Analysis device, mass spectrometry device, analysis method, and computer-readable medium

Abstract

An analysis device for data obtained by mass spectrometry includes: an information acquisition unit that acquires detection information indicating peptides detected by subjecting a sample to a cutting process and then subjecting the sample to mass spectrometry; and an information generation unit that generates allergen information related to the allergen contained in the sample based on the detection information and data indicating peptides generated when each allergen is subjected to the cutting process. When a plurality of peptides generated from one allergen among the above data are detected, the information generation unit generates allergen information based on the combination of the plurality of peptides.

Description

Technical Field

[0001] The present invention relates to an analysis device for data obtained by mass spectrometry, a mass spectrometry device, an analysis method for data obtained by mass spectrometry, and a computer-readable medium (Non-transitory computer readable medium; non-transitory computer readable medium) storing an analysis program. Background Art

[0002] In order to prevent the onset of allergies or identify substances that cause allergies when they occur, allergens are detected from food and beverages, the environment, etc. In Patent Document 1, the following is reported: An allergen is decomposed by trypsin, and the resulting allergen-derived peptide is subjected to liquid chromatography / mass spectrometry (Liquid Chromatography / Mass Spectrometry; LC / MS), thereby detecting the allergen contained in the sample.

[0003] Prior Art Documents

[0004] Patent Documents

[0005] Patent Document 1: International Publication No. 2013 / 033713 Summary of the Invention

[0006] Problems to be Solved by the Invention

[0007] It is desired to accurately derive the allergen contained in the sample based on the detected allergen-derived peptide.

[0008] Solutions to the Problems

[0009] A first aspect of the present invention relates to an analysis device for data obtained by mass spectrometry, comprising: an information acquisition unit that acquires detection information indicating a peptide detected by subjecting a sample to a cleavage process and then to mass spectrometry; and an information generation unit that generates allergen information related to the allergen contained in the sample based on the detection information and data indicating the peptides generated when each allergen is subjected to the cleavage process, wherein, when a plurality of peptides generated from one allergen in the data are detected, the information generation unit generates the allergen information based on a combination of the plurality of peptides.

[0010] A second aspect of the present invention relates to a mass spectrometry device comprising the analysis device for data obtained by mass spectrometry according to the first aspect.

[0011] A third aspect of the present invention relates to a method for analyzing data obtained by mass spectrometry, including the following processes: obtaining detection information representing peptides detected by subjecting a sample to a cutting process and then to mass spectrometry; and generating allergen information related to the allergen contained in the sample based on the detection information and data representing peptides generated when each allergen is subjected to the cutting process, wherein, when multiple peptides generated by one allergen in the data are detected, the allergen information is generated based on the combination of the multiple peptides.

[0012] A fourth aspect of the present invention relates to a computer-readable medium storing an analysis program for causing a computer to execute the following processes: an information acquisition process of obtaining detection information representing peptides detected by subjecting a sample to a cutting process and then to mass spectrometry; and an information generation process of generating allergen information related to the allergen contained in the sample based on the detection information and data representing peptides generated when each allergen is subjected to the cutting process, wherein, in the information generation process, when multiple peptides generated by one allergen in the data are detected, the allergen information is generated based on the combination of the multiple peptides.

[0013] Effects of the Invention

[0014] According to the present invention, it is possible to accurately derive the allergen contained in the sample based on the detected allergen-derived peptides. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 is a conceptual diagram showing the structure of a mass spectrometry device according to an embodiment.

[0016] Figure 2 is a conceptual diagram showing the information processing unit of the mass spectrometry device.

[0017] Figure 3 is a table showing reference data.

[0018] Figure 4 is a flowchart showing the flow of a method for analyzing data obtained by mass spectrometry according to an embodiment.

[0019] Figure 5 is a conceptual diagram for explaining the provision of a program. DETAILED DESCRIPTION OF THE INVENTION

[0020] Hereinafter, modes for implementing the present invention will be described with reference to the drawings.

[0021] - Embodiment -

[0022] In the present embodiment, a sample is provided for mass spectrometry after being subjected to a cleavage treatment, and allergen information related to the allergen contained in the sample is generated based on the peptides detected by the mass spectrometry. Hereinafter, this information will be referred to as allergen information.

[0023] Hereinafter, a molecule that causes allergy will be referred to as an allergenic molecule, a substance such as food or beverage containing the allergenic molecule will be referred to as an allergenic substance, and the allergenic molecule and the allergenic substance will be referred to as an allergen. For example, milk as an allergenic substance contains casein and lactoglobulin as allergenic molecules. Eggs as an allergenic substance contain ovalbumin and lysozyme as allergenic molecules. In addition, a peptide contains a peptide backbone composed of multiple amino acids bonded by peptide bonds, and may also contain a modifying group or the like if it can be detected by mass spectrometry.

[0024] (Regarding the sample)

[0025] The sample only needs to contain or possibly contain an allergen, and is not particularly limited. The sample can be, for example, a food or beverage whose allergen content is unknown. In this case, by the mass spectrometry method according to the present embodiment, it is possible to identify which allergen is contained in the food or beverage. If the food or beverage ingested by a patient suffering from an allergic reaction or the vomit of the patient is used as the sample, information related to the allergen that causes the allergic reaction can be obtained, which is helpful for determining or studying the treatment policy. Alternatively, the sample can also be a food or beverage known to contain an allergen, and the allergen contained in the food or beverage can be confirmed or the like. If an allergenic molecule can be detected by mass spectrometry, the sample can contain any substance such as pollen, house dust, or mites in addition to being a food or beverage. Hereinafter, it is assumed that the allergenic molecule in the target allergen contains a protein.

[0026] (Preparation of the sample for analysis)

[0027] An enzyme for decomposing proteins is added to the prepared sample, and the allergen is subjected to a cleavage treatment. A variety of peptides derived from the allergen are generated by the cleavage of the allergenic molecule by the enzyme. The enzyme used in the cleavage treatment only needs to have specificity for the cleavage site for protein cleavage, and is not particularly limited, but trypsin or Lys-C is preferred. The cleavage site of trypsin includes the cleavage site of Lys-C. Therefore, by adding both trypsin and Lys-C to the sample, the decomposition of the allergen can be more reliably performed by the sequence specificity of the cleavage by trypsin. The allergenic molecule contained in the sample can also be cleaved by chemical cleavage instead of enzymatic cleavage. Hereinafter, the peptide generated by the cleavage treatment of the allergen will be referred to as an allergen-derived peptide.

[0028] If a test sample is provided for cutting treatment, an analysis test sample is prepared from the test sample containing the allergen-derived peptide. The analysis test sample can be prepared by pre-treatment corresponding to the type of analysis performed on the test sample, such as protein extraction.

[0029] (Regarding the mass spectrometry device)

[0030] Figure 1 It is a conceptual diagram showing the structure of the mass spectrometry device 1 according to the present embodiment. The mass spectrometry device 1 includes a measurement unit 100 and an information processing unit 40. The measurement unit 100 includes a liquid chromatograph (LC) 10 and a mass spectrometer 20. The mass spectrometry device 1 is a liquid chromatography-mass spectrometry (Liquid Chromatograph-Mass Spectrometer; LC-MS) capable of performing LC / MS.

[0031] In addition, when the number of types of molecules contained in the test sample is small, the mass spectrometry device 1 may not be an LC-MS, but a mass spectrometer not including an LC may be used for tandem mass spectrometry. Hereinafter, tandem mass spectrometry is defined as mass spectrometry in two or more stages.

[0032] The mass spectrometer 20 includes: an ionization unit 21, which includes an ion source 211; a vacuum container 200; and a tube 212 for introducing ions from the ionization unit 21 into the vacuum container 200. The vacuum container 200 includes an ion guide unit 22, a first mass separation unit 23, a collision cell 24, a second mass separation unit 25, and a detection unit 30. The first mass separation unit 23 includes a first quadrupole 230. The collision cell 24 includes an ion guide 240 and a gas inlet 241. The second mass separation unit 25 includes a second quadrupole 250.

[0033] The prepared analysis test sample is introduced into the LC 10. The LC 10 separates each component contained in the introduced analysis test sample by liquid chromatography and elutes them at different retention times. The type of the LC 10 is not particularly limited as long as it can separate each allergen-derived peptide so that the allergen-derived peptide can be detected with desired accuracy in mass spectrometry. As the LC 10, nano-LC, micro-LC, high performance liquid chromatograph (HPLC), ultra high performance liquid chromatograph (UHPLC), etc. can be used. The elution sample containing the allergen-derived peptide eluted from the LC 10 is introduced into the ionization unit 21 (arrow A1) of the mass spectrometer 20.

[0034] The mass spectrometer 20 performs tandem mass spectrometry on the eluted sample containing allergen-derived peptides introduced from the LC 10. In the present embodiment, the mass spectrometer 20 is a triple quadrupole mass spectrometer, and the detection of the sample-derived ion S is performed by multiple reaction monitoring (MRM). The mass spectrometer 20 ionizes the eluted sample to generate the sample-derived ion S, performs mass separation on the sample-derived ion S, cleaves the sample-derived ion S after mass separation to generate product ions, and performs mass separation on the generated product ions and then detects them. Hereinafter, it is assumed that the product ions generated by the cleavage of the sample-derived ion S are also included in the sample-derived ion S.

[0035] The ionization unit 21 of the mass spectrometer 20 ionizes the eluted sample containing allergen-derived peptides introduced into the ionization unit 21. The ionization method is not particularly limited as long as the degree of ionization can be achieved to the extent that the product ions can be detected with the desired accuracy, but the electrospray ionization method (ESI) is preferably used, and the following embodiments will also be described in terms of performing ESI. The ion source 211 is an ion source for ESI. The sample-derived ion S generated by the ionization unit 21 moves due to the pressure difference between the ionization unit 21 and the vacuum container 200 or the action of the voltage applied to an electrode (not shown), and enters the ion guide unit 22 through the tube 212. In Figure 1 it, the path of the sample-derived ion S is schematically shown by the dotted arrow A2.

[0036] The ion guide unit 22 includes a quadrupole or a ring electrode appropriately arranged in a vacuum chamber (not shown) where the pressure is gradually reduced. The pressure can be set to about 10 -2 Pa in the vacuum chamber where the first mass separation unit 23 is arranged. The ion guide unit 22 converges the flow of the sample-derived ion S by electromagnetic action and shoots it out toward the first mass separation unit 23.

[0037] The first mass separation unit 23 selectively allows ions having a set m / z to pass through as precursor ions by the electromagnetic action based on the voltage applied to the first quadrupole 230 and shoots them out toward the collision cell 24. Hereinafter, m / z is appropriately used as the mass-to-charge ratio, but as long as it is a value representing the ratio of the mass of an ion to its charge, it is not particularly limited. The first mass separation unit 23 selectively allows precursor ions having an m / z corresponding to the ionized allergen-derived peptide to pass through.

[0038] The collision cell 24 controls the movement of the sample-derived ions S through an ion guide 240 including a quadrupole, and at the same time causes the precursor ions to dissociate by collision-induced dissociation (CID) to generate product ions. A gas (hereinafter referred to as CID gas) containing molecules that collide with the precursor ions during CID is introduced from the gas inlet 241 (arrow A3) into the collision cell so as to achieve a specified pressure. The type of the CID gas is not particularly limited as long as CID can occur with a desired efficiency, but an inert gas such as argon or nitrogen is preferred. The generated product ions are ejected toward the second mass separation unit 25.

[0039] In addition, the dissociation method is not particularly limited to CID, and can be carried out by any method such as electron capture dissociation or electron transfer dissociation.

[0040] The second mass separation unit 25 selectively passes product ions having a set m / z through electromagnetic action based on the voltage applied to the second quadrupole 250 and ejects them toward the detection unit 30.

[0041] In addition, the second mass separation unit 25 may be appropriately configured to include a linear ion trap including the second quadrupole 250.

[0042] The detection unit 30 includes an ion detector such as a secondary electron multiplier or a photomultiplier for detecting the incident product ions. The detection signal obtained by detecting the product ions is subjected to A / D conversion by an analog / digital (A / D) converter (not shown), becomes a digital signal, is input to the information processing unit 40, and is stored in the storage unit 43 (arrow A4). Hereinafter, the data based on the detection signal obtained by the detection unit 30 detecting the sample-derived ions S is referred to as measurement data.

[0043] The information processing unit 40 includes an information processing device such as a computer. In addition to appropriately serving as an interface with the user of the mass spectrometry device 1 (hereinafter simply referred to as the user), the information processing unit 40 also performs control of the measurement unit 100 and processing such as communication, storage, and calculation related to various data. The information processing unit 40 becomes an analysis device for the data obtained by mass spectrometry of the mass spectrometer 20.

[0044] In addition, the information processing unit 40 may be configured as a single device integrated with the LC 10 or the mass spectrometer 20. Also, a part of the data used in this embodiment such as reference data may be stored in a remote server or the like.

[0045] Figure 2It is a conceptual diagram showing the structure of the information processing unit 40. The information processing unit 40 includes an input unit 41, a communication unit 42, a storage unit 43, an output unit 44, and a control unit 50. The control unit 50 includes a device control unit 51, a data processing unit 52, and an output control unit 53. The data processing unit 52 includes a setting unit 521, an information acquisition unit 522, and an information generation unit 523.

[0046] The input unit 41 of the information processing unit 40 is configured to include input devices such as a mouse, a keyboard, various buttons, or a touch panel. The input unit 41 receives information required to control the operation of the measurement unit 100 and information required for the processing performed by the control unit 50 from the user.

[0047] The communication unit 42 of the information processing unit 40 is configured to include a communication device capable of communicating through wireless or wired connections via a network such as the Internet. The communication unit 42 appropriately transmits and receives required data.

[0048] The storage unit 43 of the information processing unit 40 is configured to include a non-volatile storage medium. The storage unit 43 stores analysis conditions, measurement data, programs for the control unit 50 to execute processing, etc. Reference data is stored in the storage unit 43.

[0049] Figure 3 It is a diagram showing Table A that schematically represents reference data. The reference data shows values that associate allergen-derived peptides with allergens. In Table A, the value is recorded in the element represented by the column corresponding to each allergen item P1 and the row corresponding to each peptide item P2, thereby showing the correspondence. This value is called a score. The score is used in the calculation for deriving whether each allergen is contained in the sample based on the detected allergen-derived peptide. In the example of Table A, the score is set such that the higher the score, the higher the possibility that the allergen from which the detected allergen-derived peptide is derived is contained in the sample when the allergen-derived peptide is detected.

[0050] The allergen item P1 in Table A is an item representing an allergen, and the names of each allergen such as "wheat", "barley", and "rye" are shown in the allergen item P1. The peptide item P2 is an item representing an allergen-derived peptide, and labels corresponding to each allergen-derived peptide such as "MRM1", "MRM2", and "MRM3" are shown in the peptide item P2. The score is shown numerically in the score item P3.

[0051] Reference data is data representing allergen-derived peptides generated when each allergen is subjected to cleavage treatment. The reference data is prepared according to the type of cleavage treatment such as trypsin or Lys-C. In the example of Table A, the score takes a value from 0 to 50. The score for a blank column is 0, corresponding to the case where no allergen-derived peptide is generated by the cleavage treatment of the allergen. In this case, the detection of the allergen-derived peptide is independent of the presence or absence of the allergen in the sample. A score exceeding 0 corresponds to the case where an allergen-derived peptide is generated by the cleavage treatment of the allergen. In other words, a score exceeding 0 corresponds to the case where the allergen-derived peptide is derived from the allergen. In this case, if the allergen-derived peptide is detected in the mass spectrometry of the sample for analysis, it is possible that the allergen is contained in the sample.

[0052] For example, let Table A be the reference data in the case of cleavage treatment with trypsin. In addition, the allergen-derived peptide corresponding to MRM4 in Table A is detected in the mass spectrometry of the sample subjected to trypsin treatment. In this case, since the allergen-derived peptide corresponding to MRM4 is generated by the trypsin treatment of barley or rye, it is possible that barley or rye is contained in the sample. On the other hand, the detection of the allergen-derived peptide corresponding to MRM4 does not affect the possibility of containing wheat in the sample. This is because no allergen-derived peptide corresponding to MRM4 is generated in the trypsin treatment of wheat, so the presence or absence of wheat in the sample does not affect the detection of the allergen-derived peptide corresponding to MRM4.

[0053] The score in the reference data can be appropriately set based on the number of allergens from which the allergen-derived peptide is derived in the reference data. For example, it is assumed that the allergen-derived peptide corresponding to MRM2 is not derived from allergens other than wheat, barley, or rye. In the case where the allergen-derived peptide corresponding to MRM2 is detected, it can be determined that at least one of wheat, barley, and rye is contained in the sample. However, even if the allergen-derived peptide corresponding to MRM2 is detected, all of the detected allergen-derived peptides may be derived from barley or rye, and it cannot be determined that wheat is contained in the sample. Similarly, it cannot be determined that barley or rye is contained in the sample.

[0054] On the other hand, it is assumed that the allergen-derived peptide corresponding to MRM3 does not originate from allergens other than wheat. Since the allergen-derived peptide corresponding to MRM3 is specifically generated from wheat by cleavage treatment, if the allergen-derived peptide corresponding to MRM3 is detected, it is possible to infer with a higher probability than in the case of detecting MRM2 that wheat is contained in the sample. Let the score of the allergen-derived peptide derived from one allergen in the reference data be the first score. Let the score of the allergen-derived peptide derived from multiple allergens in the reference data be the second score. At this time, it can be set that the first score contributes more to the possibility that the allergen is contained in the sample when the allergen-derived peptide is detected than the second score.

[0055] The scores of the reference data can also be set based on the ease of generating allergen-derived peptides from each allergen during cleavage treatment. For example, it is assumed that even when it is known from the amino acid sequence that a certain allergen-derived peptide may be generated from barley or rye, the possibility of generating this allergen-derived peptide by cleavage treatment in barley is very low. In this case, if this allergen-derived peptide is detected, the scoring can be set so that the possibility that rye is contained in the sample is higher than the possibility that barley is contained in the sample.

[0056] In addition, the value set as the score is not particularly limited and can be appropriately set based on the algorithm for generating allergen information described later. For example, the numerical range of the score can be arbitrarily set to 0 to 1, 0 to 100, etc. Also, as long as the values related to each allergen can be referred to based on the information indicating the detected allergen-derived peptide, the form of the reference data, etc. is not particularly limited. For example, it can be stored in the form of a two-dimensional array corresponding to Figure 3 The peptide item P2 can also be set as the name or identification number of a parent-child ion pair (transition) (described later) for mass separation of the allergen-derived peptide. This is because the allergen-derived peptide corresponds to the parent-child ion pair, so the allergen-derived peptide can be determined and represented based on the parent-child ion pair.

[0057] The allergens included in the reference data of this embodiment can be either allergic substances or sensitizing molecules. As allergic substances, milk, eggs, wheat, barley, rye, oats, canola seeds, sesame seeds, macadamia nuts, pistachios, Brazil nuts, walnuts, peanuts, and hazelnuts can be included in the reference data. As the sensitizing molecules contained in these substances, ovalbumin, lysozyme, casein, lactoglobulin, high-molecular-weight glutenin, low-molecular-weight glutenin, wheat protein, rye protein, oat protein, barley protein, canola seed protein, sesame seed protein, macadamia nut protein, pistachio protein, Brazil nut protein, walnut protein, peanut protein, and hazelnut protein can be included in the reference data. These sensitizing molecules can be measured by the parent-child ion pairs described in Patent Document 1. In addition, various allergens such as buckwheat, shrimp, or crab can also be included in the reference data according to the parent-child ion pairs for detecting peptides generated by specific cleavage processing, etc.

[0058] Return to Figure 2 The output unit 44 of the information processing unit 40 is configured to include a display device such as a liquid crystal monitor or a printer, etc., and display information related to the measurement by the measurement unit 100 or information obtained through the processing by the data processing unit 52, etc. on the display device or print it on a paper medium.

[0059] The control unit 50 of the information processing unit 40 is configured to include a processor such as a Central Processing Unit (CPU) and a storage medium such as a memory, and functions as the main body for controlling the operation of the mass spectrometry device 1. The control unit 50 becomes a processing device that performs processing such as generating information (allergen information) related to the allergens contained in the sample. The control unit 50 holds the programs stored in the storage unit 43, etc. in the memory, and the processor performs various processes by executing this program.

[0060] In addition, as long as it can be processed by the control unit 50 according to this embodiment, the physical structure, etc. of the control unit 50 are not particularly limited.

[0061] The device control unit 51 of the control unit 50 controls the operation of each part of the measurement unit 100 so as to satisfy the analysis conditions set by user input, etc. The device control unit 51 sets the allergen-derived peptides to be detected. The device control unit 51 can be set to perform mass spectrometry of all the allergen-derived peptides shown in the reference data, or can be set to perform mass spectrometry of a part of the allergen-derived peptides by user selection, etc. In the case of performing a screening test for the allergens contained in the sample, it is preferable to comprehensively detect each allergen-derived peptide included in the reference data.

[0062] The device control unit 51 may also set the allergen-derived peptides to be detected based on information pre-stored in the storage unit 43 or the like. For example, in the storage unit 43, multiple sets of allergen-derived peptides to be detected are stored according to differences in allergens in each country or region, differences in reactivity of people who ingest or come into contact with allergens in each country or region, or differences in regulations in each country or region. The device control unit 51 can set the allergen-derived peptides included in the group selected by the user's input or the allergen-derived peptides included in the group corresponding to the country or region registered by the user as the allergen-derived peptides to be detected.

[0063] The device control unit 51 acquires the parent-child ion pairs for detecting the allergen-derived peptides associated with the allergen-derived peptides shown in the reference data. The parent-child ion pairs refer to the group of the m / z of the precursor ion and the m / z of the product ion when detecting specific ions in tandem mass spectrometry. The parent-child ion pairs are preferably associated with the allergen item P1 in the reference data and pre-stored in the storage unit 43 or the like. The device control unit 51 controls the first mass separation unit 23 and the second mass separation unit 25 to allow the ions with m / z included in each parent-child ion pair to pass through.

[0064] The data processing unit 52 of the control unit 50 performs analysis processing on the measurement data obtained by mass spectrometry.

[0065] The setting unit 521 of the data processing unit 52 sets the allergen as the object for generating allergen information. The allergen information is information related to the allergen contained in the sample, and can be set as information related to whether each allergen is contained in the sample. The allergen as the object for generating allergen information is the allergen to be detected. For example, the allergen information can include information indicating whether each allergen is contained in the sample represented by binary values, characters, or words, or information indicating the possibility of each allergen being contained in the sample represented by numerical values, characters, or words. Hereinafter, the allergen as the object for generating allergen information is referred to as the target allergen.

[0066] The setting unit 521 can set all the allergens shown in the reference data as the target allergens, or can set some allergens as the target allergens by the user's selection or the like. For example, when performing a screening test for the allergens contained in the sample, it is preferable to comprehensively set each allergen included in the reference data as the target allergen.

[0067] The setting unit 521 may also set the target allergen based on information pre-stored in the storage unit 43 or the like. For example, in the storage unit 43, multiple groups of target allergens are stored according to differences in each country or region as described above. The setting unit 521 can set the allergen included in the group selected by the user's input or the allergen included in the group corresponding to the country or region registered by the user as the target allergen.

[0068] The information acquisition unit 522 of the data processing unit 52 acquires detection information. The detection information is information indicating the allergen-derived peptides detected by providing the sample to mass spectrometry after the above-described cutting process. The detection information only needs to indicate the detected allergen-derived peptides, and its expression method is not particularly limited. For example, the detected allergen-derived peptides can be indicated by using the identification numbers associated with the allergen-derived peptides of the reference data.

[0069] The information acquisition unit 522 acquires the detection intensity, which is a value indicating the magnitude of the detection signal of each allergen-derived peptide, from the measurement data. The detection intensity can be set as the cumulative value of the detection signal intensity during the mass separation using the parent-child ion pairs of each allergen-derived peptide. The information acquisition unit 522 determines whether each allergen-derived peptide is detected based on whether the detection intensity of each allergen-derived peptide satisfies the condition based on a specified threshold value. This threshold value is referred to as the first threshold value. The first threshold value can be set based on, for example, the magnitude of the noise, or a value pre-stored in the storage unit 43 can be used. For example, when the detection intensity of the allergen-derived peptide is equal to or greater than the first threshold value, the information acquisition unit 522 determines that the allergen-derived peptide is detected by mass spectrometry.

[0070] The information acquisition unit 522 determines whether each allergen-derived peptide to be subjected to mass spectrometry is detected. The information acquisition unit 522 generates detection information indicating the detected allergen-derived peptides.

[0071] In addition, the information processing unit 40 may be configured as a data processing device not included in the mass spectrometry apparatus 1. In this case, the information acquisition unit 522 may analyze the measurement data acquired via the communication unit 42 or the like to generate and acquire the detection information, or may acquire the detection information via the communication unit 42 or the like.

[0072] The information generation unit 523 of the data processing unit 52 generates allergen information based on the detection information and the reference data. The information generation unit 523 calculates the sum of the scores of a plurality of detected allergen-derived peptides derived from the target allergen for the target allergen. This sum is called the total score. The information generation unit 523 determines whether each target allergen is included in the sample according to whether the total score satisfies the condition based on a specified threshold value. This specified threshold value is called the second threshold value. The second threshold value is appropriately set based on the scores of the reference data and is pre-stored in the storage unit 43 or the like.

[0073] In addition, when there is one detected allergen-derived peptide for the target allergen, the score of this allergen-derived peptide can be set as the total score.

[0074] For example, when the total score of the target allergen is equal to or higher than the second threshold value, the information acquisition unit 522 determines that this target allergen is included in the sample. As a more specific example, mass spectrometry is used to measure the allergen-derived peptides corresponding to MRM2, MRM10, and MRM12 in the Figure 3 reference data, and it is assumed that these three allergen-derived peptides are detected. The second threshold value is set to 50. If the target allergen is wheat, the total score related to wheat is 15 + 14 + 24 = 53, which is a value equal to or higher than the second threshold value. In this case, the information acquisition unit 522 determines that wheat is contained in the sample. As another example, mass spectrometry is used to measure the allergen-derived peptides corresponding to MRM1 and MRM2, and it is assumed that these two allergen-derived peptides are detected. The second threshold value is set to 50. If the target allergen is wheat, the total score related to wheat is 40 + 15 = 55, which is a value equal to or higher than the second threshold value. In this case, the information acquisition unit 522 determines that wheat is contained in the sample.

[0075] In addition, symbols such as A, B, and C can be used instead of numerical values to represent scores. In this case, conditions such as A being two or more, A being one and B being two or more can be used instead of the second threshold value. Hereinafter, "value" includes characters such as numerical values and symbols representing scores.

[0076] In these examples, information obtained by detecting allergen-derived peptides of MRM2, MRM10, and MRM12 for peptides not specifically detected in wheat is also used for determination. Thus, in the analysis method of the present embodiment, the detection of allergen-derived peptides derived from multiple allergens is reflected in the determination of whether the target allergen is contained in the sample, so that the allergens contained in the sample can be analyzed more accurately. In addition, when multiple allergen-derived peptides generated from one allergen of the reference data are detected, the information generation unit 523 generates allergen information based on the combination of the detected multiple allergen-derived peptides. This is performed by the following structure: the information obtained by detecting multiple allergen-derived peptides is integrated using multiple scores related to the multiple allergen-derived peptides and the target allergen to determine whether the target allergen is contained in the sample.

[0077] The information generation unit 523 calculates the total score for each set target allergen, and determines whether each target allergen is contained in the sample by comparing the total score with the second threshold. The information generation unit 523 generates allergen information indicating the allergens determined to be contained in the sample.

[0078] The allergen information only needs to represent information related to whether each allergen is contained in the sample, and the manner is not particularly limited. For example, the allergen information can show whether it is contained in the sample by a binary value for each target allergen. The allergen information can also show the target allergen contained in the sample by an identification number. Or, the allergen information can also show the target allergen contained in the sample by text or graphics. The allergen information can also represent the possibility or probability that the target allergen is contained in the sample. For example, the allergen information can list multiple target allergens in the order of decreasing possibility of being contained in the sample based on the total score in a list or the like, or can show the possibility of being contained in the sample using the total score or a value or symbol based on the total score. This value or symbol can be arbitrarily set based on the above degree of possibility, for example, set as high, medium, low, etc., to make it easy for users to understand.

[0079] The output control unit 53 controls the output unit 44 to display the analysis conditions or the information obtained by the analysis of the data processing unit 52 on the display device for output. The output control unit 53 presents the allergen information to the user by outputting an image representing the allergen information.

[0080] Figure 4 It is a flowchart showing the process of a mass spectrometry method including the analysis method of data obtained by mass spectrometry according to the present embodiment. Figure 4Each step is appropriately executed by the control unit 50 of the mass spectrometry apparatus 1. In step S1001, the apparatus control unit 51 performs mass spectrometry on the sample after the cutting process. If step S1001 ends, step S1003 is started.

[0081] In step S1003, the information acquisition unit 522 generates and acquires detection information. If step S1003 ends, step S1005 is started. In step S1005, the information generation unit 523 generates allergen information. If step S1005 ends, step S1007 is started. In step S1007, the output control unit 53 controls the output unit 44 to output the allergen information. If step S1007 ends, the process ends.

[0082] Modifications as described below are also within the scope of the present invention and can be combined with the above-described embodiments. In the following modification examples, parts indicating the same configurations and functions as those in the above-described embodiments are referred to by the same reference numerals, and the description is appropriately omitted.

[0083] (Modification Example 1)

[0084] In the above-described embodiment, the sum of the scores of the detected allergen-derived peptides is used to determine whether the target allergen is contained in the sample. However, the information generation unit 523 may also generate allergen information of the target allergen using the weighted sum of the scores of the detected allergen-derived peptides. The information generation unit 523 can determine whether the target allergen is contained in the sample based on whether the weighted sum is equal to or greater than the second threshold value. When using the weighted sum, it is preferable to set the detection intensity of the detected allergen-derived peptide as the weight. It is considered that the higher the detection intensity of the allergen-derived peptide, the more reliably it is detected. Therefore, by increasing the weight of the allergen-derived peptide with a high detection intensity, the allergen contained in the sample can be derived more accurately.

[0085] (Modification Example 2)

[0086] A program for implementing the information processing function of the mass spectrometry apparatus 1 can also be recorded on a computer-readable recording medium, and the computer system reads in the program recorded on this recording medium, which is related to the processing of the above-mentioned data processing unit 52 and the control of the associated processing, and executes this program. In addition, the "computer system" mentioned here includes the OS (Operating System) and the hardware of peripheral devices. Further, the "computer-readable recording medium" refers to portable recording media such as floppy disks, optical disks, optical discs, memory cards, etc., and storage devices such as hard disks or solid state drives (SSDs) built into the computer system. Also, the "computer-readable recording medium" can also include a medium that dynamically holds a program for a short time, such as a communication line when a program is transmitted via a network such as the Internet or a line such as a telephone line, and a medium that holds a program for a fixed time, such as a volatile memory inside a computer system such as a server or a client in such a case. Additionally, the above program can either be a program for implementing a part of the above functions or a program that is implemented by combining with a program already recorded with the above functions in the computer system.

[0087] In addition, in the case of being applied to a personal computer (hereinafter referred to as PC) or the like, the program related to the above control can be provided through a recording medium such as a CD-ROM or a data signal such as the Internet. Figure 5 This is a diagram showing this situation. The PC 950 receives the provision of the program via the CD-ROM 953. In addition, the PC 950 has a function of being connected to the communication line 951. The computer 952 is a server computer that provides the above program and stores the program in a recording medium such as a hard disk. The communication line 951 is a communication line such as the Internet, personal computer communication, or a dedicated communication line. The computer 952 reads out the program using the hard disk and transmits the program to the PC 950 via the communication line 951. That is, the program is transmitted as a data signal via a carrier wave and is transmitted via the communication line 951. In this way, the program can be provided as a computer program product readable by a computer in various forms such as a recording medium, a carrier wave, etc.

[0088] (Mode)

[0089] Those skilled in the art can understand that the above-mentioned multiple exemplary embodiments and their variations are specific examples of the following mode.

[0090] (Item 1) An analysis device for data obtained by mass spectrometry includes: an information acquisition unit that acquires detection information indicating peptides detected by subjecting a sample to cutting processing and then subjecting it to mass spectrometry; and an information generation unit that generates allergen information related to the allergen contained in the sample based on the detection information and data (reference data) indicating peptides generated when each allergen is subjected to the cutting processing. When a plurality of peptides generated from one allergen in the data are detected, the information generation unit generates the allergen information based on the combination of the plurality of peptides. Thus, it is possible to accurately derive the allergen contained in the sample from the detected allergen-derived peptides.

[0091] (Item 2) Regarding an analysis device for data obtained by mass spectrometry according to another aspect, in the analysis device for data obtained by mass spectrometry according to the aspect of Item 1, the data includes values associating peptides with allergens. When a plurality of peptides generated from one allergen in the data are detected, the information generation unit generates the allergen information based on a plurality of the values related to the plurality of peptides and the one allergen. Thus, by appropriately setting the values, it is possible to more accurately derive the allergen contained in the sample.

[0092] (Item 3) Regarding an analysis device for data obtained by mass spectrometry according to another aspect, in the analysis device for data obtained by mass spectrometry according to the aspect of Item 2, the value is set based on the number of allergens from which the peptides in the data are derived. Thus, it is possible to reflect information related to allergen-derived peptides derived from multiple allergens and more accurately derive the allergen contained in the sample.

[0093] (Item 4) Regarding an analysis device for data obtained by mass spectrometry according to another aspect, in the analysis device for data obtained by mass spectrometry according to the aspect of Item 2 or Item 3, the value is a numerical value. When a plurality of peptides generated from one allergen in the data are detected, the information generation unit generates the allergen information based on whether a calculated value calculated from a plurality of the numerical values satisfies a condition based on a threshold. Thus, by appropriately setting the numerical value and the threshold, it is possible to more accurately derive the allergen contained in the sample.

[0094] (Item 5) Regarding an analysis device for data obtained by mass spectrometry according to another aspect, in the analysis device for data obtained by mass spectrometry according to the aspect of Item 4, the calculated value is the sum of a plurality of the numerical values or the weighted sum of a plurality of the numerical values. Thus, it is possible to integrate the detection information of a plurality of allergen-derived peptides derived from one target allergen and more accurately derive the allergen contained in the sample.

[0095] (Item 6) Regarding the apparatus for analyzing data obtained by mass spectrometry according to another method, in the apparatus for analyzing data obtained by mass spectrometry according to the method of Item 5, the calculated value is the weighted sum, and the weights of the weighted sum are the detection intensities of the multiple types of peptides corresponding to the multiple values respectively. Thus, allergens contained in a sample can be derived more accurately based on the detection intensities.

[0096] (Item 7) Regarding the apparatus for analyzing data obtained by mass spectrometry according to another method, in the apparatus for analyzing data obtained by mass spectrometry according to any one of the methods of Items 1 to 6, the allergens contained in the data are at least one allergen selected from milk, eggs, wheat, barley, rye, oats, canola seeds, sesame seeds, macadamia nuts, pistachios, Brazil nuts, walnuts, peanuts, hazelnuts, buckwheat, shrimp, crab, ovalbumin, lysozyme, casein, lactoglobulin, high-molecular-weight gluten, and low-molecular-weight gluten. Thus, these allergens contained in a sample can be derived accurately.

[0097] (Item 8) Regarding the apparatus for analyzing data obtained by mass spectrometry according to another method, in the apparatus for analyzing data obtained by mass spectrometry according to any one of the methods of Items 1 to 7, the data represents peptides generated when each allergen is subjected to cleavage treatment based on at least one of trypsin and Lys-C. Thus, by referring to the results of past cleavage treatments based on trypsin or Lys-C, etc., allergens contained in a sample can be derived more accurately.

[0098] (Item 9) Regarding the apparatus for analyzing data obtained by mass spectrometry according to another method, in the apparatus for analyzing data obtained by mass spectrometry according to any one of the methods of Items 1 to 8, the mass spectrometry is tandem mass spectrometry or liquid chromatography - tandem mass spectrometry. Thus, through separation in two or more stages, allergen-derived peptides can be detected with high precision.

[0099] (Item 10) A mass spectrometry apparatus according to one method includes the apparatus for analyzing data obtained by mass spectrometry according to any one of the methods of Items 1 to 9. Thus, allergen-derived peptides can be detected, and allergens contained in a sample can be derived accurately.

[0100] (Item 11) The mass spectrometry analysis method involved in one approach includes the following processes: obtaining detection information representing peptides detected by subjecting a sample to a cutting process and then to mass spectrometry analysis; and generating allergen information related to the allergen contained in the sample based on the detection information and data (reference data) representing peptides generated when each allergen is subjected to the cutting process. Wherein, when multiple peptides generated by one of the allergens in the data are detected, the allergen information is generated based on the combination of the multiple peptides. Thus, the allergen contained in the sample can be accurately derived from the detected allergen-derived peptides.

[0101] (Item 12) In a computer-readable medium storing an analysis program according to one approach, the analysis program causes a computer to execute the following processes: an information acquisition process (corresponding to Figure 4 step S1003 in the flowchart), obtaining detection information representing peptides detected by subjecting a sample to a cutting process and then to mass spectrometry analysis; and an information generation process (corresponding to step S1005), generating allergen information related to the allergen contained in the sample based on the detection information and data (reference data) representing peptides generated when each allergen is subjected to the cutting process. Wherein, in the information generation process, when multiple peptides generated by one of the allergens in the data are detected, the allergen information is generated based on the combination of the multiple peptides. Thus, the allergen contained in the sample can be accurately derived from the detected allergen-derived peptides.

[0102] The present invention is not limited to the content of the above embodiments. Other approaches conceivable within the technical idea of the present invention are also included within the scope of the present invention.

Claims

1. An analytical device for data obtained by mass spectrometry, comprising: An information acquisition unit that acquires detection information representing peptides detected by subjecting a sample to a cutting process and then to mass spectrometry; and An information generation unit that generates allergen information related to the allergen contained in the sample based on the detection information and data representing peptides generated when each allergen is subjected to the cutting process, wherein when multiple peptides generated by one allergen in the data are detected, the information generation unit generates the allergen information based on the combination of the multiple peptides.

2. The analytical device for data obtained by mass spectrometry according to claim 1, wherein the data contains values associating peptides with allergens, when multiple peptides generated by one allergen in the data are detected, the information generation unit generates the allergen information based on multiple values related to the multiple peptides and the one allergen.

3. The analytical device for data obtained by mass spectrometry according to claim 2, wherein the value is set based on the number of allergens from which the peptides in the data are derived.

4. The analytical device for data obtained by mass spectrometry according to claim 2, wherein the value is a numerical value, when multiple peptides generated by one allergen in the data are detected, the information generation unit generates the allergen information based on whether a calculated value calculated from multiple numerical values satisfies a condition based on a threshold.

5. The analytical device for data obtained by mass spectrometry according to claim 4, wherein the calculated value is the sum of multiple numerical values or the weighted sum of multiple numerical values.

6. The analytical device for data obtained by mass spectrometry according to claim 5, wherein the calculated value is the weighted sum, and the weight of the weighted sum is the detection intensity of the multiple peptides respectively corresponding to the multiple numerical values.

7. The analytical device for data obtained by mass spectrometry according to any one of claims 1 to 6, wherein the allergens contained in the data are at least one allergen selected from milk, eggs, wheat, barley, rye, oats, canola seeds, sesame seeds, macadamia nuts, pistachios, Brazil nuts, walnuts, peanuts, hazelnuts, buckwheat, shrimp, crab, ovalbumin, lysozyme, casein, lactoglobulin, high molecular weight gluten, and low molecular weight gluten.

8. The analytical device for data obtained by mass spectrometry according to any one of claims 1 to 6, wherein the data represents peptides generated when each allergen is subjected to a cutting process based on at least one of trypsin and Lys-C.

9. The analytical device for data obtained by mass spectrometry according to any one of claims 1 to 6, wherein the mass spectrometry is tandem mass spectrometry or liquid chromatography - tandem mass spectrometry.

10. A mass spectrometry device, comprising the analytical device for data obtained by mass spectrometry according to any one of claims 1 to 9.

11. A method for analyzing data obtained by mass spectrometry, comprising the following processes: Obtaining detection information representing peptides detected by subjecting a sample to a cutting process and then to mass spectrometry; and Generating allergen information related to the allergen contained in the sample based on the detection information and data representing peptides generated when each allergen is subjected to the cutting process, wherein, when multiple peptides generated by one allergen in the data are detected, the allergen information is generated based on the combination of the multiple peptides.

12. A computer-readable medium storing an analysis program for causing a computer to execute the following processes: An information acquisition process for obtaining detection information representing peptides detected by subjecting a sample to a cutting process and then to mass spectrometry; and An information generation process for generating allergen information related to the allergen contained in the sample based on the detection information and data representing peptides generated when each allergen is subjected to the cutting process, wherein, in the information generation process, when multiple peptides generated by one allergen in the data are detected, the allergen information is generated based on the combination of the multiple peptides.

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