Candidate drug screening method and system based on gene drug interaction, medium and equipment
By constructing a database of deafness gene-candidate drug relationships, and combining drug-target gene networks and KEGG pathway data, the consistency of regulatory direction is considered when screening drugs, which solves the problem of the lack of biological mechanism support for candidate drugs in the existing technology and achieves precise candidate drug matching.
Patent Information
- Application Number
- CN202511018036.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-07-23
- Publication Date
- 2025-11-18
AI Technical Summary
Existing gene-drug relationship databases do not deeply integrate gene regulatory networks at the signaling pathway level, resulting in a lack of biological mechanism support and insufficient targeting in candidate drug screening.
By acquiring abnormal gene datasets from deaf patients, and combining them with drug-target gene interaction networks and KEGG pathway data, a database of deafness gene-candidate drug relationships was constructed. When screening drugs, the consistency of the drug's regulatory direction in the signaling pathway was considered to ensure the correlation between the drug and the pathway.
It enables precise capture of gene mutation information of individual patients, improves the targeting and efficiency of drug screening, ensures that drugs can salvage pathway function by replacing gene mechanisms, and provides a scientific tool for storing and reusing screening results.
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Figure CN120977375A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The application belongs to the technical field of biological medicine, and relates to a candidate drug screening method, system, medium and equipment based on gene-drug interaction. BACKGROUND
[0002] Deafness is a sensory disorder dominated by genetic factors, and accurately positioning the mutant gene and matching the effective treatment drug are the core of individualized treatment. With the development of old drug new use strategy, the screening method based on gene-drug interaction has become a research hotspot, but the key lies in how to construct a scientific gene-drug corresponding relationship model to ensure the targeting and effectiveness of the candidate drug. At present, the construction of disease gene-drug database through integration has become an important basis to support clinical decision-making, but the quality of the database directly depends on the scientificity of the underlying screening logic.
[0003] In the prior art, the construction of the gene-drug relationship database mainly depends on the simple mapping of drug-target gene interaction, without deeply integrating the gene regulation network at the signal pathway level, and without considering the functional compensation mechanism of the mutant gene in the pathway. Specifically, only the direct binding relationship between the gene and the drug is used to screen the candidate drug, ignoring the upstream and downstream regulation relationship of the gene in the signal pathway and the functional compensation of the alternative gene; at the same time, the consistency between the drug regulation direction and the internal regulation logic of the pathway is not checked, resulting in that the gene-drug relationship stored in the database lacks biological mechanism support, and the screened candidate drug may fail to effectively rescue the pathway abnormalities, thereby reducing the clinical application value of the database. SUMMARY
[0004] The application provides a candidate drug screening method, system, medium and equipment based on gene-drug interaction, which can solve the problem of lack of pathway-level biological mechanism support and insufficient targeting of the candidate drug screened based on individual abnormal genes in the prior art.
[0005] To achieve the above-mentioned purpose, in a first aspect, the application provides a candidate drug screening method based on gene-drug interaction, comprising:
[0006] obtaining an abnormal gene data set of a deaf patient to be matched;
[0007] inputting the abnormal gene data set into a preset deaf gene-candidate drug relationship database for matching to obtain a deaf candidate drug corresponding to the deaf patient; wherein the deaf gene-candidate drug relationship database is obtained by the following way:
[0008] obtaining a deafness risk gene data set, a drug-target gene interaction relationship network and human KEGG pathway data;
[0009] mapping each gene in the deafness risk gene dataset to the drug-target gene interaction relationship network to obtain a drug-deafness risk gene interaction relationship network;
[0010] In the human KEGG pathway data, the regulation relationship between each gene in each KEGG pathway is analyzed to obtain a gene regulation relationship network of each signal pathway;
[0011] In the drug-deafness risk gene interaction relationship network, each target gene corresponding to each drug is mapped to the gene regulation relationship network of each signal pathway, and if at least two target genes corresponding to a drug exist in the gene regulation relationship network of a signal pathway, the corresponding relationship between the drug and the signal pathway is retained to obtain each drug-pathway relationship;
[0012] In each drug-pathway relationship, if the regulation direction of a drug to a first deafness risk gene and its associated genes is consistent with the regulation direction of the first deafness risk gene and its associated genes in the corresponding signal pathway, the drug is screened as a candidate drug for deafness disease caused by abnormality of the first deafness risk gene; wherein the regulation direction of the first deafness risk gene and its associated genes in the corresponding signal pathway includes the regulation direction of the first deafness risk gene to the associated genes, or the regulation direction of the first deafness risk gene and its associated genes to a common downstream gene;
[0013] According to the corresponding relationship between each first deafness risk gene and each candidate drug, a deafness gene-candidate drug relationship database is constructed.
[0014] Compared with the prior art, the embodiments of the present application have the following beneficial effects: by acquiring the abnormal gene data set of the deaf patient to be matched, the individual patient gene mutation information is accurately captured, and specific input is provided for targeted drug matching; the abnormal gene data set is input into the pre-set deaf gene-candidate drug relationship database for matching, the standardized gene-drug corresponding relationship based on scientific mechanism is directly called, repeated analysis is avoided, and the screening efficiency is improved; wherein, in the database construction process, by acquiring the deaf risk gene, drug-target gene interaction and KEGG pathway data, multi-dimensional basic data support covering "risk gene-drug interaction-pathway regulation" is provided for drug screening; the deaf risk gene is mapped to the drug-target gene network, and the core interaction relationship related to deafness is directionally screened from the massive drug-gene relationship; the gene regulation relationship is analyzed in the KEGG pathway, the limitation of the simplified model in the prior art is broken through, and the dynamic regulation mechanism such as activation and inhibition between genes is revealed in the signal pathway level; by the mapping of the drug target gene in the pathway and the screening condition of "at least two target genes", the relevance of the drug and the pathway is ensured, and the non-specific drug that only interacts with a single gene by chance is excluded; based on the consistency of the regulation direction, the candidate drug is screened, so that the regulation of the drug on the mutant gene and the associated gene conforms to the internal logic of the pathway, and it is ensured that the drug can rescue the pathway function through the alternative gene mechanism, and the defect that the existing database lacks biological mechanism support is solved; the database is constructed based on the gene-drug corresponding relationship, the standardized storage and reuse of scientific screening results are realized, and toolized support with efficiency and accuracy is provided for the clinic. Through the synergistic effect of the above features, the core logic of the database construction is upgraded from "simple interaction mapping" to "pathway regulation mechanism driving", the problem that the candidate drug in the prior art lacks specificity due to the lack of mechanism support at the pathway level is solved, and the precise candidate drug matching based on individual abnormal genes is realized.
[0015] In some embodiments of the first aspect of the present application, the mapping of each gene in the deaf risk gene data set to the drug-target gene interaction relationship network to obtain a drug-deaf risk gene interaction relationship network comprises:
[0016] Obtaining an auris hair cell highly expressed gene set;
[0017] Taking the intersection of the deaf risk gene data set and the auris hair cell highly expressed gene set to obtain an auris hair cell highly expressed deaf risk gene data set;
[0018] Mapping each gene in the auris hair cell highly expressed deaf risk gene data set to the drug-target gene interaction relationship network to obtain a drug-deaf risk gene interaction relationship network.
[0019] Compared with the prior art, the above-mentioned embodiments have the following beneficial effects: by obtaining the ear hair cell high expression gene set, focusing on the specificity of the key effector cell (ear hair cell) of the deafness disease; intersecting the deafness risk gene and the ear hair cell high expression gene to narrow the screening range to the core gene with both deafness risk and ear hair cell function correlation; and mapping the intersection gene to the drug-target gene network, the biological correlation and screening efficiency of the drug-deafness risk gene interaction are further improved.
[0020] In some embodiments of the first aspect of the present application, in each of the drug-pathway relationships, if the regulation direction of a certain drug on a certain first deafness risk gene and its associated gene is consistent with the regulation direction of the first deafness risk gene and its associated gene in the corresponding signal pathway, the drug is screened as a candidate drug for the deafness disease caused by the abnormality of the first deafness risk gene, comprising:
[0021] When the first deafness risk gene is an upstream gene of its associated gene in the corresponding signal pathway, and the regulation direction of the first deafness risk gene on the associated gene is positive regulation, if the regulation direction of the drug on the first deafness risk gene and the associated gene is both positive regulation, the drug is confirmed as a candidate drug for the deafness disease caused by the abnormality of the first deafness risk gene.
[0022] Compared with the prior art, the above-mentioned embodiments have the following beneficial effects: when the first deafness risk gene is an upstream gene of the associated gene and is positively regulated, by limiting the drug to positively regulate both, it is ensured that the drug can compensate for the functional loss of the upstream mutant gene by enhancing the activity of the downstream associated gene, realize the rescue effect on the signal pathway, and improve the matching degree of the candidate drug and the disease mechanism.
[0023] In some embodiments of the first aspect of the present application, in each of the drug-pathway relationships, if the regulation direction of a certain drug on a certain first deafness risk gene and its associated gene is consistent with the regulation direction of the first deafness risk gene and its associated gene in the corresponding signal pathway, the drug is screened as a candidate drug for the deafness disease caused by the abnormality of the first deafness risk gene, further comprising:
[0024] When the first deafness risk gene is an upstream gene of its associated gene in the corresponding signal pathway, and the regulation direction of the first deafness risk gene on the associated gene is negative regulation, if the regulation direction of the drug on the first deafness risk gene and the associated gene is both negative regulation, the drug is confirmed as a candidate drug for the deafness disease caused by the abnormality of the first deafness risk gene.
[0025] Compared with the prior art, the above-mentioned embodiment has the beneficial effect that when the first deafness risk gene is an upstream gene of the associated gene and is negatively regulated, by limiting the drug to be positively regulated for both, it is ensured that the drug can balance the abnormality of the pathway caused by the mutant gene by synergistically inhibiting the excessive activation of the downstream associated gene, maintain the steady-state regulation of the signal pathway, and enhance the action specificity of the candidate drug.
[0026] In some embodiments of the first aspect of the application, in each of the drug-pathway relationships, if the regulation direction of a certain drug on a certain first deafness risk gene and its associated gene is consistent with the regulation direction of the first deafness risk gene and its associated gene in the corresponding signal pathway, the drug is screened as a candidate drug for deafness diseases caused by abnormalities in the first deafness risk gene, further comprising:
[0027] When the first deafness risk gene and its associated gene have a common downstream gene in the corresponding signal pathway, and the regulation direction of the first deafness risk gene and the associated gene on the downstream gene is positive regulation, if the regulation direction of the drug on the first deafness risk gene and the associated gene is positive regulation, the drug is confirmed as a candidate drug for deafness diseases caused by abnormalities in the first deafness risk gene.
[0028] Compared with the prior art, the above-mentioned embodiment has the beneficial effect that when the first deafness risk gene and the associated gene share a common downstream gene and are both positively regulated, by limiting the drug to be positively regulated for both, it is ensured that the drug can compensate for the insufficient function of the mutant gene by synergistically activating the expression of the common downstream gene, strengthen the overall activation effect of the pathway, and improve the therapeutic potential of the candidate drug.
[0029] In some embodiments of the first aspect of the application, in each of the drug-pathway relationships, if the regulation direction of a certain drug on a certain first deafness risk gene and its associated gene is consistent with the regulation direction of the first deafness risk gene and its associated gene in the corresponding signal pathway, the drug is screened as a candidate drug for deafness diseases caused by abnormalities in the first deafness risk gene, further comprising:
[0030] When the first deafness risk gene and its associated gene have a common downstream gene in the corresponding signal pathway, and the regulation direction of the first deafness risk gene and the associated gene on the downstream gene is negative regulation, if the regulation direction of the drug on the first deafness risk gene and the associated gene is negative regulation, the drug is confirmed as a candidate drug for deafness diseases caused by abnormalities in the first deafness risk gene.
[0031] Compared with the prior art, the above-mentioned embodiment has the following beneficial effects: when the first deafness risk gene and the associated gene share a common downstream gene and are both negatively regulated, by limiting the drug to be negatively regulated for both, it is ensured that the drug can correct the imbalance of the pathway caused by the mutant gene by synergistically inhibiting the abnormal activation of the common downstream gene, maintain the normal expression level of the downstream gene, and improve the action accuracy of the candidate drug.
[0032] In a second aspect, the present application also provides a candidate drug screening system based on gene-drug interaction, comprising: a data acquisition module and a matching module;
[0033] The data acquisition module is configured to acquire an abnormal gene data set of a deaf patient to be matched.
[0034] The matching module is configured to input the abnormal gene data set into a preset deafness gene-candidate drug relationship database for matching to obtain a deafness candidate drug corresponding to the deaf patient; wherein the deafness gene-candidate drug relationship database is obtained by the following method:
[0035] Obtain a deafness risk gene data set, a drug-target gene interaction relationship network, and human KEGG pathway data.
[0036] Map each gene in the deafness risk gene data set to the drug-target gene interaction relationship network to obtain a drug-deafness risk gene interaction relationship network.
[0037] In the human KEGG pathway data, analyze the regulation relationship between each gene in each KEGG pathway to obtain a gene regulation relationship network of each signal pathway.
[0038] In the drug-deafness risk gene interaction relationship network, map each target gene corresponding to each drug to each gene regulation relationship network of each signal pathway, and if at least two target genes corresponding to a drug exist in the gene regulation relationship network of a signal pathway, the corresponding relationship between the drug and the signal pathway is retained to obtain each drug-pathway relationship.
[0039] In each drug-pathway relationship, if the regulation direction of a drug to a first deafness risk gene and its associated gene is consistent with the regulation direction of the first deafness risk gene and its associated gene in the corresponding signal pathway, the drug is screened as a candidate drug for a deafness disease caused by abnormality of the first deafness risk gene; wherein the regulation direction of the first deafness risk gene and its associated gene in the corresponding signal pathway includes the regulation direction of the first deafness risk gene to the associated gene, or the regulation direction of the first deafness risk gene and its associated gene to a common downstream gene.
[0040] According to the correspondence relationship between each deafness risk gene and each corresponding candidate drug, the deafness gene-candidate drug relationship database is constructed.
[0041] Compared with the prior art, the above embodiments have the following beneficial effects: by obtaining the abnormal gene data set of the deafness patient to be matched, the individual patient gene mutation information is accurately captured, and specific input is provided for targeted drug matching; the abnormal gene data set is input into the preset deafness gene-candidate drug relationship database for matching, the standardized gene-drug correspondence relationship based on scientific mechanism is directly called, repeated analysis is avoided, and the screening efficiency is improved; wherein, in the database construction process, by obtaining the deafness risk gene, drug-target gene interaction and KEGG pathway data, multi-dimensional basic data support covering "risk gene-drug interaction-pathway regulation" is provided for drug screening; the deafness risk gene is mapped to the drug-target gene network, and the core interaction relationship related to deafness is selected from the massive drug-gene relationship; the gene regulation relationship is analyzed in the KEGG pathway, the limitation of the simplified model in the prior art is broken through, and the dynamic regulation mechanism such as activation and inhibition between genes is revealed in the signal pathway level; through the mapping of the drug target gene in the pathway and the screening condition of "at least two target genes", the relevance of the drug and the pathway is ensured, and non-specific drugs that only interact with a single gene by chance are excluded; based on the consistency of the regulation direction, the candidate drug is screened, so that the regulation of the drug on the mutant gene and the associated gene conforms to the internal logic of the pathway, and it is ensured that the drug can rescue the pathway function through the alternative gene mechanism, solving the defect that the existing database lacks biological mechanism support; according to the gene-drug correspondence relationship, the database is constructed, the standardized storage and reuse of scientific screening results are realized, and tool support with efficiency and accuracy is provided for clinical treatment. Through the synergistic effect of the above features, the core logic of the database construction is upgraded from "simple interaction mapping" to "pathway regulation mechanism driven", solving the problem that the candidate drug in the prior art lacks pathway level mechanism support, and realizing the accurate candidate drug matching based on individual abnormal genes.
[0042] In some embodiments of the second aspect of the application, the matching module comprises a collection unit, an intersection processing unit and a mapping unit.
[0043] The collection unit is configured to obtain the ear hair cell highly expressed gene set.
[0044] The intersection processing unit is configured to take the intersection of the deafness risk gene data set and the ear hair cell highly expressed gene set to obtain the ear hair cell highly expressed deafness risk gene data set.
[0045] The mapping unit is configured to map each gene in the high-expression ear hair deafness risk gene dataset to the drug-target gene interaction relationship network to obtain a drug-deafness risk gene interaction relationship network.
[0046] Compared with the prior art, the above-mentioned embodiments have the following beneficial effects: by obtaining the ear hair cell high-expression gene set, the specificity of the key effector cell (ear hair cell) of the deafness disease is focused; the intersection of the deafness risk gene and the ear hair cell high-expression gene is obtained, the screening range is narrowed to the core gene with both deafness risk and ear hair cell function correlation; and the intersection gene is mapped to the drug-target gene network, so that the biological correlation and screening efficiency of the drug-deafness risk gene interaction relationship are further improved.
[0047] In a third aspect, the present application further provides a candidate drug screening device based on gene-drug interaction, comprising a memory, a processor, and a computer program stored in the memory and executable on the processor, wherein the computer program, when loaded into the processor, implements the steps of any candidate drug screening method based on gene-drug interaction of the present application.
[0048] In a fourth aspect, the present application further provides a computer readable storage medium, which stores a computer program, wherein the computer program, when executed by a processor, implements the steps of any candidate drug screening method based on gene-drug interaction of the present application. BRIEF DESCRIPTION OF DRAWINGS
[0049] Figure 1 FIG. 1 is a flowchart of a candidate drug screening method based on gene-drug interaction provided in some embodiments of the present application.
[0050] Figure 2 FIG. 5 is a structural diagram of a candidate drug screening system based on gene-drug interaction provided in some embodiments of the present application.
[0051] Figure 3 FIG. 7 is a structural diagram of a candidate drug screening device based on gene-drug interaction provided in some embodiments of the present application.
[0052] Figure 4 FIG. 11 is a flowchart of constructing a deafness gene-candidate drug relationship database provided in some embodiments of the present application.
[0053] Figure 5 FIG. 14 is a schematic diagram of a drug-deafness risk gene interaction relationship network provided in some embodiments of the present application.
[0054] Figure 6 FIG. 17 is a protein-protein regulation network diagram in the hsa05130 signal pathway provided in some embodiments of the present application.
[0055] Figure 7 Figure 1 is a schematic diagram of a signal pathway provided in some embodiments of the present application.
[0056] Figure 8 Figure 2 is a schematic diagram of the regulation relationship of asparagine-hsa00250 signal pathway-ASNS deafness risk gene provided in some embodiments of the present application. DETAILED DESCRIPTION
[0057] The technical solutions in the embodiments of the present application will be described clearly and completely below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only some of the embodiments of the present application, but not all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.
[0058] Embodiment one:
[0059] Please refer to Figure 1 To solve the problem that the candidate drugs screened based on individual abnormal genes in the prior art lack biological mechanism support at the pathway level and are not targeted enough, an embodiment of the present application provides a candidate drug screening method based on gene-drug interaction, which comprises steps S1 to S2:
[0060] Step S1: obtaining an abnormal gene data set of a deaf patient to be matched.
[0061] Step S2: inputting the abnormal gene data set into a preset deaf gene-candidate drug relationship database for matching to obtain a deafness candidate drug corresponding to the deaf patient; wherein the deaf gene-candidate drug relationship database is obtained by the following way, comprising steps S21-S26:
[0062] S21: obtaining a deafness risk gene data set, a drug-target gene interaction relationship network and human KEGG pathway data;
[0063] S22: mapping each gene in the deafness risk gene data set to the drug-target gene interaction relationship network to obtain a drug-deafness risk gene interaction relationship network;
[0064] S23: in the human KEGG pathway data, analyzing the regulation relationship between each gene in each KEGG pathway to obtain a gene regulation relationship network of each signal pathway;
[0065] S24: mapping each target gene corresponding to each drug in the drug-target gene interaction relationship network to the gene regulation relationship network of each signal pathway, if at least two target genes corresponding to a drug exist in the gene regulation relationship network of a signal pathway, the corresponding relationship between the drug and the signal pathway is retained to obtain each drug-pathway relationship;
[0066] S25: in each drug-pathway relationship, if the regulation direction of a drug to a first deafness risk gene and its associated genes is consistent with the regulation direction of the first deafness risk gene and its associated genes in the corresponding signal pathway, the drug is screened as a candidate drug for deafness disease caused by abnormality of the first deafness risk gene; wherein the regulation direction of the first deafness risk gene and its associated genes in the corresponding signal pathway includes the regulation direction of the first deafness risk gene to the associated genes, or the regulation direction of the first deafness risk gene and its associated genes to the common downstream genes;
[0067] S26: according to the corresponding relationship between each first deafness risk gene and each candidate drug, a deafness gene-candidate drug relationship database is constructed.
[0068] Further, the step S22 can be realized by the following preferred embodiment, including steps S221-S223, specifically as follows:
[0069] S221: obtaining a set of high expression genes in hair cells;
[0070] S222: taking intersection of the deafness risk gene dataset and the set of high expression genes in hair cells to obtain a set of high expression deafness risk genes in hair cells;
[0071] S223: mapping each gene in the set of high expression deafness risk genes in hair cells to the drug-target gene interaction relationship network to obtain a drug-deafness risk gene interaction relationship network.
[0072] In the preferred embodiment, by obtaining a set of high expression genes in hair cells, the specificity of the key effector cells (hair cells) of deafness disease is focused; the intersection of deafness risk genes and high expression genes in hair cells is taken to narrow the screening range to core genes with both deafness risk and ear hair cell function correlation; the intersection genes are mapped to the drug-target gene network to further improve the biological correlation and screening efficiency of the drug-deafness risk gene interaction relationship.
[0073] Further, in the step S25 of screening the candidate drug, the following preferred embodiment can be realized, including step S251:
[0074] S251: When the first deafness risk gene is an upstream gene of its associated gene in the corresponding signal pathway, and the first deafness risk gene positively regulates the associated gene, if the drug positively regulates both the first deafness risk gene and the associated gene, the drug is confirmed as a candidate drug for the deafness disease caused by the abnormality of the first deafness risk gene.
[0075] In the preferred embodiment, when the first deafness risk gene is an upstream gene of the associated gene and positively regulates the associated gene, by limiting the drug to positively regulate both, it is ensured that the drug can compensate for the loss of function of the upstream mutant gene by enhancing the activity of the downstream associated gene, achieve a rescue effect on the signal pathway, and improve the matching degree of the candidate drug and the disease mechanism.
[0076] Further, in the step S25 of screening the candidate drug, the following preferred embodiment can also be implemented, including step S252:
[0077] S252: When the first deafness risk gene is an upstream gene of its associated gene in the corresponding signal pathway, and the first deafness risk gene negatively regulates the associated gene, if the drug negatively regulates both the first deafness risk gene and the associated gene, the drug is confirmed as a candidate drug for the deafness disease caused by the abnormality of the first deafness risk gene.
[0078] In the preferred embodiment, when the first deafness risk gene is an upstream gene of the associated gene and negatively regulates the associated gene, by limiting the drug to negatively regulate both, it is ensured that the drug can balance the abnormality of the signal pathway caused by the mutant gene by synergistically inhibiting the excessive activation of the downstream associated gene, maintain the homeostatic regulation of the signal pathway, and enhance the action specificity of the candidate drug.
[0079] Further, in the step S25 of screening the candidate drug, the following preferred embodiment can also be implemented, including step S253:
[0080] S253: When the first deafness risk gene has a common downstream gene with its associated gene in the corresponding signal pathway, and the first deafness risk gene and the associated gene positively regulate the downstream gene, if the drug positively regulates both the first deafness risk gene and the associated gene, the drug is confirmed as a candidate drug for the deafness disease caused by the abnormality of the first deafness risk gene.
[0081] In the preferred embodiment, when the first deafness risk gene and the associated gene share a common downstream gene and are both positively regulated, by limiting the drug to both being positively regulated, it is ensured that the drug can compensate for the insufficient function of the mutant gene by synergistically activating the expression of the common downstream gene, strengthening the overall activation effect of the pathway, and improving the therapeutic potential of the candidate drug.
[0082] Further, in the step S25 of screening the candidate drug, the following preferred embodiment can also be implemented, including the step S254:
[0083] S254: When the first deafness risk gene and its associated gene have a common downstream gene in the corresponding signaling pathway, and the regulation direction of the first deafness risk gene and the associated gene to the downstream gene is negative regulation, if the regulation direction of the drug to the first deafness risk gene and the associated gene is negative regulation, the drug is confirmed as a candidate drug for deafness disease caused by abnormality of the first deafness risk gene.
[0084] In the preferred embodiment, when the first deafness risk gene and the associated gene share a common downstream gene and are both negatively regulated, by limiting the drug to both being negatively regulated, it is ensured that the drug can correct the imbalance of the pathway caused by the mutant gene by synergistically inhibiting the abnormal activation of the common downstream gene, maintain the normal expression level of the downstream gene, and improve the action accuracy of the candidate drug.
[0085] In the specific implementation of constructing the deafness gene-candidate drug relationship database, reference is made to Figure 4 A schematic flowchart for constructing a deafness gene-candidate drug relationship database first collects data, collects 1071 deafness risk genes related to "hearing loss" and "hearing impairment" from literature and databases, collects 14472, 51250, 46736 and 14977 drug-target gene interaction records from DrugRepursosingHub, GETdb, TTD and drugbank databases respectively, removes duplicates to obtain a total of 81891 (corresponding to 46745 drugs and 4682 genes) drug-target gene interaction relationships, that is, to constitute a drug-target gene interaction relationship network.
[0086] In order to focus on the specific genes of the key effector cells (ear hair cells) of deafness disease, the top 2000 ear hair cell highly expressed genes are collected from human inner ear organoid single cell sequencing research (PMID: 38844821) as ear hair cell highly expressed genes, and then intersected with the above deafness risk genes to obtain 131 ear hair cell highly expressed deafness risk genes.
[0087] Next, 131 ear hair highly expressed deafness risk genes are mapped into the drug-target gene interaction relationship network, and 318 drug-deafness risk gene interaction relationships (corresponding to 283 drugs and 38 deafness risk genes) are obtained, as shown in the schematic diagram of the drug-deafness risk gene interaction relationship network. Figure 5 The number of drugs interacting with each target gene is between 1 and 61.
[0088] Continue to download the human KEGG pathway data from the KEGG database, and there are 361 KGML annotation files. First, parse the regulation relationship between genes in each KEGG pathway using R language to understand the role of genes in the network and the way of function. For example Figure 6 The protein-protein regulation network diagram of the hsa05130 signal pathway (the nodes in the figure are proteins in the pathway, and the regulation relationship between proteins is shown in the figure, and the gene name of the protein has been hidden) can be seen in the figure. In the figure, it can be seen that the genes in each pathway are inhibited, activated, or phosphorylated.
[0089] After preparing the above data, in the drug-deafness risk gene interaction relationship network, each target gene corresponding to each drug is mapped to the gene-gene regulation relationship network of each KEGG signal pathway. If the target genes of a certain X drug can be mapped to the gene-gene regulation relationship network of Y signal pathway, then the relationship of “X drug-Y signal pathway” is retained. After screening, 306 drug-pathway relationships are obtained.
[0090] Further, the drug-pathway relationship is screened, referring to the schematic diagram of the signal pathway shown in Figure 7 In Figure 7 (1), genes a (i.e. the first deafness risk gene) and b (i.e. the associated gene) are in Y1 signal pathway, which are upstream and downstream genes in the pathway, and the b gene is downstream of the a gene and is regulated by the a gene. When drug X1 has positive regulation on a and b and a has positive regulation on b, or drug X1 has negative regulation on a and b and a has negative regulation on b, drug X1 can compensate for the functional loss caused by gene a mutation by positively or negatively regulating gene b, and play a rescuing role on pathway Y1. Gene b can be called “a gene loss replacement gene that rescues the function of the pathway”. Therefore, drug X1 can be used as a candidate drug for the treatment of a deafness / hearing impairment patient with a gene a mutation.
[0091] In addition, in Figure 7(2) is another case: a and b genes have common downstream genes in Y2 signal pathway and a and b genes are both positive regulation (or negative regulation) to downstream genes, and drug X2 is also positive regulation (or negative regulation) to gene a and gene b, then drug X2 can be used as a candidate drug for the treatment of deafness / hearing impairment patients with a gene mutation.
[0092] Finally, by screening 306 pairs of drug-pathway relationships and excluding some drugs with incomplete annotations, a total of 8 pairs of high-quality drug-pathway relationships were obtained, and the deafness gene-candidate drug relationships were extracted to construct the corresponding database.
[0093] Reference Figure 8 The asparagine-hsa00250 signal pathway-ASNS deafness risk gene regulation relationship schematic diagram, wherein Figure 8 (1) is the regulation network between proteins in the "alanine, aspartate and glutamate (KEGG hsa00250: Alanine, aspartate and glutamate metabolism) signal pathway", it can be seen that ASNS protein and ASRGL1 protein are regulated by ADSS2, ASS1, ASS2 and CAD, and the downstream regulatory proteins of ASNS protein and ASRGL1 are GOT2, GOT1, GOT1L1, ASPA, NAT8L and IL4I1, in Figure 8 (2) is a case where the regulation of drug asparagine on ASNS and ASRGL1 genes is positive regulation, that is, ASNS gene and ASRGL1 gene play similar roles in the pathway, so when the deafness risk gene ASNS is mutated, the positive regulation of drug asparagine on ASRGL1 partially compensates for the loss of function of ASNS, that is, drug asparagine can be used as a candidate drug for the treatment of deafness / hearing impairment patients with ASNS gene mutation.
[0094] In addition, according to the actual clinical data, ASNS gene is asparagine synthetase, which catalyzes the conversion of aspartic acid and glutamine to asparagine and glutamic acid in vivo, and its mutation will cause asparagine synthetase deficiency, leading to accumulation of aspartic acid in brain tissue and deficiency of asparagine (PMID: 29084849), and such patients have developmental disorders and hearing impairment (PMID: 29084849; PMID: 24139043; PMID: 23313584), which proves that the method can find effective candidate drugs for disease treatment according to existing drug-target gene data and KEGG signal pathway data, and is an innovative development method for new use of old drugs, which is expected to provide a new perspective and direction for disease treatment.
[0095] In summary, compared with the prior art, the above embodiments of the present application have the following beneficial effects: by obtaining the abnormal gene data set of the deaf patient to be matched, the individual patient gene mutation information is accurately captured, and specific input is provided for targeted drug matching; the abnormal gene data set is input into the pre-set deaf gene-candidate drug relationship database for matching, the standardized gene-drug corresponding relationship based on scientific mechanism is directly called, repeated analysis is avoided, and the screening efficiency is improved; wherein, in the database construction process, by obtaining the deaf risk gene, drug-target gene interaction and KEGG pathway data, multi-dimensional basic data support covering "risk gene-drug interaction-pathway regulation" is provided for drug screening; the deaf risk gene is mapped to the drug-target gene network, and the core interaction relationship related to deafness is selected from the massive drug-gene relationship; the gene regulation relationship is analyzed in the KEGG pathway, the limitation of the simplified model in the prior art is broken through, and the dynamic regulation mechanism such as activation and inhibition between genes is revealed in depth at the signal pathway level; through the mapping of the drug target gene in the pathway and the screening condition of "at least two target genes", the relevance of the drug and the pathway is ensured, and non-specific drugs that only interact with a single gene by chance are excluded; based on the consistency of the regulation direction, the candidate drug is screened, so that the regulation of the drug on the mutant gene and the associated gene conforms to the internal logic of the pathway, and it is ensured that the drug can rescue the pathway function through the alternative gene mechanism, solving the defect that the existing database lacks biological mechanism support; a database is constructed based on the gene-drug corresponding relationship, the standardized storage and reuse of scientific screening results are realized, and tool support with efficiency and accuracy is provided for clinical treatment. Through the synergistic effect of the above features, the core logic of the database construction is upgraded from "simple interaction mapping" to "pathway regulation mechanism driven", solving the problem that the candidate drug in the prior art lacks pathway level mechanism support, resulting in insufficient targeting, and realizing accurate candidate drug matching based on individual abnormal genes.
[0096] Embodiment two:
[0097] Please refer to Figure 2 , based on the same inventive concept, the present application discloses a candidate drug screening system based on gene-drug interaction, which comprises a data acquisition module M1 and a matching module M2;
[0098] The data acquisition module M1 is used to obtain the abnormal gene data set of the deaf patient to be matched.
[0099] The matching module M2 is used to input the abnormal gene data set into the pre-set deaf gene-candidate drug relationship database for matching, and obtain the deaf candidate drug corresponding to the deaf patient; wherein the deaf gene-candidate drug relationship database is obtained by the following way:
[0100] obtain a deafness risk gene dataset, a drug-target gene interaction relationship network and human KEGG pathway data;
[0101] map each gene in the deafness risk gene dataset to the drug-target gene interaction relationship network to obtain a drug-deafness risk gene interaction relationship network;
[0102] analyze the regulation relationship between each gene in each KEGG pathway in the human KEGG pathway data to obtain a gene regulation relationship network of each signal pathway;
[0103] map each target gene corresponding to each drug in the drug-deafness risk gene interaction relationship network to the gene regulation relationship network of each signal pathway, and if at least two target genes corresponding to a drug exist in the gene regulation relationship network of a signal pathway, the corresponding relationship between the drug and the signal pathway is retained to obtain a drug-pathway relationship;
[0104] if the regulation direction of a drug to a first deafness risk gene and its associated genes is consistent with the regulation direction of the first deafness risk gene and its associated genes in the corresponding signal pathway, the drug is screened as a candidate drug for a deafness disease caused by abnormality of the first deafness risk gene, in each drug-pathway relationship, wherein the regulation direction of the first deafness risk gene and its associated genes in the corresponding signal pathway includes the regulation direction of the first deafness risk gene to the associated genes or the regulation direction of the first deafness risk gene and its associated genes to a common downstream gene;
[0105] construct the deafness gene-candidate drug relationship database according to the corresponding relationship between each first deafness risk gene and each candidate drug.
[0106] Further, the matching module M2 comprises a collection unit, an intersection processing unit and a mapping unit;
[0107] The collection unit is configured to obtain a high-expression gene set of ear hair cells.
[0108] The intersection processing unit is configured to take the intersection of the deafness risk gene dataset and the high-expression gene set of ear hair cells to obtain a high-expression deafness risk gene dataset of ear hair.
[0109] The mapping unit is configured to map each gene in the high-expression deafness risk gene dataset of ear hair to the drug-target gene interaction relationship network to obtain a drug-deafness risk gene interaction relationship network.
[0110] In the preferred embodiment, by obtaining the ear hair cell high expression gene set, the specificity of the key effector cell (ear hair cell) of the deafness disease is focused; the intersection of the deafness risk gene and the ear hair cell high expression gene is taken to narrow the screening range to the core gene with both deafness risk and ear hair cell function correlation; the intersection gene is mapped to the drug-target gene network to further improve the biological correlation and screening efficiency of the drug-deafness risk gene interaction.
[0111] Further, the matching module M2 further comprises a first screening unit.
[0112] The first screening unit is configured to, when the first deafness risk gene is an upstream gene of an associated gene in the corresponding signal pathway and the first deafness risk gene has a positive regulation on the associated gene, if the drug has a positive regulation on both the first deafness risk gene and the associated gene, confirm the drug as a candidate drug for the deafness disease caused by the abnormality of the first deafness risk gene.
[0113] In the preferred embodiment, when the first deafness risk gene is an upstream gene of an associated gene and has a positive regulation, by limiting the drug to have a positive regulation on both, it is ensured that the drug can compensate for the functional loss of the upstream mutant gene by enhancing the activity of the downstream associated gene, realize the rescue effect on the signal pathway, and improve the matching degree of the candidate drug and the disease mechanism.
[0114] Further, the matching module M2 further comprises a second screening unit.
[0115] The second screening unit is configured to, when the first deafness risk gene is an upstream gene of an associated gene in the corresponding signal pathway and the first deafness risk gene has a negative regulation on the associated gene, if the drug has a negative regulation on both the first deafness risk gene and the associated gene, confirm the drug as a candidate drug for the deafness disease caused by the abnormality of the first deafness risk gene.
[0116] In the preferred embodiment, when the first deafness risk gene is an upstream gene of an associated gene and has a negative regulation, by limiting the drug to have a negative regulation on both, it is ensured that the drug can balance the pathway abnormality caused by the mutant gene by synergistically inhibiting the excessive activation of the downstream associated gene, maintain the steady-state regulation of the signal pathway, and enhance the action specificity of the candidate drug.
[0117] Further, the matching module M2 further comprises a third screening unit.
[0118] The third screening unit is configured to, when the first deafness risk gene shares a common downstream gene with the associated gene in the corresponding signal pathway and the first deafness risk gene and the associated gene positively regulate the downstream gene, confirm the drug as a candidate drug for deafness diseases caused by abnormality of the first deafness risk gene, if the drug positively regulates both the first deafness risk gene and the associated gene.
[0119] In the preferred embodiment, when the first deafness risk gene and the associated gene share a common downstream gene and both positively regulate the downstream gene, by limiting the drug to positively regulate both the first deafness risk gene and the associated gene, it is ensured that the drug can compensate for the insufficient function of the mutant gene by synergistically activating the expression of the common downstream gene, strengthen the overall activation effect of the pathway, and improve the treatment potential of the candidate drug.
[0120] Further, the matching module M2 further comprises a fourth screening unit.
[0121] The fourth screening unit is configured to, when the first deafness risk gene shares a common downstream gene with the associated gene in the corresponding signal pathway and the first deafness risk gene and the associated gene negatively regulate the downstream gene, confirm the drug as a candidate drug for deafness diseases caused by abnormality of the first deafness risk gene, if the drug negatively regulates both the first deafness risk gene and the associated gene.
[0122] In the preferred embodiment, when the first deafness risk gene and the associated gene share a common downstream gene and both negatively regulate the downstream gene, by limiting the drug to negatively regulate both the first deafness risk gene and the associated gene, it is ensured that the drug can correct the pathway imbalance caused by the mutant gene by synergistically inhibiting the abnormal activation of the common downstream gene, maintain the normal expression level of the downstream gene, and improve the action accuracy of the candidate drug.
[0123] In summary, compared with the prior art, the embodiments of the present application have the following beneficial effects: by obtaining the abnormal gene data set of the deaf patient to be matched, the individual patient gene mutation information is accurately captured, and specific input is provided for targeted drug matching; the abnormal gene data set is input into the pre-set deaf gene-candidate drug relationship database for matching, the standardized gene-drug corresponding relationship based on scientific mechanism is directly called, repeated analysis is avoided, and the screening efficiency is improved; wherein, in the database construction process, by obtaining the deaf risk gene, drug-target gene interaction and KEGG pathway data, multi-dimensional basic data support covering "risk gene-drug interaction-pathway regulation" is provided for drug screening; the deaf risk gene is mapped to the drug-target gene network, and the core interaction relationship related to deafness is selected from the massive drug-gene relationship; the gene regulation relationship is analyzed in the KEGG pathway, the limitation of the simplified model in the prior art is broken through, and the dynamic regulation mechanism such as activation and inhibition between genes is revealed in the signal pathway level; through the mapping of the drug target gene in the pathway and the screening condition of "at least two target genes", the relevance of the drug and the pathway is ensured, and non-specific drugs that only interact with a single gene by chance are excluded; based on the consistency of the regulation direction, the candidate drug is screened, so that the regulation of the drug on the mutant gene and the associated gene conforms to the internal logic of the pathway, and it is ensured that the drug can rescue the pathway function through the alternative gene mechanism, solving the defect that the existing database lacks biological mechanism support; according to the gene-drug corresponding relationship, the database is constructed, the standardized storage and reuse of scientific screening results are realized, and toolized support with efficiency and accuracy is provided for the clinic. Through the synergistic effect of the above features, the core logic of the database construction is upgraded from "simple interaction mapping" to "pathway regulation mechanism driven", solving the problem that the candidate drug in the prior art lacks pathway level mechanism support, and realizing the precise candidate drug matching based on individual abnormal genes.
[0124] Embodiment three:
[0125] Figure 3 The structure diagram of the candidate drug screening equipment based on gene-drug interaction is shown in the present application. As shown in Figure 3 the candidate drug screening equipment based on gene-drug interaction can include: a processor N1, a memory N2, a data interface N3, and a communication bus N4.
[0126] Among them: the processor N1, the memory N2, the data interface N3 complete mutual communication through the communication bus N4; the data interface N3 is used for data communication with other devices such as input devices or output devices; the processor N1 is used for executing the program N5, and can execute the related steps in any one of the above-mentioned candidate drug screening methods based on gene-drug interaction.
[0127] In particular, program N5 can include program code comprising computer-executable instructions.
[0128] Processor N1 can be a central processing unit (CPU), or an application specific integrated circuit (ASIC), or one or more integrated circuits configured to perform the functions of the embodiments of the application. The one or more processors of the candidate drug screening device based on the interaction of gene drugs can be the same type of processor, such as one or more CPUs, or different types of processors, such as one or more CPUs and one or more ASICs.
[0129] Memory N2 is used to store program N5, and memory N2 can include a high-speed RAM memory, and can also include a non-volatile memory, such as at least one disk memory.
[0130] The algorithms and displays presented herein are not inherently related to any particular computer, virtual system, or other apparatus. Furthermore, embodiments of the present application are not described with reference to any particular programming language.
[0131] Embodiment four:
[0132] The embodiments of the application also provide a computer readable storage medium, the storage medium stores at least one executable instruction, and the executable instruction makes the candidate drug screening device / system based on the interaction of gene drugs execute the candidate drug screening method based on the interaction of gene drugs in any method embodiment described above when the executable instruction runs on the candidate drug screening device / system based on the interaction of gene drugs.
[0133] In the specification provided herein, a large number of specific details are described. However, it can be understood that the embodiments of the application can be practiced without these specific details. Similarly, in order to simplify the application and help understand one or more of the various inventive aspects, in the above description of the exemplary embodiments of the application, various features of the embodiments of the application are sometimes grouped together into a single embodiment, figure, or description thereof. Among them, the claims following the detailed description are thus expressly incorporated into the detailed description, wherein each claim itself is a separate embodiment of the application.
[0134] It will be appreciated by those skilled in the art that modules in the apparatus of the embodiments can be adapted and placed in one or more apparatuses other than the embodiments. Modules or units or components in the embodiments can be combined into one module or unit or component, and further can be split into multiple sub-modules or sub-units or sub-components. Except that at least some of such features and / or processes or units are mutually exclusive.
Claims
1. A method for screening candidate drugs based on gene-drug interactions, characterized in that, include: Obtain the abnormal gene dataset of deaf patients to be matched; The abnormal gene dataset is input into a pre-defined deafness gene-candidate drug relationship database for matching to obtain deafness candidate drugs corresponding to the deaf patients; wherein, the deafness gene-candidate drug relationship database is obtained in the following way: Acquire datasets of genes at risk of hearing loss, drug-target gene interaction networks, and human KEGG pathway data; Each gene in the deafness risk gene dataset is mapped to the drug-target gene interaction network to obtain the drug-deafness risk gene interaction network; In the human KEGG pathway data, the regulatory relationships between genes in each KEGG pathway were analyzed to obtain the gene regulatory relationship network of each signaling pathway; In the drug-deafness risk gene interaction network, each target gene corresponding to each drug is mapped to the gene regulation network of each signaling pathway. If a drug has at least two corresponding target genes in the gene regulation network of a certain signaling pathway, the correspondence between the drug and the signaling pathway is retained to obtain each drug-pathway relationship. In each of the aforementioned drug-pathway relationships, if the regulatory direction of a drug on a certain first deafness risk gene and its associated genes is consistent with the regulatory direction of the first deafness risk gene and its associated genes in the corresponding signaling pathway, then the drug is screened as a candidate drug for deafness caused by abnormality of the first deafness risk gene; wherein, the regulatory direction of the first deafness risk gene and its associated genes in the corresponding signaling pathway includes: the regulatory direction of the first deafness risk gene on the associated gene, or the regulatory direction of the first deafness risk gene and its associated genes on a common downstream gene; Based on the correspondence between each of the first deafness risk genes and the corresponding candidate drugs, a deafness gene-candidate drug relationship database is constructed.
2. The candidate drug screening method based on gene-drug interaction as described in claim 1, characterized in that, The step of mapping each gene in the deafness risk gene dataset to the drug-target gene interaction network to obtain the drug-deafness risk gene interaction network includes: Obtain a set of genes highly expressed in ear hair cells; The intersection of the deafness risk gene dataset and the set of genes highly expressed in ear hair cells is used to obtain the deafness risk gene dataset with high expression in ear hair cells. Each gene in the dataset of deafness risk genes highly expressed in ear hair is mapped to the drug-target gene interaction network to obtain the drug-deafness risk gene interaction network.
3. The candidate drug screening method based on gene-drug interaction as described in claim 1, characterized in that, In each of the aforementioned drug-pathway relationships, if the regulatory direction of a drug on a certain first deafness risk gene and its associated genes is consistent with the regulatory direction of the first deafness risk gene and its associated genes in the corresponding signaling pathway, then the drug is screened as a candidate drug for deafness caused by abnormality of the first deafness risk gene, including: When the first deafness risk gene is an upstream gene of its associated gene in the corresponding signaling pathway, and the first deafness risk gene regulates the associated gene in a positive direction, if the drug regulates both the first deafness risk gene and the associated gene in a positive direction, then the drug is confirmed as a candidate drug for deafness caused by abnormality of the first deafness risk gene.
4. The candidate drug screening method based on gene-drug interaction as described in claim 3, characterized in that, In each of the aforementioned drug-pathway relationships, if the regulatory direction of a drug on a certain first deafness risk gene and its associated genes is consistent with the regulatory direction of the first deafness risk gene and its associated genes in the corresponding signaling pathway, then the drug is screened as a candidate drug for deafness caused by abnormality of the first deafness risk gene, further comprising: When the first deafness risk gene is an upstream gene of its associated gene in the corresponding signaling pathway, and the first deafness risk gene has a negative regulatory effect on the associated gene, if the drug has a negative regulatory effect on both the first deafness risk gene and the associated gene, then the drug is confirmed as a candidate drug for deafness caused by abnormality of the first deafness risk gene.
5. The candidate drug screening method based on gene-drug interaction as described in claim 1, characterized in that, In each of the aforementioned drug-pathway relationships, if the regulatory direction of a drug on a certain first deafness risk gene and its associated genes is consistent with the regulatory direction of the first deafness risk gene and its associated genes in the corresponding signaling pathway, then the drug is screened as a candidate drug for deafness caused by abnormality of the first deafness risk gene, further comprising: When the first deafness risk gene shares a common downstream gene with its associated gene in the corresponding signaling pathway, and the first deafness risk gene and the associated gene regulate the downstream gene in a positive direction, if the drug regulates both the first deafness risk gene and the associated gene in a positive direction, then the drug is confirmed as a candidate drug for deafness caused by abnormality of the first deafness risk gene.
6. The candidate drug screening method based on gene-drug interaction as described in claim 5, characterized in that, In each of the aforementioned drug-pathway relationships, if the regulatory direction of a drug on a certain first deafness risk gene and its associated genes is consistent with the regulatory direction of the first deafness risk gene and its associated genes in the corresponding signaling pathway, then the drug is screened as a candidate drug for deafness caused by abnormality of the first deafness risk gene, further comprising: When the first deafness risk gene shares a common downstream gene with its associated gene in the corresponding signaling pathway, and the first deafness risk gene and the associated gene exert negative regulation on the downstream gene, if the drug exerts negative regulation on both the first deafness risk gene and the associated gene, then the drug is confirmed as a candidate drug for deafness caused by abnormality of the first deafness risk gene.
7. A candidate drug screening system based on gene-drug interactions, characterized in that, include: Data acquisition module and matching module; The data acquisition module is used to acquire abnormal gene datasets of deaf patients to be matched. The matching module is used to input the abnormal gene dataset into a preset deafness gene-candidate drug relationship database for matching, to obtain the deafness candidate drug corresponding to the deaf patient; wherein, the deafness gene-candidate drug relationship database is obtained through the following methods: Acquire datasets of genes at risk of hearing loss, drug-target gene interaction networks, and human KEGG pathway data; Each gene in the deafness risk gene dataset is mapped to the drug-target gene interaction network to obtain the drug-deafness risk gene interaction network; In the human KEGG pathway data, the regulatory relationships between genes in each KEGG pathway were analyzed to obtain the gene regulatory relationship network of each signaling pathway; In the drug-deafness risk gene interaction network, each target gene corresponding to each drug is mapped to the gene regulation network of each signaling pathway. If a drug has at least two corresponding target genes in the gene regulation network of a certain signaling pathway, the correspondence between the drug and the signaling pathway is retained to obtain each drug-pathway relationship. In each of the aforementioned drug-pathway relationships, if the regulatory direction of a drug on a certain first deafness risk gene and its associated genes is consistent with the regulatory direction of the first deafness risk gene and its associated genes in the corresponding signaling pathway, then the drug is screened as a candidate drug for deafness caused by abnormality of the first deafness risk gene; wherein, the regulatory direction of the first deafness risk gene and its associated genes in the corresponding signaling pathway includes: the regulatory direction of the first deafness risk gene on the associated gene, or the regulatory direction of the first deafness risk gene and its associated genes on a common downstream gene; Based on the correspondence between each of the first deafness risk genes and the corresponding candidate drugs, a deafness gene-candidate drug relationship database is constructed.
8. The candidate drug screening system based on gene-drug interaction as described in claim 7, characterized in that, The matching module includes: a data acquisition unit, an intersection processing unit, and a mapping unit; The acquisition unit is used to acquire a set of genes highly expressed in ear hair cells; The intersection processing unit is used to take the intersection of the deafness risk gene dataset and the hair cell high expression gene dataset to obtain the hair cell high expression deafness risk gene dataset. The mapping unit is used to map each gene in the dataset of deafness risk genes highly expressed in ear hair to the drug-target gene interaction network to obtain the drug-deafness risk gene interaction network.
9. A candidate drug screening device based on gene-drug interaction, comprising a memory, a processor, and a computer program stored in the memory and executable on the processor, characterized in that, When the computer program is loaded into the processor, it implements the steps of a candidate drug screening method based on gene-drug interaction according to any one of claims 1-6.
10. A computer-readable storage medium storing a computer program, characterized in that, When the computer program is executed by the processor, it implements the steps of a candidate drug screening method based on gene-drug interaction according to any one of claims 1-6.