JP2019074403A - Data processing device for chromatogram, data processing program for chromatogram, and data processing method for chromatogram - Google Patents

Abstract

To provide a data processing device for chromatograms, a data processing program for chromatograms, and a data processing method for chromatograms, for reducing an isotope-derived interfering signal from a chromatogram without relying on component identification with regard to an LC-SRM-MS analysis dataset including a large number of SRMs, whereby it is expected that low analysis throughput and other problems in the present technique are resolved.SOLUTION: Provided is a data processing device for chromatograms, comprising: an information joining unit for associating compound information with a chromatogram; a relation derivation unit for deriving an SRM transition relation set in which a first SRM transition and a second SRM transition having a prescribed relation with the first SRM transition are associated with each other; and a correction unit for correcting the chromatogram on the basis of the compound information associated by the information joining unit and the SRM transition relation set.SELECTED DRAWING: Figure 4

Description

  The technology disclosed in the present application relates to a chromatogram data processing apparatus, a chromatogram data processing program, or a chromatogram data processing method that processes data obtained by operating a mass spectrometer.

  There are numerous types of proteins and nucleic acids (DNA, RNA, etc.), water-soluble and lipid-soluble compounds in vivo. The technology to analyze such a group of compounds collectively and comprehensively is omics technology, genomics (DNA), transcriptomics (RNA), proteomics (proteins / peptides), metabolomics (metabolites), lipidomics (metabolomics) Omics technology fields such as lipids) exist. For example, in the field of medicine and life sciences, search for genes, proteins, metabolites, etc. related to diseases, etc., as well as diagnosis and prediction, etc., by comprehensively detecting the components contained in the target sample. Analysis for the purpose of At present, mass spectrometry is one of the most commonly performed methods as a method for detecting various components in omics analysis.

  In the method of simultaneously detecting a large number of components contained in a sample using a mass spectrometer, it is intended to acquire information of as many components as the operating speed of the analyzer allows, with all the observed components as targets. There are methods of “target analysis method” and “target analysis method” in which specific and sensitive simultaneous analysis is performed on a large number of target components set in advance. The former uses a high mass resolution type tandem mass spectrometer represented by a quadrupole (Q) -time-of-flight (TOF) mass spectrometer (Q-TOF MS), and the latter uses a triple quadrupole. A (triple quadrupole, TQ) mass spectrometer (TQMS) is used as a representative device. These mass spectrometry methods are typically used in combination with liquid chromatography (LC), and the component elution time (retention time) of liquid chromatography and mass information by mass spectrometry (MS and MS / MS) are components. Used for the detection and identification of In target analysis, measurement in a selected-reaction monitoring (SRM) mode (also referred to as multiple reaction monitoring (MRM)) mode is performed. SRM is a type of MS / MS measurement method that obtains structural information by cleaving precursor ions in a mass spectrometer, but preselects one to a few of the product ions generated from precursor ions. Observation, it is characterized in that high sensitivity detection based on good signal-noise ratio (S / N) utilizing MS / MS structure selectivity can be simultaneously performed on a large number of target compounds. . By switching the compound to be observed in conjunction with the elution time of liquid chromatography, hundreds to thousands of target compounds can be measured by one LC-SRM-MS analysis.

  In SRM analysis, for each target compound, (1) polarity of ionization (positive ion / negative ion), (2) mass of precursor ion (or m / z, hereinafter the same), (3) mass “SRM” which is a combination of four conditions: collision energy (voltage) to cause fragmentation in the collision separation chamber in the analyzer and (4) mass of the product ion to be observed (or m / z, hereinafter the same) Set the transition in some way in advance and measure. Where standard compounds are available, SRM conditions are optimized by preliminary measurements with standard compounds, which are often used to carry out measurements with actual samples. If a standard product is not available, determine the SRM condition from the analysis result of the target component contained in the actual sample, or derive the SRM condition based on the information obtained by the analysis of the analog compound and the isomer. is there.

  When an actual sample is measured under analysis conditions including a large number of SRM transitions set in this manner, the target is in the vicinity of the target chromatogram peak or in a form that covers the target peak in a small proportion. It has been empirically known that an external peak appears and interferes with the identification and quantification of the target peak. As one of the causes, for example, when a series of SRM conditions are set based on the fragmentation mode commonly shared among related compound groups having different masses from each other, signals derived from stable isotopes of one compound are the other There is a case where it is observed as an interference signal in the chromatogram of In this case, the analyst can estimate the interference signal by comparing the related chromatograms, but it is difficult to manually remove the isotope-derived interference signal for all of the huge number of chromatograms. Only in the case of significant disturbances, negative responses such as exclusion from the data individually are possible.

  Specific examples are shown below. FIG. 1 shows the structures of phosphatidyl choline (PC) and sphingomyelin (SM). Phosphatidylcholine (PC), which is a kind of phospholipid, has phosphocholine as a common structure as shown in FIG. 1, and various aliphatic hydrocarbons (fatty acid esters and aliphatics) at the sn-1 position and the sn-2 position It is a group of compounds having an ether / aliphatic vinyl ether). Sphingomyelin (SM) is also a lipid compound having phosphocholine. For simultaneous analysis of PC and SM, it is widely practiced to set a series of SRM transitions in which a common portion, phosphocholine (m / z 184), is a common fragment ion for detection.

  However, in the actual measurement, another PC molecule species (PC (38 (38%) less in mass) has one more number of double bonds in the fatty chain than the target PC molecule (PC (38: 3)). The signal derived from the stable isotope of 4) may appear as an interfering signal on the chromatogram for detection of the target PC species. In addition, since sphingomyelin (SM) has a molecular weight different from that of PC species and molecular weight by 1 Da, an interference signal derived therefrom may appear on the chromatogram for detection of the target PC species. That is, PC species (PC (38: 4)) and SM species (SM (42: 3)) give an interference signal to the chromatogram measured to detect the target component (PC (38: 3)) It will be.

  Furthermore, the problem of isotope-derived signals can not only be found between the two chromatograms, but the chromatogram for the interfering component may also be interfered with by the isotope of another component You must consider the nature.

  Conventionally, in the method for correcting such an interference signal derived from isotope, since component identification is required before isotope correction, in the peak detection / identification process for component identification, an isotope-derived peak is After having been detected in large numbers, it was necessary to carry out a complicated procedure of excluding the data after determining that it is an isotope-derived peak. In addition, in Non-Patent Documents 1 to 3, since isotope correction is performed as correction processing on the integrated value data of the detected peak, a chromatogram in the case of removing the interference signal can not be obtained. It was difficult to scrutinize the chromatogram in the target analysis of the components. Furthermore, non-patent documents 4 and 5 are only for correcting the mass spectrum, and are not originally intended for chromatograms in target analysis such as SRM measurement.

Scherer M et al., Anal. Chem., 2010, 82, 8794-8799. Simultaneous Quantification of Cardiolipin, Bis (monoacylglycero) phosphate and their Precursors by Hydrophilic Interaction LC-MS / MS Including Correction of Isotopic Overlap Tsugawa H et al., Front. Genet., 2014, 5, 471. MRM-DIFF: data processing strategy for differential analysis in large scale MRM-based lipidomics studies Li et al., Sci. Rep., 2014, 4, 6581. Comprehensive Quantification of Triacylglycerols in Soybean Seeds by Electrolysis Ionization Mass Spectrometry with Multiple Neutral Loss Scans Kurvinen JP et al., Rapid Commun. Mass Spectrom., 2002, 16, 1812-1820. Software algorithm for automatic interpretation of mass spectra of glycolipids Han et al., Anal. Biochem., 2001, 295, 88-100. Quantitative Analysis and Molecular Species Fingerprinting of Triacylglycerol Molecular Species Directly from Lipid Extracts of Biological Samples of Biological Samples by Electrospray Ionization Tandem Mass Spectrometry

  The present invention relates to a method for solving these problems, the purpose of which is to identify isotope-derived interference signals from chromatograms for LC-SRM-MS analysis data set containing a large number of SRMs. To provide a chromatogram data processing apparatus, a chromatogram data processing program, or a chromatogram data processing method that can be reduced independently of the above to solve the problems such as low analysis throughput in the present method. It is

  As a result of intensive studies to solve the above problems, the present inventors relate compound information estimated to the chromatogram itself without performing component identification processing of each peak in the chromatogram, and based on this, Performing interference signal correction processing on the chromatogram itself, which is raw data, and repeatedly performing processing in a proper order also for multiple superimposed isotope interferences, simpler and faster than before (high throughput In the present invention, it has been found that correction of isotope-derived interference signals can be carried out in accordance with the present invention.

That is, the present invention provides a chromatogram data processing apparatus, a chromatogram data processing program, and a chromatogram data processing method according to the following aspects;
(1) An embodiment according to the present invention includes an information combining unit that relates compound information to a chromatogram, a first SRM transition, and a second SRM transition having a second predetermined relationship with the first SRM transition. A chromatograph comprising: a relationship deriving unit for deriving an associated SRM transition relationship set; and a correction unit for correcting a chromatogram based on the compound information correlated by the information combining unit and the SRM transition relationship set Data processor for gram;
(2) In one embodiment according to the present invention, the compound data is compound data related to SRM transition having a first predetermined relationship with SRM transition related to the chromatogram, chromatogram data Processing device;
(3) In one embodiment according to the present invention, the compound information includes a composition formula of precursor ions and a composition formula of product ions;
(4) In one embodiment according to the present invention, the relationship deriving unit is configured to calculate the mass (m / z) of precursor ions related to the first SRM transition and the second SRM transition and the mass (m / z) of product ions A data processor for chromatograms, characterized in that it is related on the basis;
(5) In one embodiment according to the present invention, the correction unit is a second SRM associated with the first SRM transition based on a first chromatogram related to the first SRM transition associated by the relationship deriving unit. Chromatogram data processing apparatus characterized by correcting a second chromatogram related to the transition;
(6) In one embodiment according to the present invention, the mass (m / z) of the precursor ion related to the first SRM transition is the mass (m / z) of the precursor ion related to the second SRM transition, A data processor for chromatograms, characterized in that they are equal or smaller;
(7) In one embodiment according to the present invention, the mass (m / z) of the product ion related to the first SRM transition is equal to or the mass (m / z) of the product ion related to the second SRM transition A data processing device for chromatograms characterized by a small size;
(8) In one embodiment according to the present invention, the correction unit performs correction for subtracting the first chromatogram multiplied by a predetermined coefficient from the second chromatogram. Data processing unit;
(9) In one embodiment of the present invention, a computer is connected to information combining means for associating compound information with a chromatogram, a first SRM transition, and a second SRM transition having a second predetermined relationship with the first SRM transition. Function as a correction means for correcting the chromatogram based on the compound information related by the information combining unit and the SRM transition relation set. Data processing program for chromatograms;
(10) In one embodiment according to the present invention, the compound data includes a composition formula of precursor ions and a composition formula of product ions;
(11) An embodiment according to the present invention comprises an information combining step of associating compound information with a chromatogram, a first SRM transition, and a second SRM transition having a second predetermined relationship with the first SRM transition. A chromatograph comprising: a relationship deriving step of deriving an associated SRM transition relationship set; and a correction step of correcting a chromatogram based on the compound information correlated by the information coupling unit and the SRM transition relationship set. Gram data processing method;
(12) In one embodiment according to the present invention, the compound information includes a composition formula of precursor ions and a composition formula of product ions;
(13) In one embodiment according to the present invention, a relationship deriving step of deriving an SRM transition relationship set in which a first SRM transition, and the first SRM transition and a second SRM transition having a second predetermined relationship described later are associated A chromatogram data processing method including a correction step of correcting the chromatogram based on compound information related to the measured chromatogram and the SRM transition relation set;
(14) A chromatogram data processing method according to an embodiment of the present invention, wherein the compound information includes a composition formula of precursor ions and a composition formula of product ions.

In a further embodiment, the present invention
(15) In a third chromatogram, a second chromatogram, and a first chromatogram, a third SRM transition related to the third chromatogram and a first SRM transition related to the first chromatogram Has a second predetermined relationship described later, and the mass (m / z) of the precursor ion of the first SRM transition is the mass (m / z) of the precursor ion of the third SRM transition The second SRM transition smaller than the second SRM transition according to the third chromatogram and the second SRM transition has a second predetermined relationship described later, and a precursor ion of the second SRM transition The mass (m / z) of the first SRM transition is smaller than the mass (m / z) of the precursor ion of the third SRM transition, and the second SRM transition And the first SRM transition have a second predetermined relationship described later, and the mass (m / z) of the precursor ion of the first SRM transition is the precursor of the second SRM transition If it is smaller than the mass (m / z) of the body ion, the second chromatogram is corrected to reduce the first chromatogram multiplied by the isotope correction coefficient 1-2 to obtain a corrected second chromatogram. And correction to reduce both the first chromatogram multiplied by the isotope correction coefficient 1-3 and the corrected second chromatogram multiplied by the isotope correction coefficient 2-3 from the third chromatogram. To obtain a corrected third chromatogram.

  According to one embodiment of the present invention, interference signals derived from isotopes from chromatograms can be reduced without relying on component identification.

FIG. 1 shows the chemical structures of phosphatidyl choline (PC) and sphingomyelin (SM). FIG. 2 is a diagram illustrating an isotope-derived interference signal related to a chromatogram by SRM measurement of phosphatidylcholine (PC (38: 3)). FIG. 3 is a block diagram showing a configuration according to an embodiment of the present invention. FIG. 4 is a block diagram showing a functional configuration according to an embodiment of the present invention. FIG. 5 is an example of a data structure according to an embodiment of the present invention. FIG. 6 is an example of a data structure according to an embodiment of the present invention. FIG. 7 is an example of a data structure according to an embodiment of the present invention. FIG. 8 is an example of a data structure according to an embodiment of the present invention. FIG. 9 is an example of a data structure according to an embodiment of the present invention. FIG. 10 is an example of a data structure according to an embodiment of the present invention. FIG. 11 is an example of a chromatogram according to an embodiment of the present invention. FIG. 12 is an example of data related to calculation of isotope correction factor according to an embodiment of the present invention. FIG. 13 is an example of a chromatogram according to an embodiment of the present invention. FIG. 14 is an example of a flow according to an embodiment of the present invention. FIG. 15 is an example of a flow according to an embodiment of the present invention.

1. Configuration of Information Processing Apparatus FIG. 3 shows an aspect in which the analysis apparatus 1 and the information processing apparatus 10 are connected as an embodiment of the present invention. The analyzer 1 is a tandem-type mass spectrometer, such as a triple quadrupole mass spectrometer.

  The information processing apparatus 10 will be described below for each configuration, but may be a general information processing apparatus or a dedicated information processing apparatus. In addition, a part or all of the information processing apparatus 10 may be provided inside the analysis apparatus 1.

  FIG. 3 shows an aspect in which the analysis device 1 and the information processing device 10 are connected so as to transmit information. The analysis device 1 and the information processing device 10 may be directly connected or may be indirectly connected via another information processing medium as long as information can be transmitted. For example, they may be connected via the network 17. The network 17 may be wired or wireless, and may be an optical fiber, a coaxial cable, an Ethernet cable, or the like.

  Further, in another aspect, the information processing device 10 may not be connected to the analysis device 1. For example, the information processing apparatus 10 uses, as input information, information as output from the analysis apparatus 1 or information recorded in a server having information necessary for input in the embodiment according to the present invention, a cloud, a recording medium, or the like. The information processing of an embodiment of the present invention may be implemented.

  As illustrated in FIG. 3, the information processing apparatus 10 can include the bus 11, the arithmetic unit 12, the storage unit 13, the input unit 14, the display unit 15, and the communication IF 16.

  The bus 11 has a function of transmitting information between the calculation unit 12, the storage unit 13, the input unit 14 and the display unit 15.

  The operation unit 12 is, for example, a processor. This may be a CPU or an MPU. It may also have a graphics processing unit, a digital signal processor, etc. In short, the arithmetic unit 12 may have a function capable of executing the instructions of the program.

  The storage unit 13 has a function of recording information. This may be either an external memory or an internal memory, and may be either a main storage device or an auxiliary storage device. Also, a magnetic disk (hard disk), an optical disk, a magnetic tape, a semiconductor memory, etc. may be used. In addition, a storage device via a network, a storage device on a cloud, or the like may be used. In addition, the storage unit 13 may include a database.

  The input unit 14 has a function of inputting information. Examples of the pointing device include a mouse, a keyboard, a touch panel, and a pen-shaped pointing device.

  The display unit 15 is, for example, a display. In addition, a liquid crystal display, a plasma display, an organic EL display, or the like may be used. In short, any device that can display information may be used. Moreover, you may equip the input part 14 in part like a touch panel.

  The communication IF 16 has a communication function. The communication IF 16 only needs to be able to communicate and connect with a recording medium or the like including information related to the information output from the analysis device 1 or the analysis device 1. The recording medium provided with the information related to the information output from the analyzer 1 is, for example, a recording medium in which the measurement information output from the analyzer is recorded by arranging the measurement information by another information processing apparatus There are cases such as The communication IF 16 may be either serial connection or parallel connection, and may be USB, IEEE 1394, Ethernet, PCI, SCSI, WIFI, IEEE 802, or the like.

  In FIG. 3, the information processing device 10 may be physically configured by one device or may be physically configured by a plurality of devices. In the case of a plurality of information processing apparatuses, after the function of connecting a plurality of information processing apparatuses is added, the above-mentioned bus 11, operation unit 12, storage unit 13, input unit 14, display unit 15, communication IF 16 Some or all may be distributed or arranged in the plurality of information processing devices.

  Furthermore, when the information processing apparatus 10 is physically configured by a plurality of systems, it may be a system such as a client server system, a P2P system, a grid system, or a cloud system.

  An embodiment of the invention according to the present application is not limited to the above hardware system as long as it is a hardware system capable of realizing any of the software functions described below, and can be applied to various hardware systems. .

2. Function in Information Processing Apparatus Using the hardware of the above-described information processing apparatus 10, the system according to the embodiment of the present invention is, as shown in FIG. 4, a storage unit 41, an input unit 42, an information combining unit 43, and relationship derivation The unit 44, the correction unit 45, and the display unit 46 can be included. However, the system according to an embodiment of the present invention does not have to have all of these functions, and for example, there may be a form without the information combining unit 43.

2-1. Storage unit 41
The storage unit 41 has a function of storing information. For example, the storage unit 41 has a function of recording information used by the input unit 42, the information combining unit 43, the relationship deriving unit 44, the correction unit 45, and / or the display unit 46, or information obtained by these.
For example, the storage unit 41 may hold information related to the SRM transition in a database as shown in FIG. Here, in the data structure of FIG. 5, one data structure having SRM transition information 52, reference 53 to a chromatogram, reference 54 to compound information, and reference 55 to an SRM channel to be corrected is called SRM channel 51. , And shows an example of n SRM channels 51.

The SRM transition information 52 includes information related to the SRM transition. Here, the SRM transition means the polarity of ionization, the mass (m / z) of precursor ions, the collision energy (voltage) for causing fragmentation in the collision separation chamber in the mass spectrometer, the product ions to be observed (fragment ions It is defined by four conditions of mass (m / z) of). Here, the polarity of ionization is positive or negative. In the use of the device, data or program it may be omitted if it is clear that the polarity of the ionization is one. Also, the voltage may be omitted because it may differ depending on the measuring device.
Reference 53 to the chromatogram is recorded with information indicating a reference to the chromatogram measured using SRM transition information. There are multiple references to the chromatogram, which may be recorded in a list format. Further, it goes without saying that the information of the chromatogram itself may be recorded instead of the information of reference to the information of the chromatogram.
The reference 54 to the compound information is data created by the information combining unit 43 described below.
The reference 55 to the to-be-corrected SRM channel is data created by the relationship deriving unit 44 described below.

  In addition, the storage unit 41 stores information generated and / or used by the information combining unit 43, the relationship deriving unit 44, the correction unit 45, and / or the display unit 46, etc., even in the data format of FIG. Without being limited thereto, information that can be used in the embodiments according to the present invention can be recorded. The storage unit 41 may also store information not related to the present invention.

2-2. Input unit 42
The input unit 42 has a function of acquiring information. As described above, the input unit 42 may be acquired from the analysis device, or may be acquired from a server that is another information recording device, a cloud, a recording medium, or the like.

  The information input from the input unit 42 includes, but is not limited to, SRM transitions to be measured, their measurement times, information on chromatograms obtained by measurement, information on databases regarding compound names, and the like. The information that may be recorded in the storage unit 41 described above may be used in the input unit 42.

2-3. Information combining unit 43
The information combining unit 43 has a function of associating compound information with the SRM transition. The SRM transition may be an SRM transition to be measured or may be an SRM transition used for the measurement (hereinafter, referred to as “SRMT for measurement”). In the case of the measurement SRMT used for the measurement, the chromatogram measured by the measurement SRMT may be related to the compound information via the measurement SRMT. By associating the SRMT for measurement and the compound information, it becomes possible to calculate an isotope correction coefficient to be described later.

  The chromatogram may be information of a combination of time and signal strength, or may be a graph based on the information. As information on a combination of time and signal strength, for example, [time 1-signal strength 1], [time 2-signal strength 2], [time 3-signal strength 3] ... [time n-signal strength n] ] And the like.

  The compound information is information on various compounds or their aggregation (database) prepared to associate with a specific chromatogram (apart from the chromatogram). The compound information is set for the purpose of detecting the compound name, the composition formula of the compound, the composition formula of the precursor ion, the composition formula of the product ion, the composition formula of the neutral leaving group, and / or the compound Alternatively, such as SRM transition that can be inferred as such.

  The information combining unit 43 can include a database (hereinafter, referred to as a “compound information database”) including the above-described compound information. An example of the compound information database is shown in FIG. In the example of FIG. 6, compound name 61, composition formula 65 of precursor ion, composition formula 66 of product ion, ionization polarity 64 in SRM transition, mass (m / z) 62 corresponding to composition formula of precursor ion And a mass (m / z) 63 corresponding to the composition formula of the product ion. The mass (m / z) 62 corresponding to the composition formula of the precursor ion is a value that can be calculated based on the composition formula 65 of the precursor ion, and the mass (m / z) corresponding to the composition formula of the product ion 63) is a value that can be calculated based on the composition formula 66 of the product ion. Therefore, even if the compound information database does not have the mass (m / z) 62 corresponding to the composition formula of the precursor ion and / or the mass (m / z) 63 corresponding to the composition formula of the product ion Although it is good, when these are present, there is an advantage that comparison calculation with the measurement SRMT becomes easy. The compound information database may be created based on known technical documents, or may be created based on past experimental data and the like. The compound information database may be a database limited to a specific substance, or may be a database including substances in a broader field.

The information combining unit 43 compares the SRMT for measurement with the SRM transition in the compound information database (hereinafter referred to as “in-DB SRMT”), and determines the SRMT for measurement and the first predetermined relationship with the SRMT for measurement. Relating to the compound information related to the SRMT in the DB.
The fact that the SRMT for measurement and the SRMT in DB have a first predetermined relationship means the difference between the mass (m / z) of the precursor ion of SRMT for measurement and the mass (m / z) of the precursor ion of SRMT in DB Is within the first predetermined value range, and the difference between the mass (m / z) of the product ion of the measurement SRMT and the mass (m / z) of the product ion of the SRMT within the DB is within the second predetermined value range It is. The first predetermined value and the second predetermined value may be set as threshold values to such an extent that the measurement SRMT can consider the difference from the in-DB SRMT as an error. For example, the first predetermined value and the second predetermined value Although two may be used, this is an example and may be another value, and the first predetermined value and the second predetermined value may be different values.

  Next, an example in the information combining unit 43 will be described. For example, it is assumed that the mass (m / z) of the precursor ion of the measurement SRMT is 342.130, and the mass (m / z) of the product ion of the measurement SRMT is 184.1. Further, the first predetermined value and the second predetermined value are both 0.2 here. The information combining unit 43 has a first predetermined difference between the mass (m / z) of precursor ions in the compound information database of FIG. 6 and the mass (m / z) of precursor ions of SRMT for measurement. Only PC (4: 0) is within the value (0.2). Further, the difference between the mass (184. 0733 21) of the generated ion of PC (4: 0) and the mass (184. 1) of the generated ion of the SRMT for measurement is within the second predetermined value (0.2). Therefore, the information binding unit 43 is a precursor ion and a product ion in the compound information database in which the mass difference between the precursor ion and the product ion of the SRMT for measurement is respectively within the first predetermined value and the second predetermined value. The substance is determined to be PC (4: 0). Then, the information combining unit 43 associates the measurement SRMT with the compound information (C12H25N1O8P1 and C5H15N1O4P1) of the SRMT in DB. The information combining unit 43 may record the measurement SRMT and the compound information (C12H25N1O8P1 and C5H15N1O4P1) of the SRMT in DB in the storage table. In this example, the compound SRMT in the DB is directly related to the SRMT for measurement, but it goes without saying that a reference may be used.

  That is, when the information combining unit 43 determines that the measurement SRMT and the in-DB SRMT have the above-described first predetermined relationship, for example, a specific in-DB SRMT in the compound information database corresponding to the measurement SRMT. A reference indicating may be stored in association with the SRMT for measurement. For example, as shown in FIG. 7, when it is determined that the SRMT for measurement and the SRMT in DB have the above-described first predetermined relationship, the reference list on the compound in SRM channel 1 related to the SRMT for measurement is The compound 2 related to SRMT in the DB may be stored.

When the information combining unit 43 determines that the measurement SRMT and all of the DB SRMTs in the compound information database do not have the first predetermined relationship, the measurement SRMT and the compound information Perform processing not related to any in-DB SRMT in the database.
Further, the information combining unit 43 determines that the measurement SRMT and the first in-DB SRMT have the above-described first predetermined relationship, and the measurement SRMT and the second in-DB SRMT are the above. When it is determined that the first predetermined relationship is determined, the measurement SRMT is associated with the first in-DB SRMT, and the measurement SRMT is associated with the second in-DB SRMT. May be

2-4. Relationship deriving unit 44
The relationship deriving unit 44 associates a plurality of SRM transitions having a second predetermined relationship to derive an SRM transition relationship set. For example, the relation deriving unit 44 relates the first SRM transition and the second SRM transition having a second predetermined relation with the first SRM transition to derive an SRM transition relation set. The SRM transition may be a measurement SRMT, or may not be a measurement SRMT at the time of association.

The second predetermined relationship is a relationship which satisfies all the following items i) to iv).
i) the ionization polarity of the first SRM transition matches the ionization polarity of the second SRM transition;
ii) A value obtained by subtracting the mass (m / z) of the precursor ion of the first SRM transition from the mass (m / z) of the precursor ion of the second SRM transition is a predetermined positive integer , “Precursor ion integer mass difference”) and a predetermined tolerance, which is a value equal to or less than a third predetermined value;
iii) A value obtained by subtracting the mass (m / z) of the product ion of the first SRM transition from the mass (m / z) of the product ion of the second SRM transition is 0 or a predetermined positive integer (not shown) , “The product ion integer mass difference”) and a predetermined tolerance, wherein the product ion integer mass difference is less than or equal to the precursor ion integer mass difference;
iv) A difference (absolute value) between the collision energy of the first SRM transition and the collision energy of the second SRM transition is equal to or less than a fourth predetermined value.
Here, the “predetermined positive integer” in the precursor ion integer mass difference and the product ion integer mass difference is a natural number which is a natural increase caused when atoms in the molecule are substituted by one or more stable isotopes. (E.g., 1 dalton, 2 daltons, 3 daltons, etc.) corresponding to being approximated. As a result, it is possible to make a precise correction, with a mass difference of 1 dalton as a target of the correction described later. Also, such a generalized condition definition makes it possible to systematically and comprehensively evaluate SRM transitions having various mass differences as correction targets.
The error due to this approximation is considered to be included in the “predetermined tolerance” because the error in the approximation is small when the substitution number of isotopes is about 1 to 10 compared to the above “prescribed tolerance”. Instead, if the number of substitutions is even larger, correct the “predetermined tolerance” appropriately using the accurate mass derived from the composition formula for the precursor ion and product ion for the first SRM transition. Can. For example, the predetermined tolerance includes 0, and includes, but is not limited to, a value of -0.1 to 0.1, a value of -0.2 to 0.2, and the like. Also, the predetermined tolerance of ii) and the predetermined tolerance of iii) may be the same or different. The value obtained by adding the predetermined natural number and the predetermined tolerance may be a value such as 2.1, 2.14 or the like, or the predetermined tolerance may be a negative value. There is also a possible value such as 95. In addition, although the difference of collision energy was made into one of the requirements in iv above, as mentioned above iv does not need to be taken as requirements.

  A third predetermined value is the first chromatogram obtained by measuring the first SRM transition and the second chromatogram obtained by measuring the second SRM transition. The compound (of the compound information) interferes with the compound (of the compound information) of the second chromatogram, or vice versa to determine the target range. Therefore, when the predetermined value is set to a large value, there is an advantage that the target of correction is broadened with the chromatogram (and the SRM transition for obtaining the chromatogram) which may possibly interfere with the predetermined value. On the other hand, setting the predetermined value to a small value has the advantage of reducing the burden on the computer. As a specific value based on such a viewpoint, the maximum value of the precursor ion integer mass difference according to the third predetermined value may be, for example, a value such as 5 daltons, 7 daltons, or 10 daltons. It is not restricted to these.

  The fourth predetermined value is appropriately specified in consideration of the characteristics of the measurement device and the like, and may be, for example, 0.5 volt, 1 volt, 2 volt or the like, but is not limited thereto.

  Here, an example showing that the first SRM transition and the second SRM transition have a second predetermined relationship will be described with reference to FIG. The maximum value of the precursor ion integer mass difference according to the third predetermined value is set to 10 daltons, ± 0.2 daltons is set as the predetermined tolerance, and 1 volt is set as the fourth predetermined value. Although not described in the table, it is assumed that the collision energy of the first SRM transition and the collision energy of the second SRM transition have the same value. FIG. 8 is a table regarding PS (34: 2). The first chromatogram measured in the first SRM transition is PS (34: 2) 81, and the second chromatogram measured in the second SRM transition is PS (34: 1) 82. It will be described that it has a second predetermined relationship. From the precursor ion mass (760.5) of the second chromatogram PS (34: 1) 82 which can be measured in the second SRM transition, the first chromatogram PS (34 which can be measured in the first SRM transition) : 2) The mass difference obtained by subtracting the precursor ion mass (758.5) of 81 is 2.0, which means that the precursor ion integer mass difference according to the third predetermined value is 2 daltons It corresponds to the case. Also, from the product ion mass (675.5) of the second chromatogram PS (34: 1) 82, which may be measured in the second SRM transition, a first chromatogram PS (which may be measured in the first SRM transition) 34: 2) The mass difference obtained by subtracting the product ion mass (673.5) of 81 is 2.0, and the corresponding product ion integer mass difference is 2, and the precursor ion integer mass difference (2) It is below. Further, from the premise that the collision energy of the first SRM transition and the collision energy of the second SRM transition have the same value, the difference is equal to or less than the fourth predetermined value (1).

  According to the above examination, the first chromatogram PS (34: 2) 81 measured in the first SRM transition and the second chromatogram PS (34: 1) 82 measured in the second SRM transition , Has a second predetermined relationship.

  The relationship deriving unit 44 determines the above-described second predetermined relationship, and performs the first SRM transition (SRM channel) related to the first chromatogram PS (34: 2) 81 with the second chromatogram PS (the second chromatogram PS (34: 2)). 34: 1) Relate as a corrected SRM transition (SRM channel) of the second SRM transition (SRM channel) according to 82.

  Similarly, the first chromatogram measured in the first SRM transition is PS (34: 2) 81, and the second chromatogram measured in the second SRM transition is PS (34: 0) 83. It will be described that these have a second predetermined relationship. From the precursor ion mass (762.5) of the second chromatogram PS (34: 0) 83, which can be measured in the second SRM transition, the first chromatogram PS (34), which can be measured in the first SRM transition : 2) The mass difference obtained by subtracting 81 of the precursor ion mass (758.5) 81 is 4.0, which means that the precursor ion integer mass difference according to the third predetermined value is 2 daltons It corresponds to the case. Also, from the product ion mass (677.5) of the second chromatogram PS (34: 0) 83, which may be measured in the second SRM transition, a first chromatogram PS (which may be measured in the first SRM transition) 34: 2) The mass difference obtained by subtracting the product ion mass (673.5) of 81 is 4.0, and the corresponding product ion integer mass difference is 2, and the precursor ion mass difference (4 ) Below. Further, from the premise that the collision energy of the first SRM transition and the collision energy of the second SRM transition have the same value, the difference is equal to or less than the fourth predetermined value (1).

  According to the above examination, the first chromatogram PS (34: 2) 81 measured in the first SRM transition and the second chromatogram PS (34: 0) 83 measured in the second SRM transition , Has a second predetermined relationship.

  Thereby, the relationship deriving unit 44 determines the above-mentioned second predetermined relationship, and the first SRM transition (SRM channel) relating to the first chromatogram PS (34: 2) 81 is determined by the second chromatography. Relate as a corrected SRM transition (SRM channel) of the second SRM transition (SRM channel) related to the gram PS (34: 0) 83.

  Further, among chromatograms corresponding to the target SRM transition, there are chromatograms in which the signal is not measured or chromatograms in which the signal is low. The relationship deriving unit 44 may include these chromatograms and relate them.

  On the other hand, the relationship deriving unit 44 may exclude a chromatogram for which no signal is measured or a chromatogram for which a signal is low as a target of association. A chromatogram for which no signal is measured is one that has nothing to be corrected as described later. Also, chromatograms with low signal have less advantage when corrected. Therefore, there is an advantage that the calculation time and calculation resources of these chromatograms can be made more efficient. When excluding chromatograms with low signals, the relationship deriving unit 44 may exclude chromatograms based on a predetermined value. For example, when the maximum value of the chromatogram signal is lower than a predetermined value, the relation deriving unit 44 may exclude the predetermined chromatogram. After the above-mentioned exclusion, the relation deriving unit 44 may perform the above-mentioned relation on chromatograms which are not excluded.

  Further, in FIG. 8, similarly, for the SRM transition 84 other than 82 and 83, if there is corresponding chromatogram data, it is an object to be corrected.

  In addition, the relationship deriving unit 44 may perform association before measuring the target sample using the SRM transition. In this case, the relationship deriving unit 44 may perform the association using an SRM transition including an SRM transition which is unknown to be measured or an SRM transition not to be measured.

  The relationship deriving unit 44 may store a plurality of related SRM transitions in a list format as a reference (list) to the SRM channel to be corrected as shown in FIG. In FIG. 9, the SRM channel 1 stores the SRM channel 2 and the SRM channel 3 as a reference (list) to the corrected SRM channel. That the SRM channel 1 stores the SRM channel 2 as a reference and / or the SRM channel 1 stores the SRM channel 3 as a reference is an example of the SRM transition relation set. Although the relation deriving unit 44 has been described here as a reference, the relation deriving unit 44 may create a table that directly relates information of corresponding SRM channels, in particular, SRM transition and / or compound information. The table is another example of the SRM transition relation set. Also, in FIG. 9, the order in the reference (list) to the SRM channel to be corrected is the mass (m / z) of the precursor ion of the related SRM transition and / or the mass (m / z) of the product ion May be stored based on For example, the list may be stored in ascending order of mass (m / z) of precursor ions of associated SRM transition and mass (m / z) of generated ions.

  Further, the relationship deriving unit 44 may associate information related to a plurality of SRM transitions having a second predetermined relationship based on time information. In the measurement of a chromatogram, in the case of measurement with respect to the SRM transition, measurement may be performed except for a time in which no significant information can be obtained even if it is clearly measured, in order to shorten the measurement time. Since correction can not be made between two chromatograms having different measurement time zones, it is possible to shorten the correction calculation by considering the measurement time.

For example, in the measurement by the first SRM transition, the time t1 to t2 is set, based on which the first chromatogram is measured, and in the measurement by the second SRM transition, the time t3 to t4 is set On the basis of this, it is assumed that a second chromatogram is measured. Moreover, t3 presupposes that it is the time after t2. In this case, there is no overlap between the measurement times of the first chromatogram and the second chromatogram. Therefore, there is no information required to make a correction between the first chromatogram and the second chromatogram, which are the results of measurement under these measurement conditions. Therefore, even when creating data related to association, it is not necessary to associate SRM transitions between chromatograms for which it is known that there is no overlap time.
That is, the system according to an embodiment of the present invention may include the relation deriving unit 44 that relates information related to a plurality of SRM transitions having the second predetermined relation based on time information.

  Further, the relationship deriving unit 44 determines a first SRM transition, a second SRM transition having a second predetermined relationship with the SRM transition, a measurement time of the first SRM transition, and the second SRM transition. If there is an overlap between the measurement time of and, it may be configured to relate.

  For example, FIG. 10 shows a table in which measurement times associated with SRM transitions of chromatograms are also recorded. In the table of FIG. 10, the measurement time for the SRM channel 1 indicates that the start time is T11 and the end time is T12, and the measurement time for the SRM channel 2 is that the start time is T21 and the end time is T22 or the like. And FIG. 10 has shown that the relationship is made between T11-T12 and T21-T22, when the overlap time exists. Similarly, FIG. 10 shows that there is also an overlap time between T11-T12 and T31-T32. Here, it has been described that the relationship deriving unit 44 overlaps the measurement time relating to the SRM transition as the additional condition of the second predetermined relationship. However, the relationship deriving unit 44 associates the SRM transitions with each other on the basis of the second predetermined relationship, and the correction unit 45 described later is one of the additional conditions of the correction requirement as to whether or not correction is performed. A configuration may be provided to determine whether there is an overlap time between SRM transitions.

2-5. Correction unit 45
The correction unit 45 has a function of correcting the measured chromatogram. The correction by the correction unit 45 has a function of reducing the influence of isotopes related to the chromatogram. For example, the correction unit 45 corrects the chromatogram based on the information obtained by the relation deriving unit 44.

The correction unit 45 generates a second chromatogram relating to the second SRM transition in the first SRM transition and a second SRM transition having a second predetermined relationship with the first SRM transition. The first chromatogram relating to the SRM transition of 1 is used for correction.
In addition, when the first SRM transition is related as a transition to be corrected of the second SRM transition by the relationship deriving unit, the first chromatogram related to the first SRM transition and the second SRM transition are used. It is said that the second chromatogram concerned is in a relation satisfying the correction requirement 1-2.

  The correction will be described using FIG. 11 as an example. The correction unit 45 corrects the chromatogram 111 using the chromatogram 112.

  For example, the value of the chromatogram 112 is subtracted from the value of the chromatogram 111. More specifically, the numerical value of the signal intensity of each corresponding time in the chromatogram 112 may be subtracted from the numerical value of the signal intensity of each time in the chromatogram 111 in consideration of the abundance ratio of isotopes. This makes it possible to correct the value of the chromatogram based on the information of other chromatograms that interfere with the chromatogram, and calculate a more appropriate value of the chromatogram.

  More specifically, after multiplying the numerical value of the signal intensity of each time of the chromatogram used for correction by a predetermined value taking into consideration the abundance ratio of isotope, the signal intensity of each time of the chromatogram to be corrected is multiplied. Subtracting from the numerical value for correction can reduce isotope-derived interference peaks. The predetermined value in consideration of the abundance ratio of isotopes includes isotope correction coefficients to be described later.

  That is, in the first SRM transition and the second SRM transition having a second predetermined relationship with the first SRM transition, the correction unit 45 is a second chromatogram related to the second SRM transition. A value obtained by multiplying the numerical value of the signal intensity of each time of the first chromatogram according to the first SRM transition by a predetermined value in consideration of the abundance ratio of isotope from the numerical value of the signal intensity of each time of Thereby, the second chromatogram may be corrected using the first chromatogram.

  In the example of FIG. 11, after the isotope correction coefficient of the SRM transition of the chromatogram 112 with respect to the SRM transition related to the chromatogram 111 is multiplied by the chromatogram 112, it is subtracted from the chromatogram 111 and corrected. . Thus, the chromatogram 113 could be derived. That is, the chromatogram was able to be derived from PC32: 0 by removing the influence of PC32: 1. The progress of these corrections can also be displayed on the display unit 46 or the like described later by being stored in the storage unit 41 or the like. Specifically, information such as chromatograms before correction, chromatograms used for correction, SRM transitions related to these, composition formulas of precursor ions, or composition formulas of product ions, etc. are stored. Some or all may be displayed.

Next, the isotope correction factor will be described. The isotope correction coefficient 1-2 is used as a coefficient by which the signal intensity of each time in the first chromatogram is multiplied when the second chromatogram is corrected using the first chromatogram, and the isotope is The field correction coefficient 1-2 is calculated as (R _k [A] / R ₀ [A]) × (R _{K -k} [B] / R ₀ [B]). Here, A is a composition formula of the generated ion in the compound information of the SRM channel related to the first chromatogram, and B is a generated ion separated from the precursor ion in the compound information of the SRM channel related to the first chromatogram It is a composition formula of the remainder (neutral leaving group). Also, K is a precursor ion difference, and k is a product ion difference. R _n [X] is the natural abundance ratio of isotope group Xn heavier by n Daltons than the monoisotopic mass of Compound X (the sum of abundance ratios of the same isotope of integer mass).

As an example of deriving B (neutral leaving group), when PC (4: 0) in the second row of FIG. 6 is described as an example, the composition formula of the precursor ion is C ₁₂ H ₂₅ N ₁ O ₈ P ₁ Since the composition formula of the product ion is C ₅ H ₁₅ N ₁ O ₄ P ₁ , the composition formula of B is C ₇ H ₁₀ O ₄ .

Here, the background of the above-mentioned formula is explained. Compound M which can be ionized as a monovalent positive ion is (1) M ⁺ -> A ⁺ + B (A ⁺ is an ion, B is a neutral molecule) in MS / MS
When you cause fragmentation like
(2) M ₀ −> A ₀
SRM measurement using the SRM transition can be performed. Here, M ₀ and A ₀ are monoisotopic masses of M and A (mass in the case where the molecule is constituted by only main isotopes of the respective elements constituting the molecule).

Since there are generally multiple stable isotopes in M, fragmentation of (1) is not limited to (2) but (3) M ₀ + K −> A ₀ + k
The signal is generated by measurement using various SRM transitions represented by Here, K is an integer of 0 or more, k is an integer of 0 or more and K or less, and the possible values of K and k are actually the compositional formulas of compounds and fragment ions corresponding to such K and k. It is limited to what is configurable.

Hereinafter, when the compound M is given, it is calculated what ratio each signal of the transition (3) generates with respect to the signal of the transition (2).
Fragmentation (1) is a isotope-differentiated form (4) M _K ⁺ −> A _k ⁺ + B _{K −k}
(Where M _K ⁺ , A _k ⁺ and B _K -k give masses M ₀ + K, A ₀ + k and B ₀ + K-k respectively, and the isotopes of M ⁺ , A ⁺ and B, respectively) And). The (4) means that _{the M K} is divided into two partial structures of _{A k} and _{B K-k.} The abundance ratio of isotopes detected by the SRM transition of (3) is equivalent to the abundance ratio of M _K ⁺ satisfying (4), that is, (R _k [A] / R ₀ [A]) described above It can obtain | require by x ( _RK-k [B] / _R0 [B]).

Next, a method of calculating the value of R _n [X] will be described. The compound X is an example of the case where its constituent element is (C, H, O, N), but the same calculation is possible when the compound X has other constituent elements. About each element, the kind of natural stable isotope and its abundance ratio are as FIG.

The composition formula of the compound X and _{C w H x O y N z} . The stable isotopes contained in the molecule are distinguished, and the composition formula is (5) [ ¹² C] _{w 1} [ ¹³ C] _{w 2} [ ¹ H] _x ¹ [ ² H] _{x 2} [ ¹⁶ O] _{y 1} [ ¹⁷ O] _{y 2} [2 ^{_{18 O] y3 [14 N]}} z1 [15 N] z2
And generalize. However, w1, w2, x1, x2, y1, y2, y3, z1, z2 are integers of 0 or more that satisfy w = w1 + w2, x = x1 + x2, y = y1 + y2 + y3, z = z1 + z3. The natural abundance ratio R of the individual stable isotopes of the compound X is determined using w1, w2, x1, x2, y1, y2, y3, z1, z2 (6) R = _w C _w1 [ ¹² C] ^w1 [ ^{13 _{C] w2 × x C x1 [}} 1 H] x1 [2 H] x2 × y C y1 × y-y1 C y2 [16 O] y1 [17 O] y2 [18 O] y3 × z C z1 [14 N] ^{z1 [15 N] z2}
It can be expressed as Here, the natural abundance ratio is represented by the isotope name. That is, [ ¹² C] = 0.9893, [ ¹³ C] = 0.0107, ..., [ ¹⁵ N] = 0.00364. Also, _n C _r represents the number of combinations for extracting r out of n

For a stable isotope of X, the value obtained by rounding off the mass difference to the monoisotopic mass to an integer value is (7) n = w 2 + x 2 + y 2 + 2 y 3 + z 2
The natural abundance ratio of the isotope group heavier by n Daltons than the monoisotopic mass of X (the sum of the abundance ratios of the same isotopes of integer mass) is based on (6) and (7) ( 8) R _n [X] = R R [w2, x2, y2, y3, z2 is all combinations that satisfy n = w2 + x2 + y2 + 2y3 + z2]
It is expressed as Here, the combination can be calculated by a known method including a simple counting method.

  Using the isotope correction factor described above, the correction unit 45 can set the first chromatogram and the isotope correction factor 1-1 in the second chromatogram and the first chromatogram that satisfy the correction requirement 1-2. The second chromatogram may be corrected using T.2 in order to correct the second chromatogram. The second chromatogram after correction obtained by correcting the second chromatogram using the first chromatogram is referred to as “second chromatogram Am1” (abbreviation of AmendedBy1).

  In addition, the correction unit 45 is configured such that, in the second chromatogram and the first chromatogram that satisfy the correction requirement 1-2, the signal intensity of each of a part or all of the time in the second chromatogram The signal intensity at each corresponding time of the chromatogram is multiplied by the isotope correction factor 1-2 and subtracted. This is not a correction limited to only the peaks of the chromatogram, but is subtracted (corrected) by multiplying each value (entirely) of the chromatogram on the subtraction (correction) side by the isotope correction factor. The process of specifying the peak value and the like is not necessary by performing the process of subtracting from each value (entirely) of the chromatogram of the In addition, the case where a subtraction is processed etc. can be considered for the part each time in the above, for example for the part whose signal strength is higher than predetermined value.

  However, in the case where there are a plurality of first SRM transitions (first chromatograms) satisfying a specific correction requirement (for example, the first A and the first B), the user can select one of them, depending on the case. It is also possible to select a chromatogram obtained by averaging the 1A and 1B. When the selection is performed, for example, after displaying the corrected chromatograms provisionally processed using each of the first A and the first B on the display unit 46, it is determined which is more appropriate, The chromatogram used for correction can be selected. In addition, instead of the above user's selection, correction processing is automatically performed according to a certain reference (for example, automatically selecting a chromatogram having a peak with higher intensity, etc.) from among a plurality of these. It can also be set in advance.

  In other words, the correction unit 45 uses the second chromatogram and the 1A chromatogram satisfying the correction requirement 1A-2 and the second chromatogram satisfying the correction requirement 1B-2 and the 1B chromatogram. The precursor ion integer mass difference of the 1st SRM transition concerning the 1 A chromatogram and the 2nd SRM transition concerning the 2nd chromatogram, the 1 B SRM transition according to the 1 B chromatogram and the above The precursor ion integer mass difference of the second SRM transition according to the second chromatogram is equal, and the product ion integer mass difference of the first SRM transition and the second SRM transition, and the second Product ion integer mass of 1B SRM transition and second SRM transition When and are equal, the second chromatogram Am1A and the second chromatogram Am1B are displayed on the display unit 46, and based on the information obtained from the input unit, the selected chromatogram is displayed as the second chromatogram. It may be configured as a chromatogram after correction of the chromatogram.

  In FIG. 11, the chromatogram 112 itself is an example that is not corrected. However, for example, when the third chromatogram is corrected using the second chromatogram, it is preferable that the second chromatogram itself has already been corrected. Therefore, the correction unit 45 may be configured to correct the third chromatogram using the second chromatogram corrected by the first chromatogram.

  That is, the correction unit 45 performs the third chromatogram in the third chromatogram, the second chromatogram, and the first chromatogram that satisfy the correction requirement 1-3 and the correction requirement 2-3. A configuration may be provided to correct based on the gram Am1 and the first chromatogram.

  In addition, the correction unit 45 determines the isotope correction factor from the third chromatogram in the third chromatogram, the second chromatogram, and the first chromatogram that satisfy the correction requirement 1-3 and the correction requirement 2-3. Even when the correction is performed to reduce both the first chromatogram multiplied by 1-3 and the second chromatogram Am1 multiplied by the isotope correction coefficient 2-3, a corrected third chromatogram is obtained. Good.

  Also, although the processing for three chromatograms has been described above, the correction unit 45 similarly decreases the mass (m / z) of precursor ions for four or more chromatograms (precursor (precursor It goes without saying that when the ion masses (m / z) are equal, the correction process can be continuously performed on the mass (m / z) of the generated ions in ascending order.

2-6. Display unit 46
The display unit 46 displays information on the chromatogram after correction. The information related to the chromatogram after correction is information on the chromatogram after correction, information on the progress of correction, or a combination thereof. Examples of the information that indicates the progress of the correction include the following information. For example, the display unit 46 may display both the chromatogram after correction and the chromatogram before correction. The display unit 46 may display the chromatogram after the correction and the chromatogram before the correction so as to overlap and distinguish. The display unit 46 may change the display method of the chromatogram after correction and the chromatogram before correction as an aspect to distinguish and display. For example, the display unit 46 may display the chromatogram after correction and the chromatogram before correction using different display colors or lines of different displays. The number of chromatograms used for correction displayed by the display unit 46 may be one or more. For example, when the chromatograms are corrected using three chromatograms, the display unit 46 may display these three chromatograms (the chromatogram on the side multiplied by the isotope correction coefficient). In addition, the display unit 46 may display the SRM transition related to the chromatogram before correction.

  For example, in the chromatogram 1303 after correction in FIG. 13, 1303 f is a part of the chromatogram after correction, but 1303 b is not a part of the chromatogram after correction (the part deleted by correction) . That is, the peak 1303 b of the chromatogram 1303 is one that has been subtracted (removed from the chromatogram after correction) by the correction using the peak 1301 b of the chromatogram 1301. However, in the chromatogram 1303, the peak 1303b is displayed by a color different from the peak 1303f remaining as a peak even after correction. The display unit 46 may also display the chromatogram used at the time of correction, such as the chromatogram 1301 and the chromatogram 1302. By these, there is an advantage that the user can understand based on what chromatogram the corrected chromatogram is corrected.

  In addition, the display unit 46 may display results of various processing such as peak detection, integration, statistical information output and the like of the corrected chromatogram.

3. Flowchart A flowchart according to the present invention will now be described.

3-1. Example 1
The first embodiment will be described with reference to FIG.
First, an SRM transition to be measured is identified (1401). Usually, there are a plurality of SRM transitions to be measured, and these are input from the input unit. The input may be manually input or may be recorded in advance in a file or the like.
Also, the time to measure may be input. The measurement time may be set differently for each SRM transition, or may be the same measurement time for several SRM transitions. The measurement time can be specified by a set of start time and end time after the start of measurement.

  Next, the target sample is measured based on the SRM transition to be measured, and a chromatogram corresponding to each SRM transition is acquired (1402).

  Next, compound information is associated with each of the measured chromatograms (1403). The compound information may not be related to each of the measured chromatograms for which the compound information is unknown. Also, multiple pieces of compound information may be associated with one measured chromatogram. The compound information may be related to the measured chromatogram based on a table relation in which the SRM transition related to each chromatogram and the compound information are related. The information combining step (1403) may be performed between the relationship deriving step (1404) and the correction step (1405) instead of this order.

  Further, the relationship deriving unit 44 determines whether the chromatogram has a signal before or after the step (1403) of associating the chromatogram and the compound information, and the chromatogram or the signal for which the signal is not measured has a predetermined value. It may have the step of excluding lower chromatograms from related chromatograms to be related.

  Next, the relationship deriving unit 44 associates the first SRM transition and the second SRM transition to derive an SRM transition relationship set (1404). Here, it may also be related using the measurement time according to the SRM transition.

  Next, the chromatogram is corrected (1405). In the second chromatogram and the first chromatogram that satisfy the correction requirement 1-2, the correction unit 45 determines the signal intensity of each signal in the second chromatogram at each corresponding time of the first chromatogram. The signal intensity may be multiplied by the isotope correction coefficient 1-2 to be subtracted.

  In addition, the correction unit 45 determines the third chromatogram satisfying the correction requirement 1-2 and the correction requirement 2-3, the second chromatogram, and the first chromatogram based on the first chromatogram. After correcting the second chromatogram, the method may include correcting the third chromatogram based on the corrected second chromatogram. The correction unit 45 may further include a step of correcting the third chromatogram based on the first chromatogram. In the step of the correction unit 45 correcting the third chromatogram based on the first chromatogram, the step of correcting the third chromatogram based on the corrected second chromatogram. It may be done before or after.

  In addition, the correction unit 45 determines that the first chromatogram contains isotopes in the third chromatogram, the second chromatogram, and the first chromatogram that satisfy the correction requirement 1-2 and the correction requirement 2-3. After the second chromatogram is corrected using the product obtained by multiplying the correction coefficient 1-2, the third sample obtained using the product obtained by multiplying the corrected second chromatogram by the isotope correction coefficient 2-3 The method may include the step of correcting the chromatogram of In addition, the correction unit 45 may correct the third chromatogram using the first chromatogram multiplied by the isotope correction coefficient 1-3. Note that the step of the correction unit 45 correcting the third chromatogram using the first chromatogram multiplied by the isotope correction coefficient 1-3 is the step of correcting the second chromatography described above. The step of correcting the third chromatogram may be performed before or after the step of correcting the third chromatogram using a gram multiplied by an isotope correction coefficient 2-3.

  Furthermore, in the third chromatogram, the second chromatogram, and the first chromatogram that satisfy the correction requirement 1-2 and the correction requirement 2-3, the correction unit 45 determines each time of the first chromatogram. Of each signal in the second chromatogram corrected by subtracting each value obtained by multiplying the signal intensity in the signal by the isotope correction coefficient 1-2 from the signal intensity corresponding to each time in the second chromatogram. The signal intensity in time may be corrected by subtracting each value obtained by multiplying the signal intensity in time by the isotope correction coefficient 2-3 from the signal intensity corresponding to each time in the third chromatogram. In addition, the correction unit 45 subtracts each value obtained by multiplying the signal strength at each time of the first chromatogram by the isotope correction coefficient 1-3 from the signal strength corresponding to the each time in the third chromatogram. Correction may be provided. The correction unit 45 subtracts each value obtained by multiplying the signal intensity at each time of the first chromatogram by the isotope correction coefficient 1-3 from the signal intensity corresponding to each time in the third chromatogram. And correcting the signal, the value corresponding to each time in the third chromatogram, each value obtained by multiplying the signal strength at each time of the second chromatogram corrected above by the isotope correction coefficient 2-3 It may be performed before or after the step of subtracting and correcting from the intensity.

Next, the corrected chromatogram is displayed (1406). At this time, the display unit 46 may display information related to the chromatogram used for the correction. For example, information such as a chromatogram to be subtracted (before subtraction), its SRM transition, its compound information, the composition formula of its precursor ion, or the composition formula of its product ion may be displayed. In addition, information such as a chromatogram on the side of subtraction, its SRM transition, its compound information, the composition formula of its precursor ion, or the composition formula of its product ion may be displayed.
3-2. Example 2
The second embodiment will be described with reference to FIG. Although the description of the same parts as those of the first embodiment is omitted, it goes without saying that the same parts can be applied to the second embodiment.
The second embodiment is an example in which duplicate calculations are collectively performed.

  First, the SRM transition to be measured is specified (step 1501), and the input unit acquires chromatograms measured based on the SRM transition in the form of a plurality of files (step 1502).

  Next, with respect to the chromatogram included in the first file and the SRM transition related thereto, the relation deriving unit 44 calculates the mass (m / z) of the precursor ion related to the SRM transition, and the mass (m / z) of the generated ion z) Based on the collision energy, the first SRM transition is associated with the second SRM transition having a second predetermined relationship with the first SRM transition to derive an SRM transition relationship set (step 1503).

  Next, for the second file, the relationship deriving unit 44 generates a first SRM based on the mass (m / z) of precursor ions involved in the SRM transition, the mass (m / z) of generated ions, and the collision energy. A transition is associated with a second SRM transition having a second predetermined relationship with the first SRM transition to derive an SRM transition relationship set (step 1504). Here, the relation deriving unit 44 does not have to newly add the SRM transition that has already been used for the relation in the first file. The relationship deriving unit 44 extracts a chromatogram related to the SRM transition used for association in the first file in the second file, a chromatogram related to the SRM transition already used for association in the first file. In the list (eg, reference (list) to chromatogram in FIG. 9). On the other hand, the relationship deriving unit 44 newly assigns a new SRM transition of the second file. In the above process, in the first SRM transition in the first file and the second SRM transition in the second file, the mass (m / z) of the precursor ion of the first SRM transition and the precursor ion of the second SRM transition And the mass (m / z) of the product ion of the first SRM transition and the mass (m / z) of the product ion of the second SRM transition with a predetermined tolerance. The second SRM transition may be treated as the first SRM transition considered as substantially the same as the first SRM transition and already associated in the first file.

  As a result, this embodiment has the advantage of reducing the burden of recalculation on SRM transitions derived in the first file.

Next, the information binding unit 43 associates the compound information (step 1505). The association of the compound information is also applied to only the duplicate information in the plurality of files, which has the advantage of reducing the computational burden.
The subsequent correction by the correction unit 45 and the display by the display unit 46 are the same as in the first embodiment (steps 1506 and 1507).

  The processes and procedures described in the present specification are not limited to those explicitly described in the embodiments, but can be realized by the various embodiments within the scope of the technical idea. Nor.

Claims (14)

An information binding unit that relates compound information to a chromatogram;
A relationship deriving unit that derives an SRM transition relationship set in which a first SRM transition and a second SRM transition having a predetermined relationship with the first SRM transition are associated;
A correction unit that corrects a chromatogram based on the compound information correlated by the information coupling unit and the SRM transition relation set;
Data processor for chromatograms.   The chromatogram data processing apparatus according to claim 1, wherein the compound information is compound information related to an SRM transition having a first predetermined relationship with an SRM transition related to the chromatogram.   The chromatogram data processing apparatus according to claim 1, wherein the compound information includes a composition formula of precursor ions and a composition formula of product ions.   The relationship deriving unit according to any one of claims 1 to 3, wherein the relationship deriving unit relates based on the mass of precursor ions related to the first SRM transition and the second SRM transition and the mass of a generated ion. Data processor for chromatograms as described.   The correction unit may correct the second chromatogram related to the second SRM transition related to the first SRM transition based on the first chromatogram related to the first SRM transition related by the relationship deriving unit. The chromatogram data processing apparatus according to any one of claims 1 to 4, characterized in that:   The chromatogram data processing apparatus according to claim 5, wherein a mass of precursor ions related to the first SRM transition is smaller than a mass of precursor ions related to the second SRM transition.   The data processing apparatus for chromatogram according to claim 6, wherein a mass of product ions related to the first SRM transition is equal to or smaller than a mass of product ions related to the second SRM transition.   8. The data processing apparatus for chromatograms according to claim 7, wherein the correction unit performs correction to reduce the first chromatogram multiplied by a predetermined coefficient from the second chromatogram. Computer,
Information binding means for relating compound information to chromatograms,
Relationship deriving means for deriving an SRM transition relationship set in which a first SRM transition and a second SRM transition having a predetermined relationship with the first SRM transition are associated;
Correction means for correcting a chromatogram based on the compound information correlated by the information coupling unit and the SRM transition relation set;
Data processing program for chromatograms to function as   The program for data processing for chromatogram according to claim 9, wherein the compound information includes a composition formula of precursor ions and a composition formula of product ions. An information binding step to associate compound information with the chromatogram;
A relationship deriving step of deriving a SRM transition relationship set in which a first SRM transition and a second SRM transition having a predetermined relationship with the first SRM transition are associated;
A correction step of correcting a chromatogram based on the compound information correlated by the information coupling unit and the SRM transition relation set;
Data processing method for chromatograms including:   The method for processing chromatogram data according to claim 11, wherein the compound information includes a composition formula of precursor ions and a composition formula of product ions. A relationship deriving step of deriving a SRM transition relationship set in which a first SRM transition and a second SRM transition having a predetermined relationship with the first SRM transition are associated;
Correcting the chromatogram based on compound information related to the measured chromatogram and the SRM transition relation set;
Data processing method for chromatograms including:   The method for processing chromatogram data according to claim 13, wherein the compound information includes a composition formula of precursor ions and a composition formula of product ions.

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