WO2022025104A1 - 情報提供装置、情報提供システム、情報提供方法及びプログラム - Google Patents
情報提供装置、情報提供システム、情報提供方法及びプログラム Download PDFInfo
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- G—PHYSICS
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- G16B40/00—ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
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- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6844—Nucleic acid amplification reactions
- C12Q1/6851—Quantitative amplification
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- C—CHEMISTRY; METALLURGY
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- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6844—Nucleic acid amplification reactions
- C12Q1/686—Polymerase chain reaction [PCR]
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- G01N2035/00653—Quality control of instruments statistical methods comparing labs or apparatuses
Definitions
- the present invention relates to an information providing device, an information providing system, an information providing method and a program.
- the present application claims priority based on Japanese Patent Application No. 2020-130957 filed in Japan on July 31, 2020, the contents of which are incorporated herein by reference.
- QPCR Quantitative Polymerase chain reaction
- the linearity of the calibration curve, the slope of the calibration curve, the variation in Cq value, and the repeatability are the same. However, in reality, they are not always the same, but rather often different. In particular, as can be seen from the fact that the linearity of the calibration curve, the slope of the calibration curve, and the variation in the Cq value are important, the Cq value is not used as an absolute comparison value, but is treated as a relative comparison value. There is. The reason is that the nucleic acid for obtaining the calibration curve cannot be produced in an accurate amount and cannot be arranged properly.
- the Cq value is treated as a relative value because the Cq value varies due to many factors. Therefore, even if the Cq value deviates before and after the calibration of the same device, there is no particular problem and it is allowed.
- the Cq value obtained as a result of PCR measurement varies. Therefore, the PCR measurement result cannot be simply compared with the past measurement result of the same device or the measurement result of another inspection device. Therefore, it may be difficult to determine whether or not the inspection device from which the measurement result is obtained is normal from the result of one measurement.
- An object of the present invention is to provide an information providing device, an information providing system, an information providing method, and a program capable of providing useful information for determining the normality of a testing device that performs a PCR test.
- the Cq value of the well obtained by performing a PCR (polymerase chain reaction) test on a standard device having a well having a well having a known number of copies of nucleic acid is obtained. Comparison between the acquisition unit that acquires the inspection result data shown, the information obtained from the evaluation target data that is the inspection result data to be evaluated, and the information obtained from one or more of the inspection result data different from the evaluation target data. It is provided with an information output unit for outputting the comparison information obtained by.
- FIG. 1 It is a figure which shows the whole structure of the information provision system by one Embodiment of this invention. It is a figure which shows the example of the standard plate by the same embodiment. It is a figure which shows the example of the copy number of the template nucleic acid arranged in the well of the standard plate by the same embodiment. It is a block diagram which shows the structure of the information providing apparatus by the same embodiment. It is a flow diagram which shows the operation of the inspection result data reception processing of the information providing apparatus by the same embodiment. It is a flow diagram which shows the operation of the analysis processing of the information providing apparatus by the same embodiment. It is a figure for demonstrating the calculation method of LOD and LOQ by the same embodiment. It is a figure which shows the display example of the analysis result information by the same embodiment.
- FIG. 1 is a diagram showing an overall configuration of an information providing system 1 according to an embodiment of the present invention.
- the information providing system 1 includes an information providing device 2, a terminal device 3, and an inspection device 4.
- the information providing device 2 and the terminal device 3 are connected to each other via the network 9.
- the network 9 is a public network such as the Internet.
- the network 9 may be a private network such as a dedicated line or a LAN (Local Area Network), or may be a combination of a public network and a private network.
- the inspection device 4 is connected to the terminal device 3.
- the terminal device 3 and the inspection device 4 may be connected via the network 9. Further, the terminal device 3 and the inspection device 4 may be integrated into one device. Further, the inspection device 4 may not be connected to the terminal device 3.
- the information providing device 2 may be connected to the inspection device 4 directly or via the network 9. Further, the information providing device 2 may be stand-alone. In this case, the information providing device 2 does not have to be connected to the terminal device 3 and the inspection device
- a company that provides a standard substance in a PCR test has an information providing device 2, and facilities A, B, C, ... That perform a PCR test have a terminal device 3 and a test device 4.
- the number of terminal devices 3 and inspection devices 4 possessed by each facility is arbitrary. Examples of facilities include, but are not limited to, companies, testing institutions, medical institutions, and the like.
- the facility may have a terminal device 3 or an inspection device 4 for each organization or area of the facility.
- the facility that carries out the PCR test may have the information providing system 1 or the information providing device 2.
- the information providing device 2 acquires the test result data obtained by performing the qPCR (real-time PCR) test on the standard plate by the test device 4 by receiving it from the terminal device 3.
- the standard plate has wells with a known number of copies of nucleic acid.
- the information providing device 2 provides useful information for determining the normality of the inspection device 4 by outputting the analysis result information obtained by performing the analysis using the acquired inspection result data.
- the analysis result information includes comparison information.
- the inspection result data to be evaluated is described as the evaluation target data.
- the contrast information is obtained by comparing the information obtained from the evaluation target data with the information obtained from one or more inspection result data different from the evaluation target data.
- the comparison information includes information obtained from the evaluation target data and information obtained from the inspection result data compared with the evaluation target data.
- the comparison information includes information on whether or not the inspection device 4 from which the evaluation target data was obtained is normal, and the wells from which the normal or abnormal Cq value was obtained in the inspection device 4 from which the evaluation target data was obtained. Including information.
- the inspection result data to be compared with the evaluation target data will be described as the comparison data.
- the terminal device 3 is, for example, a computer device such as a personal computer, a tablet terminal, or a smartphone.
- the terminal device 3 communicates with the information providing device 2 via the network 9.
- the terminal device 3 acquires the test result data obtained by performing the qPCR test on the standard plate by the test device 4, and transmits the acquired test result data to the information providing device 2.
- the terminal device 3 receives the analysis result information output by the information providing device 2.
- the inspection device 4 is a device that performs a real-time PCR inspection.
- Real-time PCR is a type of qPCR (quantitative PCR).
- amplification by PCR is measured over time (real time), and the template nucleic acid is quantified based on the amplification factor obtained by the measurement.
- the template nucleic acid is a nucleic acid having at least the base sequence of the primer region. Nucleic acid is, for example, DNA (deoxyribonucleic acid), RNA (ribonucleic acid), cDNA (complementary DNA) and the like, but is not limited thereto.
- a standard plate is a device with multiple wells with a specific number of copies of the template nucleic acid.
- the standard plate is an example of a standard device.
- reagents such as primers, amplification reagents, and fluorescent probes may be arranged in the wells of the standard plate.
- the test result data received by the information providing device 2 indicates the Cq value measured for each well of the standard plate.
- the Cq value is synonymous with the Ct value (Threshold Cycle).
- the Cq value means the number of PCR cycles to reach a constant amount of amplification product.
- a small Cq value indicates a large amount of template nucleic acid, and a large Cq value indicates a small amount of template nucleic acid.
- the qPCR test has stages of nucleic acid extraction, addition of extract and amplification reagents, nucleic acid amplification, and data analysis.
- the information providing device 2 provides useful information for quality control of the testing device 4 based on the result of the qPCR test performed by the testing device 4 using the standard plate. This makes it possible to guarantee the accuracy at the stage of data analysis. Normally, even if the sample is measured under the same conditions, the Cq value varies depending on the inspection device 4, so it tends to be difficult to tell from the result of one measurement whether the inspection device 4 is normal or not.
- the information providing device 2 of the present embodiment analyzes the information useful for statistically determining whether the test device 4 is operating normally by comparing the qPCR test results using the standard plate, and analyzes the analysis results.
- the facility obtains a comparison result by transmitting the result of the qPCR test performed by the test device 4 on the standard plate to the information providing device 2.
- the facility can easily confirm that the measurement system of the inspection device 4 is normal at a high frequency, so that the inspection by the reliable measurement system can always be performed.
- the skill of the worker can be measured by comparing the test result data of different workers.
- FIG. 2 is a diagram showing an example of the standard plate 5.
- FIG. 2A is a perspective view showing an example of the standard plate 5.
- 2 (b) is a cross-sectional view taken along the line b-b'of FIG. 2 (a).
- the standard plate 5 has a base material 51 and a plurality of wells 52 formed on the base material 51.
- the well 52 of the standard plate 5 is filled with the template nucleic acid 54 having a specific number of copies of the same or a specific number of copies of a plurality of types.
- the template nucleic acid 54 is a standard substance in the PCR test.
- the same type of template nucleic acid 54 is arranged in all wells 52.
- the same type of template nucleic acid has a base sequence having the same primer region.
- the template nucleic acid 54 may be a nucleic acid having a sequence that does not exist in nature, or may be a nucleic acid having a sequence that exists in nature.
- a low copy number of nucleic acid may be placed in all or part of the wells 52 of the standard plate 5.
- the low copy count is 200 copies or less that begin to be affected by Poisson, or 50 copies or less that are even more affected.
- the template nucleic acid 54 may be arranged in all or a part of the wells 52 of the plurality of wells 52 of the standard plate 5 with a copy number smaller than the copy number corresponding to the detection sensitivity required for the inspection device 4. For example, assume that the standard plate 5 has 96 wells 52 and the detection sensitivity required for the inspection device 4 is 20 copies. In this case, the template nucleic acid 54 such as 10 copies, 20 copies, or 50 copies may be arranged in all 96 wells 52.
- each well group consisting of 16 wells 52 may be further filled with one or more of a particular amount of primer, a particular amount of amplification reagent, and a particular amount of fluorescent probe.
- the fact that the template nucleic acid 54 having the same number of copies is arranged in all the wells 52 is also described as the same copy.
- the number of copies of the template nucleic acid 54 arranged in the well 52 is also referred to as the number of copies of the well 52.
- the opening of the well 52 is covered with the sealing member 55. Further, the identification means 56 is arranged between the sealing member 55 and the base material 51 and at a position other than the opening of the well 52.
- the identification means 56 is, for example, a memory, an IC chip (Integrated Circuit), an RFID (Radio Frequency Identification), or the like.
- the identification means 56 may be a character, a bar code, or a two-dimensional bar code printed on the medium or the base material 51.
- the identification means 56 stores plate identification information, plate type information, and the like of the standard plate 5.
- the plate identification information is information that identifies each standard plate 5.
- the plate type information is information indicating the type of the standard plate 5.
- the type of template nucleic acid 54, the number of copies of the template nucleic acid 54 arranged in each well 52, the type and amount of primers arranged in each well 52, and the type and amount of the primer arranged in each well 52 are arranged in each well 52. It is possible to specify the combination of the type and amount of the amplification reagent provided and the type and amount of the fluorescent probe arranged in each well 52.
- the number of copies includes the case of 0.
- the type and amount of primer include the case without primer.
- the type and amount of the amplification reagent include the case without the amplification reagent.
- the type and amount of the fluorescent probe includes the case without the fluorescent probe.
- the plate type information can be specified from the plate identification information.
- the identification means 56 replaces or adds to the plate type information, the type of the template nucleic acid 54, the number of copies of the template nucleic acid 54 arranged in each well 52, the type of the primer arranged in each well 52, and the type of the primer arranged in each well 52. Information on the amount, the type and amount of the amplification reagent arranged in each well 52, and the type and amount of the fluorescent probe arranged in each well 52 may be stored.
- the standard plate 5 By using the standard plate 5, it is possible to confirm the in-plane distribution of the Cq value, the normality of the entire surface, the detection sensitivity, and the like.
- a surface is a collection of all wells in one plate. Further, by performing the measurement using the standard plate 5 in which the nucleic acid having a low copy number is arranged in a part of the wells 52, it becomes easy to confirm the accuracy of the inspection device 4. Which type of standard plate 5 to use is selected according to the purpose.
- FIG. 3 is a diagram showing an example of the number of copies of the template nucleic acid 54 arranged in each well 52 of the standard plate 5.
- FIG. 3 shows the case where the standard plate 5 is a 96-well plate having 96 wells 52.
- Well identification information that identifies each well 52 is represented by a combination of row and column symbols. "A" to "H” in the leftmost column indicate the row symbol of the 96-well plate, and "1" to "12" in the top row indicate the column symbol of the 96-well plate.
- No template nucleic acid is arranged in all the wells 52 in row A.
- the standard plate technology has made it possible to manufacture a standard plate 5 in which the correct amount of nucleic acid is placed in each well 52. Further, if the same Cq value is obtained by inspecting the standard plate 5 using the same inspection device 4, the same reagent, and the same primer, it is easy to find an abnormality when there is a problem in any of them depending on the Cq value. For example, if one copy shows a Cq value and 10 copies show another Cq value, the performance comparison due to the difference in the inspection device 4 and the reagent can be compared more accurately and surely. In other words, since the abnormality of the inspection device 4 and the reagent appears as the Cq value, the accuracy of the inspection device 4 and the reagent can be reliably controlled.
- the standard device has a plate shape
- the present invention is not limited to this.
- the standard device may be a tube (eg, 8-tube) instead of the plate-shaped standard plate 5.
- the number of wells possessed by the standard device is not limited to 96, and may be, for example, 48 or 384.
- each facility when the same inspection device 4, the inspection device 4 of the same model, or different inspection devices 4 regardless of the model use the same primer with reference to the information provided by the information providing device 2. ,
- the inspection device 4 is calibrated so that the Cq value of a predetermined number of copies becomes a fixed value.
- each facility offsets the Cq value with reference to the information provided by the information providing device 2. In this way, the facility can strictly control the performance of the inspection device 4.
- FIG. 4 is a block diagram showing the configuration of the information providing device 2.
- the information providing device 2 is realized by, for example, one or more computer devices.
- the information providing device 2 may be a cloud server computer.
- the information providing device 2 includes a communication unit 21, a storage unit 22, an input unit 23, a display unit 24, and a processing unit 25.
- the communication unit 21 transmits / receives information to / from other devices via the network 9.
- the storage unit 22 stores various types of information including inspection result data and analysis result information.
- the storage unit 22 may further store the standard plate information.
- the standard plate information corresponds to the plate identification information or the plate type information, and includes information on whether or not the standard plate 5 is an entirely identical copy, the type of the template nucleic acid 54, and the template nucleic acid arranged in each well 52.
- the number of copies of 54, the type and amount of primer arranged in each well 52, the type and amount of amplification reagent arranged in each well 52, the type and amount of fluorescent probe arranged in each well 52 and Includes information with quantity.
- the information on the number of copies of the template nucleic acid 54 arranged in each well 52 may be used as information on whether or not the standard plate 5 has the same copy on all sides.
- the input unit 23 is a keyboard, a mouse, a button, a touch panel, or the like.
- the input unit 23 receives information input by a user operation.
- the display unit 24 is a display for displaying information.
- the processing unit 25 has an acquisition unit 26, an analysis unit 27, and an information output unit 28.
- the acquisition unit 26 acquires the inspection result data obtained by performing the PCR inspection on the standard plate 5 by the inspection device 4, and writes the acquired inspection result data in the storage unit 22.
- the acquisition unit 26 acquires the inspection result data transmitted from the terminal device 3 connected via the network 9.
- the information providing device 2 may acquire the inspection result data transmitted from the inspection device 4 connected via the network 9.
- the acquisition unit 26 may read the inspection result data from a computer-readable recording medium or the like, and may use the inspection result data input by the input unit 23. You may get it.
- Attribute information is added to the inspection result data.
- the attribute information includes the test date and time, the test device identification information of the test device 4 that performed the PCR test, the model of the test device 4 that performed the PCR test, the owner of the test device 4 that performed the PCR test, and the PCR test.
- the installation location of the inspection device 4 that performed the PCR test, the worker who performed the PCR test, the plate identification information of the standard plate 5 used for the PCR test, and the plate type information of the standard plate 5 used for the PCR test. Includes one or more of the measurement conditions from the PCR test.
- the attribute information is, in addition to or in addition to the plate type information, information on whether or not the standard plate 5 is an entirely identical copy, the type of the template nucleic acid 54, and the copy of the template nucleic acid 54 arranged in each well 52.
- Information may be included.
- the attribute information is stored in advance in the terminal device 3 or the inspection device 4, the information read from the identification means 56 of the standard plate 5 by the reading means (not shown) provided in the terminal device 3 or the inspection device 4, the information generated in the inspection device 4. It is based on the information that has been stored or the information that has been manually input to the terminal device 3 or the inspection device 4.
- the owner's information indicates the facility, the combination of the facility and the organization, and so on.
- the analysis unit 27 has a first determination unit 271, a reading unit 272, an analysis information acquisition unit 273, a second determination unit 274, and a comparison unit 275.
- the first determination unit 271 determines whether each well 52 is normal or abnormal in the measurement for which the inspection result data is obtained for each of the inspection result data acquired by the acquisition unit 26.
- the first determination unit 271 writes the well normality information in the storage unit 22 in association with the inspection result data.
- the well normality information indicates whether each well 52 is normal or abnormal.
- the reading unit 272 reads out the inspection result data used as the evaluation target data and one or more inspection result data used as the comparison data from the storage unit 22.
- the comparison data is test result data in which one or both of the timing at which the PCR test is performed and the test device 4 where the PCR test is performed are different from the evaluation target data.
- the analysis information acquisition unit 273 performs processing for each of the evaluation target data and the comparison data to remove the Cq value of the well 52 whose abnormality is indicated by the normality information from the information used for the analysis.
- the analysis information acquisition unit 273 analyzes the evaluation target data excluding the Cq value of the well 52 showing the abnormality, acquires the evaluation target data analysis information, and obtains the comparison data excluding the Cq value of the well 52 showing the abnormality. Analyze and obtain comparison data analysis information.
- the evaluation target data analysis information and comparison data analysis information include, for example, distribution of Cq value, average of Cq value, LOD (Limit of Detection, detection limit), LOC (Limit of Quantitation, lower limit of quantification), calibration curve inclination, calibration.
- the distribution of Cq values is represented, for example, by the standard deviation, relative standard deviation or interquartile range of the Cq values.
- the distribution of the Cq value in the evaluation target data analysis information is an in-plane distribution shown as a standard deviation, a relative standard deviation, or an interquartile range of the Cq value when the standard plate 5 having the same copy is used.
- LOD is the minimum number of copies that can detect the template nucleic acid
- LOQ is the minimum number of copies that can measure the Cq value.
- the evaluation target data analysis information includes well normality information of the evaluation target data.
- the second determination unit 274 determines the normality of the terminal device 3 based on one or more pieces of information indicated by the evaluation target data analysis information.
- the comparison unit 275 compares the information obtained from the evaluation target data analysis information with the information obtained from the comparison data analysis information to obtain the comparison information.
- the comparison information includes information on whether or not the inspection device 4 from which the evaluation target data was obtained is normal, and normal or abnormal Cq in the inspection device 4 from which the evaluation target data was obtained. It may include information on the well from which the value was obtained.
- the information used for comparison for acquiring the contrast information is one or more of the distribution of Cq values, the average of Cq values, LOD, LOQ, the slope of the calibration curve, and the intercept of the calibration curve.
- the information output unit 28 sets the evaluation target data analysis information and the comparison data analysis information acquired by the analysis information acquisition unit 273, the normality determination result by the second determination unit 274, and the comparison information acquired by the comparison unit 275. Generate the analysis result information.
- the information output unit 28 outputs the generated analysis result information.
- the output includes transmission to another device such as the terminal device 3, recording to the storage unit 22 or another recording medium, display on the display unit 24, printing by a printing device (not shown), and the like.
- the information output unit 28 writes the analysis result information in the storage unit 22 in association with the inspection result data used as the evaluation target data.
- FIG. 5 is a flow chart showing the operation of the inspection result data reception process by the information providing device 2.
- the terminal device 3 transmits the test result data obtained by performing the PCR test on the standard plate 5 by the test device 4 to the information providing device 2. Attribute information is added to the inspection result data.
- the information providing device 2 performs the processing shown in FIG. 5 for each inspection result data.
- the acquisition unit 26 of the information providing device 2 acquires the inspection result data received from the terminal device 3 by the communication unit 21 (step S105).
- the acquisition unit 26 associates the received inspection result data with the reception time information and writes it in the storage unit 22 (step S110).
- the reception time information indicates the time when the information providing device 2 receives the inspection result data.
- the first determination unit 271 determines whether or not the standard plate 5 having the same copy is used based on the attribute information added to the inspection result data (step S115). When the first determination unit 271 determines that the standard plate 5 having the same copy on the entire surface is not used (step S115: NO), the process ends.
- the first determination unit 271 determines that the standard plate 5 having the same copy on the entire surface is used (step S115: YES)
- the first determination unit 271 obtains the in-plane distribution of the Cq value from the inspection result data (step S120).
- the first determination unit 271 determines the normality of each well 52 by comparing the in-plane distribution of the Cq value with the Cq value of each well 52 (step S125).
- the in-plane distribution of the Cq value is the standard deviation ⁇ obtained from the Cq values of all the wells 52
- the first determination unit 271 obtains the Cq value of the standard deviation larger than a predetermined threshold value in the well 52. Is determined to be abnormal.
- predetermined thresholds are, but are not limited to, ⁇ , 2 ⁇ , 3 ⁇ , and the like. Further, when the in-plane distribution of the Cq value is in the interquartile range obtained from the Cq values of all the wells 52, the first determination unit 271 obtained the Cq value deviating from the interquartile range by a predetermined value or more. Well 52 is determined to be abnormal. The first determination unit 271 determines that the well 52 that is not determined to be abnormal is normal. The first determination unit 271 writes the well normality information in association with the inspection result data written in the storage unit 22 in step S110 (step S130). The well normality information indicates one or both of the well identification information of the normal well 52 and the well identification information of the abnormal well 52.
- the well normality information is added to the test result data.
- the first determination unit 271 acquires information on the number of copies of each well 52 based on the attribute information added to the inspection result data, and makes the same copy.
- the processing of step S120 and step S125 may be performed for each number of well groups.
- FIG. 6 is a flow chart showing the operation of the analysis process by the information providing device 2.
- the analysis process is performed, for example, when an instruction is input by the input unit 23 or at predetermined intervals after the process of FIG. 5 is performed.
- the reading unit 272 reads one of the inspection result data stored in the storage unit 22 as evaluation target data (step S205). For example, the reading unit 272 reads out the inspection result data newly written in the storage unit 22 in the process of FIG. 5 or the inspection result data designated by the input unit 23 as the evaluation target data. Alternatively, the reading unit 272 may read out the inspection result data that is predetermined or that matches the evaluation target data selection condition input by the input unit 23 as the evaluation target data, and the inspection that has not yet been selected as the evaluation target data. The result data may be read out. When there are a plurality of read inspection result data, the analysis unit 27 may use the inspection result data designated by the input unit 23 as the evaluation target data, and step S210 or less for each of the plurality of inspection result data. May be processed. Further, the reading unit 272 may receive the evaluation target data selection condition selected by the facility from the terminal device 3. In the following, the inspection device 4 from which the evaluation target data is obtained will be referred to as an evaluation target inspection device.
- the analysis information acquisition unit 273 reads out the Cq value of each well 52 from the evaluation target data, excluding the well 52 in which an abnormality is indicated by the well normality information added to the evaluation target data (step S210).
- the analysis information acquisition unit 273 acquires evaluation target data analysis information based on the information of the Cq value and the number of copies of each well 52 (step S215). Specifically, the analysis information acquisition unit 273 reads out information on the number of copies of each well 52 based on the attribute information added to the evaluation target data. Based on the Cq value of each well 52 read in step S210 and the information on the number of copies read, the analysis information acquisition unit 273 distributes the Cq value in the plane, averages the Cq values on the entire surface or for each number of copies, and copies.
- the value of one or more analysis items among the distribution of Cq values for each number, LOD, LOQ, the slope of the calibration curve, and the section of the calibration curve is calculated as the evaluation target data analysis information.
- the in-plane distribution of Cq values and the average of the Cq values on the entire surface are calculated when the standard plate 5 having the same copy on the entire surface is used.
- the average of Cq values for each number of copies, the distribution of Cq values for each number of copies, LOD, LOQ, the slope of the calibration curve, and the intercept of the calibration curve are calculated when a standard plate 5 that is not entirely the same copy is used. ..
- the standard plate 5 that is not an entirely identical copy is a standard plate 5 having wells 52 with a plurality of copy numbers.
- the in-plane distribution of Cq values and the distribution for each number of copies are represented by standard deviation, relative standard deviation, and interquartile range.
- the calibration curve is a straight line showing the relationship between the number of copies and the Cq value.
- the analysis information acquisition unit 273 adds the normality information of the evaluation target data and the Cq value of each well 52 read out in step S210 to the evaluation target data analysis information. Further, the analysis information acquisition unit 273 may add well abnormality information obtained from past test result data to the evaluation target data analysis information. In this case, the analysis information acquisition unit 273 reads the normality information from the past inspection result data in which the same inspection device identification information as the attribute information of the evaluation target data is set. The analysis information acquisition unit 273 identifies the well 52 determined to be abnormal at a frequency higher than a predetermined frequency based on the normality information set in the evaluation target data and the read past normality information. The analysis information acquisition unit 273 adds the well abnormality information in which the well identification information of the specified well 52 is set to the evaluation target data analysis information.
- the second determination unit 274 determines the normality of the terminal device 3 based on the evaluation target data analysis information (step S220). For example, the second determination unit 274 determines whether or not the value of each analysis item of the evaluation target data analysis information is included in the normal range.
- the normal range of each analysis item is stored in the storage unit 22 in advance according to, for example, the type and number of copies of the template nucleic acid 54, the type and amount of reagents (primer, amplification reagent, fluorescent probe), and measurement conditions. To.
- the second determination unit 274 may determine that the Cq value is normal when the Cq value is not detected in the well 52 of 0 copy.
- the reading unit 272 reads out one or more inspection result data that match the comparison data selection condition as comparison data based on the attribute information added to the inspection result data stored in the storage unit 22 (step S225).
- the comparison data selection condition includes at least the condition that the type and the number of copies of the template nucleic acid indicated by the attribute information of the evaluation target data are the same.
- the comparison data selection conditions include the type and amount of reagents (primer, amplification reagent, fluorescent probe), measurement conditions, inspection date and time, inspection device identification information, owner, installation location, model, and work. It may include one or more information of the person and the reception time.
- the type and number of copies of the template nucleic acid and the type and amount of the reagent may be indicated by plate identification information or plate type information.
- the comparison data selection condition may be input by the input unit 23, or may be registered in the storage unit 22 in advance corresponding to a part of the information included in the attribute information of the evaluation target data.
- the reading unit 272 may receive the comparison data selection condition selected in the facility from the terminal device 3.
- the comparison data selection conditions are that the type and number of copies of the template nucleic acid, the type and amount of the reagent, the measurement conditions, and the inspection device identification information are the same as the evaluation target data, and the evaluation target data is inspected. Includes the condition that the inspection date and time is earlier than the date and time.
- the comparison information capable of determining whether the performance has deteriorated after the relocation or calibration.
- the inspection date and time of the evaluation target data is the date and time after relocation or calibration.
- the comparison data selection conditions the type and number of copies of the template nucleic acid, the type and amount of the reagent, the measurement conditions, and the inspection device identification information are the same as the evaluation target data, and the date and time when the data was transferred or calibrated. Includes the condition that it is the previous inspection date and time.
- the comparison data selection conditions are the type and number of copies of the template nucleic acid, and the type and amount of the reagent.
- the measurement condition and the model of the inspection device 4 are the same as the evaluation target data, and the inspection device identification information is different from the evaluation target data.
- the comparison data selection conditions include the type and number of copies of the template nucleic acid, and the type and amount of the reagent.
- the measurement condition and the model of the inspection device 4 are the same as the evaluation target data, and the facility is different from the evaluation target data.
- the comparison data selection conditions are the type and number of copies of the template nucleic acid, the type and amount of the reagent, the measurement conditions, and the identification of the inspection device of the inspection device 4. It includes the condition that the information or the model is the same as the evaluation target data and the worker is different from the evaluation target data.
- the inspection result data can be used as comparison data.
- the test result data before and after the relocation of the test device 4, the test result data obtained by performing the PCR test within a predetermined period, and the test result data obtained by performing the PCR test on a specific standard plate shall be used as the evaluation target data and the comparison data. You can also.
- the performance of the inspection device 4 has deteriorated due to the passage of time from the calibration, whether the performance has not changed before and after the relocation of the inspection device 4, the performance of the inspection device 4 in one facility is in another facility. It is possible to select and compare the evaluation target data and the comparison data according to the purpose, such as how it is compared with the inspection device 4 of the above and how the skill of the worker is.
- the analysis information acquisition unit 273 reads out the Cq value of each well 52 from each of the comparison data, excluding the Cq value of the abnormal well 52 (step S230).
- the analysis information acquisition unit 273 acquires the comparison data analysis information based on the information of the Cq value of each well 52 of each comparison data read in step S230 and the number of copies of each well 52 of each comparison data (step S235). Specifically, the analysis information acquisition unit 273 reads out information on the number of copies of each well 52 based on the attribute information added to the comparison data.
- the analysis information acquisition unit 273 includes the Cq value read in step S230, the distribution of the Cq value of all the comparison data for each number of copies, the average of the Cq values of each comparison data and all comparison data for each number of copies, and the LOD of each comparison data. , LOQ of each comparison data, inclination of the calibration curve of each comparison data, and one or more of the sections of the calibration curve of each comparison data are calculated as comparison data analysis information.
- the analysis information acquisition unit 273 may acquire such information based on the analysis result information stored in the storage unit 22 corresponding to the comparison data. Further, the analysis information acquisition unit 273 may include the information obtained from the analysis result information corresponding to each comparison data in the comparison data analysis information.
- the contrast unit 275 compares the evaluation target data analysis information with the contrast data analysis information to obtain the contrast information (step S240).
- the contrast items used for the contrast are the Cq value of the well, the distribution of the Cq value, the average of the Cq values, the LOD, the LOQ, the slope of the calibration curve, and the intercept of the calibration curve. be.
- the comparison unit 275 may select a comparison item depending on whether or not the standard plate 5 having the same copy of the evaluation target data is used.
- the contrast unit 275 calculates the discrepancy between the value of the contrast item obtained from the evaluation target data analysis information and the value of the contrast item or the average of the values of the contrast items obtained from the contrast data analysis information.
- the contrast unit 275 calculates where the value of the item obtained from the evaluation target data analysis information is located in the distribution of the value of the contrast item obtained from the contrast data analysis information.
- the comparison data selection condition includes the condition that the type and amount of the reagent and the measurement condition are the same as the evaluation target data
- the comparison unit 275 further determines the evaluation target inspection device based on these calculation results. Determines whether is normal or abnormal.
- the comparison unit 275 calculates the difference between the average of the Cq values of the number of copies N in the evaluation target data and the average of the Cq values of the number of copies N of all the comparison data. The comparison unit 275 determines that the evaluation target inspection device is normal when the deviation is equal to or less than a predetermined threshold value, and determines that the evaluation target inspection device is abnormal when the deviation is larger than the threshold value.
- the evaluation target inspection device is normal when the average of the Cq values of the number of copies N in the evaluation target data is included in the average ⁇ standard deviation ⁇ of the Cq values of the number of copies N in the total comparison data. If it is not included, it is determined that the inspection device to be evaluated is abnormal. Further, in the comparison unit 275, the evaluation target inspection device is normal when the average of the Cq values of the number of copies N in the evaluation target data is included in the interquartile range of the Cq value of the number of copies N in the total comparison data. If it is determined to be present and it is not included, it may be determined that the inspection device to be evaluated is abnormal.
- the value of the comparison item is the Cq value of the well with the number of copies N.
- the comparison unit 275 is evaluated when all the Cq values of each well having the number of copies N of the evaluation target data analysis information are included in the average ⁇ standard deviation ⁇ of the Cq values of all the wells having the number of copies N in the total comparison data.
- the inspection device is determined to be normal, and if it is not included, the evaluation target inspection device is determined to be abnormal.
- the contrast unit 275 performs a significant difference test on the set of Cq values of each well having the number of copies N of the evaluation target data and the set of the Cq values of each well having the number of copies N in the total contrast data.
- the contrast unit 275 determines that the evaluation target inspection device is normal when there is no significant difference, and determines that the evaluation target inspection device is abnormal when there is a significant difference.
- the value of the contrast item is the standard deviation (distribution) of the Cq value of the well with the number of copies N.
- the contrast unit 275 calculates the difference between the standard deviation of the Cq value of the well having the number of copies N of the evaluation target data and the standard deviation of the Cq value of the well having the number of copies N in the total contrast data.
- the comparison unit 275 determines that the evaluation target inspection device is normal when the difference is within a predetermined threshold value, and determines that the evaluation target inspection device is abnormal when the difference is larger than the predetermined threshold value. do.
- the comparison unit 275 calculates the discrepancy between the LOD in the evaluation target data and the average of the LODs in all the comparison data.
- the comparison unit 275 determines that the evaluation target inspection device is normal when the deviation is equal to or less than a predetermined threshold value, and determines that the evaluation target inspection device is abnormal when the deviation is larger than the threshold value.
- the contrast unit 275 determines that the evaluation target inspection device is normal when the LOD in the evaluation target data is included within the average ⁇ standard deviation ⁇ of the LOD in the total comparison data, and when it is not included, the evaluation target is evaluated.
- the inspection device determines that it is abnormal.
- the contrast unit 275 determines that the evaluation target inspection device is normal when the LOD in the evaluation target data is included in the interquartile range of the LOD in the total comparison data, and evaluates when it is not included.
- the target inspection device may be determined to be abnormal.
- the contrast unit 275 makes the same determination when the contrast items are LOQ, the slope of the calibration curve, and the intercept of the calibration curve.
- the comparison unit 275 determines whether the evaluation target inspection device is normal or abnormal for each comparison item, and either one or a predetermined number of two or more. When it is determined that the evaluation target inspection device is abnormal for the comparison item, the final determination that the evaluation target inspection device is abnormal may be made. By using a plurality of comparison items, the normality of the inspection device 4 can be confirmed from various angles, so that the normality of the inspection device 4 can be confirmed more accurately.
- the contrast unit 275 uses the contrast information as the value of the contrast item obtained from the evaluation target data analysis information, the value of the contrast item of the contrast data analysis information used for the contrast, the average of the values, or the distribution of the values. , Generates comparison information in which information on whether or not the evaluation target inspection device determined by comparison is normal is set.
- the information output unit 28 outputs analysis result information including the comparison information generated by the comparison unit 275, the evaluation target data analysis information and the comparison data analysis information generated by the analysis information acquisition unit 273, and the comparison data selection condition (the comparison data selection condition). Step S245). That is, the information output unit 28 writes the analysis result information in the storage unit 22 in association with the evaluation target data. At this time, the information output unit 28 may add information for specifying the inspection result data used as the comparison data to the analysis result information and write it in the storage unit 22. Further, the information output unit 28 generates analysis result notification information including analysis result information, evaluation target data, and attribute information of the evaluation target data.
- the information output unit 28 further analyzes the type of the template nucleic acid 54, the number of copies of each well 52 of the standard plate 5 used for the evaluation data, the type and amount of the reagent, and the information obtained from the attribute information of the comparison data. It may be set as the result notification information.
- the analysis result notification information may include display data for displaying the analysis result information as a graph or a table. For example, in the display data, the values of the analysis items obtained from the evaluation target data analysis information and the values of the analysis items of the comparison data analysis information used for comparison and their distribution are displayed on the same graph or arranged in a table. indicate.
- the information output unit 28 transmits the analysis result notification information to the terminal device 3 of the facility specified by the attribute information of the evaluation target data.
- the terminal device 3 stores the received analysis result notification information and displays it on the display.
- the analysis result notification information received by the terminal device 3 is referred to, and evaluation is made so that the Cq value of a predetermined number of copies becomes a fixed value when the same test device 4, the same reagent, and the same primer are used.
- Calibrate the target inspection device For example, information such as the difference in the average of the Cq values between the evaluation target inspection device and the other inspection device 4 indicated by the evaluation target data analysis information and the contrast data analysis information is used for calibration of the evaluation target inspection device.
- each facility offsets the Cq value indicated by the inspection result of the inspection target inspection device with reference to the provided information.
- the information output unit 28 of the information providing device 2 may output the analysis result information or the analysis result notification information by printing or displaying it on the display unit 24, and is an illustration of a company that maintains the inspection device 4. It may be output to a terminal device that does not. Workers of the maintenance company calibrate and offset the evaluation target inspection device at the facility while checking the output analysis result information and analysis result notification information. In this way, it is possible to strictly control the performance of the inspection device 4.
- the facility will clean the wells that are shown to be abnormal by the well normality information.
- the facility will also calibrate the heat block, lamp and detection system if the contrast information indicates anomalies.
- the comparison information generated by the information providing device 2 makes it possible to more accurately compare the inspection results of different facilities, the performance difference of a certain measurement system, the inspection results in the same facility, and the performance difference of a certain measurement system. , It is easier to find defects in the inspection device 4 and reagents. Further, by using a plurality of data acquired in the past by the same inspection device 4, the defect of the current inspection device 4 can be grasped, and by using a plurality of data acquired by a plurality of facilities, the inspection device 4 of each facility can be used. It is also possible to judge the normal condition.
- the terminal device 3 may add exclusion well information to the inspection result data and transmit it to the information providing device 2.
- Excluded well information indicates information on wells 52 that are not used for analysis.
- the analysis information acquisition unit 273 reads out the Cq value of each well 52 from the evaluation target data, excluding the well 52 indicated by the excluded well information.
- the well 52 excluded from the evaluation target data may be a well whose abnormality is indicated by the well normality information or the well abnormality information added to the past inspection result data of the evaluation target inspection device.
- the inspection device 4 can use information for specifying the past inspection result data as the exclusion well information.
- the information providing device 2 may perform the processes of steps S225 to S240 for each of the comparison data groups selected according to each of the plurality of different comparison data selection conditions. Further, the information providing device 2 performs the processing of steps S210 to S220 of FIG. 5 on the inspection result data after determining NO in step S115 of FIG. 5 or after the processing of step S130, and step S215.
- the evaluation target data analysis information obtained by the process of the above and the determination result obtained by the process of step S220 may be added to the inspection result data and written to the storage unit 22.
- FIG. 7 is a diagram for explaining a method of calculating LOD and LOQ.
- the LOQ detection method is, for example, the reference “A. Forootan, et al.," Methods to determine limit of detection and limit of quantification in quantitative real-time PCR (qPCR), "Biomolecular Detection and Quantification, Volume 12, June. 2017, Pages 1-6 ”.
- FIG. 7A is a graph showing the relationship between the number of copies and the CV value.
- FIG. 7B is a diagram showing the relationship between the number of copies and the CV value, the detection rate, and the number of UDs. The number of wells for each copy number is 24 for 2 measurements of the Le1 gene. UD indicates that the Cq value was not detected.
- the CV value shown in FIG. 7 is calculated by the following equation (1). SD Cq is the standard deviation of the Cq value, and E is the qPCR efficiency.
- the analysis information acquisition unit 273 determines that the minimum number of copies in which the number of undetected wells 52 is equal to or less than a predetermined value is LOD. Further, the analysis information acquisition unit 273 sets the minimum number of copies whose CV value calculated by the equation (1) is equal to or less than a predetermined value as the LOQ. In the reference, the number of undetected wells 52 is 0, that is, the minimum number of copies with a detection rate of 100% is LOD, and the minimum number of copies with a CV value of 35% or less is LOQ. In the case of FIG. 7, the analysis information acquisition unit 273 determines the minimum number of copies “2” with a detection rate of 100% as LOD, and determines the minimum number of copies “8” with a CV of 35% or less as LOQ.
- FIG. 8 and 9 are diagrams showing display examples of analysis result information.
- the graph shown in FIG. 8 shows the in-plane distribution of the Cq value indicated by the evaluation target data.
- the graph shown in FIG. 9 shows the time-series change in the distribution of the Cq value of the inspection device to be evaluated.
- the distribution of Cq values in October is obtained from the data analysis information to be evaluated. Further, the distribution of the Cq value for each month from January to September is obtained from the contrast data analysis information using the inspection result data of each month of the evaluation target inspection device as the contrast data.
- Each facility provides information on the results of inspection by the inspection device 4 at predetermined periods using the standard plate 5 in which the template nucleic acid, primer, amplification reagent, and fluorescent probe with a known copy number are set in each well 52. It is possible to confirm the in-plane distribution and receive feedback of information useful for monthly device quality control simply by transmitting to 2.
- the detection sensitivity is confirmed by a user such as a facility manager at regular time of quality control of the inspection device 4, when the inspection device 4 is introduced, before and after the inspection device 4 is relocated, and the like.
- a user such as a facility manager at regular time of quality control of the inspection device 4, when the inspection device 4 is introduced, before and after the inspection device 4 is relocated, and the like.
- the in-plane distribution is confirmed in advance, and if it is normal, it is guaranteed to use all wells, and if there is an abnormal well, the detection sensitivity can be obtained by excluding the abnormal well. More accurate detection sensitivity information can be obtained.
- a full-copy standard plate 5 having a specific low-copy number standard substance having a sequence not found in nature is used in all wells 52.
- the number of copies arranged on the entire surface of the standard plate 5 is 2 copies, which is the highest performance when having an arrangement not found in nature, 10 copies near the detection sensitivity, 50 copies when a more reliable reaction is desired, etc. It shall correspond.
- the standard plate 5 with the number of copies according to the purpose the in-plane distribution, the normality of the entire surface, or the presence or absence of detection is confirmed.
- the information providing device 2 analyzes the test result data obtained by the test device 4 using the standard plate 5 having 10 copies arranged on the entire surface as the evaluation target data. It is desirable to confirm the in-plane distribution, the normality of the entire surface, and the presence or absence of detection. When it is desired to confirm only the normality of the entire surface and the presence or absence of detection, the test result data obtained by measuring the standard plate 5 on which 5 copies or 2 copies of the template nucleic acid 54 are arranged may be used as the evaluation target data.
- FIG. 10 is a diagram showing an example of test result data and its analysis information obtained by the test device 4 performing a qPCR test using a standard plate 5 having 10 copies on the entire surface.
- 10 copies of the entire surface means that 10 copies of the template nucleic acid 54 are arranged in all the wells 52.
- 10 (a) shows the test result data
- FIG. 10 (b) shows the analysis information obtained from the test result data shown in FIG. 10 (a).
- the test result data shows the Cq value of each well 52.
- the analysis information includes the number of copies of the template nucleic acid 54, the average Cq value (Cq Ave), the standard deviation of the Cq value ( ⁇ ), the relative standard deviation of the Cq value (RSD), and the difference between the minimum Cq value and the maximum Cq value ( ⁇ Cq), maximum Cq value (Max), minimum Cq value (Min), UD number, and detection rate are shown.
- the UD number is the number of wells 52 for which the Cq value was not detected.
- the detection rate is the ratio of the wells 52 in which the Cq value is detected.
- FIG. 11 is a diagram showing an example of test result data and analysis information thereof obtained by performing a qPCR test by the same test device 4 under the same conditions as in FIG. 10 two months after FIG. 10 was obtained.
- FIG. 11A shows the inspection result data
- FIG. 11B shows the analysis information obtained from the inspection result data shown in FIG. 11A.
- FIG. 11A is the evaluation target data
- FIG. 11B is the evaluation target data analysis information
- FIG. 10A is the comparison data
- FIG. 10B is the comparison data analysis information.
- the average of the Cq values obtained from the evaluation target data analysis information in FIG. 11B is within a predetermined range (for example, 35 ⁇ 0.5), and the standard deviation of the Cq values is predetermined. It is determined that the range is within the range (for example, ⁇ ⁇ 0.6) and the difference between the minimum Cq value and the maximum Cq value is within the predetermined range (for example, ⁇ Cq ⁇ 2.0).
- the second determination unit 274 determines that all the wells 52 are normal because there is no well 52 showing an abnormal Cq value and the number of UDs is 0.
- the comparison unit 275 compares the evaluation target data analysis information in FIG. 11 (b) with the comparison data analysis information in FIG. 10 (b), and the evaluation target data analysis information is obtained from the comparison data two months ago. It is judged that the accuracy is the same as that of the comparison data analysis information.
- the information providing device 2 confirms whether or not the entire surface of the standard plate 5 is detected, and uses the distribution, average, and standard deviation of the Cq value as control values, and the current distribution, average, and standard deviation of the Cq value. Can be compared with the distribution, average, and standard deviation of the Cq values so far, and the normality of the current state of the inspection device 4 can be confirmed. Further, by using the standard plate 5 of the template nucleic acid having a sequence that does not exist in nature, the effect of reducing the risk of contamination can be expected.
- the facility confirms the state of the detection sensitivity of the inspection device 4 using the standard plate 5 on which the template nucleic acid having a sequence (artificial sequence) that does not exist in nature is arranged.
- the inspection device 4 performs a qPCR inspection using the standard plate 5 shown in FIG.
- the 96 wells 52 of the standard plate 5 are arranged with template nucleic acids having 0, 1, 5, 10, 20, 40, and 80 copies.
- FIG. 12 is a diagram showing an example of test result data and analysis information thereof, in which the test device 4 performed a qPCR test using the standard plate 5 on which the template nucleic acid was arranged as shown in FIG. 3 after FIG. 10 was obtained.
- Is. 12 (a) shows the test result data
- FIGS. 12 (b) and 12 (c) show the analysis information obtained from the test result data shown in FIG. 12 (a).
- 12 (b) shows the same analysis item information as in FIGS. 10 (b) and 11 (b).
- FIG. 12 (c) shows a calibration curve, a coefficient of determination R2 , and amplification efficiency.
- FIG. 13 is a diagram showing an example of test result data and analysis information thereof in which the same test device 4 performed a qPCR test under the same conditions as in FIG. 12 after FIG. 11 was obtained.
- 13 (a) shows the test result data
- FIGS. 13 (b) and 13 (c) show the analysis information obtained from the test result data shown in FIG. 13 (a).
- 13 (b) contains information on the same analysis items as in FIG. 12 (b)
- FIG. 13 (c) shows the same analysis items as in FIG. 12 (c).
- the second determination unit 274 of the information providing device 2 determines that the test is established because the 0 copy is not amplified. Further, the analysis information acquisition unit 273 determines that the detection sensitivity is from 5 copies because the detection rate is 100% for 5 copies or more. Further, the second determination unit 274 determines that, in addition to the detection sensitivity, the slope of the calibration curve and the value of the intercept (the intercept is the Cq value at the time of one copy) are within a predetermined range.
- the comparison unit 275 compares the slope of the calibration curve and the value of the intercept with the slope of the calibration curve and the value of the intercept of the comparison data, which is the inspection result data so far, to obtain the current state of the inspection device 4 and the value of the intercept. Determine if performance is normal. As a result, the facility can carry out normal tests and inspections using the inspection device 4 whose normal condition is controlled. As a standard plate for confirming the in-plane distribution and the state of detection sensitivity and the like, a template nucleic acid having a natural sequence may be used as long as it can be compared with the data so far.
- the state of the inspection device 4 is managed by confirming whether the inspection device 4 can normally measure all 96 wells by qPCR / PCR.
- the information providing device 2 receives the test result data as a result of the qPCR test performed by the evaluation target test device using the standard plate 5 having 10 copies on the entire surface at a predetermined frequency, and stores the received test result data. Accumulate in unit 22.
- the information providing device 2 compares the distribution of the Cq value of the latest inspection result data (evaluation target data) with the standard, and manages whether or not the evaluation target inspection device is currently normal. As a reference for comparison, the distribution of past Cq values obtained from past inspection result data (contrast data) received from the evaluation target inspection device is used.
- FIG. 14 and 15 are diagrams showing a comparison example of the distribution of the Cq value measured in the past and the Cq value measured this time.
- FIG. 14 shows the distribution by a histogram
- FIG. 15 (a) shows the distribution by a boxplot.
- FIG. 15B shows the difference between the average (Cq Ave) and standard deviation (Cq ⁇ ) of the past and present Cq values and the maximum Cq value and the minimum Cq value of this time.
- the comparison unit 275 has a distribution of Cq values obtained from the comparison data which is the past inspection result data of the evaluation target inspection device and the evaluation target data which is the current inspection result data of the evaluation target inspection device. Compare with the distribution of Cq values obtained from.
- the contrast unit 275 determines that the state is normal if these distributions are more similar than the predetermined state, and determines that the state is abnormal if they are not similar. Further, in the second determination unit 274, the average of the Cq values this time is within a predetermined range (for example, 35 ⁇ 0.5), and the standard deviation of the Cq values is within a predetermined range (for example, ⁇ ⁇ 0.6).
- the comparison unit 275 determines whether it is judged to be a normal state, and if not, it is judged to be an abnormal state.
- the difference between the average of the past Cq values shown in FIG. 15 and the average of the current Cq values is within a predetermined range, and the standard deviation of the past Cq values and the current Cq values are within a predetermined range.
- the predetermined range for determining normality may be a value determined by the internal standards of the facility or the like.
- the comparison data is used as the past inspection result data of the inspection device to be evaluated, but it may be the past or present inspection result data of the inspection device 4 of another facility or the inspection device 4 of another model.
- Next-generation sequencers include amplicon NGS, which PCR-amplifies a specific sequence by the inspection device 4 and inspects the presence or absence and amount of the amplification product.
- NGS Next-generation sequencers
- amplicon NGS which PCR-amplifies a specific sequence by the inspection device 4 and inspects the presence or absence and amount of the amplification product.
- the reagent for performing the inspection by NGS is adjusted, the prepared reagent is added to the standard plate 5, and the inspection is performed by NGS.
- the information providing device 2 performs analysis using the inspection result data showing the inspection result by NGS instead of the inspection result data of the inspection apparatus 4.
- the analysis result information obtained by the information providing device 2, such as the result of checking the detection sensitivity described above and the result of checking the state of the inspection device 4, is stored in the storage unit 22 or on a server computer or cloud different from the information providing device 2.
- the analysis result information may be stored in the server computer of the above and output the analysis result information in response to the request input by the input unit 23 or the request received from the terminal device 3 or the inspection device 4.
- the output destination of the analysis result output information may be a computer terminal (not shown) of a company or the like that manufactures, sells, or maintains the inspection device 4.
- each facility, a company that manufactures, sells, or maintains the inspection device 4 arbitrarily selects a factor to be compared, and if there is no analysis result by the selected factor, the information providing device 2 is the factor. It is also possible to perform an analysis using and provide the results. The more the information providing device 2 collects the past inspection result data, the higher the accuracy and the more factors can be compared.
- the inspection result data of the inspection device 4 of each facility is collectively collected, the accuracy and the condition of the inspection device 4 are analyzed and judged, and the result is fed back to each facility. Can be done.
- the information providing device 2 collects the inspection result data of the inspection device 4 of the same model in different facilities, and how much the inspection result data obtained from the evaluation target inspection device in the information providing device 2 is distributed in the whole. It is possible to provide information on whether the characteristics are obtained. At the facility, it is necessary to confirm whether the current state of the inspection device 4 is normal compared with the past inspection result data, and whether it is operating normally, etc. by one qPCR measurement using a standard plate. Can be done.
- the facility confirms the normality and performance of the inspection device 4 by the information provided from the information providing device 2, and calibrates if necessary. Therefore, the inspection can always be carried out with a reliable measurement system. It is possible to store the analysis results in a cloud or the like and provide them to a company or the like that manufactures, sells, or maintains the inspection device 4 as requested.
- the functions of the information providing device 2 and the inspection device 4 in the above-described embodiment may be realized by a computer.
- a program for realizing the functions of the information providing device 2 and the inspection device 4 is recorded on a computer-readable recording medium, and the program recorded on the recording medium is read by the computer system and executed. It may be realized.
- the term "computer system” as used herein includes hardware such as a CPU (central processing unit), an OS (Operation System), and peripheral devices.
- the "computer-readable recording medium” refers to a flexible disk, a magneto-optical disk, a portable medium such as ROM (Read Only Memory), a CD-ROM, and a storage device such as a hard disk built in a computer system. Say.
- a "computer-readable recording medium” is a communication line for transmitting a program via a network such as the Internet or a communication line such as a telephone line, and dynamically holds the program for a short period of time. It may also include a program that holds a program for a certain period of time, such as a volatile memory inside a computer system that is a server or a client in that case. Further, the above-mentioned program may be for realizing a part of the above-mentioned functions, and may be further realized for realizing the above-mentioned functions in combination with a program already recorded in the computer system. All or part of each function of the information providing device 2 and the terminal device 3 is realized by using hardware such as ASIC (Application Specific Integrated Circuit), PLD (Programmable Logic Device), and FPGA (Field Programmable Gate Array). May be done.
- ASIC Application Specific Integrated Circuit
- PLD Programmable Logic Device
- FPGA Field Programmable Gate Array
- FIG. 16 is a block diagram showing an example of the hardware configuration of the information providing device 2.
- the information providing device 2 includes a processor 71, a main storage device 72, an auxiliary storage device 73, an output device 74, an input device 75, and a communication interface (communication I / F) 76. Each of these parts is connected via a bus 77.
- the processor 71 is a processing device that performs various controls and calculations.
- the processor 71 is a CPU.
- the processor 71 realizes various functions by executing an OS or a program stored in the main storage device 72 or the like. That is, the processor 71 functions as the processing unit 25 of the information providing device 2 by executing the performance evaluation program of the real-time PCR device. Further, the processor 71 controls the operation of the entire information providing device 2.
- the device that controls the operation of the entire information providing device 2 is the processor 71, but the device is not limited to this, and may be, for example, an FPGA or the like.
- the performance evaluation program and various databases of the information providing device 2 do not necessarily have to be stored in the main storage device 72, the auxiliary storage device 73, or the like.
- the information providing device 2 may acquire a program or various databases from these other information processing devices and execute the program.
- the main storage device 72 stores various programs and stores data and the like necessary for executing various programs.
- the main storage device 72 has a ROM and a RAM (RandomAccessMemory) (not shown).
- the ROM stores various programs such as BIOS (Basic Input / Output System).
- BIOS Basic Input / Output System
- the RAM functions as a work range expanded when various programs stored in the ROM are executed by the processor 71.
- the RAM is not particularly limited and may be appropriately selected according to the purpose. Examples of the RAM include DRAM (Dynamic Random Access Memory) and SRAM (Static Random Access Memory).
- the auxiliary storage device 73 is not particularly limited as long as it can store various information, and can be appropriately selected according to the purpose. Examples thereof include a solid state drive and a hard disk drive. Further, the auxiliary storage device 73 may be a portable storage device such as a CD (Compact Disc) drive, a DVD (Digital Versatile Disc) drive, or a BD (Blu-ray (registered trademark) Disc) drive.
- a CD Compact Disc
- DVD Digital Versatile Disc
- BD Blu-ray (registered trademark) Disc
- the output device 74 a display, a speaker, or the like can be used.
- the display is not particularly limited, and a known display can be used as appropriate, and examples thereof include a liquid crystal display and an organic EL display.
- the input device 75 is not particularly limited as long as it can accept various requests for the information providing device 2, and a known input device 75 can be used as appropriate, and examples thereof include a keyboard, a mouse, and a touch panel.
- the communication interface 76 is not particularly limited, and a known one can be used as appropriate, and examples thereof include a wireless or wired communication device.
- the processing function of the information providing device 2 can be realized.
- the information providing device 2 may be realized by a plurality of computer devices connected to the network.
- which of the plurality of computer devices each functional unit of the information providing device 2 is realized can be arbitrary.
- the same functional unit may be realized by a plurality of computer devices.
- the inspection device 4 may have the function of the information providing device 2.
- the present invention includes the following aspects.
- An information providing device including an information output unit.
- the information providing device according to any one of [1] to [4], which includes one or both of the information in the wells.
- the information output unit further outputs one or both of the information obtained from the evaluation target data and the information obtained from one or more of the inspection result data different from the evaluation target data [1].
- the information providing device according to any one of [5].
- the information obtained from the evaluation target data used by the information output unit for comparison and the information obtained from the inspection result data different from one or more of the evaluation target data are the distribution of Cq values and Cq.
- Each of the inspection result data further has a determination unit for determining an abnormality of the well based on the inspection result data, and the information output unit excludes the Cq value of the well determined to be abnormal. It is obtained by comparing the information obtained from the evaluation target data with the information obtained from one or more of the inspection result data different from the evaluation target data and excluding the Cq value of the well determined to be abnormal.
- the information providing device according to any one of [1] to [7], which outputs the comparison information.
- the information output unit is one or more in which the information obtained from the evaluation target data differs from the evaluation target data at the time when the PCR test is performed and one or both of the test devices on which the PCR test is performed.
- the information providing device according to any one of [1] to [8], which provides the comparison information obtained by comparing with the information obtained from the inspection result data.
- the evaluation target data includes the identification of the inspection device, the owner of the inspection device, the installation location of the inspection device, the model of the inspection device, the worker who performed the PCR inspection, and PCR.
- Attribute information indicating one or more of the reagent used for the test, the date and time when the PCR was performed, the identification of the standard device, and the type of the standard device is added, and the information output unit is evaluated.
- the comparison information obtained by comparing the information obtained from the target data with the information obtained from one or more of the inspection result data to which the predetermined attribute information is added and different from the evaluation target data.
- the information providing device according to any one of [1] to [9]. [11] Any of [1] to [10], wherein one or more of a predetermined amount of a primer, a predetermined amount of an amplification reagent, and a predetermined amount of a fluorescent probe is arranged in each of the wells of the standard device.
- the information providing device described in item 1. [12] The information providing device according to any one of [1] to [11], wherein the nucleic acid does not exist in nature. [13] Receiving test result data indicating the Cq value of the well obtained by performing a PCR (polymerase chain reaction) test on a standard device having a well having a known number of copies of nucleic acid.
- An information providing system including an information output unit that outputs comparison information obtained by comparison with information obtained from result data.
- the information providing method performed by the information providing device which is obtained by performing a PCR (polymerase chain reaction) test on a standard device having a well having a known number of copies of nucleic acid. Obtained from the acquisition step of acquiring the inspection result data indicating the Cq value of the well, the information obtained from the evaluation target data which is the inspection result data of the evaluation target, and one or more of the inspection result data different from the evaluation target data.
- An information providing method comprising an information output step for outputting comparison information obtained by comparison with information to be obtained.
- the information providing method performed by the information providing system which is obtained by performing a PCR (polymerase chain reaction) test on a standard device having a well having a known number of copies of nucleic acid.
- An information providing method including an information output step for outputting comparison information obtained by comparing information with information obtained from one or more of the inspection result data different from the evaluation target data.
- Information provision system Information provision device 2 Information provision device 3 Terminal device 4 Inspection device 5 Standard plate 9 Network 21 Communication section 22 Storage section 23 Input section 24 Display section 25 Processing section 26 Acquisition section 27 Analysis section 28 Information output section 51 Base material 52 Well 54 Template nucleic acid 55 Sealing member 56 Identification means 71 Processor 72 Main storage device 73 Auxiliary storage device 74 Output device 75 Input device 76 Communication interface 77 Bus 271 First judgment unit 272 Reading unit 273 Analysis information acquisition unit 274 Second judgment unit 275 Comparison unit
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Abstract
Description
ここでは、検査装置4のパフォーマンスとして、検出感度の確認を行う例を説明する。検出感度の確認は、施設の装置管理者などのユーザーが、検査装置4の定期的な精度管理時、検査装置4の導入時、検査装置4の移設前後などに行う。検出感度の確認を行う際には、先に面内分布の確認後を行うことが望ましい。面内分布を事前確認し、正常であった場合は全てのウェルを使用することが保証され、異常なウェルがあった場合は、その異常なウェルを除いて検出感度を求めることができる等、より精確な検出感度の情報を得ることができる。
ここでは、検査装置4がqPCR/PCRにおいて96ウェル全てを正常に測定できるかを確認することにより、検査装置4の状態を管理する。この場合、例えば、情報提供装置2は、評価対象検査装置が所定頻度で全面10コピーの標準プレート5を用いてqPCR検査を行った結果の検査結果データを受信し、受信した検査結果データを記憶部22に蓄積する。情報提供装置2は、最新の検査結果データ(評価対象データ)のCq値の分布と基準とを対比して、評価対象検査装置が現在正常であるか否かを管理する。対比する基準として、評価対象検査装置から受信した過去の検査結果データ(対比データ)から得られる過去のCq値の分布を利用する。
作業者のスキルを比較する場合、プライマー、増幅試薬、蛍光プローブが含まれない標準プレート5を使用する。作業者は、プライマー、増幅試薬、蛍光プローブなどの試薬を調整して、標準プレート5の各ウェル52に分注する。その後、作業者は、同じPCRプロトロルに従い、検査装置4により標準プレート5のqPCR検査を実施する。端末装置3は、検査装置4がqPCR検査を行った検査結果データを情報提供装置2に送信する。情報提供装置2は、異なる作業者の検査結果データを評価対象データ及び対比データとして用いて分析を行う。
次世代シーケンサー(NGS)には、検査装置4によりある特定の配列をPCR増幅し、その増幅産物の有無や量を検査するアンプリコンNGS等がある。この場合、検査装置4により標準プレート5のPCR増幅を行った後に、NGSで検査を行うための試薬を調整し、調整した試薬を標準プレート5に加えて、NGSにより検査を行う。情報提供装置2は、検査装置4の検査結果データに代えて、NGSによる検査結果を示す検査結果データを用いて分析を行う。
上述した検出感度の確認の結果や、検査装置4の状態確認の結果など、情報提供装置2により得られた分析結果情報を記憶部22、又は、情報提供装置2とは異なるサーバコンピュータやクラウド上のサーバコンピュータに保存しておき、入力部23により入力された要求や、端末装置3又は検査装置4から受信した要求に応じてそれらの分析結果情報を出力してもよい。これにより、各施設では、いつでも、他施設との差、他機種との差、同施設内の同機種間の差、作業者による力量差、増幅試薬の違い、検査装置4の移設前後などの感度や状態を比較した結果を得ることができる。また、分析結果出力情報の出力先は、検査装置4の製造、販売又は保守を行う企業等のコンピュータ端末(図示せず)でもよい。また、各施設や、検査装置4の製造、販売又は保守を行う企業等は、比較したい因子を任意に選択し、選択された因子による分析結果がない場合には、情報提供装置2がその因子を用いて分析を行い、その結果を提供することも可能である。情報提供装置2が過去の検査結果データを収集するほど、精度が向上し、より多くの因子による比較が可能となる。
[1]既知のコピー数の核酸を配したウェルを有する標準デバイスに対して検査装置がPCR(polymerase chain reaction)検査を行って得られた前記ウェルのCq値を示す検査結果データを取得する取得部と、評価対象の前記検査結果データである評価対象データから得られる情報と、前記評価対象データとは異なる1以上の前記検査結果データから得られる情報との対比により得られた対比情報を出力する情報出力部と、を備える情報提供装置。
[2]前記標準デバイスの複数の前記ウェルには、同一のコピー数又は複数種のコピー数の核酸が配される、[1]に記載の情報提供装置。
[3]前記標準デバイスの複数の前記ウェルのうち少なくとも一部のウェルには、低コピー数の核酸が配される、[1]又は[2]に記載の情報提供装置。
[4]前記標準デバイスの複数の前記ウェルのうち少なくとも一部のウェルには、前記検査装置に求められる検出感度に対応したコピー数よりも少ないコピー数の核酸が配される、[1]から[3]のいずれか一項に記載の情報提供装置。
[5]前記対比情報は、前記評価対象データが得られた前記検査装置が正常であるか否の情報と、前記評価対象データが得られた前記検査装置において正常な又は異常なCq値が得られた前記ウェルの情報との一方又は両方を含む、[1]から[4]のいずれか一項に記載の情報提供装置。
[6]前記情報出力部は、前記評価対象データから得られる情報と、前記評価対象データとは異なる1以上の前記検査結果データから得られる情報との一方又は両方をさらに出力する、[1]から[5]のいずれか一項に記載の情報提供装置。
[7]前記情報出力部が対比に用いる前記評価対象データから得られる前記情報と1以上の前記評価対象データとは異なる前記検査結果データから得られる前記情報とは、Cq値の分布と、Cq値の平均と、前記核酸を検出可能なコピー数と、Cq値を測定可能なコピー数と、検量線の傾きと、検量線の切片とのうち一以上の情報である、[1]から[6]のいずれか一項に記載の情報提供装置。
[8]前記検査結果データ毎に、当該検査結果データに基づいて前記ウェルの異常を判定する判定部をさらに有し、前記情報出力部は、異常と判定された前記ウェルのCq値を除いた前記評価対象データから得られる情報と、前記評価対象データとは異なり、かつ、異常と判定された前記ウェルのCq値を除いた1以上の前記検査結果データから得られる情報との対比により得られた対比情報を出力する、[1]から[7]のいずれか一項に記載の情報提供装置。
[9]前記情報出力部は、前記評価対象データから得られる情報と、前記評価対象データとはPCR検査が行われた時刻とPCR検査が行われた検査装置との一方又は両方が異なる1以上の前記検査結果データから得られる情報との対比により得られた対比情報を提供する、[1]から[8]のいずれか一項に記載の情報提供装置。
[10]前記評価対象データには、前記検査装置の識別と、前記検査装置の所有者と、前記検査装置の設置場所と、前記検査装置の機種と、PCR検査を行った作業者と、PCR検査に使用した試薬と、PCRを検査が行われた日時と、前記標準デバイスの識別と、前記標準デバイスの種類とのうち一以上を示す属性情報が付加され、前記情報出力部は、前記評価対象データから得られた情報と、所定の前記属性情報が付加され、かつ、前記評価対象データとは異なる1以上の前記検査結果データから得られる情報との対比により得られた対比情報を提供する、[1]から[9]のいずれか一項に記載の情報提供装置。
[11]前記標準デバイスの前記ウェルそれぞれには、所定量のプライマーと、所定量の増幅試薬と、所定量の蛍光プローブとのうち一以上が配される、[1]から[10]のいずれか一項に記載の情報提供装置。
[12]前記核酸は、自然界に存在しない、[1]から[11]のいずれか一項に記載の情報提供装置。
[13]既知のコピー数の核酸を配したウェルを有する標準デバイスに対して検査装置がPCR(polymerase chain reaction)検査を行って得られた前記ウェルのCq値を示す検査結果データを受信する受信部と、前記受信部が受信した前記検査結果データを記憶する記憶部と、評価対象の前記検査結果データである評価対象データから得られる情報と、前記評価対象データとは異なる1以上の前記検査結果データから得られる情報との対比により得られた対比情報を出力する情報出力部と、を備える情報提供システム。
[14]情報提供装置が実行する情報提供方法であって、既知のコピー数の核酸を配したウェルを有する標準デバイスに対して検査装置がPCR(polymerase chain reaction)検査を行って得られた前記ウェルのCq値を示す検査結果データを取得する取得ステップと、評価対象の前記検査結果データである評価対象データから得られる情報と、前記評価対象データとは異なる1以上の前記検査結果データから得られる情報との対比により得られた対比情報を出力する情報出力ステップと、を有する情報提供方法。
[15]情報提供システムが実行する情報提供方法であって、既知のコピー数の核酸を配したウェルを有する標準デバイスに対して検査装置がPCR(polymerase chain reaction)検査を行って得られた前記ウェルのCq値を示す検査結果データを受信する受信ステップと、前記受信ステップにおいて受信した前記検査結果データを記憶部に書き込む書き込みステップと、評価対象の前記検査結果データである評価対象データから得られる情報と、前記評価対象データとは異なる1以上の前記検査結果データから得られる情報との対比により得られた対比情報を出力する情報出力ステップと、を有する情報提供方法。
[16]コンピュータを、[1]から[12]のいずれか一項に記載の情報提供装置として機能させるためのプログラム。
2 情報提供装置
3 端末装置
4 検査装置
5 標準プレート
9 ネットワーク
21 通信部
22 記憶部
23 入力部
24 表示部
25 処理部
26 取得部
27 分析部
28 情報出力部
51 基材
52 ウェル
54 鋳型核酸
55 密閉部材
56 識別手段
71 プロセッサ
72 主記憶装置
73 補助記憶装置
74 出力装置
75 入力装置
76 通信インターフェイス
77 バス
271 第一判定部
272 読出部
273 分析情報取得部
274 第二判定部
275 対比部
Claims (16)
- 既知のコピー数の核酸を配したウェルを有する標準デバイスに対して検査装置がPCR(polymerase chain reaction)検査を行って得られた前記ウェルのCq値を示す検査結果データを取得する取得部と、
評価対象の前記検査結果データである評価対象データから得られる情報と、前記評価対象データとは異なる1以上の前記検査結果データから得られる情報との対比により得られた対比情報を出力する情報出力部と、
を備える情報提供装置。 - 前記標準デバイスの複数の前記ウェルには、同一のコピー数又は複数種のコピー数の核酸が配される、
請求項1に記載の情報提供装置。 - 前記標準デバイスの複数の前記ウェルのうち少なくとも一部のウェルには、低コピー数の核酸が配される、
請求項1又は請求項2に記載の情報提供装置。 - 前記標準デバイスの複数の前記ウェルのうち少なくとも一部のウェルには、前記検査装置に求められる検出感度に対応したコピー数よりも少ないコピー数の核酸が配される、
請求項1から請求項3のいずれか一項に記載の情報提供装置。 - 前記対比情報は、前記評価対象データが得られた前記検査装置が正常であるか否の情報と、前記評価対象データが得られた前記検査装置において正常な又は異常なCq値が得られた前記ウェルの情報との一方又は両方を含む、
請求項1から請求項4のいずれか一項に記載の情報提供装置。 - 前記情報出力部は、前記評価対象データから得られる情報と、前記評価対象データとは異なる1以上の前記検査結果データから得られる情報との一方又は両方をさらに出力する、
請求項1から請求項5のいずれか一項に記載の情報提供装置。 - 前記情報出力部が対比に用いる前記評価対象データから得られる前記情報と1以上の前記評価対象データとは異なる前記検査結果データから得られる前記情報とは、Cq値の分布と、Cq値の平均と、前記核酸を検出可能なコピー数と、Cq値を測定可能なコピー数と、検量線の傾きと、検量線の切片とのうち一以上の情報である、
請求項1から請求項6のいずれか一項に記載の情報提供装置。 - 前記検査結果データ毎に、当該検査結果データに基づいて前記ウェルの異常を判定する判定部をさらに有し、
前記情報出力部は、異常と判定された前記ウェルのCq値を除いた前記評価対象データから得られる情報と、前記評価対象データとは異なり、かつ、異常と判定された前記ウェルのCq値を除いた1以上の前記検査結果データから得られる情報との対比により得られた対比情報を出力する、
請求項1から請求項7のいずれか一項に記載の情報提供装置。 - 前記情報出力部は、前記評価対象データから得られる情報と、前記評価対象データとはPCR検査が行われた時刻とPCR検査が行われた検査装置との一方又は両方が異なる1以上の前記検査結果データから得られる情報との対比により得られた対比情報を提供する、
請求項1から請求項8のいずれか一項に記載の情報提供装置。 - 前記評価対象データには、前記検査装置の識別と、前記検査装置の所有者と、前記検査装置の設置場所と、前記検査装置の機種と、PCR検査を行った作業者と、PCR検査に使用した試薬と、PCRを検査が行われた日時と、前記標準デバイスの識別と、前記標準デバイスの種類とのうち一以上を示す属性情報が付加され、
前記情報出力部は、前記評価対象データから得られた情報と、所定の前記属性情報が付加され、かつ、前記評価対象データとは異なる1以上の前記検査結果データから得られる情報との対比により得られた対比情報を提供する、
請求項1から請求項9のいずれか一項に記載の情報提供装置。 - 前記標準デバイスの前記ウェルそれぞれには、所定量のプライマーと、所定量の増幅試薬と、所定量の蛍光プローブとのうち一以上が配される、
請求項1から請求項10のいずれか一項に記載の情報提供装置。 - 前記核酸は、自然界に存在しない、
請求項1から請求項11のいずれか一項に記載の情報提供装置。 - 既知のコピー数の核酸を配したウェルを有する標準デバイスに対して検査装置がPCR(polymerase chain reaction)検査を行って得られた前記ウェルのCq値を示す検査結果データを受信する受信部と、
前記受信部が受信した前記検査結果データを記憶する記憶部と、
評価対象の前記検査結果データである評価対象データから得られる情報と、前記評価対象データとは異なる1以上の前記検査結果データから得られる情報との対比により得られた対比情報を出力する情報出力部と、
を備える情報提供システム。 - 情報提供装置が実行する情報提供方法であって、
既知のコピー数の核酸を配したウェルを有する標準デバイスに対して検査装置がPCR(polymerase chain reaction)検査を行って得られた前記ウェルのCq値を示す検査結果データを取得する取得ステップと、
評価対象の前記検査結果データである評価対象データから得られる情報と、前記評価対象データとは異なる1以上の前記検査結果データから得られる情報との対比により得られた対比情報を出力する情報出力ステップと、
を有する情報提供方法。 - 情報提供システムが実行する情報提供方法であって、
既知のコピー数の核酸を配したウェルを有する標準デバイスに対して検査装置がPCR(polymerase chain reaction)検査を行って得られた前記ウェルのCq値を示す検査結果データを受信する受信ステップと、
前記受信ステップにおいて受信した前記検査結果データを記憶部に書き込む書き込みステップと、
評価対象の前記検査結果データである評価対象データから得られる情報と、前記評価対象データとは異なる1以上の前記検査結果データから得られる情報との対比により得られた対比情報を出力する情報出力ステップと、
を有する情報提供方法。 - コンピュータを、
請求項1から請求項12のいずれか一項に記載の情報提供装置として機能させるためのプログラム。
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