Screening and functional analysis method for radiation-resistant brain injury related genes of multiple traditional Chinese medicine components

Abstract

The invention discloses a screening and functional analysis method for radiation-resistant brain injury related genes of multiple traditional Chinese medicine components, and belongs to the technical field of biomedical treatment. The method comprises the following steps: screening active components of each component of the medicine; obtaining a disease gene target spot; searching a target spot related to the radiation brain injury in the database; obtaining potential targets of the multiple traditional Chinese medicine active ingredients on radiation brain injury; constructing a medicine active ingredient-action target spot network; obtaining a protein interaction relationship and GO and KEGG pathway analysis; and docking the micromolecules with high scores with the target molecules. Compared with the prior art, the method has the beneficial effects that aiming at radiation, brain injury is emphasized, and the thought of traditional Chinese medicine syndrome differentiation and tonification and purgation is exerted for systematic prediction. A multi-component formula closer to practical application is used, a non-single source is used as a research model, and the method has more practical reference significance. The network pharmacology and the molecular docking technology are combined to analyze the potential and the mechanism of the drug for exerting the drug effect, so that the method is more persuasive.

Description

Technical Field

[0001] The invention belongs to the field of biomedical technology and relates to a method for screening and functional analysis of genes related to radiation-resistant brain damage using multiple traditional Chinese medicine ingredients. Background Art

[0002] Since 1942, researchers have conducted a lot of research on radiation protectors and have discovered some synthetic or natural radiation protectors. Synthetic protectors mainly include: thiol compounds, nitroxide free radicals, dibenzimidazole, etc. Most synthetic protectors have the disadvantages of high price, large application dose, strong toxic side effects, etc. Therefore, it is very meaningful to develop new protectors with high efficiency, low toxicity, low cost and multiple targets. Many natural medicinal and edible ingredients - Chinese medicine meet the above requirements. Many medicinal and edible ingredients, such as polysaccharides, flavonoids, saponins, peptides, alkaloids and vitamins, have been found to have anti-radiation activity. The Chinese medicine compound is rich in ingredients and can play the role of multiple targets and multiple pathways to resist adverse environments. The compatibility of Chinese medicine is flexible and diverse, so its mechanism of exerting its efficacy is extremely complex. When the old prescription expands its indications or the new prescription conducts efficacy verification, it consumes a lot of manpower, material resources and financial resources. Therefore, before the experiment is put into use, it is low-cost and efficient to simulate the effects of drug ingredients and disease targets by computer.

[0003] In real life, it is not common to use single herbs for TCM treatment. The brain is sensitive to radiation, leading to memory loss, dizziness and headache, affecting normal life and work. In view of brain damage caused by radiation, it is of great practical significance to make full use of the characteristics and advantages of the holistic view of traditional Chinese medicine and the treatment based on syndrome differentiation. The development of anti-prescriptions has a wide variety of prescriptions. The level and potential mechanism of drug efficacy can be quickly obtained by computer simulation. By analogy, it can also be extended to other disease areas, further expanding the scope of application and efficiency of traditional Chinese medicine. Therefore, it has important clinical value and practical significance. The present invention aims to collect and screen radiation damage targets to the brain, and applies more common Chinese medicine compound prescriptions, which are more in line with realistic application scenarios.

[0004] Studies have found that the nervous system is more sensitive to the effects of the space environment. In the early stage, brain tissue may show edema, inflammation and chromatin dissolution, and then apoptosis, vacuolar degeneration, etc. may occur, and nerve fibers may swell and demyelinate. After brain tissue damage, obvious biochemical changes may occur, including metabolic disorders (including material and energy metabolism), abnormal changes in neurotransmitters and neuropeptides, changes in cytokines, and changes in nucleic acids and transcription factors. For example, the utilization and oxidation of glucose in the brain will be reduced accordingly, reactive oxygen species (ROS) will increase, and oxidative damage will occur. As a radiation protector, traditional Chinese medicine is rich in resources, and most of them are low-toxic or non-toxic substances, which has attracted widespread attention. Many active ingredients have been found, such as polysaccharides, flavonoids, saponins, peptides, alkaloids and vitamins. The radiation protection mechanism includes DNA damage repair, reducing oxidative stress, protecting hematopoiesis and immune system, etc. Network pharmacology is an effective way to reveal the pharmacological mechanism of traditional Chinese medicine formulas. Network pharmacology is an emerging discipline based on the theories of systems biology, genomics, and proteomics. It integrates a large amount of information by discovering new drug targets and molecular mechanisms, and then performing computational analysis in combination with in vivo and in vitro experiments. The mechanism of action of traditional Chinese medicine prescriptions has the characteristics of multi-target and multi-level. Its principle is similar to the integrity, systematicity, and comprehensiveness of network pharmacology. Therefore, network pharmacology is suitable for the study of the pharmacological mechanism of traditional Chinese medicine compounds.

[0005] The existing technology only provides computer simulation methods for single Chinese herbal medicine anti-radiation target points, and the collected data cover all radiation-induced damages, but there are no patents for symptomatic brain mechanisms. Summary of the invention

[0006] The purpose of the present invention is to solve the above-mentioned problems existing in the background technology and to provide a gene target and function analysis method for predicting and simulating multi-component drugs to resist radiation brain damage.

[0007] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0008] A method for screening and functional analysis of genes related to radiation-resistant brain damage using multiple traditional Chinese medicine ingredients, the method comprising:

[0009] (1) Screening the active ingredients of each component of the drug;

[0010] (2) Obtaining disease gene targets;

[0011] (3) Targets related to radiation brain damage were retrieved from GeneCards, DisGeNet, and DrugBank databases;

[0012] (4) To identify potential targets of active ingredients of multiple traditional Chinese medicines for the effects on radiation-induced brain damage;

[0013] (5) Constructing a drug active ingredient-target network;

[0014] (6) Obtain protein interaction relationships and GO and KEGG pathway analysis;

[0015] (7) Docking of high-scoring small molecules and target molecules.

[0016] The method for screening and functional analysis of genes related to radiation-induced brain damage by using traditional Chinese medicine ingredients of the present invention can be used to screen and functionally analyze genes related to radiation-induced brain damage in traditional Chinese medicine prescriptions of various drug ingredients through network pharmacology and molecular docking methods.

[0017] Furthermore, the method is specifically as follows:

[0018] (1) Screening of targets related to anti-radiation Chinese herbal compound

[0019] Through the TCMSP platform or other databases of TCM systems pharmacology research, the chemical components of multiple TCMs are searched, and the active ingredients are initially screened according to the three ADME attribute values ​​of oral availability ≥30%, drug-likeness ≥0.18, and blood-brain barrier ≥ to obtain active compounds and their protein targets. After the screening, in order to standardize the protein target information, the targets of the compounds are uniformly converted into targets in the Uniprot protein database;

[0020] (2) Radiation disease target collection

[0021] Using diseases related to radiation damage as keywords, we mined the potential targets for treating radiation sickness in the GeneCards database and the DisGeNet database, and entered the DrugBank database to find the first-line clinical western medicine targets for treating radiation sickness to supplement them. Based on experience, if there are too many targets, we set the target targets with a score greater than the median as potential targets of radiation abnormalities. After merging the targets of the four disease databases, we deleted the duplicate values ​​to obtain radiation disease targets.

[0022] (3) Construction of PPI network between anti-radiation Chinese medicine compound ingredients and radiation disease targets

[0023] In order to clarify the interaction between the targets related to traditional Chinese medicine compound and the targets of radiation diseases, the intersection of the two targets was taken using R language and a Venn diagram was drawn. The intersection targets were then submitted to the STRING11.0 database to construct a protein interaction network model. The biological species was set to "Homo sapiens", the minimum interaction threshold was set to "highest confidence" (>0.9), and the other settings were set as default. The PPI network was obtained, and the MCODE plug-in in CytoScape3.7.2 was used to further analyze the PPI network, obtain potential protein functional modules, and describe their functions by analyzing the biological processes in which they participate.

[0024] (4) Enrichment analysis of the functions and pathways of TCM compound ingredients-radiation sickness targets

[0025] The targets of the Chinese herbal compound for the treatment of radiation-induced brain injury were entered into the Metascape platform, P < 0.01 was set, and the main biological processes and metabolic pathways were analyzed and enrichment analysis was performed. The data results were saved and visualized using Origin Lab 2018.

[0026] (5) Construction of the network diagram of the anti-radiation Chinese medicine compound ingredients-radiation disease targets-pathway

[0027] CytoScape3.7.2 was used to construct a network diagram of the components of the anti-radiation Chinese medicine compound, radiation disease targets, and pathways. The built-in tools of CytoScape3.7.2 were used to analyze the network topology parameters of the effective ingredients and targets, and the core targets and the main active ingredients that exert the efficacy were determined based on the network topology parameters.

[0028] (6) Molecular docking verification

[0029] The targets with the highest degree values ​​in the TCM compound ingredient-radiation disease target network diagram were analyzed and their PDB IDs were found. The top-ranked targets were docked with the active ingredients of the TCM compound in the Systems DockWeb Site, and the binding strength and activity of the targets and active compounds were evaluated according to the Docking Score value.

[0030] Furthermore, in step (1), the other database refers to BATMAN-TCM, TCM-MESH or a chemical professional database.

[0031] Furthermore, in step (5), the network topology parameters include connectivity, betweenness and compactness.

[0032] The beneficial effects of the present invention compared to the prior art are:

[0033] 1. Focusing on radiation and brain damage, we use the idea of ​​TCM differentiation of symptoms and combination of attack and supplement to make systematic predictions.

[0034] 2. Using a multi-component formula that is closer to real-life applications and not a single source as a research model has more practical reference significance.

[0035] 3. The combined analysis of network pharmacology and molecular docking technology to analyze the potential and mechanism of drug efficacy is more convincing. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] Figure 1 This is a network diagram of effective ingredients and targets of traditional Chinese medicine compound, among which CP-dried orange peel; FL-Poria; HQ-Astragalus; SDH-Rehmannia root; LJS-Cervus antler cream; NZZ-Ligustrum lucidum; TSZ-Cuscuta seed; the blue diamonds in the middle distributed in a matrix are the gene targets, and the circle around the single medicine is its effective ingredient.

[0037] Figure 2 It is a Venn diagram of the abnormal targets of Chinese medicine compound ingredients and radiation diseases.

[0038] Figure 3 This is the PPI network diagram of Chinese medicine compound-radiation related targets.

[0039] Figure 4 This is the module diagram in the Chinese medicine compound-radiation disease target PPI network.

[0040] Figure 5 This is the GO-BP enrichment analysis diagram of potential targets of the main ingredients of traditional Chinese medicine compound.

[0041] Figure 6 This is the GO-MF enrichment analysis diagram of potential targets of the main ingredients of traditional Chinese medicine compound.

[0042] Figure 7 This is the GO-CC enrichment analysis diagram of potential targets of the main ingredients of traditional Chinese medicine compound.

[0043] Figure 8 This is the KEGG enrichment analysis diagram of the potential targets of the main ingredients of the traditional Chinese medicine compound.

[0044] Fig. 9 This is a network diagram of Chinese medicine compound ingredients-radiation disease targets-pathways.

[0045] Fig.10 Molecular docking diagram, including: (a) IL6-kaempferol; (b) TNF-kaempferol; (c) AKT-kaempferol; (d) IL6-quercetin; (e) TNF-quercetin; (f) AKT-quercetin. DETAILED DESCRIPTION

[0046] In order to make the purpose, technical scheme and advantages of the present invention clearer, the present invention will be further described in detail below with reference to the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0047] 1. Network and software resources

[0048] Traditional Chinese Medicine Systems Pharmacology Technology Platform TCMSP (http: / / lsp.nwu.edu.cn / )

[0049] Protein Data Bank (https: / / www.rcsb.org / ), UniProt (http: / / www.uniprot.org / )

[0050] Molecular docking platform Systems Dock Web Site (http: / / systemsdock.unit.oist.

[0051] jp / iddp / home / index)

[0052] Protein database UniProt (http: / / www.uniprot.org / )

[0053] Gene information databases GeneCards (http: / / www.genecards.org / ), DisGeNet

[0054] (https: / / www.disgenet.org / ), DrugBank (https: / / www.drugbank.ca)

[0055] Functional enrichment Metascape platform (http: / / metascape.org / gp / index.html)

[0056] Protein interaction analysis database String (http: / / string-db.org / )

[0057] Bioinformatics annotation database DAVID (https: / / david-d.ncifcrf.gov / )

[0058] Visualization software Cytoscape 2.7.3, Origin Lab 2018

[0059] Embodiment 1:

[0060] A method for screening and functional analysis of genes related to radiation-induced brain damage in traditional Chinese medicine compound

[0061] (1) Screening of targets related to anti-radiation Chinese herbal compound

[0062] The chemical compositions of six Chinese medicines (Rehmannia glutinosa, Fructus Ligustri Lucidi, Semen Cuscutae, Radix Astragali, Poria, and Pericarpium Citri Reticulatae) were searched through the TCMSP platform for systems pharmacology of traditional Chinese medicine (http: / / lsp.nwu.edu.cn / tcmsp.php). The active ingredients were preliminarily screened according to the three ADME attribute values ​​of oral availability (OB) ≥ 30%, drug-like property (DL) ≥ 0.18, and blood-brain barrier (BBB) ​​≥ 4.5, to obtain the active compounds and their protein targets. The pinyin names ("LU JIAO", "LU JIAO JIAO", "LUJIAO SHUANG"), English names (Deer Horn, Gelatin of Buckhorn, Degelatined Deer-horn), Latin names (Pulvis Cornu Cervi, Cornu Cervi, Cornu Cervi Degelatinatum) was used as the search term and “Herb” as the search form to search for active ingredients of deer antlers in various databases, and known targets of active compounds that were not predicted were supplemented based on manually consulted literature reports. After the screening, in order to standardize the protein target information, the targets of the compounds were uniformly converted into targets of the Uniprot protein database (http: / / www.uniprot.org / uploadlists / ).

[0063] (2) Radiation disease target collection

[0064] Using radiation damage-related diseases such as "radiation damage", "radiation syndrome", "radiation-induced brain damage", and "brain damage" as keywords, we mined the GeneCards database (https: / / www.genecards.org) and the DisGeNet database (https: / / www.disgenet.org / ) for potential targets for the treatment of radiation sickness, and entered the DrugBank database (https: / / www.drugbank.ca) to find clinical first-line Western medicine targets for the treatment of radiation sickness to supplement them. In the Genecards database, the higher the score value, the closer the target is to the disease. According to experience, if there are too many targets, the target with a score greater than the median is set as a potential target of radiation abnormality. After merging the targets of the four disease databases, the duplicate values ​​are deleted to obtain radiation disease targets.

[0065] (3) Construction of PPI network between anti-radiation Chinese medicine compound ingredients and radiation disease targets

[0066] In order to clarify the interaction between the targets related to traditional Chinese medicine compound and the targets of radiation diseases, the intersection of the two targets was obtained using R language and a Venn diagram was drawn. The intersection targets were then submitted to the STRING11.0 database (https: / / string-db.org) to construct a protein interaction (PPI) network model, the biological species was set to "Homo sapiens", the minimum interaction threshold was set to "highest confidence" (>0.9), and the rest of the settings were default settings to obtain the PPI network, which was further analyzed by the MCODE plug-in in CytoScape3.7.2 to obtain potential protein functional modules, and their functions were described by analyzing the biological processes in which they participated.

[0067] (4) Enrichment analysis of the functions and pathways of TCM compound ingredients-radiation sickness targets

[0068] The Metascape platform (http: / / metascape.org / gp / index.html) has comprehensive annotation functions and updates gene annotation data monthly. The targets of the Chinese herbal compound for the treatment of radiation-induced brain damage were entered into the Metascape platform, P<0.01 was set, and the main biological processes and metabolic pathways were analyzed and enrichment analysis was performed. The data results were saved and visualized using Origin Lab 2018.

[0069] (5) Construction of the network diagram of the anti-radiation Chinese medicine compound ingredients-radiation disease targets-pathway

[0070] CytoScape3.7.2 was used to construct a network diagram of anti-radiation Chinese herbal compound ingredients-radiation disease targets-pathways. The built-in tools of CytoScape3.7.2 were used to analyze the network topology parameters of effective ingredients and targets, including degree, betweenness, and closeness, etc. The core targets and the main active ingredients that exerted the efficacy were determined based on the network topology parameters.

[0071] (6) Molecular docking verification

[0072] Molecular docking can explore the interaction between macromolecular enzymes and small molecule ligands. It is generally believed that van der Waals forces, hydrogen bonds, hydrophobic interactions, and electrostatic interactions are the main factors in docking research. The top three targets with the highest degree value in the network diagram of TCM compound ingredients and radiation disease targets were analyzed, and their PDB IDs (https: / / www.rcsb.org / ) were searched. The three targets were docked with the active ingredients of TCM compound (quercetin and kaempferol) in the Systems Dock Web Site (http: / / systemsdock.unit.oist.jp / iddp / home / index), and the binding strength and activity of the targets and active compounds were evaluated according to the Docking Score value.

[0073] result

[0074] (1) Target acquisition and network construction of active ingredients in anti-radiation traditional Chinese medicine compounds

[0075] A total of 76 chemical components were initially extracted from Rehmannia glutinosa, 119 chemical components from Ligustrum lucidum, 29 chemical components from Cuscuta australis, 87 chemical components from Astragalus membranaceus, 34 chemical components from Poria cocos, and 63 chemical components from Citrus aurantium. After ADME screening, 2 chemical components from Rehmannia glutinosa, 13 chemical components from Ligustrum lucidum, 11 chemical components from Cuscuta australis, 20 chemical components from Astragalus membranaceus, 6 chemical components from Poria cocos, and 5 chemical components from Citrus aurantium were obtained, including sitosterol, quercetin, kaempferol, luteolin, isoflavones, etc., and 15 chemical components from antler frost were obtained.

[0076] Table 1 Main ingredients of anti-radiation Chinese herbal compound

[0077]

[0078]

[0079]

[0080]

[0081] Prepare the network and type files, input cytoscape3.7.2 software, and construct the network of effective ingredients and corresponding targets of traditional Chinese medicine compound, such as Figure 1 shown.

[0082] (2) Acquisition of radiation-related disease targets

[0083] 7920 targets of radiation-induced brain damage were obtained from the Genecards database. Based on experience, target targets with scores greater than the median were set as potential targets of radiation damage. For example, the maximum score of the target obtained through GeneCards was 102.54, the minimum was 0.13, and the three-fold median was 15.31. Therefore, 991 targets with scores>15.31 were set as potential targets of radiation diseases. The relevant targets were supplemented by combining the OMIM, TTD, and DRUGBANK databases, and duplicate values ​​were deleted after merging, and finally 1103 radiation disease-related targets were obtained.

[0084] (3) Construction of the PPI network of Chinese medicine compound ingredients and radiation disease targets

[0085] The screened anti-radiation TCM compound targets and radiation disease targets were intersected, and a Venn diagram was drawn using R language, resulting in 136 common targets for TCM compound components and dyslipidemia, see Figure 2 Then the targets were submitted to the STRING11.0 platform to obtain the PPI network of TCM compound targets. Figure 3 .

[0086] Since the effects of proteins in the PPI network are mutual, it is usually classified as an undirected graph. In the PPI complex network, there are some areas with higher density, which are called communities or modules. The network inside the module is a potential subnet of the PPI network. The subnet has a higher density of connections and fewer connections in some areas. Therefore, modules are considered to be a set with biological significance. This set has two meanings: one is a protein complex, that is, multiple proteins together form a complex and then play a biological role; the other is a functional module, such as proteins located in the same pathway, which interact more closely. Therefore, in order to more accurately analyze the mechanism of action of traditional Chinese medicine compound in the treatment of radiation sickness, it is necessary to further identify its internal module after obtaining the PPI network of the compound.

[0087] After obtaining the PPI network, the MCODE plug-in in CytoScape3.7.2 was used to analyze the interaction relationship through the molecular complex detection algorithm to obtain the module, see Figure 4According to the P value, the three best-scoring biological processes in the PPI network and module were retained for functional description, see Table 2.

[0088] Table 2 Functional description of the TCM compound-radiation disease target PPI network

[0089] GO Description Log10(P) hsa05200 Pathways in cancer -48 hsa05161 Hepatitis B -43 hsa04933 AGE-RAGEsignalingpathwayindiabeticcomplications -39

[0090] (4) Enrichment analysis of target functions and pathways

[0091] The Metascape data platform was used to analyze the signal pathways of the targets related to the treatment of radiation diseases by traditional Chinese medicine compound, and the results were visualized with the help of Origin Lab 2018. The results show that the functions of multiple targets are inseparable from the occurrence of radiation diseases. The main biological processes involved in traditional Chinese medicine compound include response to inorganic substances, apoptotic signaling pathway, cytokine-mediated signaling pathway, response to lipopolysaccharide, etc. Figure 5 The main channels involved are: Figure 8 The target pathway enrichment results are shown in Table 3.

[0092] The functions of related targets in regulating radiation diseases are mainly enriched in cofactor binding, protein kinase binding, protein domain specific binding, transcription factor binding, cytokine activity, RNA polymerase II transcription factor binding, etc., see Figure 6 .

[0093] Table 3 Enrichment results of target pathways of traditional Chinese medicine compound for the treatment of radiation diseases

[0094]

[0095]

[0096] (5) Construction of a network diagram of Chinese medicine compound ingredients, radiation disease targets and pathways

[0097] Use CytoScape3.7.2 to construct a Chinese medicine compound ingredient-radiation disease target-pathway network, see Fig. 9 The network topology parameters of the TCM compound for the treatment of radiation sickness were analyzed by using the built-in NetworkAnalyzer of cytoScape3.7.2, and the core components and core targets were obtained. Cytoscape network analysis showed that the degree of connectivity of quercetin was 154, the betweenness centrality was 0.324067, and the closeness centrality was 0.582734. It was predicted that quercetin was the main component of the TCM compound for the treatment of radiation sickness, followed by kaempferol (connectivity was 57, betweenness centrality was 0.033226, and closeness centrality was 0.430851), syringaresinol diglucoside (connectivity was 39, betweenness centrality was 0.075373, and closeness centrality was 0.455056), and taxifolin (connectivity was 29, betweenness centrality was 0.033226, and closeness centrality was 0.430851), as shown in Table 4.

[0098] Table 4. Network node characteristic parameters of the main active ingredients of traditional Chinese medicine compound

[0099]

[0100] (6) Molecular docking

[0101] Combining the results of PPI screening and enrichment analysis, molecular docking was performed on three hub genes of the PI3K-AKT signaling pathway (AKT, tumor necrosis factor TNF, and IL 6) and two key pharmacodynamic components of the traditional Chinese medicine compound (kaempferol and quercetin). Six docking results were generated through simulation ( Fig.10 ). Their binding energies are all <0 kJ / mole, indicating that they are all well bound.

Claims

1. A method for screening and functional analysis of genes related to radiation-resistant brain damage using multiple Chinese herbal ingredients, characterized in that: The method is: (1) Screening the active ingredients of each component of the drug; (2) Obtaining disease gene targets; (3) Retrieve targets related to radiation brain damage from the database; (4) To identify potential targets of active ingredients of multiple traditional Chinese medicines for the effects on radiation-induced brain damage; (5) Constructing a drug active ingredient-target network; (6) Obtain protein interaction relationships and GO and KEGG pathway analysis; (7) Docking of high-scoring small molecules and target molecules.

2. The method for screening and functional analysis of genes related to radiation-resistant brain damage using multiple Chinese herbal ingredients according to claim 1, characterized in that: The method is specifically as follows: (1) Screening of targets related to anti-radiation Chinese herbal compound Through the TCMSP platform or other databases of TCM systems pharmacology research, the chemical components of multiple TCMs are searched, and the active ingredients are initially screened according to the three ADME attribute values ​​of oral availability ≥30%, drug-likeness ≥0.18, and blood-brain barrier ≥ to obtain active compounds and their protein targets. After the screening, in order to standardize the protein target information, the targets of the compounds are uniformly converted into targets in the Uniprot protein database; (2) Radiation disease target collection Using diseases related to radiation damage as keywords, we mined the potential targets for treating radiation sickness in the GeneCards database and the DisGeNet database, and entered the DrugBank database to find the first-line clinical western medicine targets for treating radiation sickness to supplement them. Based on experience, if there are too many targets, we set the target targets with a score greater than the median as potential targets of radiation abnormalities. After merging the targets of the four disease databases, we deleted the duplicate values ​​to obtain radiation disease targets. (3) Construction of PPI network between anti-radiation Chinese medicine compound ingredients and radiation disease targets In order to clarify the interaction between the targets related to traditional Chinese medicine compound and the targets of radiation diseases, the intersection of the two targets was obtained using R language and a Venn diagram was drawn. The intersection targets were then submitted to the STRING11.0 database to construct a protein interaction network model. The biological species was set to "Homo sapiens", the minimum interaction threshold was set to "highest confidence" (>0.9), and the other settings were set as default. The PPI network was obtained and further analyzed by the MCODE plug-in in CytoScape3.7.2 to obtain potential protein functional modules, and their functions were described by analyzing the biological processes in which they participated. (4) Enrichment analysis of the functions and pathways of TCM compound ingredients-radiation sickness targets The targets of the Chinese herbal compound for the treatment of radiation-induced brain injury were entered into the Metascape platform, P < 0.01 was set, and the main biological processes and metabolic pathways were analyzed and enrichment analysis was performed. The data results were saved and visualized using Origin Lab 2018. (5) Construction of the network diagram of the anti-radiation Chinese medicine compound ingredients-radiation disease targets-pathway CytoScape3.7.2 was used to construct a network diagram of the components of the anti-radiation Chinese medicine compound, radiation disease targets, and pathways. The built-in tools of CytoScape3.7.2 were used to analyze the network topology parameters of the effective ingredients and targets, and the core targets and the main active ingredients that exert the efficacy were determined based on the network topology parameters. (6) Molecular docking verification The targets with the highest degree values ​​in the TCM compound ingredient-radiation disease target network diagram were analyzed and their PDBIDs were found. The top-ranked targets were docked with the active ingredients of the TCM compound in the Systems DockWeb Site, and the binding strength and activity of the targets and active compounds were evaluated according to the Docking Score values.

3. The method for screening and functional analysis of genes related to radiation-resistant brain damage using multiple Chinese herbal ingredients according to claim 1, characterized in that: In step (1), the other database refers to BATMAN-TCM, TCM-MESH or chemical professional database.

4. The method for screening and functional analysis of genes related to radiation-resistant brain damage using multiple Chinese herbal ingredients according to claim 1, characterized in that: In step (5), the network topology parameters include connectivity, betweenness and compactness.

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