A computing device, storage medium, and glioma IDH typing detection device and system

Abstract

The present invention discloses a computing device, a storage medium, and a glioma IDH typing detection device and system. The computing device includes a processor and a memory, wherein a program is stored in the memory, and when the processor executes the program, the following is achieved: receiving the mass spectrometry data of the tissue slice of the glioma sample to be detected of the subject; obtaining the hydroxyglutaric acid peak intensity, glutamate peak intensity, and glutamine peak intensity in the mass spectrum of the tissue slice based on the mass spectrometry data, and calculating the ratio of the hydroxyglutaric acid peak intensity to the sum of the hydroxyglutaric acid peak intensity, the glutamate peak intensity, and the glutamine peak intensity; according to the comparison relationship between the ratio of the hydroxyglutaric acid peak intensity to the sum of the hydroxyglutaric acid peak intensity, the glutamate peak intensity, and the glutamine peak intensity and the preset typing value, determining whether the glioma IDH typing of the subject is mutant or wild type.

Description

Technical Field

[0001] The present invention relates to the field of medical clinical detection, and more specifically, to a computing device, a storage medium, and a glioma IDH typing detection device and system. Background Art

[0002] In the early stages of glioma formation, there are two possible mutations of isocitrate dehydrogenase (IDH), IDH1 and IDH2. IDH mutations are common in glioma cases, so the detection of IDH mutations has become one of the important indicators for diagnosing gliomas and guiding their medication.

[0003] At present, the clinical diagnosis of IDH mutation is mainly evaluated by whole genome extraction and sequencing and immunohistochemistry methods that capture antibodies against IDH mutant proteins. Among them, in the standard process of clinical testing, immunohistochemistry is first used for diagnosis. If the result is positive, it is confirmed as IDH mutation. When the result is negative, it will be accompanied by further sequencing. Therefore, there are certain difficulties in both experimental time consumption and diagnostic accuracy. In particular, immunohistochemistry and sequencing cannot assist in intraoperative pathological diagnosis due to their time-consuming and complex experiments. Therefore, there are obvious technical limitations in intraoperative resection and timely medication guidance after surgery.

[0004] MALDI-TOF mass spectrometry has been confirmed to have accurate detection capabilities in detecting biological target markers in a variety of tumors, and the development of its potential applications has therefore received more and more attention in the field of tumor research. In recent years, 2-HG (hydroxyglutarate) has also received increasing attention as a biological target marker for diagnosing glioma mutations. 2-HG is one of the metabolites of glioma metabolic changes caused by IDH enzymes produced by IDH mutations. Its accumulation in gliomas has been shown to be accurately detected by MALDI-TOF mass spectrometry and its mass spectrometry imaging technology, helping to diagnose the type of IDH mutation in gliomas. Summary of the invention

[0005] An object of the present invention is to provide a computing device, a storage medium, and a glioma IDH typing detection device and system.

[0006] In order to achieve the above object, the present invention adopts the following technical solutions:

[0007] The first aspect of the present invention relates to a method for detecting IDH typing of glioma, comprising:

[0008] Receiving mass spectrometry data of a tissue section of a glioma sample to be tested from a subject;

[0009] Obtaining the hydroxyglutaric acid peak intensity, the glutamate peak intensity and the glutamine peak intensity in the mass spectrum of the tissue section based on the mass spectrometry data, and calculating the ratio of the hydroxyglutaric acid peak intensity to the sum of the hydroxyglutaric acid peak intensity, the glutamate peak intensity and the glutamine peak intensity;

[0010] Based on the comparison relationship between the ratio of the hydroxyglutaric acid peak intensity to the sum of the hydroxyglutaric acid peak intensity, the glutamate peak intensity and the glutamine peak intensity and the preset typing value, it is determined that the IDH typing of the glioma of the subject is mutant or wild type.

[0011] Optionally, determining whether the subject's glioma IDH typing is mutant or wild type based on a comparison relationship between the ratio of the hydroxyglutaric acid peak intensity to the sum of the hydroxyglutaric acid peak intensity, the glutamate peak intensity and the glutamine peak intensity and a preset typing value includes:

[0012] If the ratio of the peak intensity of hydroxyglutaric acid to the sum of the peak intensity of hydroxyglutaric acid, the peak intensity of glutamate and the peak intensity of glutamine is greater than the preset typing value, the IDH typing of the glioma of the subject is determined to be mutant type; if the ratio of the peak intensity of hydroxyglutaric acid to the sum of the peak intensity of hydroxyglutaric acid, the peak intensity of glutamate and the peak intensity of glutamine is less than the preset typing value, the IDH typing of the glioma of the subject is determined to be wild type.

[0013] Optionally, the preset typing value is 0.141069046504922.

[0014] Optionally, before receiving the tissue section mass spectrometry data of the glioma sample to be detected of the subject, the method further includes:

[0015] preparing tissue sections of glioma samples to be tested from the subject;

[0016] Using a sprayer, the tissue sections of the glioma samples to be tested of the subject are sprayed with matrix;

[0017] The tissue slices of the glioma sample to be detected after the matrix is ​​sprayed are collected by using a mass spectrometer to obtain the mass spectrum data of the tissue slices of the glioma sample to be detected.

[0018] A second aspect of the present invention relates to a computing device, comprising a processor and a memory, wherein a program is stored in the memory, and when the processor executes the program, the following is achieved:

[0019] Receiving mass spectrometry data of a tissue section of a glioma sample to be tested from a subject;

[0020] Obtaining the hydroxyglutaric acid peak intensity, the glutamate peak intensity and the glutamine peak intensity in the mass spectrum of the tissue section based on the mass spectrometry data, and calculating the ratio of the hydroxyglutaric acid peak intensity to the sum of the hydroxyglutaric acid peak intensity, the glutamate peak intensity and the glutamine peak intensity;

[0021] Based on the comparison relationship between the ratio of the hydroxyglutaric acid peak intensity to the sum of the hydroxyglutaric acid peak intensity, the glutamate peak intensity and the glutamine peak intensity and the preset typing value, it is determined that the IDH typing of the glioma of the subject is mutant or wild type.

[0022] Optionally, determining whether the subject's glioma IDH typing is mutant or wild type based on a comparison relationship between the ratio of the hydroxyglutaric acid peak intensity to the sum of the hydroxyglutaric acid peak intensity, the glutamate peak intensity and the glutamine peak intensity and a preset typing value includes:

[0023] If the ratio of the peak intensity of hydroxyglutaric acid to the sum of the peak intensity of hydroxyglutaric acid, the peak intensity of glutamate and the peak intensity of glutamine is greater than the preset typing value, the IDH typing of the glioma of the subject is determined to be mutant type; if the ratio of the peak intensity of hydroxyglutaric acid to the sum of the peak intensity of hydroxyglutaric acid, the peak intensity of glutamate and the peak intensity of glutamine is less than the preset typing value, the IDH typing of the glioma of the subject is determined to be wild type.

[0024] Optionally, the preset typing value is 0.141069046504922.

[0025] A third aspect of the present invention relates to a storage medium storing a program, wherein when the program is executed, the following is achieved:

[0026] Receiving mass spectrometry data of a tissue section of a glioma sample to be tested from a subject;

[0027] Obtaining the hydroxyglutaric acid peak intensity, the glutamate peak intensity and the glutamine peak intensity in the mass spectrum of the tissue section based on the mass spectrometry data, and calculating the ratio of the hydroxyglutaric acid peak intensity to the sum of the hydroxyglutaric acid peak intensity, the glutamate peak intensity and the glutamine peak intensity;

[0028] Based on the comparison relationship between the ratio of the hydroxyglutaric acid peak intensity to the sum of the hydroxyglutaric acid peak intensity, the glutamate peak intensity and the glutamine peak intensity and the preset typing value, it is determined that the IDH typing of the glioma of the subject is mutant or wild type.

[0029] Optionally, determining whether the subject's glioma IDH typing is mutant or wild type based on a comparison relationship between the ratio of the hydroxyglutaric acid peak intensity to the sum of the hydroxyglutaric acid peak intensity, the glutamate peak intensity and the glutamine peak intensity and a preset typing value includes:

[0030] If the ratio of the peak intensity of hydroxyglutaric acid to the sum of the peak intensity of hydroxyglutaric acid, the peak intensity of glutamate and the peak intensity of glutamine is greater than the preset typing value, the IDH typing of the glioma of the subject is determined to be mutant type; if the ratio of the peak intensity of hydroxyglutaric acid to the sum of the peak intensity of hydroxyglutaric acid, the peak intensity of glutamate and the peak intensity of glutamine is less than the preset typing value, the IDH typing of the glioma of the subject is determined to be wild type.

[0031] Optionally, the preset typing value is 0.141069046504922.

[0032] The fourth aspect of the present invention relates to a glioma IDH typing detection device, comprising:

[0033] A spraying device is used to spray and cover the tissue sections of the glioma samples to be tested of the subject with the matrix;

[0034] A mass spectrometer is used to collect tissue slices of the glioma sample to be detected after the matrix is ​​sprayed, so as to obtain mass spectrum data of the tissue slices of the glioma sample to be detected; and

[0035] The computing device described in the second aspect of the present invention.

[0036] The fifth aspect of the present invention relates to a glioma IDH typing detection system, comprising

[0037] The device of the fourth aspect of the present invention;

[0038] A display is used to display the determination result.

[0039] Optionally, the sprayer is a HTX sprayer.

[0040] Optionally, the mass spectrometer is a QuanTOF II MALDI-TOF mass spectrometer.

[0041] The beneficial effects of the present invention are as follows:

[0042] The present invention uses a sprayer to spray a mixed matrix on the tissue slice of the glioma sample to be detected, collects the mass spectrum data of the tissue slice of the glioma sample to be detected by a mass spectrometer, and calculates the ratio of the hydroxyglutaric acid peak intensity to the sum of the hydroxyglutaric acid peak intensity, the glutamate peak intensity and the glutamine peak intensity in the mass spectrum result in combination with the software, and successfully achieves efficient and accurate differentiation of IDH mutants and wild types by comparing the ratio with the size of the preset typing value. Therefore, the present invention is superior to the existing technology of second-generation gene sequencing (Next Generation Sequencing, referred to as NGS) and immunohistochemistry (Immunohistochemistry, referred to as IHC) detection in multiple angles in terms of detection time, personnel consumption, materials and costs. The entire experiment time can be controlled to give an experimental conclusion within just one hour, and the pathological IDH typing of the tissue slice is judged. Each step of the experiment has a simple experimental step operation, and the acquisition speed and analysis can be fully automatic. In addition, the material consumption is only ITO glass slides, chemical matrix, and isotope internal standards after dilution, which greatly saves the cost of the experiment; the sample itself does not need to consume a large amount of tissue, only a single sample with a thickness of 10-12 microns is needed to provide the current molecular distribution intensity information of the complete slice. The typing interpretation is highly accurate. All interpretation results have complete spectrum data and imaging data traceability, and the same sample supports multiple acquisitions, which can be used for repeated verification of data. BRIEF DESCRIPTION OF THE DRAWINGS

[0043] The specific implementation modes of the present invention are further described in detail below in conjunction with the accompanying drawings.

[0044] Figure 1 A flow chart of the glioma IDH typing detection method provided in an embodiment of the present invention is shown.

[0045] Figure 2 A schematic diagram of imaging data from one of the 111 real patient samples is shown.

[0046] Figure 3 Show corresponding Figure 2 Schematic diagram of the peak intensities corresponding to hydroxyglutarate (2-HG), glutamate (Glu), and glutamine (Gln) in the imaging data.

[0047] Figure 4 A schematic diagram of imaging data from another sample of 111 real patients is shown.

[0048] Figure 5 Show corresponding Figure 4 Schematic diagram of the peak intensities corresponding to 2-HG, Glu, and Gln in the imaging data.

[0049] Figure 6The following is a schematic diagram of the CV verification results based on ratio calculation using slice data of 111 real patients as independent samples.

[0050] Figure 7 The ROC diagram of the ratio calculation using the detection method provided by the present invention is shown in the formula.

[0051] Figure 8 The following is a diagram of a computer system architecture suitable for implementing the detection method according to an embodiment of the present invention. DETAILED DESCRIPTION

[0052] In order to more clearly illustrate the present invention, the present invention is further described below in conjunction with preferred embodiments and accompanying drawings. Similar components in the accompanying drawings are represented by the same reference numerals. It should be understood by those skilled in the art that the content specifically described below is illustrative rather than restrictive, and should not be used to limit the scope of protection of the present invention.

[0053] In the early stages of glioma formation, there are two possible mutant forms of isocitrate dehydrogenase (IDH), IDH1 and IDH2. Among them, IDH mutations are common in glioma cases, so the detection of IDH mutations has become a common method for diagnosing gliomas. At present, the clinical diagnosis of IDH mutations is mainly evaluated by whole genome extraction and sequencing and immunohistochemistry methods for antibody capture of IDH mutant proteins. Among them, in the standard process of clinical testing, immunohistochemistry is first used for diagnosis. If the result is positive, it is confirmed to be an IDH mutation. When the result is negative, it will be accompanied by further sequencing judgment. Therefore, there are certain difficulties in both experimental time consumption and diagnostic accuracy. In particular, immunohistochemistry and sequencing cannot assist in intraoperative pathological diagnosis due to their time-consuming and complex experiments. Therefore, there are obvious limitations in intraoperative resection and timely medication guidance after surgery.

[0054] MALDI-TOF mass spectrometry has been confirmed to have accurate detection capabilities in detecting biological target markers in a variety of tumors, and the development of its potential applications has therefore received more and more attention in the field of tumor research. In recent years, 2-HG (hydroxyglutarate) has also received increasing attention as a biological target marker for diagnosing glioma mutations. 2-HG is one of the metabolites of glioma metabolic changes caused by IDH enzymes produced by IDH mutations. Its accumulation in gliomas has been shown to be accurately detected by MALDI-TOF mass spectrometry and its mass spectrometry imaging technology, helping to diagnose the type of IDH mutation in gliomas.

[0055] The inventors found that by performing qualitative ratio calculations for glioma IDH typing based on target small molecule metabolites such as 2-HG and amino acids with similar mass, efficient and accurate differentiation between IDH mutants and wild types can be achieved.

[0056] Therefore, if Figure 1 As shown, an embodiment of the present invention provides a glioma IDH typing detection method, comprising:

[0057] S101, receiving mass spectrometry data of a tissue section of a glioma sample to be detected from a subject;

[0058] S103, obtaining the hydroxyglutaric acid peak intensity, the glutamate peak intensity and the glutamine peak intensity in the mass spectrum result of the tissue section based on the mass spectrometry data, and calculating the ratio of the hydroxyglutaric acid peak intensity to the sum of the hydroxyglutaric acid peak intensity, the glutamate peak intensity and the glutamine peak intensity;

[0059] S105. Determine whether the IDH typing of the subject's glioma is mutant or wild type based on the comparison relationship between the ratio of the hydroxyglutaric acid peak intensity to the sum of the hydroxyglutaric acid peak intensity, the glutamate peak intensity and the glutamine peak intensity and a preset typing value.

[0060] Optionally, determining whether the subject's glioma IDH typing is mutant or wild type based on a comparison relationship between the ratio of the hydroxyglutaric acid peak intensity to the sum of the hydroxyglutaric acid peak intensity, the glutamate peak intensity and the glutamine peak intensity and a preset typing value includes:

[0061] If the ratio of the peak intensity of hydroxyglutaric acid to the sum of the peak intensity of hydroxyglutaric acid, the peak intensity of glutamate and the peak intensity of glutamine is greater than the preset typing value, the IDH typing of the glioma of the subject is determined to be mutant type; if the ratio of the peak intensity of hydroxyglutaric acid to the sum of the peak intensity of hydroxyglutaric acid, the peak intensity of glutamate and the peak intensity of glutamine is less than the preset typing value, the IDH typing of the glioma of the subject is determined to be wild type.

[0062] Optionally, the preset typing value is 0.141069046504922.

[0063] Optionally, before receiving the tissue section mass spectrometry data of the glioma sample to be detected of the subject, the method further includes:

[0064] preparing tissue sections of glioma samples to be tested from the subject;

[0065] Using a sprayer, the tissue sections of the glioma samples to be tested of the subject are sprayed with matrix;

[0066] The tissue slices of the glioma sample to be detected after the matrix is ​​sprayed are collected by using a mass spectrometer to obtain the mass spectrum data of the tissue slices of the glioma sample to be detected.

[0067] In a specific example, the glioma sample to be detected of the subject of the present invention is obtained during surgery, and the specific operation process of the glioma IDH typing detection method provided by the embodiment of the present invention is as follows:

[0068] (1) Intraoperative sampling: Glioma samples were removed during clinical glioma resection surgery;

[0069] (2) Cryosectioning: The glioma samples removed during surgery are quickly frozen in liquid nitrogen, and then the tissue is frozen and sectioned using a cryostat, such as a Leica cryostat, with a slice thickness of 10-12 μm. The slicing temperature in the cryostat is -20°C to -22°C. It is recommended to slice the middle of the tissue to ensure the comprehensiveness of the tissue as much as possible. The cut tissue is attached to an ITO glass slide;

[0070] (3) Vacuum drying: Use a vacuum drying oven to quickly vacuum dry the ITO glass slide with tissue attached for 5 minutes at a pressure of >15 psi;

[0071] (4) Matrix spraying:

[0072] Matrix preparation: NEDC (N-(1-naphthyl)ethylenediamine dihydrochloride) was placed in a solution of methanol: water = 70%:30% (v:v), with a ratio of 10 mg / mL NEDC, and the internal standard was used 13 C5 isotope labeled 2-HG is added to the prepared matrix. 13 The concentration of C5-2-HG was 500 pmol / μL;

[0073] Spraying with a sprayer: The dried ITO glass slide with tissue attached was covered with matrix spraying using a sprayer. The sprayer used was a HTX TM-Sprayer (HTX Imaging Technologies) mass spectrometer. The experimental parameters were set as follows: liquid flow rate 0.07 mL / min, spraying layer number (passes) 10 layers, spraying temperature 75 degrees Celsius, nitrogen pressure 10 psi; drying time 3 seconds, moving speed 1000 mm / min;

[0074] (5) Mass spectrometer acquisition: A mass spectrometer is used to acquire the tissue slices of the glioma sample to be detected after the matrix is ​​sprayed, and the mass spectrometry data of the tissue slices of the glioma sample to be detected is obtained. The mass spectrometer is a QuanTOF II MALDI-TOF mass spectrometer, and its parameters are set as follows: acquisition mode: linear negative ion mode (Linear Negative Ion Mode), spatial resolution: 50 μm2 , Focus quality: 140 m / z, laser frequency: 5,000 Hz, mass range: 50 - 1,000 m / z, acceleration voltage: 10 kV, detection voltage: -0.8 kV, laser energy: 12 μJ, laser diameter: 10 μm, number of laser bombardments per single spectrum: 50 shots;

[0075] (6) Computational device analysis:

[0076] Spectrum adjustment and imaging:

[0077] The mass spectrometry data after acquisition is opened using the analysis software QuanViewer of the computational device. After data baseline calibration and internal standard mass calibration, one - key imaging is performed. Select the region within the tissue section to view the calculation result of the ratio of the peak intensity of hydroxyglutaric acid to the sum of the peak intensities of hydroxyglutaric acid, glutamic acid, and glutamine. Compare with the established standard typing cut - off value (i.e., the preset typing value) to obtain the IDH typing result of the glioma of the subject based on relative quantification, that is, mutant or wild type.

[0078] In a specific example, the accuracy of baseline correction is 10. After automatic internal calibration, the imaging quality of the internal standard 13 C5 - 2 - HG (M - H + ) is 151.35 m / z. Using the internal standard as mass calibration, the imaging quality of the target metabolite hydroxyglutaric acid 2 - HG (M - H + ) is 147.00 m / z, with an error within plus or minus 0.5 Da. The imaging quality of glutamine Gln (M - H + ) is 145.15 m / z, with an error within plus or minus 0.5 Da. The imaging quality of glutamic acid Glu (M - H + ) is 146.13 m / z, with an error within plus or minus 0.5 Da.

[0079] Ratio operation:

[0080] Perform ratio operation on the peak intensities: Compare the ratio of the peak intensity of 2 - HG to the peak intensity of (2 - HG + Gln + Glu) with the cut - off value to determine its IDH typing. If the ratio of the peak intensity of 2 - HG to the peak intensity of (2 - HG + Gln + Glu) > cut - off value, the result is mutant; if the ratio of the peak intensity of 2 - HG to the peak intensity of (2 - HG + Gln + Glu) < cut - off value, the result is wild type, where the cut - off value is calculated from the ROC curve and its KS statistics of hundreds of real and independent glioma samples.

[0081] Next, verify this statistical law.

[0082] In a specific example, NGS is the current gold standard for IDH typing in clinical molecular diagnosis. Therefore, the inventors compared and verified the results obtained by the detection method provided by the present invention with the results of the existing NGS method for 111 independent samples (from 42 real patients) with NGS results.

[0083] Using the detection method provided by the present invention, 2-HG can be detected in samples of 111 real patients, and Glu and Gln have clear peaks. Figure 2-5 The following are the imaging data of 2 patients among 111 real patients and the corresponding peak intensity maps of 2-HG, Gln and Glu.

[0084] The slice data of 111 real patients were regarded as independent samples for CV verification based on ratio calculation, such as Figure 6 As shown, the probability of CV>0.1 of the collated data is 9.17%, that is, the detection method provided by the present invention has a low degree of computational discreteness.

[0085] The consistency was calculated by combining all the results, kappa = 0.92695652, indicating that the detection method provided by the present invention has a high consistency with the NGS method.

[0086] Combining all samples to analyze the ratio of the hydroxyglutaric acid peak intensity to the sum of the hydroxyglutaric acid peak intensity, the glutamate peak intensity and the glutamine peak intensity, it was found that there was a clear cut-off value boundary between the mutant and the wild type, such as Figure 7 As shown, the ROC result can determine the significant relationship between the mutant and the wild type, and obtain AUC=0.954, CI=95%, cut-off=0.141069046504922.

[0087] The present invention uses a sprayer to spray a mixed matrix on the tissue slice of the glioma sample to be detected, collects the mass spectrometry data of the tissue slice of the glioma sample to be detected by a mass spectrometer, and calculates the ratio of the peak intensity of hydroxyglutaric acid to the sum of the peak intensity of hydroxyglutaric acid, the peak intensity of glutamate, and the peak intensity of glutamine in the mass spectrum result in combination with the software, and successfully achieves efficient and accurate distinction between IDH mutants and wild types by comparing the ratio with the size of the preset typing value. Thus, the present invention achieves NGS and IHC detection that is superior to the prior art in terms of detection time, personnel consumption, materials and cost. The entire experiment time can be controlled to give an experimental conclusion within just one hour, and the pathological IDH typing of the tissue slice can be judged. Each step of the experiment has a simple and mature experimental step operation, and the collection and analysis can be fully automatic. In addition, the material consumption is only ITO glass slides, chemical matrices, and isotope internal standards after dilution ratios, which greatly saves the cost of the experiment; the sample itself does not need to consume a large amount of tissue, and only a single sample with a thickness of 10-12 microns is needed to give the current molecular distribution intensity information of the complete slice. High accuracy of typing interpretation All interpretation results have complete spectrum data and imaging data traceability, and the same sample supports multiple acquisitions, which can be used for repeated verification of data.

[0088] The present invention provides a computing device, comprising a processor, wherein when the processor executes a program, Figure 1 The method steps are shown.

[0089] In a specific example, if Figure 8 As shown, a computer system suitable for implementing the glioma IDH typing detection method provided in this embodiment includes a central processing module (CPU), which can be based on a program stored in a read-only memory (ROM) or a program loaded from a storage portion into a random access memory (RAM), the program, for example, implementing an application program of the present application recruitment method or executing the method when executing a program. The CPU, ROM, and RAM are connected to each other via a bus. An input / output (I / O) interface is also connected to the bus.

[0090] The following components are connected to the I / O interface: an input part including a keyboard, a mouse, etc.; an output part including a liquid crystal display (LCD), etc. and a speaker, etc.; a storage part including a hard disk, etc.; and a communication part including a network interface card such as a LAN card, a modem, etc. The communication part performs communication processing via a network such as the Internet. A drive is also connected to the I / O interface as needed. Removable media, such as a magnetic disk, an optical disk, a magneto-optical disk, a semiconductor memory, etc., are installed on the drive as needed so that the computer program read therefrom is installed into the storage part as needed.

[0091] In particular, according to this embodiment, the process described in the flowchart above can be implemented as a computer software program. For example, this embodiment includes a computer program product, which includes a computer program tangibly contained on a computer-readable medium, and the computer program includes program code for executing the method shown in the flowchart. In such an embodiment, the computer program can be downloaded and installed from a network through a communication part, and / or installed from a removable medium.

[0092] The flow chart and schematic diagram in the accompanying drawings illustrate the possible architecture, function and operation of the system, method and computer program product of the present embodiment. In this regard, each square box in the flow chart or schematic diagram can represent a part of a module, program segment or code, and a part of the above-mentioned module, program segment or code contains one or more executable instructions for realizing the specified logical function. It should also be noted that in some alternative implementations, the functions marked in the square box can also occur in a sequence different from that marked in the accompanying drawings. For example, two square boxes represented in succession can actually be executed substantially in parallel, and they can sometimes be executed in the opposite order, depending on the functions involved. It should also be noted that each square box in the schematic diagram and / or flow chart, and the combination of the square boxes in the schematic diagram and / or flow chart can be implemented with a dedicated hardware-based system that performs a specified function or operation, or can be implemented with a combination of dedicated hardware and computer instructions.

[0093] The modules involved in the description of this embodiment may be implemented by software and may also be arranged in a processor.

[0094] As another aspect, the present embodiment further provides a non-volatile computer storage medium, which may be the non-volatile computer storage medium contained in the above-mentioned device in the above-mentioned embodiment, or may be a non-volatile computer storage medium that exists independently and is not assembled in the terminal. The above-mentioned non-volatile computer storage medium stores one or more programs, and when the above-mentioned one or more programs are executed by a device, the above-mentioned device executes the glioma IDH typing detection method of the present application.

[0095] The present invention also provides a glioma IDH typing detection device, comprising

[0096] A spraying device is used to spray and cover the tissue sections of the glioma samples to be tested of the subject with the matrix;

[0097] A mass spectrometer is used to collect tissue slices of the glioma sample to be detected after the matrix is ​​sprayed to obtain mass spectrum data of the tissue slices of the glioma sample to be detected; and the above-mentioned computing device.

[0098] The present invention also provides a glioma IDH typing detection system, comprising

[0099] The above-mentioned glioma IDH typing detection device; and

[0100] A display is used to display the determination result.

[0101] Specifically, the result report is displayed as, for example, "mutant type" and "wild type".

[0102] Optionally, the sprayer is a HTX sprayer.

[0103] Optionally, the mass spectrometer is a QuanTOF II MALDI-TOF mass spectrometer.

[0104] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not limitations on the implementation methods of the present invention. For ordinary technicians in the relevant field, other different forms of changes or modifications can be made based on the above description. It is impossible to list all the implementation methods here. All obvious changes or modifications derived from the technical solution of the present invention are still within the protection scope of the present invention.

Claims

1. A computing device, comprising a processor and a memory, wherein a program is stored in the memory, characterized in that: When the processor executes the program, the following is achieved: Receiving mass spectrometry data of a tissue section of a glioma sample to be tested from a subject; The mass spectrometer is used to collect the mass spectrometry data of the tissue slice of the glioma sample to be detected, and the mass spectrometry data is calibrated by the computing device to perform the limit calibration and the internal standard mass calibration to obtain the mass spectrum; Obtaining the hydroxyglutaric acid peak intensity, the glutamate peak intensity and the glutamine peak intensity in the mass spectrum of the tissue section based on the mass spectrometry data, and calculating the ratio of the hydroxyglutaric acid peak intensity to the sum of the hydroxyglutaric acid peak intensity, the glutamate peak intensity and the glutamine peak intensity; According to the comparison relationship between the ratio of the hydroxyglutaric acid peak intensity to the sum of the hydroxyglutaric acid peak intensity, the glutamate peak intensity and the glutamine peak intensity and the preset typing value, determining whether the IDH typing of the glioma of the subject is mutant or wild type; The determining whether the subject's glioma IDH typing is mutant or wild type according to the comparison relationship between the ratio of the hydroxyglutaric acid peak intensity to the sum of the hydroxyglutaric acid peak intensity, the glutamate peak intensity and the glutamine peak intensity and the preset typing value comprises: If the ratio of the peak intensity of hydroxyglutaric acid to the sum of the peak intensity of hydroxyglutaric acid, the peak intensity of glutamate and the peak intensity of glutamine is greater than the preset typing value, the IDH typing of the glioma of the subject is determined to be mutant type; if the ratio of the peak intensity of hydroxyglutaric acid to the sum of the peak intensity of hydroxyglutaric acid, the peak intensity of glutamate and the peak intensity of glutamine is less than the preset typing value, the IDH typing of the glioma of the subject is determined to be wild type.

2. The computing device according to claim 1, wherein: The preset classification value is 0.141069046504922.

3. A storage medium storing a program, characterized in that: When the program is executed, it achieves: Receiving mass spectrometry data of a tissue section of a glioma sample to be tested from a subject; The mass spectrometer is used to collect the mass spectrometry data of the tissue slice of the glioma sample to be detected, and the mass spectrometry data is calibrated by the computing device to perform the limit calibration and the internal standard mass calibration to obtain the mass spectrum; Obtaining the hydroxyglutaric acid peak intensity, the glutamate peak intensity and the glutamine peak intensity in the mass spectrum of the tissue section based on the mass spectrometry data, and calculating the ratio of the hydroxyglutaric acid peak intensity to the sum of the hydroxyglutaric acid peak intensity, the glutamate peak intensity and the glutamine peak intensity; According to the comparison relationship between the ratio of the hydroxyglutaric acid peak intensity to the sum of the hydroxyglutaric acid peak intensity, the glutamate peak intensity and the glutamine peak intensity and the preset typing value, determining whether the IDH typing of the glioma of the subject is mutant or wild type; The determining whether the subject's glioma IDH typing is mutant or wild type according to the comparison relationship between the ratio of the hydroxyglutaric acid peak intensity to the sum of the hydroxyglutaric acid peak intensity, the glutamate peak intensity and the glutamine peak intensity and the preset typing value comprises: If the ratio of the peak intensity of hydroxyglutaric acid to the sum of the peak intensity of hydroxyglutaric acid, the peak intensity of glutamate and the peak intensity of glutamine is greater than the preset typing value, the IDH typing of the glioma of the subject is determined to be mutant type; if the ratio of the peak intensity of hydroxyglutaric acid to the sum of the peak intensity of hydroxyglutaric acid, the peak intensity of glutamate and the peak intensity of glutamine is less than the preset typing value, the IDH typing of the glioma of the subject is determined to be wild type.

4. The storage medium according to claim 3, characterized in that The preset classification value is 0.141069046504922.

5. A glioma IDH typing detection device, characterized in that: include: A spraying device is used to spray and cover the tissue sections of the glioma samples to be tested of the subject with the matrix; A mass spectrometer is used to collect tissue slices of the glioma sample to be detected after the matrix is ​​sprayed, so as to obtain mass spectrum data of the tissue slices of the glioma sample to be detected; as well as A computing device as claimed in claim 1 or 2.

6. A glioma IDH typing detection system, characterized in that: include The device according to claim 5; A display is used to display the determination result.

7. The system according to claim 6, characterized in that The sprayer is a HTX sprayer.

8. The system according to claim 6, characterized in that The mass spectrometer is a QuanTOF IMALDDI-TOF mass spectrometer.

Images