Mass spectrum data processing method and system, mass spectrometer, electronic equipment and medium

Abstract

The invention discloses a mass spectrum data processing method and system, a mass spectrometer, electronic equipment and a medium. The method comprises the following steps: determining a dynamic threshold value according to a mass spectrum to be detected, wherein the dynamic threshold value comprises a mass number deviation dynamic threshold value or / and an intensity dynamic threshold value; correcting the mass axis of the mass spectrum to be measured according to the dynamic threshold value to obtain a corrected mass spectrum; presetting target site information, wherein the target site information comprises a primer mass number or / and a product mass number; and matching the target site information with the ion peak in the corrected mass spectrum to obtain the ion peak information corresponding to the target site. According to the method, the dynamic threshold is determined according to the to-be-detected mass spectrum, the mass axis of the to-be-detected mass spectrum is corrected according to the dynamic threshold, the mass axis of the whole to-be-detected mass spectrum can be balanced, the problem of inaccurate judgment of a fixed threshold can be solved by adopting the dynamic threshold, and the accuracy of a detection result is improved.

Description

Technical Field

[0001] The present application relates to the technical field of mass spectrometry data processing, and in particular to a mass spectrometry data processing method and system, a mass spectrometer, an electronic device and a medium. Background Art

[0002] Nucleic acid mass spectrometry analysis software can preset site-related information, such as the primer mass number of gene site A, the mass number of normal wild-type products, and the mass number of other possible mutant products. According to the preset site-related information and the relevant information of the peak list in the mass spectrum (peak highest point mass number, signal-to-noise ratio, relative intensity, etc.), the peak situation of each site is obtained and statistics are performed to obtain the gene mutation situation of each site.

[0003] For example, existing nucleic acid mass spectrometry analysis software calculates the difference between the mass number of the target site product and the mass number of the highest point of each ion peak in the mass spectrum, and determines whether the peak is the product peak of the target site based on whether the difference is less than a certain threshold and the signal-to-noise ratio of the peak. However, the judgment conditions of this method are too simple. In practical applications, as the mass number increases, the difference will also increase. Therefore, a single threshold cannot meet actual needs, which will reduce the accuracy of the ion peak matched to the target site. Summary of the invention

[0004] In view of the above-mentioned defects or deficiencies in the prior art, it is desirable to provide a mass spectrometry data processing method and system, a mass spectrometer, an electronic device and a medium.

[0005] In a first aspect, a mass spectrometry data processing method is provided, comprising: the mass spectrometry data processing method comprises:

[0006] Determine a dynamic threshold according to the mass spectrum to be measured, wherein the dynamic threshold includes a mass number deviation dynamic threshold and / or an intensity dynamic threshold;

[0007] Correcting the mass axis of the mass spectrum to be measured according to the dynamic threshold value to obtain a corrected mass spectrum;

[0008] Preset target site information, wherein the target site information includes primer mass number and / or product mass number;

[0009] The target site information is matched with the ion peaks in the corrected mass spectrum to obtain the ion peak information corresponding to the target site.

[0010] Preferably, before determining the dynamic threshold according to the mass spectrum to be measured, the method further includes:

[0011] Determining whether the mass spectrum to be measured is a primer mass spectrum or a product mass spectrum specifically comprises:

[0012] Searching for primer ion peaks and product ion peaks matching each target site from the mass spectrum to be tested;

[0013] Subtract the mass number of the primer in each target site information from the mass number of the primer ion peak of the corresponding target site matched to obtain the primer mass number deviation of the corresponding target site, and average the primer mass number deviations of each target site to obtain the mean value of the primer mass number deviation;

[0014] Subtract the mass number of the product in each target site information from the mass number of the product ion peak of the corresponding target site matched to obtain the product mass number deviation of the corresponding target site, and average the product mass number deviations of each target site to obtain the product mass number deviation mean;

[0015] If the mean value of the primer mass number deviation is less than half of the mean value of the product mass number deviation, the mass spectrum to be measured is the primer mass spectrum; otherwise, the mass spectrum to be measured is the product mass spectrum.

[0016] Preferably, the step of determining the dynamic threshold value of mass number deviation according to the mass spectrum to be measured comprises:

[0017] Assume that the mass number range of the mass spectrum to be measured is from A to B, wherein A is the minimum mass number of the mass spectrum to be measured, and B is the maximum mass number of the mass spectrum to be measured;

[0018] Set up the function y 1 =ax+b, where coefficient a=2 / (BA), coefficient b=1-A×a; x represents the mass number of the primer or product at the target site; y 1 Indicates the dynamic threshold of mass deviation of the corresponding site.

[0019] Preferably, determining the intensity dynamic threshold according to the mass spectrum to be measured includes:

[0020] Set up the function y 2 =cx+b, where coefficient c=1 / 2(BA), coefficient b=1-A×a; x represents the mass number of the primer or product at the target site; y 2 Indicates the intensity dynamic threshold of the corresponding site.

[0021] Preferably, the step of correcting the mass axis of the mass spectrum to be measured according to the deviation dynamic threshold value to obtain a corrected mass spectrum comprises:

[0022] Difference is made between the mass number in each target site information and the mass number of the ion peak at the corresponding site in the mass spectrum to be measured. If the mass number difference of the ion peak at the site is less than the dynamic threshold of the mass number deviation of the corresponding site, and the ion peak intensity of the site in the mass spectrum to be measured is greater than the dynamic threshold of the intensity of the corresponding site, then the ion peak at the site in the mass spectrum to be measured is the ion peak that needs to be corrected;

[0023] At least three ion peaks are selected from the ion peaks required for correction, the mass numbers and intensities of the corresponding ion peaks are obtained, and the mass axis of the mass spectrum to be measured is corrected according to the mass numbers and intensities corresponding to the selected at least three ion peaks to obtain a corrected mass spectrum.

[0024] Preferably, matching the target site information with the ion peaks in the corrected mass spectrum to obtain the ion peak information corresponding to the target site includes:

[0025] The difference between the mass number in each target site information and the mass number of each ion peak in the corrected mass spectrum is calculated, and the ion peak with the smallest difference is used as the initial matching peak corresponding to the target site.

[0026] Preferably, each of the target site initial matching peaks is filtered, and the filtering conditions are as follows:

[0027] The difference between the mass number in the target site information and the mass number of the initial matching peak of the corresponding target site is less than the dynamic threshold of mass number deviation, the signal-to-noise ratio of the initial matching peak of the target site is less than the signal-to-noise ratio threshold, and the resolution of the initial matching peak of the target site is less than the resolution threshold;

[0028] If any of the above filtering conditions is not met, the corresponding initial matching peak of the target site is filtered out; otherwise, the corresponding initial matching peak of the target site is used as the final matching peak of the target site.

[0029] Preferably, the filtering condition further includes: the peak area of ​​the initial matching peak of the target site is less than the peak area threshold.

[0030] Preferably, the target initial matching peak is a wild-type product matching peak or a mutant product matching peak. If the target site has both a wild-type product matching peak and a mutant product matching peak in the corrected mass spectrum, an addition peak threshold is set. If the intensity ratio of the lower intensity ion peak to the higher intensity ion peak in the wild-type product matching peak and the mutant product matching peak is less than the addition peak threshold, the lower intensity ion peak is filtered out, and the higher intensity ion peak is the final matching peak corresponding to the target site.

[0031] In a second aspect, a mass spectrometry data processing system is provided, comprising:

[0032] A dynamic threshold determination unit, used to determine a dynamic threshold according to the mass spectrum to be measured, wherein the dynamic threshold includes a mass number deviation dynamic threshold and / or an intensity dynamic threshold;

[0033] A mass axis correction unit, used for correcting the mass axis of the mass spectrum to be measured according to the dynamic threshold value to obtain a corrected mass spectrum;

[0034] A site information setting unit, used to preset target site information, wherein the target site information includes a primer mass number and / or a product mass number;

[0035] The ion peak matching unit is used to match the target site information with the ion peaks in the corrected mass spectrum to obtain the ion peak information corresponding to the target site.

[0036] In a third aspect, a mass spectrometer is provided, wherein the mass spectrometer adopts the mass spectrometry data processing method described in any embodiment of the present application to collect mass spectra, or the mass spectrometer includes the mass spectrometry data processing system described in any embodiment of the present application.

[0037] In a fourth aspect, an electronic device is provided, including:

[0038] one or more processors;

[0039] a memory for storing one or more programs,

[0040] When one or more programs are executed by one or more processors, the one or more processors execute the mass spectrometry data processing method provided in each embodiment of the present application.

[0041] In a fifth aspect, a computer-readable storage medium storing a computer program is provided, and when the program is executed by a processor, the mass spectrometry data processing method provided in each embodiment of the present application is implemented.

[0042] According to the technical solution provided in the embodiments of the present application, the present application provides a mass spectrometry data processing method and system, a mass spectrometer, an electronic device and a medium. The method determines a dynamic threshold according to a mass spectrum to be measured, and corrects the mass axis of the mass spectrum to be measured according to the dynamic threshold, which can balance the mass axis of the entire mass spectrum to be measured, and the use of a dynamic threshold can solve the problem of inaccurate fixed threshold judgment. The mass spectrometry data processing method provided in the embodiments of the present application can improve the accuracy of microbial or nucleic acid identification, such as the identification of deafness gene mutations. BRIEF DESCRIPTION OF THE DRAWINGS

[0043] Other features, objects and advantages of the present application will become more apparent by reading the detailed description of non-limiting embodiments made with reference to the following drawings:

[0044] Figure 1A first exemplary flow chart of a mass spectrometry data processing method provided in an embodiment of the present application;

[0045] Figure 2 A second exemplary flow chart of the mass spectrometry data processing method provided in an embodiment of the present application;

[0046] Figure 3 A third exemplary flow chart of the mass spectrometry data processing method provided in the embodiment of the present application;

[0047] Figure 4 An exemplary structural block diagram of a mass spectrometry data processing system provided in an embodiment of the present application;

[0048] Figure 5 Another exemplary structural block diagram of a mass spectrometry data processing system provided in an embodiment of the present application;

[0049] Figure 6 A schematic diagram of the structure of an electronic device provided in an embodiment of the present application. DETAILED DESCRIPTION

[0050] The present application is further described in detail below in conjunction with the accompanying drawings and embodiments. It is to be understood that the specific embodiments described herein are only used to explain the relevant invention, rather than to limit the invention. It is also necessary to explain that, for ease of description, only the parts related to the invention are shown in the accompanying drawings.

[0051] It should be noted that, in the absence of conflict, the embodiments and features in the embodiments of the present application can be combined with each other. The present application will be described in detail below with reference to the accompanying drawings and in combination with the embodiments.

[0052] The technical terms involved in this application are defined as follows:

[0053] Primer: A macromolecule with a specific nucleotide sequence that stimulates synthesis at the initiation of nucleotide polymerization and is connected to the reactants by hydrogen bonds. Such a molecule is called a primer.

[0054] Wild-type product: refers to the new nucleic acid chain formed by the primer during PCR amplification based on the normal DNA template sequence.

[0055] Mutation product: refers to the new nucleic acid chain formed by the primer during PCR amplification based on the DNA template sequence with gene mutation.

[0056] Nucleic acid mass spectrometry analysis software can preset site-related information, such as the primer mass number of gene site A, the mass number of normal wild-type products, and the mass number of other possible mutant products. The analysis software can compare and calculate the relevant information of the peak list in the mass spectrum (peak highest point mass number, signal-to-noise ratio, relative intensity, etc.) with the site information in the preset method, obtain the peak situation of each site, perform statistics, and thus obtain the gene mutation situation of each site. This can be used as a reference to determine whether the source of the sample may have physiological defects, such as deafness.

[0057] The existing analysis algorithm calculates the difference between the mass number of the product at the target site and the mass number of the highest point of each peak in the mass spectrum, and determines whether the peak is the product peak of the target site based on whether the difference is less than a fixed threshold and the signal-to-noise ratio of the peak. However, the judgment conditions of this method are too simple. In practical applications, as the mass number increases, the difference between the target peak and the ion peak in the mass spectrum will also increase, and it is difficult for the fixed threshold to obtain an ideal value, which will reduce the accuracy of the ion peak matched to the target site.

[0058] To solve the above technical problems, refer to Figure 1 According to a first aspect of an embodiment of the present application, a mass spectrometry data processing method 100 is provided, comprising:

[0059] S120: determining a dynamic threshold according to the mass spectrum to be measured, wherein the dynamic threshold includes a mass number deviation dynamic threshold and / or an intensity dynamic threshold;

[0060] S130: Correcting the mass axis of the mass spectrum to be measured according to the dynamic threshold value to obtain a corrected mass spectrum;

[0061] S140: Preset target site information, where the target site information includes primer mass number and / or product mass number;

[0062] S150: Match the target site information with the ion peaks in the corrected mass spectrum to obtain the ion peak information corresponding to the target site.

[0063] Specifically, a dynamic threshold is determined according to the mass spectrum to be tested, and the mass axis of the mass spectrum to be tested is corrected according to the dynamic threshold, so that the mass axis of the entire mass spectrum to be tested can be balanced, and the use of a dynamic threshold can solve the problem of inaccurate fixed threshold judgment. The mass spectrometry data processing method provided in the embodiment of the present application can improve the accuracy of microbial or nucleic acid identification, such as the identification of deafness gene mutations.

[0064] In some embodiments, reference Figure 2 , before step S120, it also includes:

[0065] S110: Determining whether the mass spectrum to be measured is a primer mass spectrum or a product mass spectrum, specifically comprising:

[0066] Searching for primer ion peaks and product ion peaks matching each target site from the mass spectrum to be tested;

[0067] Subtract the mass number of the primer in each target site information from the mass number of the primer ion peak of the corresponding target site matched to obtain the primer mass number deviation of the corresponding target site, and average the primer mass number deviations of each target site to obtain the mean value of the primer mass number deviation;

[0068] Subtract the mass number of the product in each target site information from the mass number of the product ion peak of the corresponding target site matched to obtain the product mass number deviation of the corresponding target site, and average the product mass number deviations of each target site to obtain the product mass number deviation mean;

[0069] If the mean value of the primer mass number deviation is less than half of the mean value of the product mass number deviation, the mass spectrum to be measured is the primer mass spectrum; otherwise, the mass spectrum to be measured is the product mass spectrum.

[0070] Specifically, the product can be a wild-type product or a mutant product. Since there are relatively few sites for mutant products, this example is mainly used to determine whether the mass spectrum to be tested is a blank primer mass spectrum or a conventional wild-type mass spectrum. It can effectively clarify the correction target site information, improve the correction effect, and provide a basis for subsequent difference judgment.

[0071] According to the ion peak list of the mass spectrum to be tested, the matching peaks of the corresponding primers and wild-type products are queried for each target site, and then the difference between the mass number of each matching peak and the corresponding target site information (mass number of the primer or the wild-type product) is calculated, and the absolute value of the difference of each target site is obtained. The absolute value of the difference of all target sites is summed and then divided by the number of all target sites to obtain the mean mass number deviation of the wild-type product and the mean mass number deviation of the primers. If the mean mass number deviation of the primers is less than half of the mean mass number deviation of the wild-type product, the mass spectrum to be tested is the primer mass spectrum; otherwise, the mass spectrum to be tested is the wild-type product mass spectrum.

[0072] For example, if there are three sites, namely site 1, site 2 and site 3, the primer mass number of site 1 is 200 and the product mass number is 4000; the primer mass number of site 2 is 250 and the product mass number is 4200; the primer mass number of site 3 is 230 and the product mass number is 4400. There are 16 ion peaks in the mass spectrum to be tested. From the 16 ion peaks in the mass spectrum to be tested, the ion peaks that match the primers corresponding to the three sites are queried respectively. The matching principle is that the ion peak with the smallest difference between the primer mass number of the site and the mass number of each ion peak in the mass spectrum to be tested is the ion peak matched to the site. For example, if the primer at site 1 matches ion peak 1 in the mass spectrum to be tested, the primer at site 2 matches ion peak 4 in the mass spectrum to be tested, and the primer at site 3 matches ion peak 3 in the mass spectrum to be tested, then the mean primer mass number deviation = (|mass number of ion peak 1 - 200| + |mass number of ion peak 4 - 250| + |mass number of ion peak 3 - 230|) / 3.

[0073] If the product of site 1 matches ion peak 2 in the mass spectrum to be tested, the product of site 2 matches ion peak 6 in the mass spectrum to be tested, and the product of site 3 matches ion peak 7 in the mass spectrum to be tested, then the mean product mass number deviation = (|mass number of ion peak 2 - 4000| + |mass number of ion peak 6 - 4200| + |mass number of ion peak 7 - 4400|) / 3.

[0074] If the mean value of the primer mass number deviation is less than half of the mean value of the wild-type product mass number deviation, the mass spectrum to be measured is the primer mass spectrum; otherwise, the mass spectrum to be measured is the wild-type product mass spectrum.

[0075] It can be understood that if step S110 determines that the mass spectrum to be measured is a primer mass spectrum, the corresponding dynamic threshold in the subsequent S120 is the primer dynamic threshold, and the target site primer information is matched with the ion peak in the corrected mass spectrum in S150 to obtain the primer ion peak information corresponding to the target site. If step S110 determines that the mass spectrum to be measured is a product mass spectrum, the corresponding dynamic threshold in the subsequent S120 is the product dynamic threshold, and the target site product information is matched with the ion peak in the corrected mass spectrum in S150 to obtain the product ion peak information corresponding to the target site.

[0076] In some embodiments, in step S120, determining the dynamic threshold of mass number deviation according to the mass spectrum to be measured includes:

[0077] Assume that the mass number range of the mass spectrum to be measured is from A to B, wherein A is the minimum mass number of the mass spectrum to be measured, and B is the maximum mass number of the mass spectrum to be measured;

[0078] Set up the function y1 =ax+b, where coefficient a=2 / (BA), coefficient b=1-A×a; x represents the mass number of the primer or product at the target site; y 1 Indicates the dynamic threshold of mass deviation of the corresponding site.

[0079] Specifically, according to the phenomenon that the deviation increases with the increase of mass number, a weighted judgment is adopted for the mass number deviation threshold. The larger the mass number, the larger the allowed difference. Linear fitting is adopted, and the linear function form is y 1 =ax+b, the reciprocal of half of the mass range difference of the mass spectrum to be measured is taken as the linear coefficient a, and the coefficient b=1-A×a. The preset target site primer or product mass number x is used as a known quantity and substituted into the linear function y 1 =ax+b, and the dynamic threshold value y of the mass deviation of the primer or product corresponding to each site is obtained. 1 In this example, based on the phenomenon that the larger the mass number, the larger the deviation, the dynamic threshold of mass number deviation can be calculated to effectively increase the number of site peak matches. The larger the number, the better the correction effect.

[0080] For example, if the mass number x of the product at the target site is 4500, and the mass number range of the mass spectrum to be measured is 4000-9000, then a=2 / (BA)=2 / 5000; b=1-A×a=-0.6, the mass number 4500 of the product at the target site is substituted into the above function to obtain the dynamic threshold value y of the mass number deviation of the site. 1 =1.2.

[0081] In some embodiments, in step S120, determining the intensity dynamic threshold according to the mass spectrum to be measured includes:

[0082] Set up the function y 2 =cx+b, where coefficient c=1 / 2(BA), coefficient b=1-A×a; x represents the mass number of the primer or product at the target site; y 2 Indicates the intensity dynamic threshold of the corresponding site.

[0083] Specifically, according to the phenomenon that the intensity decreases as the mass number increases, the threshold of the peak intensity is judged by weight. The larger the mass number, the lower the intensity threshold. Linear fitting is adopted, and the linear function form is y 2 =cx+b, linear coefficient c=0.5 / difference in mass range of mass spectrum to be measured, coefficient b=1-A×a. Substitute the preset target site primer or product mass x as a known quantity into the linear function y 2 =cx+b, and obtain the dynamic threshold y of the intensity of the primer or product corresponding to each site 2In this example, based on the phenomenon that the larger the mass number, the lower the intensity, the noise peak interference can be effectively removed by calculating the dynamic intensity threshold, while ensuring that the product peak with a large mass number but low intensity will not be filtered, avoiding the product peak with too low intensity from being misjudged as a noise peak, and effectively increasing the number of site peak matches. The larger the number, the better the effect after correction.

[0084] In some embodiments, in step S130, the mass axis of the mass spectrum to be measured is corrected according to the dynamic threshold to obtain a corrected mass spectrum, including:

[0085] Difference is made between the mass number in each target site information and the mass number of the ion peak at the corresponding site in the mass spectrum to be measured. If the mass number difference of the ion peak at the site is less than the dynamic threshold of the mass number deviation of the corresponding site, and the ion peak intensity of the site in the mass spectrum to be measured is greater than the dynamic threshold of the intensity of the corresponding site, then the ion peak at the site in the mass spectrum to be measured is the ion peak that needs to be corrected;

[0086] At least three ion peaks are selected from the ion peaks required for correction, the mass numbers and intensities of the corresponding ion peaks are obtained, and the mass axis of the mass spectrum to be measured is corrected according to the mass numbers and intensities corresponding to the selected at least three ion peaks to obtain a corrected mass spectrum.

[0087] Specifically, the ion peaks that need to be corrected and the corresponding site information are screened through the dynamic threshold of mass number deviation and the dynamic threshold of intensity. The mass axis of the mass spectrum to be measured is corrected according to the screened ion peaks, which can improve the matching degree of the site peaks and improve the efficiency of correction.

[0088] The correction process for the mass spectrum to be measured is as follows: first, the peak intensity of the ion peak list of the mass spectrum to be measured is normalized, the highest peak intensity can be set to 10000, and the intensity value of the highest peak can also be set to other values, such as the highest peak intensity in the mass spectrum to be measured. For the normalized mass spectrum, step S110 is used to determine whether the normalized mass spectrum is a primer mass spectrum or a product mass spectrum, and then the ion peaks in the mass spectrum (primer mass spectrum or product mass spectrum) of the type are determined using the mass number deviation dynamic threshold of step S120 and the intensity dynamic threshold of step S130 to filter and screen the ion peaks that need to be corrected. A quadratic fit is performed on the ion peaks that need to be corrected and their corresponding site information, and the quadratic fitting function is y 3 =a 1 x 3 2 +b 1 x 3 +c 1 , where x 3 Indicates the mass number of the ion peak that needs to be corrected after screening; y 3In this example, at least three ion peaks are selected from the ion peaks required for calibration, and the mass numbers and intensities of at least three groups of corresponding ion peaks are substituted into the above quadratic fitting function to obtain the corresponding coefficient a. 1 , b 1 and c 1 The value can be obtained to obtain a quadratic fitting function curve and complete the calibration of the mass axis. It can be understood that the more ion peaks are selected from the ion peaks required for calibration, the higher the calibration accuracy of the mass axis.

[0089] In the embodiment of the present application, the ion peaks after filtering by the dynamic threshold of mass number deviation and the dynamic threshold of intensity are fitted and corrected so that the overall deviation of the mass axis tends to be average, providing a basis for subsequent difference analysis and facilitating the threshold tuning of subsequent difference analysis.

[0090] In some embodiments, reference Figure 3 In step S150, the target site information is matched with the ion peak in the corrected mass spectrum to obtain the ion peak information corresponding to the target site, including:

[0091] The difference between the mass number in each target site information and the mass number of each ion peak in the corrected mass spectrum is calculated, and the ion peak with the smallest difference is used as the initial matching peak corresponding to the target site.

[0092] Specifically, after the mass axis correction is completed, according to the target site information, the nearest peak is searched in the corrected mass spectrum for each wild-type product and mutant product. The nearest peak is the ion peak with the smallest mass number difference between the wild-type product in the target site and each ion peak in the corrected mass spectrum. The ion peak with the smallest difference is used as the wild-type product matching peak of the target site. The matching principle of mutant products is similar, and the embodiments of this application will not be repeated.

[0093] It is understandable that the product of each target site generally has a unique matching ion peak in the calibrated mass spectrum. If there are multiple matching ion peaks at the same site, an additive peak may appear. The additive peak is generally caused by incomplete desalting during sample pretreatment, resulting in a small peak on the right side of the product peak. The small peak on the right side of the product peak is the additive peak. If the wild-type product and mutant product of the same target site both find matching ion peaks in the calibrated mass spectrum, there may be an ion peak that is an additive peak among the matching ion peaks of the wild-type product and mutant product of the site. Of course, if the number of target sites is large, and the number of corresponding ion peaks in the calibrated mass spectrum is small (i.e., the number of ion peaks is insufficient), some target sites may not be matched to the corresponding ion peaks, and the target sites that cannot match the ion peaks are judged to be empty.

[0094] In some embodiments, reference Figure 3 , after step S150, further comprising:

[0095] S160: Filter each of the target site initial matching peaks, and the filtering conditions are as follows:

[0096] The difference between the mass number in the target site information and the mass number of the initial matching peak of the corresponding target site is less than the dynamic threshold of mass number deviation, the signal-to-noise ratio of the initial matching peak of the target site is less than the signal-to-noise ratio threshold, and the resolution of the initial matching peak of the target site is less than the resolution threshold;

[0097] If any of the above filtering conditions is not met, the corresponding initial matching peak of the target site is filtered out; otherwise, the corresponding initial matching peak of the target site is used as the final matching peak of the target site.

[0098] Specifically, the initial matching peaks matched to each target site in step S150 are filtered, and the filtering conditions are as described above. If any of the above filtering conditions is not met, the corresponding initial matching peak of the target site is filtered out; otherwise, the corresponding initial matching peak of the target site is used as the final matching peak of the target site. Among them, the signal-to-noise ratio threshold and the resolution threshold can be set according to actual needs. By setting the filtering conditions, the matching degree of the ion peaks matched by the target site in the corrected mass spectrum can be improved, the accuracy of the results can be improved, and the false positive rate can be reduced.

[0099] In some embodiments, in step S160, the filtering condition further includes: the peak area of ​​the initial matching peak of the target site is less than the peak area threshold.

[0100] Specifically, in the embodiment of the present application, the dynamic threshold of mass number deviation, signal-to-noise ratio threshold and resolution threshold set in step S160 are used as the main filtering conditions, and those skilled in the art can also set the peak area threshold as an auxiliary filtering condition according to actual needs. The combination of the main filtering condition and the auxiliary filtering condition can further improve the matching degree of the ion peak and improve the accuracy of the result. Among them, the peak area threshold is set by those skilled in the art according to actual needs.

[0101] In some embodiments, reference Figure 3 , after step S160, further comprising:

[0102] S170: The target initial matching peak is a wild-type product matching peak or a mutant product matching peak. If the target site has both a wild-type product matching peak and a mutant product matching peak in the corrected mass spectrum, an additive peak threshold is set. If the intensity ratio of the lower intensity ion peak to the higher intensity ion peak in the wild-type product matching peak and the mutant product matching peak is less than the additive peak threshold, the lower intensity ion peak is filtered out, and the higher intensity ion peak is the final matching peak corresponding to the target site.

[0103] Specifically, the target initial matching peak may be a wild-type product matching peak or a mutant product matching peak. When the same target site has both a wild-type product matching peak and a mutant product matching peak in the corrected mass spectrum, one of the two ion peaks of the matched wild-type product matching peak and the mutant product matching peak may be an additive peak. If the intensity ratio of the ion peak with lower intensity to the ion peak with higher intensity in the two ion peaks of the matched wild-type product matching peak and the mutant product matching peak is less than the additive peak threshold (the additive peak threshold can be set to 0.5, 0.4, etc.), it means that the ion peak with lower intensity is an additive peak. Therefore, it is necessary to filter out the ion peak with lower intensity to eliminate the influence of the additive peak and improve the accuracy of the result. If the intensity ratio of the ion peak with lower intensity to the ion peak with higher intensity in the two ion peaks of the matched wild-type product matching peak and the mutant product matching peak is greater than the additive peak threshold, the site may be matched to the corresponding wild-type product and mutant product at the same time. Generally, the intensity ratio of the wild-type product and the mutant product is 1:1. After step S150 to step S170, the ion peak information of the product or primer corresponding to each site can be obtained. By counting the product or primer information of each site, it can be determined whether mutation occurs at each site, such as determining whether deafness exists.

[0104] The mass spectrometry data processing method provided in the embodiment of the present application can be used for microbial or nucleic acid mass spectrometry data processing. The mass axis of the mass spectrum is calibrated to balance the mass axis of the entire mass spectrum, and a dynamic threshold is used to solve the problem of inaccurate difference judgment; weighted judgment of the peak is used to determine whether the peak is a noise peak, thereby reducing the interference of the noise peak; and the added peak is removed by the intensity ratio of adjacent peaks, thereby avoiding false positives and failure to find results in the calculation, effectively improving the calculation accuracy and making the calculation results more reliable.

[0105] Second, refer to Figure 4 , a mass spectrometry data processing system 200 is provided, comprising:

[0106] A dynamic threshold determination unit 220, used to determine a dynamic threshold according to the mass spectrum to be measured, wherein the dynamic threshold includes a mass number deviation dynamic threshold and / or an intensity dynamic threshold;

[0107] A mass axis correction unit 230, used to correct the mass axis of the mass spectrum to be measured according to the dynamic threshold value to obtain a corrected mass spectrum;

[0108] A site information setting unit 240, used to preset target site information, wherein the target site information includes a primer mass number and / or a product mass number;

[0109] The ion peak matching unit 250 is used to match the target site information with the ion peaks in the corrected mass spectrum to obtain the ion peak information corresponding to the target site.

[0110] Specifically, the mass spectrometry data processing system 200 provided in the embodiment of the present application is used to execute the mass spectrometry data processing method 100 provided in any embodiment of the present application. The effect of the mass spectrometry data processing system 200 provided in any embodiment of the present application is similar to the effect of the corresponding mass spectrometry data processing method, and the embodiments of the present application will not be repeated one by one. The mass spectrometry data processing system 200 determines the dynamic threshold of the mass spectrogram to be measured through the dynamic threshold determination unit 220, and calibrates the mass axis of the mass spectrogram to be measured through the mass axis correction unit 230, which can balance the mass axis of the entire mass spectrogram to be measured, and the use of dynamic thresholds can solve the problem of inaccurate fixed threshold judgment.

[0111] In some embodiments, reference Figure 5 , the mass spectrometry data processing system 200 further includes:

[0112] The spectrum type determination unit 210 is used to determine whether the mass spectrum to be measured is a primer mass spectrum or a product mass spectrum.

[0113] In some embodiments, the spectrum type determination unit 210 includes:

[0114] A search and match module is used to search for primer ion peaks and product ion peaks matching each target site from the mass spectrum to be tested;

[0115] A primer deviation calculation module is used to subtract the primer mass number in each target site information from the mass number of the primer ion peak of the matched corresponding target site to obtain the primer mass number deviation of the corresponding target site, and average the primer mass number deviations of each target site to obtain the primer mass number deviation mean;

[0116] A product deviation calculation module is used to subtract the product mass number in each target site information from the mass number of the product ion peak of the corresponding target site matched to obtain the product mass number deviation of the corresponding target site, and average the product mass number deviations of each target site to obtain the product mass number deviation mean;

[0117] The comparison and judgment module is used for determining that if the mean value of the primer mass number deviation is less than half of the mean value of the product mass number deviation, the mass spectrum to be measured is the primer mass spectrum; otherwise, the mass spectrum to be measured is the product mass spectrum.

[0118] In some implementations, the dynamic threshold determination unit 220 includes:

[0119] The mass number deviation dynamic threshold determination module is configured to determine the mass number deviation dynamic threshold of the site, and the mass number deviation dynamic threshold is calculated as follows:

[0120] Assume that the mass number range of the mass spectrum to be measured is from A to B, wherein A is the minimum mass number of the mass spectrum to be measured, and B is the maximum mass number of the mass spectrum to be measured;

[0121] Set up the function y 1 =ax+b, where coefficient a=2 / (BA), coefficient b=1-A×a; x represents the mass number of the primer or product at the target site; y 1 Indicates the dynamic threshold of mass deviation of the corresponding site.

[0122] In some implementations, the dynamic threshold determination unit 220 further includes:

[0123] The intensity dynamic threshold determination unit is configured to determine the intensity dynamic threshold of the site. The intensity dynamic threshold is calculated as follows: Set the function y 2 =cx+b, where coefficient c=1 / 2(BA), coefficient b=1-A×a; x represents the mass number of the primer or product at the target site; y 2 Indicates the intensity dynamic threshold of the corresponding site.

[0124] In some embodiments, the mass axis correction unit 230 is configured to:

[0125] Difference is made between the mass number in each target site information and the mass number of the ion peak at the corresponding site in the mass spectrum to be measured. If the mass number difference of the ion peak at the site is less than the dynamic threshold of the mass number deviation of the corresponding site, and the ion peak intensity of the site in the mass spectrum to be measured is greater than the dynamic threshold of the intensity of the corresponding site, then the ion peak at the site in the mass spectrum to be measured is the ion peak that needs to be corrected;

[0126] At least three ion peaks are selected from the ion peaks required for correction, the mass numbers and intensities of the corresponding ion peaks are obtained, and the mass axis of the mass spectrum to be measured is corrected according to the mass numbers and intensities corresponding to the selected at least three ion peaks to obtain a corrected mass spectrum.

[0127] In some embodiments, the ion peak matching unit 250 is configured to:

[0128] The difference between the mass number in each target site information and the mass number of each ion peak in the corrected mass spectrum is calculated, and the ion peak with the smallest difference is used as the initial matching peak corresponding to the target site.

[0129] In some embodiments, reference Figure 5 , the mass spectrometry data processing system 200 further includes:

[0130] The filtering unit 260 is used to filter each of the target site initial matching peaks, and the filtering conditions are as follows:

[0131] The difference between the mass number in the target site information and the mass number of the initial matching peak of the corresponding target site is less than the dynamic threshold of mass number deviation, the signal-to-noise ratio of the initial matching peak of the target site is less than the signal-to-noise ratio threshold, and the resolution of the initial matching peak of the target site is less than the resolution threshold;

[0132] If any of the above filtering conditions is not met, the corresponding initial matching peak of the target site is filtered out; otherwise, the corresponding initial matching peak of the target site is used as the final matching peak of the target site.

[0133] In some embodiments, the filtering condition further includes: the peak area of ​​the initial matching peak of the target site is less than the peak area threshold.

[0134] In some embodiments, reference Figure 5 , the mass spectrometry data processing system 200 further includes:

[0135] The adduct peak elimination unit 270 is used to set an adduct peak threshold if both a wild-type product matching peak and a mutant product matching peak exist at the target site in the corrected mass spectrum. If the intensity ratio of the lower intensity ion peak to the higher intensity ion peak in the wild-type product matching peak and the mutant product matching peak is less than the adduct peak threshold, the lower intensity ion peak is filtered out.

[0136] In a third aspect, a mass spectrometer is provided, wherein the mass spectrometer adopts the mass spectrometry data processing method described in any embodiment of the present application to collect mass spectra, or the mass spectrometer includes the mass spectrometry data processing system described in any embodiment of the present application.

[0137] Specifically, the mass spectrometer may be a MALDI-TOF mass spectrometer, which is mainly composed of a matrix-assisted laser desorption ion source (MALDI) and a time-of-flight mass detector (TOF). The principle of MALDI is to irradiate a co-crystallized film formed by a sample and a matrix with a laser of a certain intensity, and the matrix absorbs energy from the laser and vaporizes, and rapidly degrades, causing the sample to decompose and adsorb, and charge transfer occurs between the matrix and the sample, thereby ionizing the sample molecules; the principle of TOF is that the charged sample molecules are accelerated to fly through the flight channel under the action of an electric field, and because the mass-to-charge ratio of an ion is proportional to the flight time of the ion, ions of different masses are detected due to different flight times to reach the detector, and a characteristic mass spectrum is formed with the ion peak as the ordinate and the ion mass-to-charge ratio as the abscissa.

[0138] The mass spectrometer provided in the embodiment of the present application includes the mass spectrometry data processing system 200 described in any embodiment of the present application, and the dynamic threshold value of the mass spectrogram to be measured is determined by the dynamic threshold value determination unit 220, and the mass axis of the mass spectrogram to be measured is calibrated by the mass axis correction unit 230, so that the mass axis of the entire mass spectrogram to be measured can be balanced, and the use of the dynamic threshold value can solve the problem of inaccurate fixed threshold value judgment. The mass spectrometer can also be a nucleic acid analyzer for analyzing nucleic acid mass spectrometry data.

[0139] Figure 6 A schematic structural diagram of an electronic device provided according to an embodiment of the present application is shown.

[0140] like Figure 6 As shown, as another aspect, the present application also provides an electronic device 300, including one or more central processing units (CPU) 301, which can perform various appropriate actions and processes according to the program stored in the read-only memory (ROM) 302 or the program loaded from the storage part 308 to the random access memory (RAM) 303. In the RAM 303, various programs and data required for system operation are also stored. The CPU 301, the ROM 302, and the RAM 303 are connected to each other via a bus 304. An input / output (I / O) interface 305 is also connected to the bus 304.

[0141] The following components are connected to the I / O interface 305: an input section 306 including a keyboard, a mouse, etc.; an output section 507 including a cathode ray tube (CRT), a liquid crystal display (LCD), etc., and a speaker, etc.; a storage section 308 including a hard disk, etc.; and a communication section 309 including a network interface card such as a LAN card, a modem, etc. The communication section 309 performs communication processing via a network such as the Internet. A drive 310 is also connected to the I / O interface 305 as needed. A removable medium 311, such as a magnetic disk, an optical disk, a magneto-optical disk, a semiconductor memory, etc., is installed on the drive 310 as needed, so that a computer program read therefrom is installed into the storage section 308 as needed.

[0142] In particular, according to the embodiments of the present disclosure, the above reference Figures 1 to 3 The described process can be implemented as a computer software program. For example, an embodiment of the present disclosure includes a computer program product, which includes a computer program tangibly contained on a machine-readable medium, and the computer program includes program code for performing the mass spectrometry data processing method. In such an embodiment, the computer program can be downloaded and installed from a network through the communication portion 309, and / or installed from a removable medium 311.

[0143] The flow chart and block diagram in the accompanying drawings illustrate the possible architecture, function and operation of the system, method and computer program product according to various embodiments of the present invention. In this regard, each square box in the flow chart or block diagram can represent a module, a program segment or a part of a code, and the module, program segment or a part of a code contains one or more executable instructions for realizing the specified logical function. It should also be noted that in some alternative implementations, the functions marked in the square box can also occur in a different order from the order marked in the accompanying drawings. For example, two square boxes represented in succession can actually be executed substantially in parallel, and they can sometimes be executed in the opposite order, depending on the functions involved. It should also be noted that each square box in the block diagram and / or flow chart, and the combination of the square boxes in the block diagram and / or flow chart can be implemented with a dedicated hardware-based system that performs the specified function or operation, or can be implemented with a combination of dedicated hardware and computer instructions.

[0144] As another aspect, the present application also provides a computer-readable storage medium, which may be a computer-readable storage medium included in the device described in the above embodiment; or a computer-readable storage medium that exists independently and is not assembled into the device. The computer-readable storage medium stores one or more programs, and the programs are used by one or more processors to execute the mass spectrometry data processing method described in the present application.

[0145] The flow chart and block diagram in the accompanying drawings illustrate the possible architecture, function and operation of the system, method and computer program product according to various embodiments of the present invention. In this regard, each square box in the flow chart or block diagram can represent a module, a program segment or a part of a code, and the module, the program segment or a part of the code contains one or more executable instructions for realizing the specified logical function. It should also be noted that in some alternative implementations, the functions marked in the square box can also occur in a sequence different from that marked in the accompanying drawings. For example, two square boxes represented in succession can actually be executed substantially in parallel, and they can sometimes be executed in the opposite order, depending on the functions involved. It should also be noted that each square box in the block diagram and / or flow chart, and the combination of the square boxes in the block diagram and / or flow chart can be realized by a dedicated hardware-based system that performs a specified function or operation, or can be realized by a combination of dedicated hardware and computer instructions.

[0146] The units or modules involved in the embodiments described in the present application may be implemented by software or by hardware. The units or modules described may also be arranged in a processor. For example, each of the units may be a software program arranged in a computer or a mobile smart device, or may be a separately configured hardware device. The names of these units or modules do not, in some cases, constitute limitations on the units or modules themselves.

[0147] The above description is only a preferred embodiment of the present application and an explanation of the technical principles used. Those skilled in the art should understand that the scope of the invention involved in the present application is not limited to the technical solution formed by a specific combination of the above technical features, but should also cover other technical solutions formed by any combination of the above technical features or their equivalent features without departing from the inventive concept. For example, the above features are replaced with (but not limited to) technical features with similar functions disclosed in the present application.

Claims

1. A mass spectrometry data processing method, characterized in that: The mass spectrometry data processing method comprises: Determine a dynamic threshold according to the mass spectrum to be measured, wherein the dynamic threshold includes a mass number deviation dynamic threshold and / or an intensity dynamic threshold; Correcting the mass axis of the mass spectrum to be measured according to the dynamic threshold value to obtain a corrected mass spectrum; Preset target site information, wherein the target site information includes primer mass number and / or product mass number; The target site information is matched with the ion peaks in the corrected mass spectrum to obtain the ion peak information corresponding to the target site.

2. The mass spectrometry data processing method according to claim 1, characterized in that: Before determining the dynamic threshold according to the mass spectrum to be measured, the method further includes: Determining whether the mass spectrum to be measured is a primer mass spectrum or a product mass spectrum specifically comprises: Searching for primer ion peaks and product ion peaks matching each target site from the mass spectrum to be tested; Subtract the mass number of the primer in each target site information from the mass number of the primer ion peak of the matched corresponding target site to obtain the primer mass number deviation of the corresponding target site, and average the primer mass number deviations of each target site to obtain the mean value of the primer mass number deviation; Subtract the mass number of the product in each target site information from the mass number of the product ion peak of the corresponding target site matched to obtain the product mass number deviation of the corresponding target site, and average the product mass number deviations of each target site to obtain the product mass number deviation mean; If the mean value of the primer mass number deviation is less than half of the mean value of the product mass number deviation, the mass spectrum to be measured is the primer mass spectrum; otherwise, the mass spectrum to be measured is the product mass spectrum.

3. The mass spectrometry data processing method according to claim 2, characterized in that: Determining the dynamic threshold value of mass number deviation according to the mass spectrum to be measured includes: Assume that the mass number range of the mass spectrum to be measured is from A to B, wherein A is the minimum mass number of the mass spectrum to be measured, and B is the maximum mass number of the mass spectrum to be measured; Function y1=ax+b is set, wherein coefficient a=2 / (BA), coefficient b=1-A×a; x represents the mass number of the primer or product at the target site; y1 represents the dynamic threshold value of the mass number deviation of the corresponding site.

4. The mass spectrometry data processing method according to claim 3, characterized in that: Determining the intensity dynamic threshold according to the mass spectrum to be measured includes: Function y2=cx+b is set, where coefficient c=1 / 2(BA), coefficient b=1-A×a; x represents the mass number of the primer or product at the target site; y2 represents the intensity dynamic threshold of the corresponding site.

5. The mass spectrometry data processing method according to claim 4, characterized in that: The method of correcting the mass axis of the mass spectrum to be measured according to the dynamic threshold value to obtain a corrected mass spectrum includes: Difference is made between the mass number in each target site information and the mass number of the ion peak at the corresponding site in the mass spectrum to be measured. If the mass number difference of the ion peak at the site is less than the dynamic threshold of the mass number deviation of the corresponding site, and the ion peak intensity of the site in the mass spectrum to be measured is greater than the dynamic threshold of the intensity of the corresponding site, then the ion peak at the site in the mass spectrum to be measured is the ion peak that needs to be corrected; At least three ion peaks are selected from the ion peaks required for correction, the mass numbers and intensities of the corresponding ion peaks are obtained, and the mass axis of the mass spectrum to be measured is corrected according to the mass numbers and intensities corresponding to the selected at least three ion peaks to obtain a corrected mass spectrum.

6. The mass spectrometry data processing method according to any one of claims 1 to 5, characterized in that: The step of matching the target site information with the ion peaks in the corrected mass spectrum to obtain the ion peak information corresponding to the target site includes: The difference between the mass number in each target site information and the mass number of each ion peak in the corrected mass spectrum is calculated, and the ion peak with the smallest difference is used as the initial matching peak corresponding to the target site.

7. The mass spectrometry data processing method according to claim 6, characterized in that: Each of the target site initial matching peaks is filtered, and the filtering conditions are as follows: The difference between the mass number in the target site information and the mass number of the initial matching peak of the corresponding target site is less than the dynamic threshold of mass number deviation, the signal-to-noise ratio of the initial matching peak of the target site is less than the signal-to-noise ratio threshold, and the resolution of the initial matching peak of the target site is less than the resolution threshold; If any of the above filtering conditions is not met, the corresponding initial matching peak of the target site is filtered out; otherwise, the corresponding initial matching peak of the target site is used as the final matching peak of the target site.

8. The mass spectrometry data processing method according to claim 7, characterized in that: The filtering condition also includes: the peak area of ​​the initial matching peak of the target site is less than the peak area threshold.

9. The mass spectrometry data processing method according to claim 7 or 8, characterized in that: The target initial matching peak is a wild-type product matching peak or a mutant product matching peak. If the target site has both a wild-type product matching peak and a mutant product matching peak in the corrected mass spectrum, an addition peak threshold is set. If the intensity ratio of the lower intensity ion peak to the higher intensity ion peak in the wild-type product matching peak and the mutant product matching peak is less than the addition peak threshold, the lower intensity ion peak is filtered out, and the higher intensity ion peak is the final matching peak corresponding to the target site.

10. A mass spectrometry data processing system, characterized in that: The mass spectrometry data processing system comprises: A dynamic threshold determination unit, used to determine a dynamic threshold according to the mass spectrum to be measured, wherein the dynamic threshold includes a mass number deviation dynamic threshold and / or an intensity dynamic threshold; A mass axis correction unit, used for correcting the mass axis of the mass spectrum to be measured according to the dynamic threshold value to obtain a corrected mass spectrum; A site information setting unit, used to preset target site information, wherein the target site information includes a primer mass number and / or a product mass number; The ion peak matching unit is used to match the target site information with the ion peaks in the corrected mass spectrum to obtain the ion peak information corresponding to the target site.

11. A mass spectrometer, characterized in that: The mass spectrometer adopts the mass spectrometry data processing method according to any one of claims 1 to 9 to collect mass spectra, or the mass spectrometer includes the mass spectrometry data processing system according to claim 10.

12. An electronic device, characterized in that: include: one or more processors; a memory for storing one or more programs, When the one or more programs are executed by the one or more processors, the one or more processors are caused to perform the mass spectrometry data processing method according to any one of claims 1 to 9.

13. A computer-readable storage medium storing a computer program, characterized in that: When the program is executed by a processor, the mass spectrometry data processing method according to any one of claims 1 to 9 is implemented.

Images