Analysis system, analysis method, and program

Abstract

To provide an analysis system or the like capable of easily quantifying the object substance in a plurality of pieces of spectrum data in a short period of time while enabling a detailed comparison display of chromatograms in different samples and different object substances.SOLUTION: In an analysis system 1, a selection unit 12 can select a plurality of chromatograms astride a plurality of samples and a plurality of object substances from among chromatograms stored in a storage unit 10 on the basis of input command information inputted to an input unit 11. A display unit 13 overlaps and displays the plurality of chromatograms selected by the selection unit 12. A setting unit 14 sets reference position information to be reference for performing calculation to the plurality of chromatograms displayed in the display unit 13 on the basis of the input command information inputted to the input unit 11. A quantitation unit 15 collectively quantifies object substances of each of the plurality of chromatograms displayed in the display unit 13 on the basis of the reference position information set by the setting unit 14.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to an analysis system, an analysis method, and a program. [Background technology]

[0002] Metabolomic analysis is performed by detecting compounds detected in vivo, i.e., metabolites. Various methods are used to detect metabolites. For example, chromatography mass spectrometry, as disclosed in Patent Documents 1 and 2, is one such method.

[0003] In chromatography mass spectrometry, a sample is first introduced into a column of a chromatograph, and an eluate in which various components of the sample are separated in the time direction is extracted. The various components of the extracted eluate are then ionized in an ion source of a mass spectrometer, and ions derived from the sample components are separated according to their mass-to-charge ratios using a quadrupole mass filter or the like, and the target substance is detected. As a result of this detection, a chromatogram is obtained in which peaks indicating the target substance appear.

[0004] Each metabolite is quantified by calculating the area or height of the peak appearing in the chromatogram. However, this quantification must take into account the chemical properties of the metabolite or background conditions such as the measurement conditions in the chromatography mass spectrometer. Therefore, an experienced analyst visually checks the peaks in the displayed chromatogram and specifies the range for calculation by operating the calculator to perform the quantification. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] International Publication No. 2018 / 207228 [Patent Document 2] International Publication No. 2017 / 002156 Summary of the Invention [Problem to be solved by the invention]

[0006] Metabolomic analysis requires the quantification of many metabolites in many samples. For example, to quantify 500 metabolites in 100 samples, a total of 50,000 chromatograms are required. However, as mentioned above, in order to accurately quantify metabolites, the analyst had to display each chromatogram one by one and visually check the peaks. This meant that the entire analysis took a long time and placed a huge workload on the analyst.

[0007] In addition, in metabolome analysis, it is extremely useful to be able to compare chromatograms between different samples and different metabolites. However, in the device disclosed in Patent Document 1, the chromatograms displayed simultaneously are limited to the target ions and confirmation ions for the target substance. In addition, the device disclosed in Patent Document 2 displays chromatograms in a reduced form in a two-dimensional table, which is not suitable for detailed comparison of the waveforms of chromatograms.

[0008] The present invention has been made in light of the above-mentioned circumstances, and aims to provide an analysis system, an analysis method, and a program that enable detailed comparison display of chromatograms for different samples and different target substances, while quickly and easily quantifying target substances in multiple spectrum data. [Means for solving the problem]

[0009] In order to achieve the above object, an analysis system according to a first aspect of the present invention comprises: a storage unit that stores spectrum data obtained by analyzing a sample containing a target substance in such a manner that the spectrum data can be retrieved using the sample and the target substance as keys; an input unit for inputting user input command information; a selection unit capable of selecting a plurality of pieces of spectrum data across a plurality of the samples and a plurality of the target substances from the spectrum data stored in the storage unit based on input command information input to the input unit; a display unit that displays the plurality of spectrum data selected by the selection unit in an overlapping manner; a setting unit that sets reference position information serving as a reference for performing an operation on the plurality of spectrum data displayed on the display unit based on input command information input to the input unit; The plurality of spectrum data displayed on the display unit are based on the reference position information set by the setting unit. of A quantification unit that collectively quantifies each of the target substances; Equipped with picture, The storage unit is storing dummy spectrum data defining a settable range in which the reference position information can be set by the setting unit; The display unit is The plurality of spectrum data selected by the selection unit and the dummy spectrum data are displayed in an overlapping manner; The setting unit is The reference position information cannot be set outside the settable range defined by the dummy spectrum data.

[0011] Moreover, the selection unit a first list generating unit that generates a first list, which is a list of samples corresponding to the spectrum data stored in the storage unit, and displays the first list on the display unit; a second list generating unit that generates a second list in which spectrum data corresponding to the sample selected from the first list can be selected for each of the target substances based on input command information input to the input unit, and displays the second list on the display unit; a data acquisition unit that acquires, based on input command information input to the input unit, the spectrum data selected from the second list displayed on the display unit, which corresponds to the sample selected from the first list displayed on the display unit, as the spectrum data to be displayed on the display unit; Equipped with This may also be the case.

[0012] The setting unit is setting a range for quantifying the target substance in the plurality of spectrum data displayed on the display unit as the reference position information; The quantification unit is quantification of the target substance within the range set by the setting unit using each of the plurality of spectrum data displayed on the display unit; This may also be the case.

[0013] The setting unit is setting a baseline of the spectrum data based on input command information input to the input unit; The quantification unit is quantification of the target substance based on the baseline set by the setting unit; This may also be the case.

[0014] The display unit is enlarging or reducing each of the plurality of spectrum data to be displayed at the same time based on input command information input to the input unit; This may also be the case.

[0015] The display unit is performing smoothing processing on each of the plurality of spectrum data to be displayed collectively based on input command information inputted to the input unit, and then displaying the plurality of spectrum data in an overlapping manner; The quantification unit quantifies the target substance in each of the plurality of spectrum data that have been smoothed. This may also be the case.

[0016] The display unit is The spectrum data are displayed in a superimposed state with an offset or magnification applied to each of the spectrum data in the time axis direction so that the peaks coincide with each other in the time axis direction; The setting unit is collectively setting reference position information for performing quantification on the plurality of spectrum data items displayed in an overlapping manner; The quantification unit is changing the reference position information so that an offset or a magnification factor applied to each of the spectrum data is cancelled, and quantifying the target substance in each of the plurality of spectrum data based on the changed reference position information; This may also be the case.

[0017] The analysis method according to the second aspect of the present invention comprises: An analysis method executed by an analysis system that quantifies a target substance based on spectrum data obtained by analyzing a sample containing the target substance, comprising: a selection step of selecting a plurality of pieces of spectrum data across a plurality of the samples and a plurality of the target substances based on input command information from a database that stores the spectrum data retrievably using the samples and the target substances as keys; a display step of displaying the plurality of spectrum data selected in the selection step in an overlapping manner; a setting step of setting reference position information that is a reference for performing an operation on the plurality of spectrum data displayed in the display step, based on input command information from a user; The plurality of spectrum data displayed in the display step are displayed based on the reference position information set in the setting step. of A quantification step of collectively quantifying each of the target substances; Including fruit, The database includes: storing dummy spectrum data defining a settable range within which the reference position information can be set in the setting step; In the display step, displaying the plurality of spectrum data selected in the selection step and the dummy spectrum data in an overlapping manner; In the setting step, The reference position information cannot be set outside the settable range defined by the dummy spectrum data.

[0018] A program according to a third aspect of the present invention comprises: Computer, a storage unit that stores spectrum data obtained by analyzing a sample containing a target substance in a manner retrievable using the sample and the target substance as keys; an input unit for inputting user input command information; a selection unit that selects a plurality of pieces of spectrum data across a plurality of the samples and a plurality of the target substances from the spectrum data stored in the storage unit based on input command information input to the input unit; a display unit that displays the plurality of spectrum data selected by the selection unit in an overlapping manner; a setting unit that sets reference position information serving as a reference for performing an operation on the plurality of spectrum data displayed on the display unit based on input command information inputted to the input unit; And, The plurality of spectrum data displayed on the display unit are based on the reference position information set by the setting unit. of A quantification unit that collectively quantifies each of the target substances; Functions as height, The storage unit is storing dummy spectrum data defining a settable range in which the reference position information can be set by the setting unit; The display unit is The plurality of spectrum data selected by the selection unit and the dummy spectrum data are displayed in an overlapping manner; The setting unit is The reference position information cannot be set outside the settable range defined by the dummy spectrum data. Effect of the Invention

[0019] According to the present invention, a plurality of spectrum data across a plurality of samples and a plurality of target substances are displayed in an overlapping manner. This allows detailed comparison of the waveforms of spectrum data for different samples and different target substances. Furthermore, since a plurality of spectrum data are displayed in an overlapping manner, it is possible to collectively quantify the target substances in each of the plurality of spectrum data in a state in which reference position information serving as a reference for performing calculations on the plurality of spectrum data is set while taking into account background conditions such as the chemical properties of metabolites or measurement conditions according to input command information from an analyst. As a result, it is possible to easily quantify the target substances in the plurality of spectrum data in a short time while allowing detailed comparison and display of spectrum data for different samples and different target substances. [Brief description of the drawings]

[0020] [Figure 1] 1 is a block diagram showing a configuration of an analysis system according to a first embodiment of the present invention. [Diagram 2] FIG. 1 is a diagram showing an example of a chromatogram. [Diagram 3] FIG. 2 is a schematic diagram showing a functional configuration for displaying overlapping chromatograms in the analysis system of FIG. 1. [Figure 4] FIG. 13 is a schematic diagram showing how spectrum data is expanded or contracted. [Diagram 5] FIG. 2 is a schematic diagram showing the functions of a setting unit and a quantification unit in FIG. 1. [Figure 6] (A) and (B) are examples of waveforms of spectrum data. [Figure 7] (A) is an example of spectrum data displayed in an overlapping manner. (B) is an example of spectrum data displayed in an overlapping manner so that peaks match. [Figure 8] FIG. 13 is a schematic diagram showing how spectrum data is smoothed. [Figure 9] FIG. 2 is a block diagram showing a hardware configuration of the analysis system of FIG. [Figure 10]2 is a flowchart showing the operation of the analysis system of FIG. 1. [Figure 11] FIG. 11 is a diagram showing an example of a dummy chromatogram which is a feature of the analysis system according to the second embodiment of the present invention. [Figure 12] FIG. 11 is a block diagram showing a configuration of an analysis system according to a second embodiment of the present invention. [Figure 13] FIG. 13 illustrates an example of an input table. [Figure 14] FIG. 1 is a diagram showing a display example of a chromatogram of cholesterol ester. [Figure 15] FIG. 13 is a diagram showing another example of a chromatogram of cholesterol ester. [Figure 16] FIG. 16 is a diagram showing an example of a display in which the cholesterol chromatogram shown in FIG. 14 and the chromatogram shown in FIG. 15 are superimposed. [Figure 17] FIG. 15 is a diagram showing a state in which a range for quantification is set in the chromatogram shown in FIG. 14. [Figure 18] FIG. 13 is a diagram showing a display example of a cholesterol chromatogram. [Figure 19] FIG. 19 is a diagram showing an example of a display in which the cholesterol chromatogram shown in FIG. 17 and the chromatogram shown in FIG. 18 are superimposed. [Figure 20] FIG. 13 is a diagram showing a case where chromatograms of all transitions are superimposed and displayed. [Figure 21] FIG. 13 is a diagram showing a case where chromatograms of the same molecular species as target substances are superimposed and displayed. [Figure 22] FIG. 22 is a diagram showing how the quantification range is set in the chromatogram of FIG. 21. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0021] Hereinafter, an embodiment of the present invention will be described in detail with reference to the drawings. In each drawing, the same or equivalent parts are denoted by the same reference numerals.

[0022] Embodiment 1 First, a first embodiment of the present invention will be described. An analysis system 1 according to the present embodiment quantifies a target substance. As shown in Fig. 1, the analysis system 1 is connected to a liquid chromatography mass spectrometer (LC-MS) 2.

[0023] LC-MS2 is a device that combines a liquid chromatograph and a mass spectrometer. A liquid chromatograph uses a liquid as the mobile phase and separates substances by utilizing the difference in the affinity of solutes for the stationary phase and the mobile phase. A mass spectrometer further ionizes the substances separated by the liquid chromatograph, separates the resulting positive and negative ions, and measures the intensity of each ion.

[0024] Using LC-MS2, it is possible to obtain spectrum data, i.e., chromatograms, obtained by analyzing target substances contained in a sample. As shown in Figure 1, samples A1, A2, ..., Am are injected into LC-MS2, and chromatograms corresponding to target substances a1, a2, a3, ... contained therein are detected.

[0025] An example of a chromatogram is shown in Figure 2. As shown in Figure 2, the horizontal axis of the chromatogram indicates the time from when the sample is injected into the LC-MS2. Meanwhile, the vertical axis indicates the intensity of the signal detected by the LC-MS2. A peak P appears in the chromatogram shown in Figure 2. The time from when the sample is injected, that is, the time from the origin until when the peak P reaches its apex, is defined as the elution time (retention time) RT. The elution time RT differs depending on the target substance.

[0026] In the chromatogram, the portion where the peak P does not appear is defined as the baseline BL. The height or area of ​​the peak P based on the baseline BL increases or decreases depending on the concentration of the target substance. The analysis system 1 quantifies the target substance by determining the height or area of ​​the peak P in the chromatogram.

[0027] Returning to FIG. 1, the analysis system 1 is an information processing device including a storage unit 10, an input unit 11, a selection unit 12, a display unit 13, a setting unit 14, and a quantification unit 15.

[0028] The storage unit 10 is a database that stores chromatograms obtained by analyzing a sample containing a target substance through detection in the LC-MS2. This database is configured to be able to acquire chromatograms using the sample and the target substance as keys. For example, in the example shown in FIG. 1, measurements are performed on samples A1 to Am (m is a natural number of 3 or more) in the LC-MS2, and chromatograms corresponding to the target substances a1, a2, a3, . . . contained in the sample A1, chromatograms corresponding to the target substances a1, a2, a3, . . . contained in the sample A2, chromatograms corresponding to the target substances a1, a2, a3, . . . contained in the sample Am are acquired and stored in the storage unit 10. In this case, the storage unit 10 is configured to be able to read out the chromatograms corresponding to the sample A1 and the target substance a1 by inputting, for example, the sample A1 and the target substance a1 as keys.

[0029] When performing metabolomic analysis in the analysis system 1, the sample is a part of a living body, for example, a cell, and the target substance is a metabolite. In metabolomic analysis, for example, hundreds of samples and chromatograms of hundreds of metabolites are used. For example, if the number of samples to be analyzed is 100 and the number of metabolites is 500, it is necessary to analyze 100 x 500 chromatograms.

[0030] Returning to FIG. 1, the input unit 11 inputs input command information of a user who is an analyst who quantifies a target substance. The input command information includes, for example, information on a sample and a target substance that serve as keys for the storage unit 10. The input command information may be input by an operational input by the analyst, or may be input by importing a file. The operational input by the analyst can be realized by numerical input using a pointing device or a keyboard that constitutes a man-machine interface 43 in FIG. 9 described later.

[0031] The selection unit 12 can select a plurality of chromatograms across a plurality of samples and a plurality of target substances from among the chromatograms stored in the storage unit 10, based on input command information input to the input unit 11. For example, as shown in Fig. 1, when analyzing target substances a1, a2, and a3 of sample A1 and target substances a1, a2, and a3 of sample A2, the corresponding chromatograms are selected.

[0032] [Function configuration for overlaying chromatograms] Here, the functional configuration for displaying the overlapped chromatograms will be described. As shown in Fig. 3, the display unit 13 has a display screen that can be confirmed by the user. The input unit 11 and the display unit 13 are linked, and the user can input, into the input unit 11, input command information related to various information displayed on the display screen.

[0033] The display unit 13 displays a plurality of chromatograms selected by the selection unit 12 in a window 13a displayed on the display screen in an overlapping manner. As shown in FIG. 3, the window 13a is divided into a sample list display area 20, a target substance list display area 21, and a chromatogram display area 22.

[0034] The selection unit 12 also includes a first list creation unit 30, a second list creation unit 31, and a data acquisition unit 32.

[0035] The first list generating unit 30 generates a first list, i.e., a sample list 25, which is a list of samples corresponding to the chromatograms stored in the memory unit 10. The first list generating unit 30 displays the generated sample list 25 on the display unit 13. For example, as shown in Fig. 3, the sample list display area 20 of the window 13a of the display unit 13 displays the sample list 25 of samples A1, A2, ... Am stored in the memory unit 10.

[0036] The second list creation unit 31 creates a target substance list 26 that enables selection, for each target substance, of a chromatogram corresponding to a sample selected from the sample list 25, based on input command information entered into the input unit 11. The second list creation unit 31 displays the created target substance list 26 in the target substance list display area 21 of the window 13a of the display unit 13.

[0037] 3, for example, when input command information to the effect that samples A1 and A2 have been selected in the sample list 25 displayed in the sample list display area 20 is input to the input unit 11, the second list generation unit 31 generates a target substance list 26 corresponding to samples A1 and A2 and displays it in the target substance list display area 21 of the display unit 13. As a result, the target substance list 26 of chromatograms corresponding to the target substances a1, a2, a3, ... contained in the samples A1 and A2 is displayed in the target substance list display area 21 of the window 13a of the display unit 13.

[0038] The data acquisition unit 32 acquires, based on input command information input to the input unit 11, a chromatogram selected from the target substance list 26 displayed on the display unit 13, which corresponds to a sample selected from the sample list 25 displayed in the window 13a of the display unit 13, as a chromatogram 27 to be displayed in the chromatogram display area 22 of the window 13a of the display unit 13. In the example shown in Fig. 3, by repeating the selection of a sample in the sample list 25 and the selection of a target substance in the target substance list in this manner, chromatograms for a plurality of samples and a plurality of target substances can be acquired from the memory unit 10.

[0039] Thus, in the chromatogram display area 22 of the display window of the display unit 13, a plurality of chromatograms 27 corresponding to different samples A1, A2 and different target substances a1, a2, a3, ... are displayed in an overlapping manner. In FIG. 3, in order to distinguish between them, the chromatogram 27 corresponding to sample A1 is shown by a solid line, and the chromatogram 27 corresponding to sample A2 is shown by a dotted line. However, in practice, both can be displayed by solid lines. Depending on the case, the plurality of chromatograms 27 can be displayed by different colors or by varying the thickness.

[0040] 4, in the chromatogram display area 22 of the display unit 13, it is possible to simultaneously enlarge or reduce each of the multiple chromatograms 27 displayed based on the input command information input to the input unit 11. In this way, it is possible to easily check the waveforms of the chromatograms 27.

[0041] [Functional configuration for quantification] Returning to Figure 1, the setting unit 14 sets reference position information that serves as the basis for performing calculations on the multiple chromatograms 27 displayed in the chromatogram display area 22 of the display unit 13, based on the input command information input to the input unit 11.

[0042] For example, the setting unit 14 sets, as reference position information, a range in which the target substance is quantified in the multiple chromatograms 27 displayed on the display unit 13. For example, as shown in Fig. 5, the setting unit 14 sets, as reference position information, a start point S1 and an end point S2 for searching for the apex of a peak P. The quantification unit 15 searches for the apex of the peak P within the search range (S1 to S2) specified by the setting unit 14 in each of the multiple chromatograms 27 displayed on the display unit 13, and performs quantification based on the apex of the peak P found.

[0043] 5, peak P is a combination of the peak on the left (target substance) and the peak on the right (a substance with an m / z similar to that of the target substance, such as a derivative thereof). When the peak on the left is selected, S1 to S2 are set as the range to be quantified.

[0044] Further, based on the input command information input to the input unit 11, the setting unit 14 sets a baseline BL in the chromatogram 27 in accordance with the input command information, for example, as shown in Fig. 5. The quantification unit 15 quantifies the target substance based on the baseline BL set by the setting unit 14.

[0045] The ranges S1 to S2 to be quantified can be set by, for example, operating a pointing device (corresponding to the man-machine interface 43 in FIG. 9 described later) to move the pointer to the positions to be specified as S1 and S2 in the chromatogram 27 displayed in the chromatogram display area 22 of the display unit 13 and clicking to specify the ranges. That is, the ranges S1 to S2 to be quantified can be set using a GUI (Graphic User Interface). The ranges S1 to S2 to be quantified may also be set by, for example, inputting numerical values ​​from a keyboard (corresponding to the man-machine interface 43 in FIG. 9). In any case, the input unit 11 inputs the contents of the operation input to the man-machine interface 43 as input command information and sends the input information to the setting unit 14 as reference position information.

[0046] The quantification unit 15 collectively quantifies the target substance in each of the multiple chromatograms 27 displayed on the display unit 13, using the reference position information set by the setting unit 14 as a reference. For example, as shown in Fig. 5, the quantification unit 15 quantifies the target substance within the range set by the setting unit 14, using each of the multiple chromatograms 27 displayed on the display unit 13. For example, as shown in Fig. 2, the quantification unit 15 calculates the height from the baseline BL to the apex of the peak P or the area of ​​the peak P indicated by the diagonal lines. The target substance is quantified based on the height or area of ​​the peak P.

[0047] In addition, since the chromatogram 27 is data obtained by actual measurement, a slight shift may occur in the time axis direction, and the shift may become large enough to be ignored. For example, the chromatogram 27A shown in Fig. 6(A) and the chromatogram 27B shown in Fig. 6(B) have a peak P corresponding to the same target substance, but there is a shift in the elution time RT.

[0048] In such a case, even if the chromatograms 27A and 27B are simply superimposed and displayed as shown in Fig. 7(A), it is difficult to perform quantification for all of the chromatograms 27A and 27B by specifying the range once. Therefore, the analysis system 1 according to the present embodiment has a function of aligning the individual chromatograms 27A and 27B in the time axis direction.

[0049] The display unit 13 displays a plurality of chromatograms 27 (e.g., 27A, 27B) by superimposing them with an offset or magnification in the time axis direction so that the peaks coincide with each other in the time axis direction. Such an offset or magnification is called an alignment number. In the case of an offset, the unit can be a unit indicating time, for example, hours, minutes, or seconds. The display unit 13 sets this alignment number automatically or manually. For example, when the elution time RT of the chromatogram 27A is 4.22 min, the alignment number ΔT1 (offset) of the chromatogram 27A is set to 4.22 min. Also, when the elution time RT of the chromatogram 27B is 4.4 min, the alignment number (offset) ΔT2 of the chromatogram 27B is set to 4.44 min.

[0050] The display unit 13 subtracts the set alignment numbers ΔT1 and ΔT2 from the time axis values ​​of chromatograms 27 (e.g., chromatograms 27A and 27B). As a result, each chromatogram 27 is shifted in the time axis direction by the alignment numbers ΔT1 and ΔT2. The quantification unit 15 displays the chromatograms 27 in an overlapping state after shifting by the alignment numbers ΔT1 and ΔT2. In FIG. 7(B), chromatograms 27A and 27B are displayed in an overlapping state after shifting by the alignment numbers ΔT1 and ΔT2.

[0051] In this state, the setting unit 14 can simultaneously specify the ranges S1 to S2 to be quantified for the chromatograms 27A and 27B. The setting unit 14 collectively sets the ranges S1 to S2 to be quantified for the multiple chromatograms 27 (27A and 27B) that are displayed in an overlapping manner, as shown in FIG. 7(B).

[0052] The quantification unit 15 changes the ranges S1 to S2 so that the offset or magnification factor applied to each chromatogram 27 is cancelled, and quantifies the target substance in each of the multiple chromatograms 27A and 27B based on the changed ranges. For example, when the ranges S1 to S2 to be quantified are set by the setting unit 14, the quantification unit 15 performs quantification for the chromatogram 27A in a range S1' to S2' obtained by adding ΔT1 to the ranges S1 to S2, as shown in FIG. 6(A). In addition, the quantification unit 15 performs quantification for the chromatogram 27B in a range S1" to S2", shifting the ranges S1 to S2 by ΔT2, as shown in FIG. 6(B).

[0053] As described above, the alignment numbers ΔT1 and ΔT2 can be set manually. Basically, if the time when the peak P of the chromatograms 27A and 27B is at its maximum is set, the two chromatograms can be superimposed with their respective peaks P aligned.

[0054] The display unit 13 may display the peaks of the chromatograms 27 in a superimposed manner so as to match the peaks in the time axis direction. In this case, the position of the peak P does not have to be 0. For example, the alignment numbers ΔT1 and ΔT2 may be determined so that the peak of one of the chromatograms 27 in the superimposed chromatograms 27 is aligned with the peak of the other chromatogram 27.

[0055] The alignment number can also be set by the magnification. In this case, the chromatogram 27 is expanded or reduced in the time axis direction according to the magnification, centered on the origin 0. The alignment number is set to, for example, 1.0001. In this case, the quantification unit 15 performs quantification in a state in which the magnification of the range S1 to S2 in which quantification is performed is canceled, which is the same as in the case of offset. Furthermore, the display unit 13 may be capable of finely adjusting the scale in the intensity axis direction, i.e., the vertical axis direction, for each chromatogram 27.

[0056] The display unit 13 may be configured to be able to switch the display state of the chromatogram 27 among a single display as shown in Fig. 6(A) or Fig. 6(B), a superimposed display as shown in Fig. 7(A), and an alignment superimposed display as shown in Fig. 7(B) by operation input of the input unit 11. Such a switching operation is performed based on input command information input to the input unit 11.

[0057] In this manner, in this embodiment, it is possible to simultaneously quantify a plurality of chromatograms 27 regardless of errors that occur in the actual measurement.

[0058] 8, display unit 13 performs smoothing processing on each of the multiple chromatograms 27 to be displayed collectively based on the input command information input to input unit 11, and then displays the multiple chromatograms 27 in an overlapping manner. Quantification unit 15 may quantify the target substance in each of the multiple chromatograms 27 that have been displayed on display unit 13 and subjected to the smoothing processing. For example, a moving average method can be used as such a smoothing processing.

[0059] [Hardware configuration] Fig. 9 shows a hardware configuration of the analysis system 1. As shown in Fig. 9, the analysis system 1 includes a CPU (Central Processing Unit) 40, a memory 41, an auxiliary storage device 42, a man-machine interface 43, a communication interface 44, and an input / output interface 45. The components of the analysis system 1 are connected to each other via an internal bus 50 so as to be able to communicate with each other.

[0060] The CPU 40 is a processor (arithmetic device) that executes a software program (hereinafter, simply referred to as a "program"). An analysis program 51 is loaded into the memory 41 from an auxiliary storage device 42. The CPU 40 executes the analysis program 51 stored in the memory 41 to realize the functions of the selection unit 12, the setting unit 14, and the quantification unit 15.

[0061] The memory 41 is, for example, a RAM (Random Access Memory). As described above, the analysis program 51 executed by the CPU 40 is read into the memory 41, and the chromatogram 27 is stored from the auxiliary storage device 42. The analysis system 1 also includes a ROM (Read Only Memory). A startup program for the analysis system 1 is implemented in the ROM, and the analysis system 1 is started up by the CPU 40 executing the startup program in the ROM.

[0062] The auxiliary storage device 42 is, for example, a hard disk. The auxiliary storage device 42 stores an analysis program 51 executed by the CPU 40. The auxiliary storage device 42 also stores a chromatogram data group 52. In this embodiment, the auxiliary storage device 42 corresponds to the storage unit 10.

[0063] The man-machine interface 43 comprises an operation input unit through which an operator performs operation input, and a display having a display screen. In this embodiment, the man-machine interface 43 is a touch panel. Alternatively, a keyboard and a pointing device may be provided as the operation input unit, and a display may be provided separately. This man-machine interface 43 realizes the functions of the input unit 11 and the display unit 13. Selection of the sample list 25 and the target substance list 26, and setting of the quantification range are performed by this man-machine interface 43.

[0064] The communication interface 44 is a communication interface that complies with a communication network such as the Internet. The analysis program 51 can also be stored in the auxiliary storage device 42 via the communication interface 44. When the analysis system 1 and the LC-MS 2 are connected via a communication network, a group of chromatogram data is transmitted to the auxiliary storage device 42 via the communication interface 44 and stored therein.

[0065] The input / output interface 45 is an interface with a recording medium 60 (a recording medium for non-temporary recording) such as a portable USB (Universal Serial Bus) memory. An analysis program 51 is stored in the recording medium 60. The analysis program 51 can be input via the input / output interface 45 and stored in the auxiliary storage device 42. In addition, when the analysis system 1 and the LC-MS 2 are not communicatively connected via a communication network or the like, a chromatogram data group 52 obtained from the recording medium 60 may be stored in the auxiliary storage device 42.

[0066] Next, the operation of the analysis system 1 according to the present embodiment will be described.

[0067] As shown in Fig. 10, first, the selection unit 12 selects a plurality of chromatograms across a plurality of samples and a plurality of target substances from the storage unit 10 as a database that stores chromatograms 27 retrievably using samples and target substances as keys, based on input command information from the user input to the input unit 11 (step S10; selection step). Here, as shown in Fig. 3, the first list generation unit 30 of the selection unit 12 generates a sample list 25, and the display unit 13 displays the sample list 25 in the sample list display area 20. Furthermore, when a sample is selected from the sample list 25 based on the input command information input to the input unit 11, the second list generation unit 31 generates a target substance list 26 corresponding to that sample. The display unit 13 displays the target substance list 25 in the target substance list display area 21 of the display unit 13. Furthermore, when a target substance is selected from the target substance list 25 based on the input command information input to the input unit 11, the data acquisition unit 32 reads a chromatogram 27 corresponding to the selected sample and target substance from the memory unit 10.

[0068] Next, the display unit 13 displays the multiple chromatograms 27 selected in step S10, i.e., the selection step, in an overlapping manner (step S20; display step). By executing steps S10 and S20, the chromatograms 27 corresponding to the multiple samples A1 and A2 and the multiple target substances a1, a2, and a3, respectively, are displayed in an overlapping manner in the chromatogram display area 22 of the display unit 13, as shown in FIG.

[0069] Next, the setting unit 14 sets reference position information that is a reference for performing calculations on the multiple chromatograms 27 displayed in step S20, i.e., the display step, based on the user's input command information input to the input unit 11 (step S30; setting step). Here, for example, as shown in Fig. 5, the range (S1 to S2) in which quantification is performed in the chromatogram 27 and the baseline BL are set as the reference position information.

[0070] Next, the quantification unit 15 collectively quantifies the target substance in each of the multiple chromatograms 27 displayed in step S20, i.e., the display step, using the reference position information set in step S30, i.e., the setting step, as a reference (step S40; quantification step). In this quantification, for each of the multiple chromatograms 27, a peak P of the chromatogram 27 is searched for within a set range (S1 to S2) as shown in Fig. 5, and the height or area of ​​the peak P is calculated based on the set baseline BL.

[0071] Embodiment 2 Next, a second embodiment of the present invention will be described. The analysis system 1 according to this embodiment differs from the above-mentioned embodiment in that, as shown in Fig. 11, dummy spectrum data, i.e., a dummy chromatogram 28, is further superimposed on a plurality of chromatograms 27 displayed on the display unit 13. The dummy chromatogram 28 is statistically estimated based on the waveforms of chromatograms 27 of the target substance that have been obtained so far, and is also called a guide chromatogram.

[0072] 11, in the dummy chromatogram 28, the portion where the peak P appears in the target substance in the chromatogram 27 is at a high level, and the other portion is at a low level (the same level as the baseline BL). The shape of the dummy chromatogram 28 makes it easy for the user to distinguish between the peak P1 corresponding to the target substance and the peak P2 other than the elution time RT of the chromatogram.

[0073] Furthermore, in this embodiment, it is not possible to specify the range in which the target substance is quantified, other than the section in which the dummy chromatogram 28 is at a high level. This makes it possible for the user to avoid selecting peak P2, rather than peak P1, as the range for quantification. After checking whether peak P1 is within the high-level portion of the dummy chromatogram 28, the user can perform accurate quantification simply by finely adjusting the range for quantification.

[0074] 12, the storage unit 10 stores, for each of the target substances a1, a2, and a3, a dummy chromatogram 28 that defines a specifiable range in which the reference position information can be set by the setting unit 14. The display unit 13 displays the dummy chromatogram 28 in an overlapping manner on the multiple chromatograms 27 selected by the selection unit 12. In this case, the displayed dummy chromatogram 28 has a waveform that is the logical sum of the dummy chromatograms 28 of the target substances a1, a2, and a3, with the high level being 1 and the low level being 0.

[0075] By comparing and displaying the chromatogram 27 and the dummy chromatogram 28, it is possible to confirm whether the peak P corresponds to the target substances a1, a2, a3 or not. In addition, the setting unit 14 makes it possible to set reference position information for quantification within a settable range defined by the dummy chromatogram 28.

[0076] When the range for quantification is to be set for each chromatogram 27, i.e., individually, an input table 29 as shown in Fig. 13 may be displayed on the display unit 13, and the input unit 11 may be made to allow input to the input table 29. In this input table 29, the range for quantification (start time, end time) can be input for each sample and each target substance. The quantification unit 15 uses the range input in the input table 29 as the range for quantification for each sample and each target substance. In this case, it may be arranged so that values ​​in the range that are not at a high level in the dummy chromatogram 28 cannot be input.

[0077] [Example of metabolomic analysis] Next, an example of metabolome analysis performed using the analysis system 1 according to the present embodiment will be described. Fig. 14 to Fig. 16 show examples of display of a chromatogram 27 when a standard sample of cholesterol ester is measured. Fig. 14 shows a display image in which the same MRM (Multiple Reaction Monitoring) transitions of 10 samples are displayed in an overlapping manner, and Fig. 15 shows a display image in which MRM transitions different from those in Fig. 14 of 10 samples are displayed in an overlapping manner.

[0078] Here, the MRM transition is a combination of the mass-to-charge ratio of the precursor ion passing through the front-stage quadrupole mass filter (Q1) and the mass-to-charge ratio of the product ion passing through the rear-stage quadrupole mass filter (Q3). The m / z of the precursor ion in the chromatogram 27 shown in Fig. 14 is 675.7, and the m / z of the product ion is 369.4. The m / z of the precursor ion in the chromatogram 27 in Fig. 15 is 675.7, and the m / z of the product ion is 147.4.

[0079] Chromatograms 27 with the same MRM transitions mean that the chromatograms contain the same target substance. In Figures 14 and 15, chromatograms 27 with the same MRM transitions, i.e., chromatograms corresponding to the same target substance, are displayed for multiple samples.

[0080] According to the analysis system 1 of this embodiment, as shown in FIG. 16, the MRM transition (waveform M) shown in FIG. 14 and the MRM transition (waveform N) shown in FIG. 15 can be displayed in an overlapping manner. In this way, the two MRM transitions can be displayed for comparison. When the chromatogram 27 (waveform M) in FIG. 14 and the chromatogram 27 (waveform N) in FIG. 15 are displayed in an overlapping manner for comparison, the difference between the two can be confirmed at a glance. For example, as shown in FIG. 16, the waveforms M and N have the same elution time RT (2.83 to 2.89 minutes) and are very similar, but it can be recognized at a glance that the intensity level of the waveform M is greater than that of the waveform N.

[0081] Here, as shown in FIG. 17, if the setting unit 14 sets the quantification range S1 to S2 for the 20 specified chromatograms 27 based on the input command information input to the input unit 11 as follows, the quantification unit 15 can simultaneously quantify two MRM transitions according to the set range S1 (2.25 minutes) to S2 (3.72 minutes).

[0082] Since the above two MRM transitions are derived from the same compound, the waveforms of the chromatogram 27 are similar, as described above. However, the intensity level of the waveform N of the chromatogram 27 shown in FIG. 15 is about 1.5% of the intensity level of the waveform M of the chromatogram 27 shown in FIG. 14. For this reason, in FIG. 16, in which the waveforms M and N are simultaneously superimposed and displayed, the chromatogram 27 corresponding to the MRM transition shown in FIG. 13 appears to be stuck on the baseline BL. However, if the chromatogram 27 of the waveform N is enlarged as shown in FIG. 15, the shape of the waveform N can be confirmed.

[0083] In the analysis system 1 according to this embodiment, not only two MRM transitions but all selected MRM transitions can be displayed, and the target substance can be quantified at the same time. The waveforms of the chromatograms 27 shown in Figs. 14 to 16 are similar because the samples are the same. However, in the analysis system 1, there is no such restriction, and all selected chromatograms 27 can be displayed.

[0084] On the other hand, the MRM transition of cholesterol (m / z=369.4 of precursor ion / m / z=287.4 of product ion) is as shown in FIG. 18, for example. As shown in FIG. 18, the waveform of chromatogram 27 of cholesterol is very similar to the waveform of chromatogram 27 of cholesterol ester shown in FIG. 16 and FIG. 17. This is because cholesterol ester has the same skeleton as cholesterol. When chromatogram 27 shown in FIG. 16 and chromatogram 27 shown in FIG. 18 are superimposed and displayed, it becomes as shown in FIG. 19. When the chromatograms are superimposed and displayed for comparison as in chromatogram 27 shown in FIG. 19, it can be seen that there is a peak P3 (elution time RT is about 4.4 minutes) that does not appear in chromatogram 27 shown in FIG. 16 but appears in chromatogram 27 shown in FIG. 18. This comparative display makes it clear that peak P3 is not derived from cholesterol ester but from cholesterol.

[0085] In addition, in metabolome analysis, the target sample (e.g., animal blood) is almost always the same, and there is no comparison between, for example, a plant extract and animal blood. In such cases, as shown in Figure 20, for example, a rough comparison can be made by displaying the chromatogram 27 of all transitions (603 transitions).

[0086] Furthermore, Figure 21 (10 samples x 81 transitions) shows the selection of only the target substance, i.e., molecular species, for example, phosphasidylcholine (PC), from among the 603 transitions. Since it is the same molecular species, these chromatograms 27 have similar waveforms and their elution times RT are close. When quantifying these molecular species, it is sufficient to set the range to be quantified for all chromatograms 27, for example, as shown in Figure 22. In other words, it is possible to visually check 10 samples x 81 transitions = 810 chromatograms, set the range to be quantified at once, calculate the peak areas all at once, and perform quantification.

[0087] As described above in detail, according to the analysis system 1 of this embodiment, a plurality of chromatograms 27 spanning a plurality of samples A1, A2, A3, ... and a plurality of target substances a1, a2, a3, ... are superimposed and displayed on the display unit 13. This enables detailed comparison of the waveforms of chromatograms 27 for different samples and different target substances.

[0088] Furthermore, according to the analysis system 1 of the present embodiment, since a plurality of chromatograms 27 are displayed in an overlapping manner, it is possible to collectively quantify the target substance in each of the plurality of chromatograms 27 in a state in which reference position information serving as a basis for performing calculations on the plurality of chromatograms 27 is set while taking into consideration background conditions such as the chemical properties of the target substance or the measurement conditions according to command information input by the analyst. As a result, it is possible to easily quantify the target substance in the plurality of chromatograms 27 in a short time while enabling detailed comparative display of chromatograms 27 for different samples and different target substances.

[0089] Furthermore, according to the second embodiment, the storage unit 10 stores a dummy chromatogram 28 that defines a settable range in which the reference position information can be set by the setting unit 14. The display unit 13 displays the dummy chromatogram 28 and the multiple chromatograms 27 selected by the selection unit 12 in an overlapping manner. Furthermore, the setting unit 14 makes it possible to set the reference position information for quantification within the settable range defined by the dummy chromatogram 28. In this way, it becomes easier for the user performing the analysis to identify peaks and also makes it easier to set the range of quantification.

[0090] Furthermore, according to this embodiment, the selection unit 12 includes a first list generation unit 30 that generates and displays a sample list 25 corresponding to the dummy chromatograms 28 stored in the storage unit 10, a second list generation unit 31 that generates and displays a target substance list 26 in which chromatograms 27 corresponding to samples selected from the sample list 25 are compiled for each target substance based on an operational input or an imported file, and a data acquisition unit 32 that acquires chromatograms 27 selected from the target substance list 26, which correspond to the sample selected from the sample list 25. In this way, even when there are a large number of samples and target substances to select, it is possible to make it easier to identify the displayed samples and target substances.

[0091] Furthermore, according to this embodiment, setting unit 14 sets a range for quantifying the target substance in chromatogram 27 based on input command information input to input unit 11. Quantification unit 15 quantifies the target substance within the range set by setting unit 14. This enables accurate quantification of the target substance that reflects background information.

[0092] Furthermore, according to this embodiment, the quantification unit 15 sets a baseline BL in the chromatogram based on the input command information input to the input unit 11, and performs quantification based on the set baseline BL. In this way, it is possible to accurately quantify the target substance while reflecting the background information.

[0093] Furthermore, according to this embodiment, the display unit 13 enlarges or reduces the displayed spectrum data collectively based on the input command information input to the input unit 11. In this way, the display is performed according to the scale of the chromatogram 27, making it easier to visually check the chromatogram 27.

[0094] In the above embodiment, the analysis system 1 is an information processing device connected to the LC-MS 2, but the present invention is not limited to this. The analysis system 1 may be incorporated in the LC-MS 2.

[0095] Furthermore, the analysis system 1 is not limited to one that quantifies the measurement results of LC-MS2. The analysis system 1 may be one that quantifies the measurement results of a gas chromatography device that uses a gas as a mobile phase or a supercritical fluid chromatography device that uses a supercritical fluid as a mobile phase.

[0096] Furthermore, the spectral data to be quantified by the analysis system 1 is not limited to chromatograms. For example, the spectral data to be quantified may be spectral data obtained by analysis using capillary electrophoresis, spectroscopic analysis, X-ray analysis, electron beam analysis, or nuclear magnetic resonance analysis.

[0097] Furthermore, the hardware configuration and software configuration of the analysis system 1 are merely examples and can be changed and modified as desired.

[0098] The core part of the analysis system 1, which is composed of a storage unit 10, an input unit 11, a selection unit 12, a display unit 13, a setting unit 14, a quantification unit 15, etc., can be realized by using a normal computer system, not a dedicated system. For example, the analysis system 1 that executes the above-mentioned processing may be configured by storing and distributing a computer-readable computer program for executing the above-mentioned operations on a computer-readable recording medium (flexible disk, CD-ROM, DVD-ROM, etc.) and installing the computer program on a computer. Also, the analysis system 1 may be configured by storing the computer program in a storage device of a server device on a communication network such as the Internet, and downloading the computer program by a normal computer system.

[0099] When the functions of the analysis system 1 are shared between an OS (operating system) and an application program, or are realized by the OS and the application program working together, only the application program portion may be stored in a recording medium or storage device.

[0100] It is also possible to superimpose a computer program on a carrier wave and distribute it via a communication network. For example, the computer program may be posted on a bulletin board system (BBS) on the communication network and distributed via the network. Then, the computer program may be started and executed under the control of the OS in the same way as other application programs, thereby enabling the above-mentioned processing to be performed.

[0101] Various embodiments and modifications of the present invention are possible without departing from the broad spirit and scope of the present invention. The above-described embodiments are for the purpose of explaining the present invention and do not limit the scope of the present invention. That is, the scope of the present invention is indicated by the claims, not the embodiments. Various modifications made within the scope of the claims and the scope of the invention equivalent thereto are considered to be within the scope of the present invention. [Industrial Applicability]

[0102] The present invention is particularly applicable to metabolomic analysis as well as chemical substance analysis. [Explanation of symbols]

[0103] 1 Analysis system, 2 Liquid chromatography mass spectrometer (LC-MS), 10 Memory unit, 11 Input unit, 12 Selection unit, 13 Display unit, 13a Window, 14 Setting unit, 15 Quantification unit, 20 Sample list display area, 21 Target substance list display area, 22 Chromatogram display area, 25 Sample list, 26 Target substance list, 27 Chromatogram, 28 Dummy chromatogram, 29 Input table, 30 First list generation unit, 31 Second list generation unit, 32 Data acquisition unit, 40 CPU, 41 Memory, 42 Auxiliary storage device, 43 Man-machine interface, 44 Communication interface, 45 Input / output interface, 50 Internal bus, 51 Analysis program, 52 Data group, 60 Recording medium, P, P1, P2, P3 Peak

Claims

1. a storage unit that stores spectrum data obtained by analyzing a sample containing a target substance in such a manner that the spectrum data can be retrieved using the sample and the target substance as keys; an input unit for inputting user input command information; a selection unit capable of selecting a plurality of pieces of spectrum data across a plurality of the samples and a plurality of the target substances from the spectrum data stored in the storage unit based on input command information input to the input unit; a display unit that displays the plurality of spectrum data selected by the selection unit in an overlapping manner; a setting unit that sets reference position information serving as a reference for performing an operation on the plurality of spectrum data displayed on the display unit based on input command information input to the input unit; a quantification unit that collectively quantifies the target substance in each of the plurality of spectrum data displayed on the display unit, based on the reference position information set by the setting unit; Equipped with The storage unit is storing dummy spectrum data defining a settable range in which the reference position information can be set by the setting unit; The display unit is The plurality of spectrum data selected by the selection unit and the dummy spectrum data are displayed in an overlapping manner; The setting unit is The reference position information cannot be set outside the settable range defined by the dummy spectrum data. Analysis system.

2. The selection unit is a first list generating unit that generates a first list, which is a list of samples corresponding to the spectrum data stored in the storage unit, and displays the first list on the display unit; a second list generating unit that generates a second list in which spectrum data corresponding to the sample selected from the first list can be selected for each of the target substances based on input command information input to the input unit, and displays the second list on the display unit; a data acquisition unit that acquires, based on input command information input to the input unit, the spectrum data selected from the second list displayed on the display unit, which corresponds to the sample selected from the first list displayed on the display unit, as the spectrum data to be displayed on the display unit; Equipped with The analysis system according to claim 1 .

3. The setting unit is setting a range for quantifying the target substance in the plurality of spectrum data displayed on the display unit as the reference position information; The quantification unit is quantification of the target substance within the range set by the setting unit using each of the plurality of spectrum data displayed on the display unit; The analysis system according to claim 1 or 2.

4. The setting unit is setting a baseline of the spectrum data based on input command information input to the input unit; The quantification unit is quantification of the target substance based on the baseline set by the setting unit; The analysis system according to claim 3 .

5. The display unit is enlarging or reducing each of the plurality of spectrum data to be displayed at the same time based on input command information input to the input unit; The analysis system according to claim 1 .

6. The display unit is performing smoothing processing on each of the plurality of spectrum data to be displayed collectively based on input command information inputted to the input unit, and then displaying the plurality of spectrum data in an overlapping manner; The quantification unit quantifies the target substance in each of the plurality of spectrum data that have been smoothed. The analysis system according to claim 1 .

7. The display unit is The spectrum data are displayed in a superimposed state with an offset or magnification applied to each of the spectrum data in the time axis direction so that the peaks coincide with each other in the time axis direction; The setting unit is collectively setting reference position information for performing quantification on the plurality of spectrum data items displayed in an overlapping manner; The quantification unit is changing the reference position information so that an offset or a magnification factor applied to each of the spectrum data is cancelled, and quantifying the target substance in each of the plurality of spectrum data based on the changed reference position information; The analysis system according to any one of claims 1 to 6.

8. An analysis method executed by an analysis system that quantifies a target substance based on spectrum data obtained by analyzing a sample containing the target substance, comprising: a selection step of selecting a plurality of pieces of spectrum data across a plurality of the samples and a plurality of the target substances based on input command information from a database that stores the spectrum data retrievably using the samples and the target substances as keys; a display step of displaying the plurality of spectrum data selected in the selection step in an overlapping manner; a setting step of setting reference position information that is a reference for performing an operation on the plurality of spectrum data displayed in the display step, based on input command information from a user; a quantification step of collectively quantifying the target substance in each of the plurality of spectrum data displayed in the display step, based on the reference position information set in the setting step; Including, The database includes: storing dummy spectrum data defining a settable range within which the reference position information can be set in the setting step; In the display step, displaying the plurality of spectrum data selected in the selection step and the dummy spectrum data in an overlapping manner; In the setting step, The reference position information cannot be set outside the settable range defined by the dummy spectrum data. Analysis method.

9. Computer, a storage unit that stores spectrum data obtained by analyzing a sample containing a target substance in a manner retrievable using the sample and the target substance as keys; an input unit for inputting user input command information; a selection unit that selects a plurality of pieces of spectrum data across a plurality of the samples and a plurality of the target substances from the spectrum data stored in the storage unit based on input command information input to the input unit; a display unit that displays the plurality of spectrum data selected by the selection unit in an overlapping manner; a setting unit that sets reference position information serving as a reference for performing an operation on the plurality of spectrum data displayed on the display unit based on input command information input to the input unit; and a quantification unit that collectively quantifies the target substance in each of the plurality of spectrum data displayed on the display unit, based on the reference position information set by the setting unit; Function as a The storage unit is storing dummy spectrum data defining a settable range in which the reference position information can be set by the setting unit; The display unit is The plurality of spectrum data selected by the selection unit and the dummy spectrum data are displayed in an overlapping manner; The setting unit is The reference position information cannot be set outside the settable range defined by the dummy spectrum data. program.

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