JP7678546B2 - Analysis system, analysis method, and program - Google Patents

Description

The present invention relates to an analysis system, an analysis method, and a program.

Metabolomic analysis is performed by detecting compounds found 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.

In chromatography mass spectrometry, a sample is first introduced into a chromatograph column, and an eluate in which the various components of the sample are separated in the time direction is extracted. The various components of the extracted eluate are then ionized in the ion source of the mass spectrometer, and the ions derived from the sample components are separated according to their mass-to-charge ratio 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.

Each metabolic substance is quantified by calculating the area or height of the peak that appears in the chromatogram. However, this quantification must take into account background conditions such as the chemical properties of the metabolic substance or the measurement conditions in the chromatography mass spectrometer. Therefore, quantification is performed by an experienced analyst who visually checks the peaks in the displayed chromatogram and specifies the range for calculation by operating input.

International Publication No. 2018/207228 International Publication No. 2017/002156

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, to accurately quantify metabolites, it was necessary for the analyst 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.

In addition, in metabolomic 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.

The present invention has been made in light of the above circumstances, and aims to provide an analysis system, analysis method, and program that can quickly and easily quantify target substances in multiple spectrum data while enabling detailed comparative display of chromatograms for different samples and different target substances.

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;
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.

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.

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.

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.

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.

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.

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.

An analysis method according to a 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;
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.

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 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
displaying the plurality of spectrum data selected by the selection unit and the dummy spectrum data 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.

According to the present invention, multiple spectrum data across multiple samples and multiple 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 multiple spectrum data are displayed in an overlapping manner, it is possible to simultaneously quantify the target substances in each of the multiple spectrum data while taking into account background conditions such as the chemical properties of metabolic substances or measurement conditions according to input command information from the analyst and setting reference position information that serves as a basis for performing calculations on the multiple spectrum data. As a result, it is possible to easily quantify the target substances in the multiple spectrum data in a short time while allowing detailed comparison of the spectrum data for different samples and different target substances.

1 is a block diagram showing a configuration of an analysis system according to a first embodiment of the present invention. FIG. 1 is a diagram showing an example of a chromatogram. FIG. 2 is a schematic diagram showing a functional configuration for displaying overlapping chromatograms in the analysis system of FIG. 1 . FIG. 13 is a schematic diagram showing how spectrum data is expanded or contracted. FIG. 2 is a schematic diagram showing functions of a setting unit and a quantification unit in FIG. 1 . 13A and 13B are examples of waveforms of spectrum data. 1A is an example of spectrum data that is displayed in an overlapping manner, and FIG. 1B is an example of spectrum data that is displayed in an overlapping manner so that peaks coincide with each other. FIG. 13 is a schematic diagram showing how spectrum data is smoothed. FIG. 2 is a block diagram showing a hardware configuration of the analysis system of FIG. 1. 2 is a flowchart showing the operation of the analysis system of FIG. 1 . 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. FIG. 11 is a block diagram showing a configuration of an analysis system according to a second embodiment of the present invention. FIG. 13 illustrates an example of an input table. FIG. 1 is a diagram showing a display example of a chromatogram of cholesterol ester. FIG. 13 is a diagram showing another example of a chromatogram of cholesterol ester. 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 and displayed. FIG. 15 is a diagram showing a state in which a range for quantification is set in the chromatogram shown in FIG. 14. FIG. 13 is a diagram showing a display example of a cholesterol chromatogram. 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. FIG. 13 is a diagram showing a case where chromatograms of all transitions are superimposed and displayed. FIG. 13 is a diagram showing a case where chromatograms of the same molecular species as target substances are superimposed and displayed. FIG. 22 is a diagram showing how the quantification range is set in the chromatogram of FIG. 21.

The following describes in detail an embodiment of the present invention with reference to the drawings. In each drawing, the same or equivalent parts are denoted by the same reference numerals.

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.

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.

By 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 the LC-MS2, and chromatograms corresponding to the target substances a1, a2, a3, ... contained therein are detected.

Figure 2 shows an example of a chromatogram. 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. 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 peak P reaches its apex, is defined as the elution time (retention time) RT. The elution time RT differs depending on the target substance.

In the chromatogram, the portion where peak P does not appear is defined as the baseline BL. The height or area of 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 peak P in the chromatogram.

Returning to FIG. 1, the analysis system 1 is an information processing device that includes a memory unit 10, an input unit 11, a selection unit 12, a display unit 13, a setting unit 14, and a quantification unit 15.

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 sample A1, chromatograms corresponding to the target substances a1, a2, a3, ... contained in sample A2, ..., and chromatograms corresponding to the target substances a1, a2, a3, ... contained in 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.

When metabolomic analysis is performed 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 there are 100 samples to be analyzed and the number of metabolites is 500, it is necessary to analyze 100 x 500 chromatograms.

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

The selection unit 12 can select multiple chromatograms across multiple samples and multiple target substances from among the chromatograms stored in the storage unit 10 based on the 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.

[Functional configuration for displaying overlapping chromatograms]
Here, the functional configuration for displaying the chromatograms in an overlapping manner 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.

The display unit 13 displays multiple chromatograms selected by the selection unit 12 in a window 13a displayed on the display screen, superimposed on each other. 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.

The selection unit 12 also includes a first list generation unit 30, a second list generation unit 31, and a data acquisition unit 32.

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.

The second list generation unit 31 generates a target substance list 26 that allows selection of a chromatogram corresponding to a sample selected from the sample list 25 for each target substance based on the input command information input to the input unit 11. The second list generation unit 31 displays the generated target substance list 26 in the target substance list display area 21 of the window 13a of the display unit 13.

For example, as shown in FIG. 3, when input command information is input to the input unit 11 to the effect that samples A1 and A2 have been selected from the sample list 25 displayed in the sample list display area 20, 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 samples A1 and A2 is displayed in the target substance list display area 21 of the window 13a of the display unit 13.

The data acquisition unit 32 acquires, based on the 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 multiple samples and multiple target substances can be acquired from the memory unit 10.

In this way, a plurality of chromatograms 27 corresponding to different samples A1, A2 and different target substances a1, a2, a3, ... are displayed superimposed in the chromatogram display area 22 of the display window of the display unit 13. 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.

As shown in FIG. 4, in the chromatogram display area 22 of the display unit 13, each of the multiple displayed chromatograms 27 can be enlarged or reduced at the same time based on the input command information input to the input unit 11. This makes it easier to check the waveforms of the chromatograms 27.

[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.

For example, the setting unit 14 sets the range in which the target substance is quantified in the multiple chromatograms 27 displayed on the display unit 13 as reference position information. For example, as shown in FIG. 5, the setting unit 14 sets a start point S1 and an end point S2 for searching for the apex of peak P as reference position information. The quantification unit 15 searches for the apex of 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 that has been searched for.

In the example shown in Figure 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). When selecting the peak on the left, S1 to S2 are set as the range to be quantified.

Furthermore, based on the input command information input to the input unit 11, the setting unit 14 sets a baseline BL in the chromatogram 27 according to 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.

The ranges S1 to S2 to be quantified can be set by, for example, using 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 click to specify them. 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, entering 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.

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 determines the height from the baseline BL to the apex of peak P or the area of peak P, which is indicated by diagonal lines. The target substance is quantified based on this height or area of peak P.

Note that because chromatogram 27 is data obtained by actual measurement, there may be a slight deviation in the time axis direction, and the deviation may be large enough to be negligible. For example, chromatogram 27A shown in FIG. 6(A) and chromatogram 27B shown in FIG. 6(B) have peaks P corresponding to the same target substance, but there is a difference in their elution times RT.

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

The display unit 13 displays multiple chromatograms 27 (e.g., 27A, 27B) superimposed with an offset or magnification applied in the time axis direction so that the peaks coincide 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, such as hours, minutes, or seconds. The display unit 13 sets this alignment number automatically or manually. For example, if the elution time RT of chromatogram 27A is 4.22 min, the alignment number ΔT1 (offset) of chromatogram 27A is set to 4.22 min. Also, for example, if the elution time RT of chromatogram 27B is 4.4 min, the alignment number (offset) ΔT2 of chromatogram 27B is set to 4.44 min.

The display unit 13 subtracts the alignment numbers ΔT1 and ΔT2 set respectively from the time axis values of the 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 superimposed in a state where they have been shifted by the alignment numbers ΔT1 and ΔT2. In FIG. 7(B), chromatograms 27A and 27B are displayed superimposed in a state where they have been shifted by the alignment numbers ΔT1 and ΔT2.

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

The quantification unit 15 changes the range S1-S2 so that the offset or magnification applied to each chromatogram 27 is cancelled, and quantifies the target substance in each of the multiple chromatograms 27A and 27B using the changed range as a reference. For example, when the range S1-S2 to be quantified is set by the setting unit 14, the quantification unit 15 quantifies chromatogram 27A in the range S1'-S2', which is the range obtained by adding ΔT1 to the range S1-S2, as shown in FIG. 6(A). Furthermore, the quantification unit 15 quantifies chromatogram 27B in the range S1"-S2", which is obtained by shifting the range S1-S2 by ΔT2, as shown in FIG. 6(B).

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

The display unit 13 may display the peaks of the chromatograms 27 overlapping each other by aligning them 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 overlappingly displayed is aligned with the peak of the other chromatogram 27.

The alignment number can also be set by the magnification. In this case, the chromatogram 27 is scaled 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 where 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. The display unit 13 may also be capable of fine-tuning the scale in the intensity axis direction, i.e., the vertical axis direction, for each chromatogram 27.

The display unit 13 may be configured to be able to switch the display state of the chromatogram 27 between 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 switching operation is performed based on input command information input to the input unit 11.

In this way, in this embodiment, it is possible to simultaneously quantify multiple chromatograms 27 regardless of errors that occur in the actual measurement.

The display unit 13 performs smoothing processing on each of the multiple chromatograms 27 displayed in a batch based on the input command information input to the input unit 11, as shown in FIG. 8, and then displays the multiple chromatograms 27 in an overlapping manner. The quantification unit 15 may be configured to quantify the target substance in each of the multiple chromatograms 27 displayed on the display unit 13 and subjected to the smoothing processing. For example, a moving average method may be used as such a smoothing processing.

[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.

The CPU 40 is a processor (computing device) that executes a software program (hereinafter simply referred to as a "program"). An analysis program 51 is loaded into the memory 41 from the 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.

The memory 41 is, for example, a RAM (Random Access Memory). As described above, the analysis program 51 executed by the CPU 40 is loaded 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.

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.

The man-machine interface 43 includes an operation input section where the operator inputs operations, 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 section, and a display may be provided separately. This man-machine interface 43 realizes the functions of the input section 11 and the display section 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.

The communication interface 44 is a communication interface that conforms to 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. In addition, 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.

The input/output interface 45 is an interface with a recording medium 60 (a recording medium that performs 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 connected for communication 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.

Next, the operation of the analysis system 1 according to this embodiment will be described.

10, first, the selection unit 12 selects multiple chromatograms across multiple samples and multiple target substances from the storage unit 10 as a database that stores chromatograms 27 retrievably using samples and target substances as keys, based on the user's input command information 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 the chromatogram 27 corresponding to the selected sample and target substance from the memory unit 10.

Then, 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, as shown in FIG. 3, the chromatograms 27 corresponding to the multiple samples A1, A2 and the multiple target substances a1, a2, and a3 are displayed in an overlapping manner in the chromatogram display area 22 of the display unit 13.

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

Then, the quantification unit 15 collectively quantifies the target substances 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, for example, and the height or area of the peak P is calculated based on the set baseline BL.

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 the chromatograms 27 of the target substance that have been obtained so far, and is also called a guide chromatogram.

As shown in FIG. 11, in the dummy chromatogram 28, the portion of the chromatogram 27 where the peak P appears in the target substance is at a high level, and the other portions are at a low level (the same level as the baseline BL). The shape of the dummy chromatogram 28 makes it easier 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.

In addition, 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 as the range for quantification rather than peak P1. After checking whether peak P1 is within the high-level portion of the dummy chromatogram 28, the user can simply make minor adjustments to the range for quantification, enabling accurate quantification.

As shown in FIG. 12, the memory 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 setting unit 14 can set the reference position information. The display unit 13 displays the dummy chromatogram 28 on top of 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.

By comparing the chromatogram 27 with the dummy chromatogram 28, it is possible to confirm whether the peak P corresponds to the target substances a1, a2, and a3. In addition, 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.

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 possible to prevent input of values in the range that are not at a high level in the dummy chromatogram 28.

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

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

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

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 elution time RT (2.83 to 2.89 minutes) is the same for the waveform M and the waveform N, and they 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.

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 shown below, the quantification unit 15 can simultaneously quantify two MRM transitions according to the set range S1 (2.25 minutes) to S2 (3.72 minutes).

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

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 Figures 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.

On the other hand, the MRM transition of cholesterol (m/z of precursor ion = 369.4/m/z of product ion = 287.4) is, for example, as shown in FIG. 18. 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 is derived from cholesterol.

In metabolomic analysis, the target sample (e.g., animal blood) is almost always the same, and there is no need to compare, for example, plant extracts with animal blood. In such cases, as shown in Figure 20, a rough comparison can be made by displaying, for example, chromatogram 27 of all transitions (603 transitions).

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 quantification range 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 quantification range at once, calculate the peak areas all at once, and perform quantification.

As described above in detail, the analysis system 1 according to this embodiment displays multiple chromatograms 27 spanning multiple samples A1, A2, A3, ... and multiple target substances a1, a2, a3, ... in an overlapping manner on the display unit 13. This enables detailed comparison of the waveforms of chromatograms 27 for different samples and different target substances.

Furthermore, according to the analysis system 1 of this embodiment, since multiple chromatograms 27 are displayed in an overlapping manner, the target substances in each of the multiple chromatograms 27 can be quantified simultaneously in a state where reference position information serving as a basis for performing calculations on the multiple chromatograms 27 is set while taking into account background conditions such as the chemical properties of the target substances or measurement conditions according to the command information input by the analyst. As a result, the target substances in the multiple chromatograms 27 can be quantified quickly and easily while enabling detailed comparative display of chromatograms 27 for different samples and different target substances.

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.

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 organized by target substance based on an operation input or an imported file, and a data acquisition unit 32 that acquires chromatograms 27 corresponding to samples selected from the sample list 25 and selected from the target substance list 26. In this way, even when there are a large number of samples and target substances to select, it is possible to easily identify the displayed samples and target substances.

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

In addition, 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.

In addition, according to this embodiment, the display unit 13 enlarges or reduces the multiple displayed spectrum data simultaneously based on the input command information input to the input unit 11. In this way, the display is made to match the scale of the chromatogram 27, making it easier to visually check the chromatogram 27.

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 into the LC-MS 2.

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

The spectral data to be quantified by the analysis system 1 is not limited to chromatograms. For example, spectral data obtained by analysis using capillary electrophoresis, spectroscopic analysis, X-ray analysis, electron beam analysis, and nuclear magnetic resonance analysis can be quantified.

In addition, the hardware and software configurations of the analysis system 1 are merely examples and can be changed and modified as desired.

The core part of the analysis system 1 that performs the processing, which is composed of the storage unit 10, input unit 11, selection unit 12, display unit 13, setting unit 14, quantification unit 15, etc., can be realized by using a normal computer system, not a dedicated system. For example, the analysis system 1 that performs the processing may be configured by distributing a computer program stored in a computer-readable recording medium (flexible disk, CD-ROM, DVD-ROM, etc.) for performing the above operations and installing the computer program on a computer. In addition, 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 it by a normal computer system.

When the functions of the analysis system 1 are realized by sharing the functions between an OS (operating system) and an application program, or by cooperation between an OS and an application program, only the application program portion may be stored on a recording medium or storage device.

It is also possible to superimpose a computer program on a carrier wave and distribute it over a communications network. For example, the computer program may be posted on a bulletin board system (BBS) on the communications network and distributed over the network. The computer program may then 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.

This invention is open to various embodiments and modifications without departing from the broad spirit and scope of the invention. Furthermore, the above-described embodiments are intended to explain the invention and do not limit the scope of the invention. In other words, the scope of the invention is indicated by the claims, not the embodiments. Furthermore, various modifications made within the scope of the claims and within the scope of the meaning of the invention equivalent thereto are considered to be within the scope of the invention.

The present invention can be particularly applied to metabolomic analysis as well as chemical analysis.

1 Analysis system, 2 Liquid chromatography mass spectrometry (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 (9)

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. 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 . 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 . 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 . 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 . 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 . 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 . 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. 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
displaying the plurality of spectrum data selected by the selection unit and the dummy spectrum data 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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