JP7154582B2 - Mixture identification support system - Google Patents

Description

The present invention relates to a mixture identification support system.

Conventionally, a search device used to identify an unknown compound is known (for example, Non-Patent Document 1).

According to the search device of Non-Patent Document 1, a mass spectrum file of a compound contained in a measured unknown sample is read, and a compound having a spectrum similar to the mass spectrum of the compound contained in the unknown sample is searched from the mass spectrum library. By searching, it is possible to search for compounds that are highly likely to be contained in the unknown sample.

Chemical Information Society of Japan, "NIST Simple Manual ver.1.4", "1-1. [Example] Searching for compounds with similar spectra to the measured mass spectrum", [online], December 2017, Chemical Information Society, [searched June 29, 2018], Internet (https://www.jaici.or.jp/wcas/pdf/NIST17.pdf)

It is conceivable to use the search device of Non-Patent Document 1 as a system that assists a user in identifying an unknown mixture composed of a combination of multiple compounds.

However, although the search device of Non-Patent Document 1 can search for compounds that are highly likely to be contained in an unknown sample, the combination of a plurality of compounds extracted as a result of the search further extracts the unknown sample. No consideration has been given to searching for mixtures that are likely to be contained in .

Therefore, the user compares the mass spectra of each of the plurality of compounds in the search results obtained by the search device of Non-Patent Document 1 with the mass spectra of the plurality of compounds contained in the known mixture, one by one. Therefore, it is necessary to search for a mixture that is highly likely to be contained in the unknown sample from among the combinations of compounds, which poses a problem that causes a huge amount of trouble for the user.

An object of the present invention is to provide a mixture identification support system capable of efficiently supporting the identification of mixtures that are likely to be contained in unknown samples in view of the problems of the prior art.

The mixture identification support system according to the first invention is
A system for supporting the identification of an unknown mixture composed of a plurality of compounds contained in a substance,
Mixture identification information that is information identifying each of a plurality of known mixtures, and total ion current (TIC) obtained by pyrolyzing each of the plurality of known mixtures and analyzing using GC / MS a mixture library that stores chromatograms, known mixture TIC chromatograms that are TIC chromatograms that include at least one known compound mass spectrum that is a mass spectrum of a compound detected in each peak of the TIC chromatogram;
A TIC chromatogram obtained by pyrolyzing a substance containing an unknown mixture and analyzing it using GC/MS, wherein the mass spectrum of the compound detected in each peak of the TIC chromatogram is an unknown compound. an acquisition unit for acquiring an unknown mixture TIC chromatogram, which is a TIC chromatogram containing at least one mass spectrum;
Approximation between each unknown compound mass spectrum included in the unknown mixture TIC chromatogram acquired by the acquisition unit and each known compound mass spectrum included in each of a plurality of known mixture TIC chromatograms stored in the mixture library an estimation unit that calculates a compound match rate that is a degree;
an extraction unit for extracting the mixture identification information corresponding to the known mixture TIC chromatogram containing each known compound mass spectrum having the compound matching rate equal to or higher than a predetermined threshold;
An output unit that outputs data containing the mixture-specific information extracted by the extraction unit ,
In the known mixture TIC chromatogram, the peak area of the peak where each known compound mass spectrum is detected occupies the total value of the peak areas where each of the known compound mass spectra included in the known mixture TIC chromatogram is detected. contains an area ratio, which is a value indicating the percentage of
The output unit outputs the sum of the area ratios of all known compound mass spectra whose compound matching rate is equal to or higher than a predetermined threshold among the known compound mass spectra included in each known mixture TIC chromatogram extracted by the extraction unit. Output data with values
It is characterized by
In addition, the mixture identification support system according to the second invention is
A system for supporting the identification of an unknown mixture composed of a plurality of compounds contained in a substance,
Mixture identification information that is information identifying each of a plurality of known mixtures, and total ion current (TIC) obtained by pyrolyzing each of the plurality of known mixtures and analyzing using GC / MS a mixture library that stores chromatograms, known mixture TIC chromatograms that are TIC chromatograms that include at least one known compound mass spectrum that is a mass spectrum of a compound detected in each peak of the TIC chromatogram;
A TIC chromatogram obtained by pyrolyzing a substance containing an unknown mixture and analyzing it using GC/MS, wherein the mass spectrum of the compound detected in each peak of the TIC chromatogram is an unknown compound. an acquisition unit for acquiring an unknown mixture TIC chromatogram, which is a TIC chromatogram containing at least one mass spectrum;
Approximation between each unknown compound mass spectrum included in the unknown mixture TIC chromatogram acquired by the acquisition unit and each known compound mass spectrum included in each of a plurality of known mixture TIC chromatograms stored in the mixture library an estimation unit that calculates a compound match rate that is a degree;
an extraction unit for extracting the mixture identification information corresponding to the known mixture TIC chromatogram containing each known compound mass spectrum having the compound matching rate equal to or higher than a predetermined threshold;
An output unit that outputs data containing the mixture-specific information extracted by the extraction unit,
The output unit outputs a single Only included in the extracted known mixture TIC chromatogram
Output data containing information indicating that
It is characterized by
And the mixture identification support system according to the third invention is
A system for supporting the identification of an unknown mixture composed of a plurality of compounds contained in a substance,
Mixture identification information that is information identifying each of a plurality of known mixtures, and total ion current (TIC) obtained by pyrolyzing each of the plurality of known mixtures and analyzing using GC / MS a mixture library that stores chromatograms, known mixture TIC chromatograms that are TIC chromatograms that include at least one known compound mass spectrum that is a mass spectrum of a compound detected in each peak of the TIC chromatogram;
A TIC chromatogram obtained by pyrolyzing a substance containing an unknown mixture and analyzing it using GC/MS, wherein the mass spectrum of the compound detected in each peak of the TIC chromatogram is an unknown compound. an acquisition unit for acquiring an unknown mixture TIC chromatogram, which is a TIC chromatogram containing at least one mass spectrum;
Approximation between each unknown compound mass spectrum included in the unknown mixture TIC chromatogram acquired by the acquisition unit and each known compound mass spectrum included in each of a plurality of known mixture TIC chromatograms stored in the mixture library an estimation unit that calculates a compound match rate that is a degree;
an extraction unit for extracting the mixture identification information corresponding to the known mixture TIC chromatogram containing each known compound mass spectrum having the compound matching rate equal to or higher than a predetermined threshold;
An output unit that outputs data containing the mixture-specific information extracted by the extraction unit,
The known mixture TIC chromatogram contains index information on the retention time, which is the time at which the compound indicated by each known compound mass spectrum was detected,
The unknown mixture TIC chromatogram contains index information on the retention time, which is the time at which the compound indicated by each unknown compound mass spectrum was detected,
The output unit outputs the degree of approximation between index information on the retention time of compounds indicated by the known compound mass spectra whose compound match rate is equal to or higher than a predetermined threshold and index information on the retention times of compounds indicated by the unknown compound mass spectra. is less than or equal to a predetermined threshold, output data containing information indicating that the degree of approximation is less than or equal to a predetermined threshold
It is characterized by

According to the present invention, a mixture identification support system is obtained by analyzing mixture identification information identifying each of a plurality of known mixtures and each of the plurality of known mixtures by pyrolyzing and using GC / MS. A mixture library for storing known mixture TIC chromatograms containing at least one mass spectrum of a compound detected in each peak of the obtained TIC chromatogram.

Then, the mixture identification support system of the present invention is a mass of compounds detected in each peak of an unknown mixture TIC chromatogram obtained by pyrolyzing a substance containing an unknown mixture and analyzing it using GC/MS. Known mixture TIC chromatogram containing each known compound mass spectrum whose degree of similarity between the spectrum and each known compound mass spectrum included in each of a plurality of known mixture TIC chromatograms stored in the mixture library is equal to or greater than a predetermined threshold and extracts mixture identification information corresponding to and outputs data including the mixture identification information.

As a result, the mass spectrum of each of the compounds contained in the unknown mixture and the mass spectrum of the compounds contained in the known mixture can be compared manually one by one, and the unknown mixture can be analyzed. It is possible to search for mixtures that are likely to be contained in samples of

Thus, the mixture identification support system of the present invention can efficiently support identification of mixtures that are likely to be contained in unknown samples.

The mixture is composed of a plurality of compounds, and among the mass spectra of the compounds contained in the known mixture, the larger the peak area of the peak detected in each mass spectrum, the more characteristic the compound is. is considered to be the peak showing

Therefore, the mixture in which the sum of the peak areas of the peaks detected in all the mass spectra matching the mass spectrum of the compound contained in the unknown mixture is larger is the mixture contained in the unknown sample. It is highly likely that there is.

According to the first invention, the known mixture TIC chromatogram is obtained by detecting each known compound mass spectrum occupying the total value of the peak areas of the detected peaks of all the known compound mass spectra included in the known mixture TIC chromatogram. It contains an area ratio, which is a value that indicates the percentage of the peak area of the peak that was observed.

Then, the output unit outputs a value obtained by summing the area ratios of all known compound mass spectra whose compound matching rate is equal to or higher than a predetermined threshold among the known compound mass spectra included in each known mixture TIC chromatogram extracted by the extraction unit. Output data containing

Therefore, the user considers the sum of the area ratios of all known compound mass spectra whose compound match rate is equal to or higher than a predetermined threshold value, which is included in the data output by the output unit, and determines which known mixture is more unknown. It is possible to know more efficiently whether the mixture is likely to be contained in the sample.

In this way, the mixture identification support system of the present invention considers the sum of the area ratios of all known compound mass spectra whose compound matching rate is equal to or higher than a predetermined threshold value, and identifies possible compounds contained in an unknown sample. identification of mixtures with high susceptibility can be assisted more efficiently.

In addition, if the compound indicated by each known compound mass spectrum having a compound matching rate equal to or higher than a predetermined threshold is included only in the single extracted known mixture TIC chromatogram, the unknown mixture is the known mixture High certainty that it is a mixture.

According to the second invention, the data output by the output unit includes information indicating that the data is included only in the single extracted known mixture TIC chromatogram. Therefore, the user can efficiently know from the data output by the output unit which known mixture is the mixture with high certainty contained in the unknown sample.

In this way, the mixture identification support system of the present invention efficiently supports the identification of a highly certain mixture contained in an unknown sample among mixtures that are likely to be contained in an unknown sample. be able to.

Even if the compound match rate of the mass spectrum of the known compound and the mass spectrum of the unknown compound is high, if the degree of approximation of the index information related to the detection time of the compound indicated by these mass spectra is low, the unknown compound is the known compound. Not likely.

According to the third invention, the known-mixture TIC chromatogram and the unknown-mixture TIC chromatogram contain index information relating to the time at which the compound indicated by the mass spectrum of each compound included in the TIC chromatogram was detected.

The data output by the output unit includes index information on the retention time of compounds indicated by the known compound mass spectra and index information on the retention times of compounds indicated by the unknown compound mass spectra, the compound matching rate of which is equal to or greater than a predetermined threshold. is less than or equal to a predetermined threshold, data including information indicating that the degree of approximation is less than or equal to the predetermined threshold is included.

Therefore, by looking at the data output by the output unit, the user can identify the mixture by considering not only the degree of approximation of the mass spectrum of the compound but also the index information regarding the retention time of the compound.

In this way, the mixture identification support system of the present invention can support identification of mixtures that are likely to be contained in an unknown sample by taking into consideration index information regarding retention times of compounds.

In the mixture identification support system according to the present invention,
The output unit provides information indicating the ratio of the known compound mass spectra whose compound match rate is equal to or higher than a predetermined threshold among the known compound mass spectra included in each known mixture TIC chromatogram extracted by the extraction unit. It is preferable to output data including

Since a mixture is composed of a plurality of compounds, a mixture with a high proportion of mass spectra of compounds contained in a known mixture that matches mass spectra of compounds contained in an unknown mixture. is more likely to be a mixture contained in a more unknown sample.

According to the present invention, in the mixture identification support system, the data output by the output unit includes information indicating the proportion of known compound mass spectra whose compound matching rate is equal to or greater than a predetermined threshold.

Therefore, the user can more efficiently know which known mixture is likely to be contained in an unknown sample from the data output by the output unit.

Thus, the mixture identification support system of the present invention can more efficiently support identification of mixtures that are likely to be contained in unknown samples.

In the mixture identification support system according to the present invention,
The estimating unit performs the compound match rate based on the ion intensity of the peaks for each m/z value included in the unknown compound mass spectrum and the ion intensity of the peaks for each m/z value included in each known compound mass spectrum. of the peaks for each m/z value contained in the unknown compound mass spectrum and each known compound mass spectrum, the m/z value for the peak below a certain value It is preferable to calculate the matching rate of the compound by giving a lower weight to the peaks in which the value exceeds a certain value.

According to the present invention, the estimating unit is based on the ion intensity of the peak for each m/z value included in the unknown compound mass spectrum and the ion intensity of the peak for each m/z value included in each known compound mass spectrum. It is configured to calculate the compound matching rate.

When obtaining a mass spectrum of a compound contained in an unknown mixture, many ions with small m/z values are also detected. Ions with a large m/z value are ions of high importance in identifying the compound from which the ion is detected, but ions with a small m/z value are detected in a large number of compounds. are of relatively low importance in identifying the compound from which the ion is detected.

Therefore, if these ions with small m/z values and ions with large m/z values are treated with the same weight when calculating the compound matching rate, the calculation accuracy of the compound matching rate may be lowered. .

Therefore, in the estimation unit of the present invention, the m/z value is constant for peaks with m/z values below a certain value among the peaks for each m/z value contained in the unknown compound mass spectrum and each known compound mass spectrum. Compound identity calculations are performed with lower weightings for peaks that exceed values.

As a result, when calculating the compound identity rate, the calculation accuracy of the compound identity rate is increased compared to the case where these ions with small m / z values and ions with large m / z values are treated with the same weighting. be able to.

In this way, the mixture identification support system of the present invention can support with high accuracy the identification of mixtures that are likely to be contained in unknown samples.

1 is a configuration diagram showing an example of the overall configuration of a mixture identification support system according to this embodiment; FIG. Table showing an example of the content of the mixture library of the present embodiment Table showing an example of the contents of the unknown mixture TIC chromatogram of the present embodiment Flowchart showing an example of processing contents of the mixture identification support system of the present embodiment Flowchart showing an example of content of estimation processing of the mixture identification support system of the present embodiment Flowchart showing an example of content of estimation processing of the mixture identification support system of the present embodiment Table showing an example of a table storing thresholds used for processing by the mixture identification support system of the present embodiment FIG. 4 is an image diagram explaining the calculation process of the compound matching rate of the mixture identification support system of the present embodiment. FIG. 4 is an image diagram explaining the calculation process of the compound matching rate of the mixture identification support system of the present embodiment. Table showing an example of output contents of the mixture identification support system of the present embodiment

Embodiments of the present invention will be described below with reference to the drawings.

First, an example of the overall configuration of the mixture identification support system of this embodiment will be described with reference to FIGS. 1 to 3. FIG.

A mixture identification support system 1 of this embodiment is a computer including a control unit 10 , a storage unit 20 , an output unit 30 and an input unit 40 .

The control unit 10 includes an arithmetic processing unit such as a CPU (Central Processing Unit), a memory, an I/O (Input/Output) device, and the like. The control unit 10 may be configured by one processor, or may be configured by a plurality of mutually communicable processors.

The control unit 10 functions as an acquiring unit 11, an estimating unit 12, and an extracting unit 13 that execute arithmetic processing, which will be described later, by reading and executing predetermined programs.

The acquisition unit 11 obtains a TIC (Total Ion Current) chromatogram obtained by pyrolyzing a substance containing an unknown mixture and analyzing it using a GC/MS (Gas Chromatograph/Mass Spectrometer) 50, which is an unknown mixture TIC. A chromatogram 22 is obtained from the GC/MS 50 .

The mixture identification support system 1 and the GC/MS 50 are communicably connected using, for example, a wired or wireless network. The network is, for example, a LAN (Local Area Network), a WAN (Wide Area Network) or an Internet communication network. The acquisition unit 11 acquires the unknown mixture TIC chromatogram 22 from the GC/MS 50 via the network in response to user's operation or automatically, and stores it in the storage unit 20 .

Alternatively, the acquisition unit 11 may acquire the unknown mixture TIC chromatogram 22 via an external storage medium such as a USB memory or CD-ROM.

Alternatively, the mixture identification support system 1 and the GC/MS 50 may be configured by the same computer. In this case, the acquiring unit 11 acquires the unknown mixture TIC chromatogram 22 from the storage device of the same computer.

The estimating unit 12 acquires each unknown compound mass spectrum contained in the unknown mixture TIC chromatogram 22 acquired by the acquiring unit 11 according to the user's operation or automatically each time the acquiring unit 11 acquires the unknown mixture TIC chromatogram 22. Then, the compound match rate, which is the degree of approximation with each known compound mass spectrum included in each of the plurality of known mixture TIC chromatograms stored in the mixture library 21 of the storage unit 20, is calculated.

The extraction unit 13 extracts mixture identification information corresponding to the known mixture TIC chromatogram including each known compound mass spectrum having a compound matching rate calculated by the estimation unit 12 equal to or higher than a predetermined threshold.

The storage unit 20 includes a storage device such as a ROM (Read Only Memory), a RAM (Random Access Memory), and a HDD (Hard Disk Drive). store the processing result of

The mixture library 21 stores mixture identification information and known mixture TIC chromatograms for each of one or more known mixtures, as shown in FIG.

The mixture identification information is, for example, an ID and a name for identifying the mixture.

The ID is composed of a combination of alphabets, numbers, and symbols including, for example, the name of the mixture manufacturer and an identifier representing the symbol/number of the manufacturing lot.

The name is composed of, for example, a combination of alphabets, numerals, and symbols representing the product name, abbreviation of the product name, common name, scientific name, etc. of each mixture.

In addition, even a known mixture TIC chromatogram obtained by pyrolyzing a known mixture of the same name and analyzing it using GC/MS50, for example, measured at a measurement temperature (e.g., 400 ° C. measured, etc.) or the source of acquisition (whether it is a mixture obtained from Company A or a mixture obtained from Company B), etc., if the conditions are different, one of the different IDs and names as another mixture, or Both can be given and exist in the mixture library 21 .

A known mixture TIC chromatogram is a TIC chromatogram obtained by pyrolyzing each of the known mixtures and analyzing using GC/MS50.

The known mixture TIC chromatogram includes at least one known compound mass spectrum (for example, known compound mass spectrum 1 to known compound mass spectrum m) that is the mass spectrum of the compound detected in each peak of the known mixture TIC chromatogram. is

Each known compound mass spectrum includes, for example, the compound name, retention index (RI), retention time, area ratio, and mass spectrum of the compound from which the known compound mass spectrum was detected.

For example, if the GC / MS used to obtain the known mixture TIC chromatogram and the GC / MS used to obtain the unknown mixture TIC chromatogram are different, even if the TIC chromatogram is obtained for the same compound , retention time discrepancies may occur between the known mixture TIC chromatogram and the unknown mixture TIC chromatogram.

Considering that such a retention time shift may occur, in this example, a retention index (RI) indexed for the retention time of each compound is used as index information regarding the retention time, so that each known compound The mass spectrum contains retention index (RI).

The area ratio is a value indicating the ratio of the peak area of each known compound mass spectrum detected to the total peak area of each known compound mass spectrum included in the known mixture TIC chromatogram. is.

For example, the number of known compound mass spectra included in a known mixture TIC chromatogram is 3, the total value of the peak areas of the peaks detected in each of the known compound mass spectra is 1000, and each known compound mass When the peak areas of the detected spectra are 250, 350 and 400 respectively, the area ratios of each known compound mass spectrum are 0.25, 0.35 and 0.40 respectively.

In addition, in the mass spectrum, one or more m / z values (for example, m / z value 1 to m / z value n) where each peak of the mass spectrum is detected and the ion intensity of each peak are expressed in percent A value is included (eg percent 1 to percent n). The value expressed as a percentage of the ionic strength of each peak is the peak with the strongest ionic strength among the peaks of each mass spectrum as the reference peak, the ionic strength of the reference peak as 100%, and the ionic strength of the other peaks as the reference. This is a value that indicates what percentage it corresponds to the peak.

The unknown mixture TIC chromatogram 22 is a TIC chromatogram obtained by pyrolyzing a substance containing an unknown mixture and analyzing it using the GC/MS50.

In the unknown mixture TIC chromatogram 22, as shown in FIG. 3, at least one unknown compound mass spectrum (for example, unknown compound mass spectrum 1 ~ unknown compound mass spectrum x) included.

Each unknown compound mass spectrum includes, for example, the RI, retention time, and mass spectrum of the unknown compound from which the unknown compound mass spectrum was detected. In addition, in the mass spectrum, one or more m / z values (for example, m / z value 1 to m / z value y) where each peak of the mass spectrum is detected and the ion intensity of each peak are expressed in percent A value is included (eg percent 1 to percent y).

The RI of an unknown compound stores a value obtained by, for example, the following method.

An unknown compound mass spectrum of any one or more compounds (for example, one to five; the quantity can be changed as appropriate) from the unknown mixture TIC chromatogram 22 is obtained by obtaining an unknown compound mass spectrum for each unknown compound contained in the unknown mixture TIC chromatogram. Extract as an unknown compound mass spectrum of the compound that serves as a reference for determining the RI of the compound. Then, with reference to the known mixture TIC chromatogram contained in the mixture library 21, identify the compound indicated by the extracted unknown compound mass spectrum, obtain the RI contained in the known compound mass spectrum of the identified compound, The obtained RI value is determined as the RI value of the reference compound. Then, based on the determined RI value of the reference compound, the RI value of the unknown compound in each unknown compound mass spectrum included in the unknown mixture TIC chromatogram 22 is determined.

Note that such RI processing of unknown compounds in each unknown compound mass spectrum contained in the unknown mixture TIC chromatogram 22 may be performed in advance before the acquisition unit 11 acquires the unknown mixture TIC chromatogram 22. Alternatively, the acquisition unit 11 may be configured to execute when acquiring the unknown mixture TIC chromatogram 22 . Alternatively, the estimating unit 12 may be configured to execute in an estimating process to be described later.

The output unit 30 is a part that displays information output to the user by the mixture identification support system 1, and is, for example, a liquid crystal display or an organic EL display.

The input unit 40 is a part that receives information input by the user, and is, for example, a keyboard, mouse, touch pad, touch panel, or other pointing device.

Next, processing contents of the mixture identification support system of the present embodiment will be described with reference to FIGS. 4 to 9. FIG.

When starting processing, the mixture identification support system 1 of the present embodiment first acquires an unknown mixture TIC chromatogram (FIG. 4/STEP 100).

Next, the mixture identification support system 1 executes estimation processing (FIG. 4/STEP 200), outputs data including mixture identification information to the output unit 30 (FIG. 4/STEP 300), and ends the processing.

(estimation process)
When the estimation process is started, the estimation unit 12 recognizes the unknown mixture TIC chromatogram 22 to be processed stored in the storage unit 20, for example, in response to the user's operation using the input unit 40 (FIG. 5A/STEP 201 ), from the unknown mixture TIC chromatogram 22, important peaks, which are peaks with a total ion intensity equal to or greater than a predetermined value, are extracted (FIG. 5A/STEP 202).

The estimating unit 12 recognizes the threshold value of the total ion intensity of the peak to be extracted as the important peak by referring to a table such as that shown in FIG. 6, for example.

In this embodiment, when the maximum value of the total ion intensity represented by the difference from the baseline to the peak top is, for example, 100, if the value is 10 or more, it is extracted as an important peak.

The thresholds stored in the table as shown in FIG. 6 can be arbitrarily changed by the user's operation. For example, when it is desired to set smaller peaks as important peaks, they may be extracted as important peaks when the value is 5 or more. Alternatively, when it is desired to set only larger peaks as important peaks, when the value is 50 or more or 70 or more, it may be extracted as an important peak.

Subsequently, the estimation unit 12 refers to the mixture library 21 stored in the storage unit 20 to recognize the mixture identification information to be processed and the known mixture TIC chromatogram (FIG. 5A/STEP 210). The estimation unit 12 performs the processing of STEP 210 to STEP 251 for each known mixture TIC chromatogram included in the mixture library 21 (loop L1).

Next, the estimation unit 12 recognizes the known compound mass spectrum to be processed from the known compound mass spectrum included in the known mixture TIC chromatogram to be processed (FIG. 5A/STEP 220).

Note that the estimation unit 12 performs the processing of STEP 230 to STEP 235 for each known compound mass spectrum included in the known mixture TIC chromatogram to be processed (loop L2).

Then, the estimation unit 12 recognizes the unknown compound mass spectrum to be processed from the unknown compound mass spectrum of the important peaks included in the unknown mixture TIC chromatogram 22 (FIG. 5A/STEP 230). The estimation unit 12 performs the processing of STEP230 to STEP235 for each unknown compound mass spectrum included in the unknown mixture TIC chromatogram 22 (loop L3).

Then, the estimating unit 12 calculates the compound matching rate between the known compound mass spectrum to be processed and the unknown compound mass spectrum to be processed (FIG. 5A/STEP 231).

The estimating unit 12 calculates the compound matching rate between the known compound mass spectrum to be processed and the unknown compound mass spectrum to be processed, for example, as follows.

As shown in FIG. 7, peaks in the unknown compound mass spectrum were detected at m/z values of 72, 88, 95, 100, 106, 120, and 150, and the ionic strength of each peak was expressed as a percentage of 60, 80, 100, 60, 50, 40, 50, and the known compound mass spectrum peaks were detected at m/z values of 88, 91, 100, 106, and 150, and the ion intensity of each peak was expressed as a percentage of 60. , 40, 100, 60, 40 will be described.

In this case, the estimation unit 12 detects eight m/z values of 72, 88, 91, 95, 100, 106, 120, and 150 at which peaks are detected in either the unknown compound mass spectrum or the known compound mass spectrum, for example. Therefore, let the unknown compound mass spectrum and the known compound mass spectrum be two eight-dimensional vectors, each coordinate of which is a percentage of the ion intensity at each of these m/z values, and these two vectors are The compound match rate is calculated by calculating the square of cos θ of the angle formed.

In addition, regarding m / z values where peaks were detected only in either the unknown compound mass spectrum or the known compound mass spectrum (m / z values 72, 91, 95, 120 in this example), peaks were detected Values at the m/z values of the compound mass spectrum on the untreated side are calculated as 0.

Further, the compound matching rate is 1 when the known compound mass spectrum to be processed and the unknown compound mass spectrum to be processed completely match.

The estimation unit 12 calculates the unknown compound mass spectrum vector as

とし、既知化合物マススペクトルのベクトルを

and let the vector of known compound mass spectra be

とし、化合物合致率を以下の式（３）により求める。

, and the compound match rate is calculated by the following formula (3).

ここで、
Ｍは、化合物合致率である。

here,
M is the compound match rate.

Vector of unknown compound mass spectrum in this example

であり、既知化合物マススペクトルのベクトル

and the vector of known compound mass spectra

である。

is.

And the calculation result in a present Example is as follows.

M = {(60x0) + (80x60) + (0x40) + (100x0) + (60x100) + (50x60) + (40x0) + (50x40) }×{(60×0)+(80×60)+(0×40)+(100×0)+(60×100)+(50×60)+(40×0)+(50×40) }/{(60×60+80×80+0×0+100×100+60×60+50×50+40×40+50×50)×(0×0+60×60+40×40+0×0+100×100+60×60+0×0+40×40)}
= 249640000/(30200 x 20400)
= 0.4052
= 40.52%

An unknown sample may contain a plurality of different compounds whose peaks are detected at the same retention time in the unknown TIC chromatogram. It is conceivable that the mass spectrum of such an unknown TIC chromatogram contains mass spectra derived from multiple compounds.

On the other hand, the known compound mass spectrum is usually obtained by pyrolyzing and analyzing a sample containing only a single compound.

Therefore, for example, when calculating the degree of matching between an unknown compound mass spectrum containing mass spectra of a plurality of unknown compounds X and Y and a known compound mass spectrum obtained from a single known compound A, the actual unknown compound Even if the compound X is a known compound A, the mass spectrum derived from the unknown compound Y becomes noise, and the inconvenience that the degree of matching with the known compound mass spectrum obtained from the known compound A is calculated is low. may cause

Therefore, it is more preferable that the mixture identification support system be configured so as to avoid such inconveniences. In order to avoid this inconvenience, for example, the estimating unit 12 selects m/ It may be configured to calculate the compound matching rate between the known compound mass spectrum to be processed and the unknown compound mass spectrum to be processed using only the values related to the peaks detected in the z value.

That is, in the example shown in FIG. 7, the ion intensity of each peak detected at m/z values of 88, 91, 100, 106, and 150 in the known compound mass spectrum is 60, 40, 100, 60, 40, and the ion intensities of each peak of the unknown compound mass spectrum at the m/z values at which the peaks were detected in the known compound mass spectrum were expressed as percentages of 80, 0, 60, 50, 50.

Note that the estimating unit 12 sets the m/z value (m/z value 91 in this example) at which a peak is detected only in the known compound mass spectrum to 0 in the unknown compound mass spectrum. Calculate as

The calculation results in this embodiment are as follows.

M = {(80 x 60) + (0 x 40) + (60 x 100) + (50 x 60) + (50 x 40)} x {(80 x 60) + (0 x 40) + (60 x 100) + (50 x 60) + (50 x 40)} / {(80 x 80 + 0 x 0 + 60 x 60 + 50 x 50 + 50 x 50) x (60 x 60 + 40 x 40 + 100 x 100 + 60 x 60 + 40 x 40)}
= 249640000/(15000 x 20400)
= 0.8158
= 81.58%
The calculation result by the estimation unit 12 when the possibility that the mass spectrum derived from multiple compounds is not considered in the mass spectrum of the unknown TIC chromatogram described above is 40.52%. , the calculation result when this possibility is considered is 81.58%, and the compound matching rate is calculated to be high.

In this way, considering the possibility that the mass spectrum of the unknown TIC chromatogram contains mass spectra derived from multiple compounds, the compound of the known compound mass spectrum to be processed and the unknown compound mass spectrum to be processed By configuring the estimating unit 12 to calculate the matching rate, even when the mass spectrum of the unknown TIC chromatogram contains mass spectra derived from a plurality of compounds, it is possible that the unknown sample contains It is possible to provide a mixture identification support system capable of efficiently supporting identification of mixtures with high susceptibility.

Alternatively, the estimating unit 12 may calculate the compound match rate by calculating cos θ of the angle formed by the unknown compound mass spectrum vector and the known compound mass spectrum vector, for example.

Alternatively, the estimating unit 12 uses, for example, an approximate curve obtained by using the ion intensity of each peak of the unknown compound mass spectrum expressed as a percentage, and the ion intensity of each peak of the known compound mass spectrum expressed as a percentage. The compound matching rate may be obtained by calculating the degree of approximation with the approximated curve obtained by the method.

In addition, among the peaks for each m/z value contained in the unknown compound mass spectrum and each known compound mass spectrum, the peaks with m/z values below a certain value are weighted lower than the peaks with m/z values above a certain value. It is also possible to calculate the compound matching rate by

For example, as shown in FIG. 8, for peaks with an m/z value of 100 or less, the weighting for peaks with an m/z value of 100 is 100%, and as the m/z value decreases from 100 to 0, weighting The weighting is determined such that the is continuously or stepwise reduced to 0%. For peaks with an m/z value of 100 or more, the weighting is constant at 100%.

The estimating unit 12 recognizes a constant value that should be given a low weight to calculate the compound match rate by referring to a table such as that shown in FIG. 6, for example. In this embodiment, when the m/z value is less than 100, the weighting is lowered in stages for calculation.

Note that the constant value can be changed as appropriate. For example, the constant value may be 50 or 200. Smaller or larger values are also possible.

Also, the method of determining the weighting of peaks below a certain value may be changed as appropriate. For example, a constant value of 0% or 50% may be used to weight peaks below a certain value.

As a result, when calculating the compound identity rate, the calculation accuracy of the compound identity rate is increased compared to the case where these ions with small m / z values and ions with large m / z values are treated with the same weighting. be able to.

Then, the extraction unit 13 determines whether or not the compound match rate thus obtained is equal to or greater than a predetermined threshold (FIG. 5A/STEP 232).

The extraction unit 13 recognizes the threshold value of the compound match rate by referring to a table such as that shown in FIG. 6, for example. In this embodiment, when the compound matching rate is 80% or higher, it is determined that the compound matching rate is equal to or higher than the threshold.

Note that the threshold can be changed as appropriate. For example, if you want to extract only compounds with a higher compound matching rate, the threshold may be set to 90%, and if you want to extract more compounds, the threshold may be set to 70%, 50%, etc. .

If the determination is negative (FIG. 5A/STEP232: No), the extraction unit 13 does not execute FIG. The processing from STEP 230 is repeated.

On the other hand, if the determination is affirmative (FIG. 5A/STEP 232: Yes), the extraction unit 13 adds mixture identification information to mixture candidate data, which is information indicating a mixture candidate that is likely to be contained in an unknown substance. Write compound identification information and compound match rate (FIG. 5A/STEP 233).

Subsequently, the extraction unit 13 determines whether the degree of similarity between the RI of the compound indicated by the known compound mass spectrum to be processed and the RI of the compound indicated by the unknown compound mass spectrum is equal to or less than a predetermined threshold. (Fig. 5A/STEP234)
The extraction unit 13 recognizes the predetermined threshold by referring to a table such as that shown in FIG. 6, for example. In this embodiment, the threshold for the degree of approximation of the index information regarding the retention time is RI difference of 100 or less.

If the determination is negative (FIG. 5A/STEP234: No), the extraction unit 13 shifts the processing target to the next known compound mass spectrum without executing FIG. repeat the process.

On the other hand, if the determination is affirmative (FIG. 5A/STEP 234: Yes), the extraction unit 13 adds information indicating that the degree of approximation is equal to or less than a predetermined threshold to the mixture candidate data. (Fig. 5A/STEP235)
As a result, by viewing the data output by the output unit 30, the user can identify the mixture by considering not only the degree of approximation of the mass spectrum of the compound, but also the RI, which is index information regarding the retention time of the compound. .

When the extraction unit 13 completes these processes (STEP230 to STEP235) for all unknown compound mass spectra contained in the unknown mixture TIC chromatogram 22, it exits the loop L3.

The extraction unit 13 exits the loop L2 when completing these processes (FIG. 5A/STEP220 to STEP235) for all known compound mass spectra included in the known mixture TIC chromatogram to be processed.

Then, the extracting unit 13 calculates the proportion of known compound mass spectra whose compound matching rate is equal to or higher than a predetermined threshold, and extracts information indicating the proportion of known compound mass spectra whose compound matching rate is equal to or higher than the predetermined threshold as a mixture candidate. append to the data. (Fig. 5B/STEP250)
This allows the user to more efficiently know which known mixture is likely to be contained in an unknown sample, from the data output by the output unit 30 .

That is, for example, the extraction unit 13 determines that the number of known compound mass spectra included in a known mixture TIC chromatogram to be processed is 4, and the number of known compound mass spectra whose compound matching rate is equal to or greater than a predetermined threshold is 3. In this case, for example, the ratio of known compound mass spectra whose compound matching rate is equal to or higher than a predetermined threshold is calculated as 0.75, and the compound matching rate of the known mixture TIC chromatogram to be processed in the mixture candidate data is calculated as 0.75. Information indicating the ratio is added to the data on each known compound mass spectrum that is equal to or higher than the threshold.

Then, the extraction unit 13 calculates a value obtained by totaling the area ratios of all known compound mass spectra whose compound match rate is equal to or higher than a predetermined threshold value, and adds the calculation result to the mixture candidate data. (Fig. 5B/STEP251)
For example, the number of known compound mass spectra included in a known mixture TIC chromatogram is three, the area ratios of each known compound mass spectrum are 0.25, 0.35, and 0.40, respectively, and the compound match rate is the second and third known compound mass spectra, the mass spectra of known compounds having a predetermined threshold value or more, the area ratio of all known compound mass spectra having a compound match rate of the predetermined threshold value or more is The summed value is 0.35+0.40=0.75.

And the number of known compound mass spectra contained in another known mixture TIC chromatogram is three, and the area ratios of each known compound mass spectrum are 0.50, 0.25, and 0.25, respectively, and the compound If the known compound mass spectra with matching rates equal to or greater than the predetermined threshold are the second and third known compound mass spectra, the area of all known compound mass spectra with compound matching rates equal to or greater than the predetermined threshold The sum of the ratios is 0.25+0.25=0.50.

In this case, for these two known mixture TIC chromatograms, the proportion of known compound mass spectra in which the compound match rate was equal to or greater than the predetermined threshold is both 0.67. However, there is a possibility that the mixture with a larger value of 0.75, which is the sum of the area ratios of all known compound mass spectra in which the compound match rate is equal to or higher than a predetermined threshold, is contained in a more unknown sample. is considered to be a mixture with a high

As a result, the user can determine which known mixture is more important by considering the sum of the area ratios of all known compound mass spectra in which the compound matching rate is equal to or higher than a predetermined threshold, which is included in the data output by the output unit 30. It is possible to know more efficiently whether the mixture is likely to be contained in an unknown sample.

The extraction unit 13 exits the loop L1 when these processes (FIG. 5A/STEP210 to FIG. 5B/STEP251) are completed for all known mixture TIC chromatograms contained in the mixture library 21. FIG.

Next, the extraction unit 13 refers to the mixture candidate data, and determines whether or not the compound is contained only in the single extracted known mixture TIC chromatogram for each data included in the mixture candidate data. (FIG. 5B/STEP 260).

Note that the extraction unit 13 performs the processing of STEP260 to STEP261 for each mixture candidate data (loop L4).

If the determination is negative (FIG. 5B/STEP260: No), the extraction unit 13 does not execute STEP261, but shifts the processing target to the next data and repeats the processing from STEP260.

If the determination is affirmative (FIG. 5B/STEP 260: Yes), the extraction unit 13 adds information indicating that the extracted known mixture TIC chromatogram is contained only to the target mixture candidate data. (FIG. 5B/STEP 261).

Accordingly, the user can efficiently know which known mixture is the mixture with high certainty contained in the unknown sample from the data output by the output unit 30 .

When the extraction unit 13 completes these processes (FIG. 5B/STEP 260 to 261) for all of the mixture candidate data, the extraction unit 13 exits the loop L4 and terminates the estimation process.

The mixture candidate data obtained in this manner is, for example, as shown in FIG.

The mixture candidate data includes, for example, the ID of a known mixture that is likely to be contained in an unknown substance, the name of the known mixture, the known Compound name of compound, compound matching ratio between known compound mass spectrum and unknown compound mass spectrum for each known compound, number of matching mass spectra (number of matching compounds), total number of mass spectra (total number of compounds), ratio of matching mass spectra (compound match ratio), match area ratio, RI, and remarks. Alternatively, the retention time may be included.

The number of matched mass spectra (number of matched compounds) is the number of known compound mass spectra in which the compound matching rate with the unknown compound mass spectrum is equal to or higher than a predetermined threshold among the known compound mass spectra included in each known mixture TIC chromatogram. , that is, the number of known compounds whose mass spectra match the unknown compounds.

The total number of mass spectra (total number of compounds) is the total number of known compound mass spectra contained in each known mixture TIC chromatogram, that is, the total number of known compounds contained in the known mixture. The mass spectrum matching ratio (compound matching ratio) is the value obtained by dividing the number of matching mass spectra (number of matching compounds) by the total number of mass spectra (total number of compounds). It is information indicating the proportion of known compound mass spectra in which the compound matching rate is equal to or higher than a predetermined threshold among the spectra.

The matching area ratio is the sum of the area ratios of all known compound mass spectra whose compound matching rate is equal to or higher than a predetermined threshold among the known compound mass spectra included in each known mixture TIC chromatogram extracted by the extraction unit 13. value.

The percentage of known compound mass spectra or the matching area ratio in which the compound matching rate is equal to or higher than a predetermined threshold is displayed using a figure such as a pie chart or bar graph that shows the percentage, in addition to or instead of simply expressing it numerically. You may

In the remark column, the display of "single" and the display of "different RI" are stored.

A "single" designation is information indicating that the compound represented by each known compound mass spectrum is contained only in a single extracted known mixture TIC chromatogram.

The display of "different RI" is information indicating that the degree of similarity between the RI of the compound indicated by each known compound mass spectrum and the RI of the compound indicated by the unknown compound mass spectrum is equal to or less than a predetermined threshold.

As described above, according to the present invention, the mass spectra of each of a plurality of compounds contained in an unknown mixture and the mass spectra of a plurality of compounds contained in a known mixture are manually obtained one by one. It is possible to search for mixtures that are likely to be contained in unknown samples without the need for comparison.

Thus, the mixture identification support system of the present invention can efficiently support identification of mixtures that are likely to be contained in unknown samples.

Although the embodiments of the present invention have been described above with reference to the drawings, the present invention is not limited thereto. Various modifications are possible without departing from the scope of the present invention.

1... mixture identification support system, 10... control unit, 11... acquisition unit, 12... estimation unit, 13... extraction unit, 20... storage unit, 21... mixture library, 22... unknown mixture TIC chromatogram, 30... output unit, 40... Input section, 50... GC/MS

Claims (5)

A system for supporting the identification of an unknown mixture composed of a plurality of compounds contained in a substance,
Mixture identification information that is information identifying each of a plurality of known mixtures, and a TIC chromatogram obtained by pyrolyzing each of the plurality of known mixtures and analyzing using GC / MS, a known mixture TIC chromatogram, which is a TIC chromatogram containing at least one known compound mass spectrum, which is a mass spectrum of a compound detected in each peak of the TIC chromatogram; and
A TIC chromatogram obtained by pyrolyzing a substance containing an unknown mixture and analyzing it using GC/MS, wherein the mass spectrum of the compound detected in each peak of the TIC chromatogram is an unknown compound. an acquisition unit for acquiring an unknown mixture TIC chromatogram, which is a TIC chromatogram containing at least one mass spectrum;
Degree of approximation between each unknown compound mass spectrum contained in the unknown mixture TIC chromatogram acquired by the acquisition unit and each known compound mass spectrum contained in each of a plurality of known mixture TIC chromatograms stored in the mixture library an estimating unit that calculates a compound matching rate that is
an extraction unit for extracting the mixture identification information corresponding to the known mixture TIC chromatogram containing each known compound mass spectrum having the compound matching rate equal to or higher than a predetermined threshold;
An output unit that outputs data containing the mixture-specific information extracted by the extraction unit ,
In the known mixture TIC chromatogram, the peak area of the peak where each known compound mass spectrum is detected occupies the total value of the peak areas where each of the known compound mass spectra included in the known mixture TIC chromatogram is detected. contains an area ratio, which is a value indicating the percentage of
The output unit outputs the sum of the area ratios of all known compound mass spectra whose compound matching rate is equal to or higher than a predetermined threshold among the known compound mass spectra included in each known mixture TIC chromatogram extracted by the extraction unit. Output data with values
A mixture identification support system characterized by: A system for supporting the identification of an unknown mixture composed of a plurality of compounds contained in a substance,
Mixture identification information that is information identifying each of a plurality of known mixtures, and a TIC chromatogram obtained by pyrolyzing each of the plurality of known mixtures and analyzing using GC / MS, a known mixture TIC chromatogram, which is a TIC chromatogram containing at least one known compound mass spectrum, which is a mass spectrum of a compound detected in each peak of the TIC chromatogram; and
A TIC chromatogram obtained by pyrolyzing a substance containing an unknown mixture and analyzing it using GC/MS, wherein the mass spectrum of the compound detected in each peak of the TIC chromatogram is an unknown compound. an acquisition unit for acquiring an unknown mixture TIC chromatogram, which is a TIC chromatogram containing at least one mass spectrum;
Degree of approximation between each unknown compound mass spectrum contained in the unknown mixture TIC chromatogram acquired by the acquisition unit and each known compound mass spectrum contained in each of a plurality of known mixture TIC chromatograms stored in the mixture library an estimating unit that calculates a compound matching rate that is
an extraction unit for extracting the mixture identification information corresponding to the known mixture TIC chromatogram containing each known compound mass spectrum having the compound matching rate equal to or higher than a predetermined threshold;
An output unit that outputs data containing the mixture-specific information extracted by the extraction unit ,
The output unit outputs a single Only included in the extracted known mixture TIC chromatogram
Output data containing information indicating that
A mixture identification support system characterized by: A system for supporting the identification of an unknown mixture composed of a plurality of compounds contained in a substance,
Mixture identification information that is information identifying each of a plurality of known mixtures, and a TIC chromatogram obtained by pyrolyzing each of the plurality of known mixtures and analyzing using GC / MS, a known mixture TIC chromatogram, which is a TIC chromatogram containing at least one known compound mass spectrum, which is a mass spectrum of a compound detected in each peak of the TIC chromatogram; and
A TIC chromatogram obtained by pyrolyzing a substance containing an unknown mixture and analyzing it using GC/MS, wherein the mass spectrum of the compound detected in each peak of the TIC chromatogram is an unknown compound. an acquisition unit for acquiring an unknown mixture TIC chromatogram, which is a TIC chromatogram containing at least one mass spectrum;
Degree of approximation between each unknown compound mass spectrum contained in the unknown mixture TIC chromatogram acquired by the acquisition unit and each known compound mass spectrum contained in each of a plurality of known mixture TIC chromatograms stored in the mixture library an estimating unit that calculates a compound matching rate that is
an extraction unit for extracting the mixture identification information corresponding to the known mixture TIC chromatogram containing each known compound mass spectrum having the compound matching rate equal to or higher than a predetermined threshold;
An output unit that outputs data containing the mixture-specific information extracted by the extraction unit ,
The known mixture TIC chromatogram contains index information on the retention time, which is the time at which the compound indicated by each known compound mass spectrum was detected,
The unknown mixture TIC chromatogram contains index information on the retention time, which is the time at which the compound indicated by each unknown compound mass spectrum was detected,
The output unit outputs the degree of approximation between index information on the retention time of compounds indicated by the known compound mass spectra whose compound match rate is equal to or higher than a predetermined threshold and index information on the retention times of compounds indicated by the unknown compound mass spectra. is less than or equal to a predetermined threshold, output data containing information indicating that the degree of approximation is less than or equal to a predetermined threshold
A mixture identification support system characterized by: In the mixture identification support system according to any one of claims 1 to 3 ,
The output unit provides information indicating the ratio of the known compound mass spectra whose compound match rate is equal to or higher than a predetermined threshold among the known compound mass spectra included in each known mixture TIC chromatogram extracted by the extraction unit. A mixture identification support system characterized by outputting data including In the mixture identification support system according to any one of claims 1 to 4 ,
The estimating unit performs the compound match rate based on the ion intensity of the peaks for each m/z value included in the unknown compound mass spectrum and the ion intensity of the peaks for each m/z value included in each known compound mass spectrum. of the peaks for each m/z value contained in each known compound mass spectrum, for which the m/z value is a certain value or less, the m/z value exceeds a certain value A mixture identification support system, wherein the compound identity rate is calculated with lower weighting.

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