Prediction method, system and equipment for paraphoid bone

Abstract

The invention provides a method, a system and equipment for predicting a paravichoid bone. According to the system, the equipment and the computer readable storage medium for predicting the paraphovicular bone, whether the paraphovicular bone exists in a sample or not can be well predicted by detecting expression of one or more proteins in P55291, Q9H3S7, P49748, Q9NPH2 and Q5KU26, a new direction is provided for effective diagnosis of the paraphovicular bone, and the system and the equipment have wide application prospects.

Description

Technical Field

[0001] The present invention belongs to the field of intelligent medical treatment, and in particular relates to a method, system and device for predicting accessory scaphoid bone. Background Art

[0002] The accessory navicular bone develops from the secondary ossification center of the navicular tuberosity and is located on the medial side of the navicular arch. It is an autosomal dominant trait. The cause of the accessory navicular bone symptoms is unknown, but it may be related to posterior tibial tendinitis, bone inflammation, ligament laxity, and changes in the mechanical structure of the midfoot after trauma. Currently, the diagnosis of the accessory navicular bone mainly relies on clinical manifestations and imaging results, including X-ray examinations, CT examinations, and MRI examinations. However, due to the hidden X-ray signs of the accessory navicular bone, it is often neglected by clinical and radiologists, and misdiagnosis and missed diagnosis are prone to occur.

[0003] Therefore, it is very necessary to study the genetic markers related to the accessory navicular bone to provide new directions for the early diagnosis and intervention of the accessory navicular bone. Summary of the invention

[0004] To overcome the deficiencies of the prior art, the present invention provides a method, system and device for predicting the accessory navicular bone.

[0005] To achieve the above object, the present invention adopts the following technical solution:

[0006] A first aspect of the present invention provides a method for constructing a prediction model of an accessory navicular bone, the method comprising:

[0007] Obtain target sample data;

[0008] Standardize the target sample data and screen for differentially expressed genes / proteins, wherein the differentially expressed genes / proteins include any one or more of the following: P55291, Q9H3S7, P49748, Q9NPH2, Q5KU26;

[0009] The accessory navicular bone is predicted based on the differentially expressed genes / proteins obtained by screening, and a prediction result of whether the patient has the accessory navicular bone is obtained.

[0010] Furthermore, the target sample data is proteome sequencing data.

[0011] Furthermore, the proteins were labeled by TMT.

[0012] Furthermore, the screening criteria for the differentially expressed genes / proteins are p<0.05&(FC<0.83 or FC>1.20).

[0013] A second aspect of the present invention provides a prediction system for accessory navicular bone, the system comprising:

[0014] Data acquisition module: obtain gene / protein data of the sample to be tested;

[0015] Classification prediction module: performs classification prediction based on gene / protein data to obtain the classification result of whether the patient has accessory navicular bone;

[0016] The genes / proteins include any one or more of the following: P55291, Q9H3S7, P49748, Q9NPH2, Q5KU26.

[0017] A third aspect of the present invention provides an accessory navicular bone prediction device, the device comprising a memory and a processor;

[0018] The memory is used to store program instructions;

[0019] The processor is used to call program instructions, and when the program instructions are executed, it is used to execute the method described in the first aspect of the present invention.

[0020] A fourth aspect of the present invention provides a computer-readable storage medium having a computer program stored thereon, wherein the computer program, when executed by a processor, implements the method described in the first aspect of the present invention.

[0021] A fifth aspect of the present invention provides a computer program product, comprising a computer program, which implements the method described in the first aspect of the present invention when executed by a processor.

[0022] The sixth aspect of the present invention provides the use of a reagent for detecting the expression level of a marker in the preparation of a product for diagnosing accessory navicular bone, wherein the marker comprises any one or more of the following: P55291, Q9H3S7, P49748, Q9NPH2, Q5KU26.

[0023] Furthermore, the reagents include primers that specifically amplify the marker, probes that specifically recognize the marker, or binding agents that specifically bind to the marker protein.

[0024] The seventh aspect of the present invention provides a product for diagnosing accessory navicular bone, the product comprising a reagent for detecting marker levels, the marker comprising any one or more of the following: P55291, Q9H3S7, P49748, Q9NPH2, Q5KU26.

[0025] Furthermore, the product includes a kit, a chip or a nucleic acid membrane strip.

[0026] Furthermore, the kit also includes a detectable reagent.

[0027] Furthermore, the detectable markers include magnetic beads, fluorescent dyes, radioactive markers, and enzymes.

[0028] Furthermore, the kit also includes instructions.

[0029] Furthermore, the kit also includes a buffer solution.

[0030] Advantages and beneficial effects of the present invention:

[0031] The present invention provides a system, device, and computer-readable storage medium for predicting accessory navicular bone. By detecting the expression of one or more proteins among P55291, Q9H3S7, P49748, Q9NPH2, and Q5KU26, it is possible to well predict whether a sample has accessory navicular bone, thereby providing a new direction for the effective diagnosis of accessory navicular bone and having broad application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 is a flowchart of a method for constructing a prediction model for the accessory navicular bone;

[0033] Figure 2 It is a schematic diagram of the predicted system of the accessory navicular bone;

[0034] Figure 3 It is a schematic diagram of the predicted device of the accessory navicular bone;

[0035] Figure 4 is the PCA plot of differentially expressed proteins;

[0036] Figure 5 is the differential protein volcano plot;

[0037] Figure 6 is the differential protein heat map;

[0038] Figure 7 is the GO enrichment map of differentially expressed proteins;

[0039] Figure 8 It is the KEGG functional enrichment map of differentially expressed proteins;

[0040] Fig. 9 is a graph of differential protein expression levels;

[0041] Fig.10 It is the ROC curve diagram of differentially expressed proteins. DETAILED DESCRIPTION

[0042] In order to enable those skilled in the art to better understand the solutions of the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the accompanying drawings in the embodiments of the present invention.

[0043] In some of the processes described in the specification and claims of the present invention and the above-mentioned figures, multiple operations that appear in a specific order are included, but it should be clearly understood that these operations may not be executed in the order in which they appear in this article or executed in parallel. The serial numbers of the operations, such as 101, 102, etc., are only used to distinguish different operations, and the serial numbers themselves do not represent any execution order. In addition, these processes may include more or fewer operations, and these operations may be executed in sequence or in parallel. It should be noted that the descriptions of "first", "second", etc. in this article are used to distinguish different messages, devices, modules, etc., do not represent the order of precedence, and do not limit the "first" and "second" to be different types.

[0044] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative work are within the scope of protection of the present invention.

[0045] Figure 1 The present invention provides a flow chart of a method for constructing a prediction model of the accessory navicular bone. Specifically, the method comprises the following steps:

[0046] 101: Get target sample data

[0047] In some embodiments, the types of samples include normal bones, accessory navicular bones, and 5 samples in each group.

[0048] In some embodiments, the sample data includes transcript sequencing data and proteome sequencing data.

[0049] In a specific embodiment, the sample data is selected from proteome sequencing data.

[0050] 102: Standardize the target sample data and screen for differentially expressed genes / proteins, wherein the differentially expressed genes / proteins include any one or more of the following: P55291, Q9H3S7, P49748, Q9NPH2, Q5KU26

[0051] The specific process of screening differentially expressed genes / proteins is as follows:

[0052] In the process from receiving samples - pre-processing - finally obtaining data, the best experimental methods are selected and quality control work is done at each step to ensure the reliability and accuracy of the data.

[0053] In terms of pretreatment, the whole protein of the sample is first extracted, quantified, quality tested, enzyme digested, TMT labeled, labeling efficiency tested, and the labeled samples are mixed in equal amounts and then desalted. The mass spectrometry raw data is finally obtained through high pH reverse liquid phase separation and mass spectrometry scanning.

[0054] The experimental operation process is as follows: Mascot software is used to search the database of raw data, Scaffold3 software is used for quality control and quantification, statistical analysis is performed to obtain differentially expressed proteins, and bioinformatics analysis is used to further study their functions and involved pathways.

[0055] Quality control: The chromatographic mass spectrometry instrument is precisely constructed. There are many factors that can cause systematic errors in sample collection during use, such as temperature, humidity, and instrument cleanliness. Therefore, ensuring instrument stability is the basis for a successful experiment. The original data was quality controlled and processed by Scaffold Q+ (version 4.5.1). The quality control parameters were: the false discovery rate (FDR) of peptides and proteins was <1.0%, at least one specific peptide was identified for each protein, and the median data was normalized.

[0056] Protein quantification: Protein quantification was performed by two-dimensional liquid chromatography-mass spectrometry.

[0057] PCA analysis: PCA analysis detects differences between experimental groups and repeatability within groups by performing dimensionality reduction analysis on the data. In the PCA two-dimensional graph, the smaller the spatial distribution difference, the closer the data of the two samples are ( Figure 4 ). Each point in the figure represents an experimental sample, and different experimental groups are distinguished by different colors.

[0058] Differential protein analysis: Paired t-test was performed on the protein quantitative data of the two groups of samples F (accessory navicular bone) vs Z (normal bone). The screening criteria for significantly differentially expressed proteins set in this project were: p < 0.05 & (FC < 0.83 or FC > 1.20). The volcano map and heat map of differentially expressed proteins are shown in Figure 2. Figure 5 and Figure 6 shown.

[0059] GO and KEGG enrichment analysis of differentially expressed proteins: using DAVID

[0060] (https: / / david.ncifcrf.gov / tools.jsp) The genes corresponding to the 147 differentially expressed proteins were enriched in biological process (BP), cellular component (CC), molecular function (MF) and KEGG pathway, and the screening standard was Pvalue<0.05. The top 10 enriched GO function items (sorted from large to small according to -LOG10PValue) were plotted ( Figure 7 ). Make a bubble chart of the enriched KEGG pathways (in order of Pvalue from small to large) ( Figure 8 ), the KEGG enrichment degree in the figure is measured by Rich factor, P value and the number of proteins enriched in this pathway. Rich factor refers to the ratio of the number of differentially expressed proteins enriched in the pathway to the number of annotated proteins. The larger the Rich factor, the greater the degree of enrichment. The closer the P value is to zero, the more reliable the enrichment significance of the differentially expressed proteins in the pathway.

[0061] The final differentially expressed proteins screened were: P55291, Q9H3S7, P49748, Q9NPH2, and Q5KU26. The protein expression levels and ROC curves were shown in Figure 2. Fig. 9 and Fig.10 shown.

[0062] 103: Predict the accessory navicular bone based on the differentially expressed genes / proteins obtained through screening to obtain the prediction result of whether the patient has the accessory navicular bone

[0063] In one embodiment, if the expression level of P55291 in the test sample is higher than that of the healthy control, the classification result is obtained that the test sample suffers from accessory navicular bone; if the expression level of P55291 in the test sample is lower than that of the healthy control, the classification result is obtained that the test sample does not suffer from accessory navicular bone.

[0064] In one embodiment, if the expression level of Q9H3S7 in the test sample is higher than that of the healthy control, the classification result is obtained that the test sample suffers from accessory navicular bone; if the expression level of Q9H3S7 in the test sample is lower than that of the healthy control, the classification result is obtained that the test sample does not suffer from accessory navicular bone.

[0065] In one embodiment, if the expression level of P49748 in the test sample is higher than that of the healthy control, the classification result is obtained that the test sample suffers from accessory navicular bone; if the expression level of P49748 in the test sample is lower than that of the healthy control, the classification result is obtained that the test sample does not suffer from accessory navicular bone.

[0066] In one embodiment, if the expression level of Q9NPH2 in the test sample is higher than that of the healthy control, the classification result is obtained that the test sample suffers from accessory navicular bone; if the expression level of Q9NPH2 in the test sample is lower than that of the healthy control, the classification result is obtained that the test sample does not suffer from accessory navicular bone.

[0067] In one embodiment, if the expression level of Q5KU26 in the test sample is higher than that of the healthy control, the classification result is obtained that the test sample suffers from accessory navicular bone; if the expression level of Q5KU26 in the test sample is lower than that of the healthy control, the classification result is obtained that the test sample does not suffer from accessory navicular bone.

[0068] Figure 2 The invention provides a prediction system for accessory navicular bone, the system comprising:

[0069] Data acquisition module 201: Acquire gene / protein data of the sample to be tested

[0070] Classification prediction module 202: Classification prediction is performed based on gene / protein data to obtain a classification result of whether the patient has accessory navicular bone

[0071] Figure 3 The present invention provides a device for predicting accessory navicular bone, the device comprising a memory and a processor;

[0072] The memory is used to store program instructions;

[0073] The processor is used to call program instructions, and when the program instructions are executed, it is used to execute the above method.

[0074] Those skilled in the art can clearly understand that, for the convenience and brevity of description, the specific working processes of the systems, devices and units described above can refer to the corresponding processes in the aforementioned method embodiments and will not be repeated here.

[0075] The present invention provides the use of a reagent for detecting the expression level of a marker in preparing a product for diagnosing accessory navicular bone, wherein the marker comprises any one or more of the following: P55291, Q9H3S7, P49748, Q9NPH2, and Q5KU26.

[0076] The reagents include primers that specifically amplify the marker, probes that specifically recognize the marker, or binding agents that specifically bind to the marker protein.

[0077] In some embodiments, primer and amplification primer are interchangeable, and primer refers to the oligonucleotide that hybridizes with target nucleic acid or its complement and participates in nucleic acid amplification reaction. Amplification primer hybridizes with template nucleic acid, and has 3'-OH (3'-hydroxyl) group that can be extended by polymerization reaction. In some embodiments, amplification primer is 15-60,15-55,15-50,15-45,15-40,15-35,15-30 bases in length. In some embodiments, the length of amplification primer is 18-30 bases. In some embodiments, the length of amplification primer is 18-60 bases, and comprises 18-30 continuous bases (target hybridization region) that hybridize with the corresponding 18-30 nucleotide oligonucleotide hybridization sequences present in the target nucleic acid sequence. In some embodiments, 18-30 continuous bases are at the 3' end of amplification primer.

[0078] In some embodiments, a probe refers to an oligonucleotide capable of hybridizing to a target nucleic acid of interest. One skilled in the art will appreciate that, depending on the stringency of the hybridization conditions, a probe will typically substantially allow a target sequence lacking complete complementarity to form a chemical bond with the probe sequence. The probe may be associated with an appropriate tag or reporter moiety so that the probe (and its target) can be detected, visualized, measured and / or determined.

[0079] The product includes a test kit, a chip or a nucleic acid membrane strip.

[0080] In some embodiments, a test kit refers to any delivery system for delivering materials. In the context of nucleic acid purification systems and reaction assays, such delivery systems include systems that allow storage of reagents and devices (e.g., chaotropic salts, particles, buffers, denaturants, oligonucleotides, filters, etc. in appropriate containers) and / or support materials (e.g., sample processing or sample storage containers, written instructions for executing procedures, etc.), transportation from one location to another or delivery. For example, a test kit includes one or more housings (e.g., boxes) containing relevant reaction reagents and / or support materials.

[0081] In some embodiments, the kit includes a fragmentation kit and a combination kit. A fragmentation kit refers to a delivery system comprising two or more separate containers, each container comprising a sub-portion of all kit components. The containers can be delivered to the intended recipient together or individually. For example, a first container may contain materials and buffer for sample collection, while a second container contains capture oligonucleotides and denaturants. A combination kit refers to a delivery system comprising all components of a reaction assay in a single container (e.g., in a single box containing each required component).

[0082] The kit also includes a detectable label.

[0083] In some embodiments, suitable detectable labels include, but are not limited to, magnetic beads (e.g., Dynabeads™), fluorescent dyes (e.g., fluorescein isothiocyanate, Texas red, rhodamine, green fluorescent protein, red fluorescent protein, yellow fluorescent protein, etc.), radioactive labels (e.g., 3 H, 125 I, 35 S, 14 C, or 32 P), enzymes (e.g., horseradish peroxidase, alkaline phosphatase, luciferase, and others commonly used in enzyme-linked immunosorbent assays (ELISA)), and colorimetric labels such as colloidal gold or colored glass or plastic (e.g., polystyrene, polypropylene, latex, etc.) beads.

[0084] In the several embodiments provided in the present application, it should be understood that the disclosed systems, devices and methods can be implemented in other ways. For example, the device embodiments described above are only schematic. For example, the division of the units is only a logical function division. There may be other division methods in actual implementation, such as multiple units or components can be combined or integrated into another system, or some features can be ignored or not executed. Another point is that the mutual coupling or direct coupling or communication connection shown or discussed can be an indirect coupling or communication connection through some interfaces, devices or units, which can be electrical, mechanical or other forms.

[0085] The units described as separate components may or may not be physically separated, and the components shown as units may or may not be physical units, that is, they may be located in one place or distributed on multiple network units. Some or all of the units may be selected according to actual needs to achieve the purpose of the solution of this embodiment.

[0086] In addition, each functional unit in each embodiment of the present invention may be integrated into one processing unit, or each unit may exist physically separately, or two or more units may be integrated into one unit. The above-mentioned integrated unit may be implemented in the form of hardware or in the form of software functional units.

[0087] A person of ordinary skill in the art can understand that all or part of the steps in the various methods of the above embodiments can be completed by instructing related hardware through a program, and the program can be stored in a computer-readable storage medium, and the storage medium may include: a read-only memory (ROM), a random access memory (RAM), a disk or an optical disk, etc.

[0088] A person skilled in the art can understand that all or part of the steps in the above-mentioned embodiment method can be completed by instructing related hardware through a program, and the program can be stored in a computer-readable storage medium. The above-mentioned storage medium can be a read-only memory, a disk or an optical disk, etc.

[0089] The above is a detailed introduction to a computer device provided by the present invention. For a person skilled in the art, according to the concept of the embodiments of the present invention, there may be changes in the specific implementation method and application scope. In summary, the content of this specification should not be understood as limiting the present invention.

Claims

1. A method for constructing a prediction model for accessory navicular bone, characterized in that: The method comprises: Obtain target sample data; Standardize the target sample data and screen for differentially expressed genes / proteins, wherein the differentially expressed genes / proteins include any one or more of the following: P55291, Q9H3S7, P49748, Q9NPH2, Q5KU26; The accessory navicular bone is predicted based on the differentially expressed genes / proteins obtained by screening, and a prediction result of whether the patient has the accessory navicular bone is obtained.

2. The method according to claim 1, characterized in that: The target sample data is proteome sequencing data; Preferably, the protein is labeled by TMT.

3. The method according to claim 1, characterized in that The screening criteria for the differentially expressed genes / proteins were p<0.05&(FC<0.83 or FC>1.20).

4. A prediction system for accessory navicular bone, characterized in that: The system comprises: Data acquisition module: obtain gene / protein data of the sample to be tested; Classification prediction module: performs classification prediction based on gene / protein data to obtain the classification result of whether the patient has accessory navicular bone; The genes / proteins include any one or more of the following: P55291, Q9H3S7, P49748, Q9NPH2, Q5KU26.

5. A device for predicting accessory navicular bone, characterized in that: The device comprises a memory and a processor; The memory is used to store program instructions; The processor is used to call program instructions, and when the program instructions are executed, it is used to execute the method described in any one of claims 1-3.

6. A computer-readable storage medium having a computer program stored thereon, characterized in that: When the computer program is executed by a processor, the method described in any one of claims 1 to 3 is implemented.

7. A computer program product, comprising a computer program, characterized in that When the computer program is executed by a processor, the method according to any one of claims 1 to 3 is implemented.

8. Use of a reagent for detecting marker expression levels in the preparation of a product for diagnosing accessory navicular bone, wherein the markers include any one or more of the following: P55291, Q9H3S7, P49748, Q9NPH2, Q5KU26.

9. The use according to claim 8, characterized in that: The reagents include primers that specifically amplify the marker, probes that specifically recognize the marker, or binding agents that specifically bind to the marker protein.

10. A product for diagnosing accessory navicular bone, characterized in that: The product includes reagents for detecting marker levels, and the markers include any one or more of the following: P55291, Q9H3S7, P49748, Q9NPH2, Q5KU26; Preferably, the product comprises a kit, a chip or a nucleic acid membrane strip; Preferably, the kit further comprises a detectable reagent; Preferably, the detectable markers include magnetic beads, fluorescent dyes, radioactive markers, enzymes; Preferably, the kit further comprises instructions; Preferably, the kit further comprises a buffer.

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