to be tested that meets the stability conditions, the stability of the nucleic acid molecule configuration in the first environment is determined, and then the long-term effectiveness and long-term specificity of the nucleic acid molecule configuration in the first environment are determined based on the stability of these nucleic acid molecule configurations in the first environment and the short-term effectiveness and short-term specificity obtained through experiments in the first environment. Since the experimental data is short-term, it will not cause the problem of long time consumption. In addition, this method combines the stability of the nucleic acid molecule configuration in the first environment and the short-term effectiveness and short-term specificity obtained through experiments in the first environment, so that the accuracy of the long-term effectiveness and long-term specificity of the determined nucleic acid molecule configuration in the first environment is guaranteed.

[0101] Figure 4 is a flow chart of a nucleic acid molecular structure screening method provided by an embodiment of the present disclosure. Figure 4 , the method comprising:

[0102] 400: Training effectiveness and specificity models.

[0103] Among them, the effectiveness and specificity model is used to determine the long-term effectiveness and long-term specificity of the nucleic acid molecule configuration to be tested in the first environment based on the stability of the nucleic acid molecule configuration in the first environment and the short-term effectiveness and short-term specificity in the first environment.

[0104] Here, the short-term effectiveness and short-term specificity under the first environment refer to the short-term effectiveness and short-term specificity of the nucleic acid molecule solution of the first concentration under the first environment, and accordingly, the long-term effectiveness and long-term specificity under the first environment refer to the long-term effectiveness and long-term specificity of the nucleic acid molecule solution of the first concentration under the first environment.

[0105] When the first concentration input is different, the concentrations corresponding to the determined long-term effectiveness and long-term specificity are also different. Therefore, the model can determine the long-term effectiveness and long-term specificity of nucleic acid molecule solutions of different concentrations. In the subsequent description, if the concentration is not emphasized, it can refer to the short-term effectiveness and short-term specificity for different concentrations, or the long-term effectiveness and long-term specificity.

[0106] Exemplarily, the scheme for training effectiveness and specificity models is as follows:

[0107] Acquire a training set and a test set based on the nucleic acid library;

[0108] The effectiveness and specificity models are trained using the training set and the test set.

[0109] The data types in the training and test sets are the same as the data types input to the validity and specificity models.

[0110] The effectiveness and specificity model can realize the mapping from the stability of the nucleic acid molecule configuration in the first environment and the short-term effectiveness and short-term specificity in the first environment to the long-term effectiveness and long-term specificity of the nucleic acid molecule configuration in the first environment. In the training set, the sample data includes the stability, short-term effectiveness and short-term specificity, long-term effectiveness and long-term specificity of the nucleic acid molecule configuration in the first environment. The stability, short-term effectiveness and short-term specificity of the nucleic acid molecule configuration in the first environment are used as input, and the model will map and output the predicted long-term effectiveness and long-term specificity, and then use the real long-term effectiveness and long-term specificity in the sample data as feedback to optimize the parameters in the model.

[0111] Of course, the model can also use more parameters as input when designing, for example, including the long-term effectiveness and long-term specificity of similar nucleic acid molecular structures, and / or other experimental data of nucleic acid molecular configurations in the first environment.

[0112] 401: Obtain a nucleic acid molecule configuration to be tested, wherein the stability of the nucleic acid molecule configuration to be tested in an aqueous solution environment meets a condition.

[0113] Here, the stability of the nucleic acid molecule to be tested in the aqueous solution environment meets the conditions and can be used Figure 5 and Figure 6 The method flow is screened.

[0114] 402: Perform a physical simulation test on the nucleic acid molecule configuration to be tested to simulate the stability of the nucleic acid molecule configuration to be tested in a first environment, wherein the first environment includes at least one of the following: a plasma environment and a physiological saline environment.

[0115] Exemplarily, when the first environment is the physiological saline environment, step 402 includes:

[0116] The nucleic acid molecule configuration is used to carry out a physical simulation test in an aqueous solution environment in a physical simulation software, and salt ions are added to the three-dimensional model space where the nucleic acid molecule configuration is located, wherein the salt ions added to the three-dimensional model space are used to simulate the salt in the physiological saline environment.

[0117] Exemplarily, the step of adding salt ions in the three-dimensional model space where the nucleic acid molecule configuration is located includes:

[0118] The required molar number of salt ions is calculated according to the salt ion concentration in the physiological saline environment to be simulated; the parameters of the salt ions are determined; based on the molar number of salt ions, the spatial coordinate distribution of the salt ions is determined by a random distribution method in the three-dimensional model space where the nucleic acid molecule configuration is located; based on the salt ion parameters and the salt ion spatial coordinate distribution, salt ions are added to the three-dimensional model space where the nucleic acid molecule configuration is located, so that the salt ion model can interact with the nucleic acid molecule configuration, thereby simulating the nucleic acid molecule configuration in the physiological saline environment.

[0119] The parameters for determining the salt ions include the charge number of the salt ions, for example, Na ions carry 1 positive charge and Cl ions carry 1 negative charge.

[0120] After the molar number of salt ions is determined, the number of salt ions is calculated based on the concentration of physiological saline and the molar number of salt ions, and then the spatial coordinate distribution is determined according to the number of salt ions.

[0121] The three-dimensional model space is the three-dimensional model space where the nucleic acid molecule configuration simulated in the physics simulation software is located.

[0122] To add salt ions to the three-dimensional model space, you can specify the charge number of the added ions and the spatial coordinates of the distribution in the physics simulation software. For example, specifying Na + Ion or Cl - The spatial coordinates of ions and their distribution.

[0123] Salt ions and nucleic acid molecules generate electromagnetic interactions in the same three-dimensional model space, thereby affecting the configuration of nucleic acid molecules and obtaining the configuration of nucleic acid molecules in physiological saline.

[0124] Exemplarily, when the first environment is the plasma environment or the physiological saline environment, step 402 includes:

[0125] The nucleic acid molecule configuration is used to carry out a physical simulation test in an aqueous solution environment in a physical simulation software, and an interaction potential energy for simulating the plasma environment or the physiological saline environment is added during the test. The interaction potential energy is the interaction potential energy between the nucleic acid molecule configuration and the blood in the plasma environment or the salt ions in the physiological saline environment.

[0126] Since current physics simulation software simulates physics experiments in aqueous solution environments or vacuum environments, the simulation in the first environment needs to be achieved by adding salt ions or correcting the interaction energy.

[0127] Exemplarily, the step of adding interaction potential energy comprises:

[0128] Model the energy size or energy density distribution generated by salt ions or plasma in a solution environment; determine the interaction mode between nucleic acid molecules and salt ions or plasma, which can be expressed in the form of an energy function, such as the Coulomb interaction potential energy of charge; calculate the interaction potential energy between the nucleic acid molecules and salt ions or plasma based on the interaction mode; add the calculated interaction potential energy to the energy calculation step of the computational physics simulation software to perform energy correction.

[0129] The energy size or energy density distribution generated by salt ions or plasma in a solution environment is modeled, and the obtained model includes the following physical information, which is used to characterize the energy size or energy density distribution generated by salt ions or plasma in a solution environment. The physical information includes the number of electrons, the number of net charges, the spatial coordinates, etc. The modeling process is implemented using software such as Visual Molecular Dynamics (VMD), Discovery studio, and Spartan.

[0130] After modeling, an assumption is made on the expression of the interaction potential energy between the nucleic acid molecule and the model according to the model obtained by modeling, and the real interaction potential energy expression is determined based on the assumption. The classical interaction potential energy expression can be: Coulomb interaction potential energy expression or gravitational interaction potential energy expression. The interaction potential energy of salt ions or plasma solutions on nucleic acid molecules generally satisfies a classical interaction potential energy expression. In addition to the above expressions, in molecular dynamics theory, there are also a large number of solution modeling forms that define interaction expressions, such as long-range electromagnetic interactions (Coulomb interactions) and short-range van der Waals interactions, etc., which will not be elaborated in the embodiments of the present disclosure.

[0131] After determining the interaction potential energy expression, the interaction potential energy can be calculated by substituting the known relevant parameters of the nucleic acid molecules and salt ions or plasma into the expression.

[0132] In this step, the concentration of the nucleic acid molecules in the solution may be ignored or may be set according to the concentration of the nucleic acid molecule solution when determining the long-term effectiveness and long-term specificity, and the concentration of the nucleic acid molecules in physiological saline or plasma.

[0133] 403: Obtaining the short-term effectiveness and short-term specificity of the nucleic acid molecule configuration to be tested obtained through experiments under the first environment.

[0134] The experiment here refers to the experiment on the nucleic acid molecule configuration to be tested under the first environment.

[0135] 404: Input the stability of the nucleic acid molecule configuration under the first environment and the short-term effectiveness and short-term specificity under the first environment into the effectiveness and specificity model.

[0136] Exemplarily, before input, the stability of the nucleic acid molecule configuration in the first environment and the short-term effectiveness and short-term specificity in the first environment are quantified and normalized, and the quantified and normalized stability of the nucleic acid molecule configuration in the first environment and the short-term effectiveness and short-term specificity in the first environment are input into the model.

[0137] Optionally, the method further comprises:

[0138] Searching a nucleic acid library for a similar nucleic acid molecular structure of each nucleic acid molecular configuration in the nucleic acid molecular configuration to be tested;

[0139] Obtain the long-term effectiveness and long-term specificity of the similar nucleic acid molecular structure.

[0140] Among them, the nucleic acid library refers to a database that stores known nucleic acid molecular structure data, including nucleic acid molecular configuration, stability, and various experimental data of nucleic acid molecules.

[0141] Exemplarily, the search for similar nucleic acid molecule structures is implemented using a similar nucleic acid molecule search model.

[0142] Exemplarily, step 404 includes:

[0143] The stability of the nucleic acid molecule configuration in the first environment, the short-term effectiveness and short-term specificity in the first environment, and the long-term effectiveness and long-term specificity of the similar nucleic acid molecule structure are input into the effectiveness and specificity model, and the effectiveness and specificity model is used to determine the long-term effectiveness and long-term specificity of the nucleic acid molecule configuration to be tested in the first environment based on the stability of the nucleic acid molecule configuration in the first environment, the short-term effectiveness and short-term specificity in the first environment, and the long-term effectiveness and long-term specificity of the similar nucleic acid molecule structure.

[0144] In this implementation, the long-term effectiveness and long-term specificity of similar nucleic acid molecular structures are used as input parameters as parameters for determining the long-term effectiveness and long-term specificity of the nucleic acid molecular configuration in the first environment, which can further improve the accuracy of the determined long-term effectiveness and long-term specificity of the nucleic acid molecular configuration in the first environment.

[0145] 405: Obtaining the long-term effectiveness and long-term specificity of the nucleic acid molecule configuration to be tested under the first environment determined by the effectiveness and specificity model.

[0146] Optionally, the method further comprises: calculating long-term effectiveness and long-term specificity scores, for example, converting the stability, long-term effectiveness and long-term specificity of the nucleic acid molecule configuration into scores, and then weighting them to obtain weighted scores. The weighted scores are used to evaluate the properties of the nucleic acid molecule configuration.

[0147] The following provides a method for screening nucleic acid molecule structures to determine the nucleic acid molecule configuration to be tested in step 301 from nucleic acid molecule parameters.

[0148] Figure 5 is a flow chart of a nucleic acid molecular structure screening method provided by an embodiment of the present disclosure. Figure 5 , the method comprising:

[0149] 501: Obtain nucleic acid molecule parameters.

[0150] 502: Searching the nucleic acid library for a similar nucleic acid molecular structure of each nucleic acid molecular configuration in the plurality of nucleic acid molecular configurations to be screened.

[0151] 503: Based on the stability of the similar nucleic acid molecular structures, the energies corresponding to the multiple nucleic acid molecular configurations to be screened, and the experimental data, calculate the probability distribution of the multiple nucleic acid molecular configurations to be screened.

[0152] After searching for similar nucleic acid molecular structures from the nucleic acid library, the stability of the similar nucleic acid molecular structures can also be obtained from the nucleic acid library, and the probability of stability of the nucleic acid molecular configuration to be screened can be calculated based on the stability of the similar nucleic acid molecular structures.

[0153] The calculation of the probability distribution of the configurations of the multiple nucleic acid molecules to be screened refers to the calculation of the stability probability of the configurations of the multiple nucleic acid molecules to be screened. The stability probability refers to the probability that the configuration of the nucleic acid molecules to be screened will not change. The higher the stability probability, the better the stability.

[0154] 504: According to the probability distribution of the plurality of nucleic acid molecule configurations to be screened, screen a plurality of nucleic acid molecule configurations whose stability meets a condition among the plurality of nucleic acid molecule configurations to be screened.

[0155] Figure 6 is a flow chart of a nucleic acid molecular structure screening method provided by an embodiment of the present disclosure. Figure 6 , the method comprising:

[0156] 600: Training similar nucleic acid molecule search model and nucleic acid molecule configuration probability distribution calculation model.

[0157] Among them, the similar nucleic acid molecule search model is used to respectively determine the first similarity between the nucleic acid molecule sequence and each nucleic acid molecule sequence in the nucleic acid library, determine the difference between the length of the nucleic acid molecule sequence and the length of each nucleic acid molecule sequence in the nucleic acid library, and determine the second similarity between the chemical modification of the nucleic acid molecule and the chemical modification of each nucleic acid molecule sequence in the nucleic acid library, select nucleic acid molecules from the nucleic acid library whose first similarity, the difference and the second similarity all meet the threshold requirements, determine the configuration of the selected nucleic acid molecule and the distance between the multiple nucleic acid molecule configurations to be screened in turn, and obtain the similar nucleic acid molecule structure of each nucleic acid molecule configuration based on the distance.

[0158] The nucleic acid molecule configuration probability distribution calculation model is used to calculate the energy of the same nucleic acid molecule configuration, the stability of similar nucleic acid molecule structures and the normalized values ​​of the experimental data of the nucleic acid molecule configuration, and obtain the stability probability of each nucleic acid molecule configuration through the calculation; wherein, the calculation process is as follows: the energy of the nucleic acid molecule configuration, the stability of similar nucleic acid molecule structures and the normalized values ​​of the experimental data of the nucleic acid molecule configuration are combined into an array, which is conducive to the trained stability probability algorithm to solve the array to obtain the stability probability of each nucleic acid molecule configuration.

[0159] Exemplarily, the scheme for training the similar nucleic acid molecule search model is as follows:

[0160] Acquire a first training set and a first test set based on the nucleic acid library;

[0161] The first training set and the first test set are used to train the similar nucleic acid molecule search model.

[0162] The data types in the training set and the test set are the same as the data types input into the similar nucleic acid molecule search model.

[0163] The similar nucleic acid molecule search model can realize the calculation of the first similarity, difference, second similarity and distance, and the first similarity, difference, second similarity and distance can calculate the similarity of two nucleic acid molecule configurations according to a certain weight. Among them, the calculation formula of the first similarity and the second similarity can be realized by using a mature similarity algorithm. Initially, the parameters in the formula for calculating the first similarity, the parameters in the formula for calculating the second similarity, the parameters in the formula for calculating the distance, and the weights when calculating the similarity of two nucleic acid molecule configurations are all initial values. Similar nucleic acid molecule configurations are marked in advance in the sample set, and the output and input of the similar nucleic acid molecule search model are judged according to the marking during the training process. Whether is a similar configuration, thereby realizing feedback optimization of the above parameters and weights. The training of the similar nucleic acid molecule search model is completed by continuous feedback optimization. Of course, in the above process, it is also possible not to mark the sample set, and to judge whether the output and input of the similar nucleic acid molecule search model are similar configurations by manpower.

[0164] Similarly, the computational model for the probability distribution of nucleic acid molecular configurations is also trained in a similar way, for example:

[0165] Acquire a second training set and a second test set based on the nucleic acid library;

[0166] The second training set and the second test set are used to train the nucleic acid molecule configuration probability distribution calculation model.

[0167] The data types in the training set and the test set are the same as the data types input into the nucleic acid molecule configuration probability distribution calculation model.

[0168] The calculation model of nucleic acid molecule configuration probability distribution adopts a stability probability algorithm to calculate the energy of nucleic acid molecule configuration, the stability of similar nucleic acid molecule structure and the experimental data of nucleic acid molecule configuration to obtain the stability probability. The stability probability algorithm can be a weighted sum of the normalized values ​​of parameters such as energy, stability of similar nucleic acid molecule structure, and experimental data. Initially, the parameters in the stability probability algorithm (i.e., weighted weights) are initial values, and the parameters in the stability probability algorithm are adjusted through training, so that the stability probability calculated by the model is more accurate.

[0169] During training, the energy of the nucleic acid molecule configuration, the stability of similar nucleic acid molecule structures, and the normalized values ​​of the experimental data of the nucleic acid molecule configuration are combined into an array, and the array is input into the nucleic acid molecule configuration probability distribution calculation model as an input value. According to the stability probability output by the nucleic acid molecule configuration probability distribution calculation model and the actual stability of the nucleic acid molecule configuration, the parameters of the stability probability algorithm are feedback-adjusted, thereby optimizing the above-mentioned model parameters. Through continuous feedback iteration, the training of the nucleic acid molecule configuration probability distribution calculation model is completed.

[0170] Exemplarily, the effectiveness and specificity model, the similar nucleic acid molecule search model and the nucleic acid molecule configuration probability distribution calculation model use neural networks, decision trees, support vector machines, wherein the neural network can be a deep neural network.

[0171] 601: Obtain nucleic acid molecule parameters.

[0172] The nucleic acid molecule parameters include: nucleic acid molecule sequence, length of nucleic acid molecule sequence, chemical modification of nucleic acid molecule, and multiple nucleic acid molecule configurations to be screened and corresponding energy and experimental data obtained by computational simulation based on quantum mechanics and molecular dynamics.

[0173] In the embodiments of the present disclosure, computational simulation based on quantum mechanics and molecular dynamics refers to the prediction of nucleic acid molecule configurations through computational physics simulation software, using the software to simulate physical experiments on nucleic acid molecule configurations during the prediction process, and determining the energy distribution of each nucleic acid molecule configuration through quantum mechanics and molecular dynamics.

[0174] 602: Inputting the nucleic acid molecule sequence, the length of the nucleic acid molecule sequence, the chemical modification of the nucleic acid molecule and a plurality of nucleic acid molecule configurations to be screened into a similar nucleic acid molecule search model.

[0175] Here, when inputting the above parameters, these parameters are characterized and converted into a format that is easily recognized and processed by the similar nucleic acid molecule search model, for example, these parameters are digitized and normalized, and then input into the similar nucleic acid molecule search model.

[0176] 603: Obtaining a similar nucleic acid molecule structure of each nucleic acid molecule configuration in the multiple nucleic acid molecule configurations to be screened that is searched from the nucleic acid library by the similar nucleic acid molecule search model.

[0177] The nucleic acid molecule structure similar to each nucleic acid molecule configuration is determined through a similar nucleic acid molecule search model, thereby preparing for determining the stability of each nucleic acid molecule configuration.

[0178] 604: Inputting the stability of the similar nucleic acid molecule structure, the energy corresponding to the multiple nucleic acid molecule configurations to be screened, and the experimental data into a nucleic acid molecule configuration probability distribution calculation model.

[0179] Similarly, when inputting the above parameters, these parameters can be characterized and converted into a format that can be easily recognized and processed by the nucleic acid molecule configuration probability distribution calculation model, for example, these parameters can be digitized and normalized, and then input into the nucleic acid molecule configuration probability distribution calculation model.

[0180] That is, the method further comprises:

[0181] Performing data cleaning and completion on the experimental data of the nucleic acid molecule;

[0182] The cleaned and completed experimental data of the nucleic acid molecule are normalized, and the non-numerical experimental data are digitized and normalized.

[0183] Among them, the experimental data of the nucleic acid molecule configuration to be screened refers to the data obtained by experiments on nucleic acid molecules with the nucleic acid molecule configuration to be screened, and the experimental data include data from biological molecule experiments and animal experiments, and the data from biological molecule experiments and animal experiments include at least one of the experimental environment, half-life, annealing temperature, drug enrichment, membrane permeability, and water absorption rate.

[0184] Among them, biomolecular experiments can be polymerase chain reaction (PCR) experiments, mass spectrometry experiments, electron microscope structure analysis experiments and cell experiments, and animal experiments can be mouse and monkey experiments, etc. The experimental environment can be water, saline, plasma, etc.

[0185] 605: Obtain the plurality of nucleic acid molecule configuration probability distributions to be screened calculated by the nucleic acid molecule configuration probability distribution calculation model, wherein the plurality of nucleic acid molecule configuration probability distributions to be screened include the stability probability of each nucleic acid molecule configuration.

[0186] 606: According to the probability distribution of the multiple nucleic acid molecule configurations to be screened, screen multiple nucleic acid molecule configurations whose stability meets the condition among the multiple nucleic acid molecule configurations to be screened.

[0187] Figure 7 Schematic diagram of a nucleic acid molecule solution concentration recommendation device provided by an embodiment of the present disclosure. Figure 7 The device includes: an acquisition module 701 and a recommendation module 702.

[0188] Among them, the acquisition module 701 is used to obtain multiple nucleic acid molecular configurations to be recommended and their parameters, wherein the multiple nucleic acid molecular configurations to be recommended are multiple nucleic acid molecular configurations designed for the same genetic disease based on different chemical modification methods, and the parameters of the nucleic acid molecular configurations include nucleic acid molecular chemical modification, stability of the nucleic acid molecular configuration under a first environment, and long-term effectiveness and long-term specificity of nucleic acid molecular solutions of different concentrations under the first environment, wherein the first environment includes at least one of the following: a plasma environment and a physiological saline environment;

[0189] The recommendation module 702 is used to input the multiple nucleic acid molecule configurations and their parameters into the recommendation model, and obtain the nucleic acid molecule configurations and nucleic acid molecule solution concentrations recommended by the recommendation model, wherein the recommendation model is used to quantify the chemical modification of the nucleic acid molecule, the stability of the nucleic acid molecule configuration, and the long-term effectiveness and long-term specificity of the nucleic acid molecule solutions of different concentrations, and calculate the recommendation degree of the nucleic acid molecule configuration using the quantified chemical modification of the nucleic acid molecule, the stability of the nucleic acid molecule configuration, and the long-term effectiveness and long-term specificity of the nucleic acid molecule solutions of different concentrations, and select the nucleic acid molecule configuration and the nucleic acid molecule solution concentration for recommendation based on the recommendation degree.

[0190] Optionally, the parameters of the nucleic acid molecule configuration further include: production line cost corresponding to the nucleic acid molecule configuration;

[0191] The recommendation model is used to quantify the chemical modification of the nucleic acid molecules, the stability of the nucleic acid molecule configuration, the long-term effectiveness and long-term specificity of the nucleic acid molecule solutions of different concentrations, and the production line cost corresponding to the nucleic acid molecule configuration, and calculate the recommendation degree of the nucleic acid molecule configuration using the quantified chemical modification of the nucleic acid molecules, the stability of the nucleic acid molecule configuration, the long-term effectiveness and long-term specificity of the nucleic acid molecule solutions of different concentrations, and the production line cost corresponding to the nucleic acid molecule configuration, and select the nucleic acid molecule configuration and the nucleic acid molecule solution concentration for recommendation based on the recommendation degree.

[0192] Optionally, the device also includes a training module 703 for obtaining a training set, wherein the training set includes multiple training samples, each of the multiple training samples includes multiple nucleic acid molecule configurations and parameters thereof designed for the same genetic disease; and the recommendation model is trained using the multiple training samples.

[0193] Optionally, the training module 703 is used to input the training samples into the recommendation model; obtain the nucleic acid molecule configuration and nucleic acid molecule solution concentration output by the recommendation model; and use the known nucleic acid molecule configuration and nucleic acid molecule solution concentration for the genetic disease as feedback to update the parameters of the recommendation model.

[0194] Optionally, the device further comprises a determination module 704 for determining the long-term effectiveness and long-term specificity of the nucleic acid molecule configuration in nucleic acid molecule solutions of different concentrations under the first environment.

[0195] Optionally, the determination module 704 is used to obtain a nucleic acid molecule configuration to be tested, wherein the stability of the nucleic acid molecule configuration to be tested in an aqueous solution environment meets a condition; perform a physical simulation test on the nucleic acid molecule configuration to be tested to simulate the stability of the nucleic acid molecule configuration to be tested in a first environment, wherein the first environment includes at least one of the following: a plasma environment and a physiological saline environment; obtain the short-term effectiveness and short-term specificity of nucleic acid molecule solutions of different concentrations obtained by experiment for the nucleic acid molecule configuration to be tested in the first environment; determine the long-term effectiveness and long-term specificity of nucleic acid molecule solutions of different concentrations of the nucleic acid molecule configuration to be tested in the first environment based on the stability of the nucleic acid molecule configuration to be tested in the first environment and the short-term effectiveness and short-term specificity in the first environment.

[0196] It should be noted that: the nucleic acid molecule solution concentration recommendation device provided in the above embodiment only uses the division of the above functional modules as an example when determining the structural properties of nucleic acid molecules. In actual applications, the above functions can be assigned to different functional modules as needed, that is, the internal structure of the device can be divided into different functional modules to complete all or part of the functions described above. In addition, the nucleic acid molecule solution concentration recommendation device provided in the above embodiment and the nucleic acid molecule solution concentration recommendation method embodiment belong to the same concept. The specific implementation process is detailed in the method embodiment and will not be repeated here.

[0197] Figure 8 801 and 802. The computer device 802 includes a processor 801 and a memory 802.

[0198] The processor 801 may include one or more processing cores, such as a 4-core processor, an 8-core processor, etc. The processor 801 may be implemented in at least one hardware form of DSP (Digital Signal Processing), FPGA (Field-Programmable Gate Array), and PLA (Programmable Logic Array). The processor 801 may also include a main processor and a coprocessor. The main processor is a processor for processing data in the awake state, also known as a CPU (Central Processing Unit); the coprocessor is a low-power processor for processing data in the standby state.

[0199] The memory 802 may include one or more computer-readable storage media, which may be non-transitory. The memory 802 may also include a high-speed random access memory, and a non-volatile memory, such as one or more disk storage devices, flash memory storage devices. In some embodiments, the non-transitory computer-readable storage medium in the memory 802 is used to store at least one instruction, which is used to be executed by the processor 801 to implement the nucleic acid molecule solution concentration recommendation method provided in the method embodiment of the present application.

[0200] A person skilled in the art will understand that all or part of the steps to implement the above embodiments may be accomplished by hardware or by instructing related hardware through a program, and the program may be stored in a computer-readable storage medium, and the above-mentioned storage medium may be a read-only memory, a disk or an optical disk, etc.

[0201] The above description is only an optional embodiment of the present disclosure and is not intended to limit the present disclosure. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present disclosure shall be included in the protection scope of the present disclosure.

Claims

1. A method for recommending the concentration of a nucleic acid molecule solution, characterized in that: The method comprises: Acquiring multiple nucleic acid molecule configurations to be recommended and parameters thereof, wherein the multiple nucleic acid molecule configurations to be recommended are multiple nucleic acid molecule configurations designed for the same genetic disease based on different chemical modification methods, the parameters of the nucleic acid molecule configurations include nucleic acid molecule chemical modification, stability of the nucleic acid molecule configuration under a first environment, and long-term effectiveness and long-term specificity of nucleic acid molecule solutions of different concentrations under the first environment, wherein the first environment includes at least one of the following: a plasma environment and a physiological saline environment; The multiple nucleic acid molecule configurations and their parameters are input into a recommendation model to obtain the nucleic acid molecule configurations and nucleic acid molecule solution concentrations recommended by the recommendation model, wherein the recommendation model is used to quantify the chemical modification of the nucleic acid molecules, the stability of the nucleic acid molecule configurations, and the long-term effectiveness and long-term specificity of the nucleic acid molecule solutions of different concentrations, and the recommendation degree of the nucleic acid molecule configuration is calculated using the quantified chemical modification of the nucleic acid molecules, the stability of the nucleic acid molecule configurations, and the long-term effectiveness and long-term specificity of the nucleic acid molecule solutions of different concentrations, and the nucleic acid molecule configuration and the nucleic acid molecule solution concentration are selected for recommendation based on the recommendation degree.

2. The method according to claim 1, characterized in that The method further comprises: Acquire a training set, wherein the training set includes a plurality of training samples, each of the plurality of training samples includes a plurality of nucleic acid molecule configurations and parameters thereof designed for the same genetic disease; The recommendation model is trained using the multiple training samples.

3. The method according to claim 2, wherein the using the plurality of training samples to train the recommendation model comprises: Inputting the training samples into the recommendation model; Obtaining the nucleic acid molecule configuration and nucleic acid molecule solution concentration output by the recommended model; The parameters of the recommendation model are updated using the known nucleic acid molecule configuration and nucleic acid molecule solution concentration for the genetic disease as feedback.

4. The method according to any one of claims 1 to 3, characterized in that: The parameters of the nucleic acid molecule configuration also include: the production line cost corresponding to the nucleic acid molecule configuration; The recommendation model is used to quantify the chemical modification of the nucleic acid molecules, the stability of the nucleic acid molecule configuration, the long-term effectiveness and long-term specificity of the nucleic acid molecule solutions of different concentrations, and the production line cost corresponding to the nucleic acid molecule configuration, and calculate the recommendation degree of the nucleic acid molecule configuration using the quantified chemical modification of the nucleic acid molecules, the stability of the nucleic acid molecule configuration, the long-term effectiveness and long-term specificity of the nucleic acid molecule solutions of different concentrations, and the production line cost corresponding to the nucleic acid molecule configuration, and select the nucleic acid molecule configuration and the nucleic acid molecule solution concentration for recommendation based on the recommendation degree.

5. The method according to any one of claims 1 to 3, characterized in that: The method comprises: The long-term effectiveness and long-term specificity of the nucleic acid molecule configuration in nucleic acid molecule solutions of different concentrations under the first environment are determined.

6. The method according to claim 5, characterized in that The method of determining the long-term effectiveness and long-term specificity of nucleic acid molecule solutions of different concentrations under the first environment comprises: Obtaining a nucleic acid molecule configuration to be tested, wherein the stability of the nucleic acid molecule configuration to be tested in an aqueous solution environment meets a condition; Performing a physical simulation test on the nucleic acid molecule configuration to be tested to simulate the stability of the nucleic acid molecule configuration to be tested under a first environment; Obtaining the short-term effectiveness and short-term specificity of nucleic acid molecule solutions of different concentrations obtained through experiments under the first environment for the nucleic acid molecule configuration to be tested; According to the stability of the nucleic acid molecule configuration to be tested in the first environment and the short-term effectiveness and short-term specificity in the first environment, the long-term effectiveness and long-term specificity of the nucleic acid molecule solution of different concentrations of the nucleic acid molecule configuration to be tested in the first environment are determined.

7. A nucleic acid molecule solution concentration recommendation device, characterized in that: The device comprises: an acquisition module, for acquiring a plurality of nucleic acid molecule configurations to be recommended and parameters thereof, wherein the plurality of nucleic acid molecule configurations to be recommended are a plurality of nucleic acid molecule configurations designed for the same genetic disease based on different chemical modification methods, wherein the parameters of the nucleic acid molecule configurations include chemical modification of nucleic acid molecules, stability of the nucleic acid molecule configurations under a first environment, and long-term effectiveness and long-term specificity of nucleic acid molecule solutions of different concentrations under the first environment, wherein the first environment includes at least one of the following: a plasma environment and a physiological saline environment; A recommendation module is used to input the multiple nucleic acid molecule configurations and their parameters into a recommendation model, and obtain the nucleic acid molecule configurations and nucleic acid molecule solution concentrations recommended by the recommendation model, wherein the recommendation model is used to quantify the chemical modification of the nucleic acid molecule, the stability of the nucleic acid molecule configuration, and the long-term effectiveness and long-term specificity of the nucleic acid molecule solutions of different concentrations, and calculate the recommendation degree of the nucleic acid molecule configuration using the quantified chemical modification of the nucleic acid molecule, the stability of the nucleic acid molecule configuration, and the long-term effectiveness and long-term specificity of the nucleic acid molecule solutions of different concentrations, and select the nucleic acid molecule configuration and the nucleic acid molecule solution concentration for recommendation based on the recommendation degree.

8. The device according to claim 7, characterized in that The parameters of the nucleic acid molecule configuration also include: the production line cost corresponding to the nucleic acid molecule configuration; The recommendation model is used to quantify the chemical modification of the nucleic acid molecules, the stability of the nucleic acid molecule configuration, the long-term effectiveness and long-term specificity of the nucleic acid molecule solutions of different concentrations, and the production line cost corresponding to the nucleic acid molecule configuration, and calculate the recommendation degree of the nucleic acid molecule configuration using the quantified chemical modification of the nucleic acid molecules, the stability of the nucleic acid molecule configuration, the long-term effectiveness and long-term specificity of the nucleic acid molecule solutions of different concentrations, and the production line cost corresponding to the nucleic acid molecule configuration, and select the nucleic acid molecule configuration and the nucleic acid molecule solution concentration for recommendation based on the recommendation degree.

9. A computer device, characterized in that: The computer device includes a processor and a memory, wherein the memory stores at least one program code, and the program code is loaded and executed by the processor to implement the method for recommending the concentration of a nucleic acid molecule solution as described in any one of claims 1 to 6.

10. A computer-readable storage medium, characterized in that: The computer-readable storage medium stores at least one program code, and the program code is loaded and executed by a processor to implement the method for recommending the concentration of a nucleic acid molecule solution as described in any one of claims 1 to 6.

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