Patent Application
20200350035
The present invention relates to a gene analysis method performed by a computer in order to analyze mutations of genes, a gene analysis apparatus, a management server, a gene analysis system, a program, and a storage medium.
Associated with the development of genetic test technologies in recent years, there is increasing expectancy for individualized medical care in which gene sequences of a subject are analyzed to appropriately select therapies and drugs suitable for characteristics of the subject. As gene sequence analysis, for example, a panel test is known in which abnormalities in specific genes related to specific diseases or abnormalities in exon regions to be translated into proteins are analyzed at a high-throughput by use of a next-generation sequencer.
Japanese Translation of PCT International Application Publication No. 2015-200678 describes a system in which whether a gene or the like has an abnormality when compared with a reference sequence is determined; a drug therapy to be used in accordance with the gene or the like having an abnormality is identified; and a therapeutic strategy is determined in accordance with the subject.
In a genetic test, each gene to be analyzed requires a different analysis. For example, in a panel test using a next-generation sequencer, fragmented genes are simultaneously read in a parallel manner, and read sequence information which is the base sequence of each read fragment is mapped on a reference sequence, whereby base sequence analysis is performed. Here, when genes to be analyzed are different for each gene panel, a different analysis program is sometimes required for each gene panel that is used to perform measurement. Therefore, when a panel test is performed, a different analysis program needs to be selectively used for each gene panel, which is inconvenient.
In addition, in a genetic test, when the entire exon region is analyzed, many mutations are detected in genes of a subject. Here, mutations include those of which the clinical significance has not been confirmed or for which therapeutically effective drugs have not been established. Thus, such mutations provide information other than information that can be utilized by doctors for actual therapies. Doctors trying to apply the result of a genetic test to an actual therapy for a subject desire to selectively know mutations that can be utilized in the actual therapy among the many detected mutations.
In such circumstances, a user who is going to perform a panel test needs to prepare, for each panel, a dedicated analysis program to be used in gene analysis performed by a sequencer, in accordance with genes to be tested and a desire, before performing the gene analysis.
An object of an aspect of the present invention is to realize, for analyzing analysis target genes by use of a gene panel, a gene analysis method, a gene analysis apparatus, a management server, a gene analysis system, and the like that are highly convenient for a user and that can be applied to various gene panels.
In order to solve the above problem, a gene analysis method according to an aspect of the present invention is for analyzing gene sequence information, and includes obtaining read sequence information read by a sequencer (2) and gene panel information related to a gene panel including a plurality of genes to be analyzed; and outputting an analysis result of the read sequence information on the basis of the obtained gene panel information.
According to this aspect, an analysis result of read sequence information is outputted on the basis of the obtained gene panel information. Due to this aspect, for example, when analysis target genes in various combinations are analyzed by use of various gene panels, a user who performs a panel test can obtain an output according to the gene panel. Thus, convenience for the user is improved.
“Gene” includes a sequence on a genome from a start codon to a stop codon, mRNA generated from a sequence on the genome, a promoter region on the genome, and the like. The gene to be analyzed includes mRNA transcribed from a gene on the genome. mRNA includes pre-mRNA.
“Read sequence” means a polynucleotide sequence obtained through sequencing. “Read sequence information” means information of a read sequence outputted from the sequencer 2.
“Gene panel” means a reagent kit for analyzing a plurality of analysis targets by performing a series of analysis processes once (one run). In many cases, the gene panel includes a set of reagents such as a primer and a probe. Here, a “plurality of analysis targets” may be a plurality of gene sequences or may be a plurality of exons of a certain gene. For example, a reagent kit for analyzing the sequence of gene A and the sequence of gene B, a reagent kit for analyzing the sequence of exon 1 of gene A and the sequence of exon 2 of gene A, and the like are included. A more specific example of the gene panel includes a reagent kit for analyzing a plurality of gene sequences related to a specific disease. When this gene panel is used, it is possible to analyze amplification of one or a plurality of genes, substitution, deletion, and insertion of a sequence, methylation of a promoter region, a fused gene, and the like that are important for treatment. The gene panel includes a plurality of genes as analysis targets. As the gene panel, a large panel with which 100 or more genes can be analyzed is useable, for example.
“Gene panel information” may be any information that can be used for specifying a gene panel, and may be, for example, the gene panel name, the name of a gene to be analyzed in the panel test, or the like.
The gene analysis method may include selecting, on the basis of the obtained gene panel information, a gene for which the analysis result is to be outputted.
According to this aspect, an analysis result with respect to an analysis target gene of the gene panel can be outputted.
The gene analysis method may include selecting, on the basis of the obtained gene panel information, an analysis algorithm for analyzing a gene for which the analysis result is to be outputted.
According to this aspect, when target genes of the gene panel is analyzed, it is not necessary to set, for each gene, an analysis program to be used in the analysis.
The gene analysis method may include displaying, on a display unit (16), an input screen for allowing information associated with a plurality of genes to be inputted as the gene panel information.
The gene analysis method may include displaying, on a display unit (16), an input screen for allowing at least one piece of information to be selected from a plurality of pieces of the gene panel information.
The gene analysis method may include displaying, on a display unit (16), an input screen for allowing a reagent kit name to be inputted as the gene panel information.
The gene analysis method may include displaying, on a display unit (16), an input screen for allowing a plurality of genes to be analyzed, to be inputted as the gene panel information.
The gene analysis method may include displaying, on a display unit (16), an input screen for allowing a disease to be analyzed, to be inputted as the gene panel information.
The gene analysis method may include selecting, on the basis of the obtained gene panel information, reference sequence information with which the read sequence information should be compared; and outputting the analysis result based on comparison between the read sequence information and the selected reference sequence information.
“Reference sequence” is a sequence with respect to which a read sequence is mapped in order to determine which region on the gene the read sequence corresponds to, which mutation on the gene the read sequence corresponds to, and the like. “Mapping” means a process of aligning each read sequence to a corresponding reference sequence. Specifically, the mapping is performed to find, in the genome sequence that is referred to, a region that has a sequence identical or similar to the read sequence having been read, and to cause the read sequence to belong to the region.
The gene analysis method may include on the basis of the obtained gene panel information, selecting, from a plurality of pieces of reference sequence information each including a mutation sequence, reference sequence information with which the read sequence information should be compared; and outputting the analysis result based on the selected reference sequence information.
“Mutation” means at least one of polymorphism, substitution, Indel, and the like of a gene. “Indel (Insertion and/or Deletion)” means a mutation that includes insertion, deletion, or both of insertion and deletion. “Polymorphism” of a gene includes SNV (single nucleotide variant, single nucleotide polymorphism), VNTR (variable nucleotide of tandem repeat, repeat sequence polymorphism), STRP (short tandem repeat polymorphism, microsatellite polymorphism), and the like.
The gene analysis method may include outputting the analysis result of the read sequence information, using a gene-panel-related information database (121) which stores, for each gene panel, information related to an analysis target gene of the gene panel.
The gene analysis method may include reading a selected reference sequence from a reference sequence database (122), and mapping the read sequence information with respect to the read reference sequence, to perform alignment.
The gene analysis method may include reading a selected reference sequence from a reference sequence database, determining a position of the read sequence information on the basis of a degree of matching between the reference sequence and the read sequence information, and identifying a mutation included in the read sequence information.
The gene analysis method may include outputting an analysis result that includes information related to a mutation associated with the obtained gene panel information, among mutations identified through analysis of the read sequence information.
The gene analysis method may include, on the basis of the obtained gene panel information, outputting drug information related to a mutation identified through analysis of the read sequence information, as the analysis result of the read sequence information.
The gene analysis method may include, on the basis of a mutation identified through analysis of the read sequence information, searching a drug database (124) which stores a mutation of an analysis target gene and a drug related to the gene panel in association with each other.
The gene analysis method may include generating a list of a drug related to the mutation identified through the analysis of the read sequence information and extracted through the search of the drug database (124).
The gene analysis method may include outputting, as the analysis result of the read sequence information, drug information including an approval state of a drug.
The gene analysis method may include, on the basis of a mutation identified through analysis of the read sequence information, searching a reference database (125) which stores a mutation of an analysis target gene and reference information related to the mutation in association with each other.
The gene analysis method may include creating a report on the basis of the analysis result of the read sequence information. The report may include information related to a mutation that corresponds to the obtained information related to the gene panel among mutations identified through analysis of the read sequence information.
The gene analysis method may include selecting, on the basis of the gene panel information, a mutation that corresponds to the obtained gene panel information from all identified mutations, and outputting information related to the selected mutation, as the analysis result of the read sequence information.
The report may include information related to the gene panel.
The report may include at least one of a list of a drug and reference information.
The gene analysis method may include transmitting, to a management server (3), information related to an analysis state of the gene sequence information.
The gene analysis method may include transmitting, for each piece of the gene panel information to a management server (3), information related to an analysis state of the gene sequence information.
The gene analysis method may include transmitting, for each piece of the gene panel information to a management server (3), the number of times of sequence analysis of the genes.
The gene analysis method may include transmitting, for each piece of the gene panel information to a management server (3), the number of the genes having being analyzed.
The gene analysis method may include transmitting, for each piece of the gene panel information to a management server (3), information related to an amount of data having been processed in sequence analysis of the genes.
The gene analysis method may include outputting, as the analysis result of the read sequence information, a comparison result obtained by comparing the read sequence information with sequence information of an analysis target gene of the gene panel associated with the obtained gene panel information.
The gene analysis method may include displaying an error when the obtained gene panel information does not match gene panel information that has been registered.
For example, when the obtained gene panel information does not match gene panel information that has been registered in the gene-panel-related information database (121) or the like, if analysis is performed using the gene panel, an inappropriate analysis result may be obtained. According to this aspect, it is possible to prevent outputting an inappropriate result caused by use of an unregistered gene panel, and to prevent performing unnecessary analysis.
The gene analysis method may include displaying an error when the obtained gene panel information does not match gene panel information that has been designated by a medical institution (210).
The gene analysis method may include when an input that asks permission of use of a gene panel inputted by a user is made after the error has been displayed, permitting analysis that uses the gene panel.
The gene analysis method may include when the obtained gene panel information does not match gene panel information that has been registered, prohibiting analysis that uses the gene panel.
The gene analysis method may include when the obtained gene panel information does not match gene panel information that has been designated by a medical institution (210), prohibiting analysis that uses the gene panel.
The obtaining of the gene panel information may have a plurality of modes, and one of the plurality of modes may be selectable.
The gene analysis method may include displaying an error when pieces of the read sequence information include not less than a predetermined number of pieces of the read sequence information that include sequences of genes that are not analysis target genes of the gene panel indicated by the obtained gene panel information.
The read sequence information may include an index sequence associated with the gene panel information.
The index sequence may be different for each piece of gene panel information.
The gene analysis method may include displaying an error when gene panel information associated with the index sequence included in the read sequence information is different from the obtained gene panel information.
The gene analysis method may include analyzing, with respect to a first sample, first read sequence information read by use of a first gene panel for analyzing a first analysis target gene group; analyzing, with respect to a second sample, second read sequence information read by use of a second gene panel for analyzing a second analysis target gene group; receiving selection of information that specifies the gene panel, to obtain gene panel information; and outputting, on the basis of the selected gene panel information, an analysis result obtained by analyzing the first read sequence information and an analysis result obtained by analyzing the second read sequence information.
Here, a “sample” can be also referred to as a specimen, and is used synonymously with a preparation in this technical field. A “sample” is intended to mean any preparation obtained from a biological material (for example, individual, body fluid, cell strain, cultured tissue, or tissue section) as a supply source.
The gene analysis method may further include evaluating a quality of a gene panel test, and the outputting of the analysis result may include outputting an evaluation result of the quality on the basis of the obtained gene panel information.
According to this aspect, when analysis target genes in various combinations are analyzed by use of various gene panels, appropriate quality control according to the gene panel can be performed.
“Quality evaluation index” is an index for evaluating the quality of a gene panel test. Examples of the quality evaluation index include indexes such as the reading quality included in read sequence information outputted by the sequencer (2); the proportion of bases read by the sequencer (2), to bases included in a plurality of genes as analysis targets; the depth of reading of read sequence information; the variation of the depth of reading of read sequence information; and whether or not all of mutations of each standard gene included in a quality control sample have been detected.
The evaluating of the quality of the gene panel test may include selecting, on the basis of the obtained gene panel information, a quality control index to be used when evaluating the quality.
The evaluating of the quality of the gene panel test may include selecting, on the basis of the obtained gene panel information, an evaluation criterion for a quality control index to be used when evaluating the quality.
The evaluating of the quality of the gene panel test may include selecting, on the obtained gene panel information, the number of quality control indexes to be used when evaluating the quality.
In order to solve the above problem, a gene analysis apparatus (1) according to an aspect of the present invention is a gene analysis apparatus (1) configured to analyze gene sequence information, and includes a controller (11) configured to obtain read sequence information read by a sequencer (2) and gene panel information related to a gene panel including a plurality of genes to be analyzed; and an output unit (13). The controller (11) outputs, to the output unit (13), an analysis result of the read sequence information on the basis of the obtained gene panel information.
According to this aspect, the gene analysis apparatus (1) outputs an analysis result of the read sequence information on the basis of the obtained gene panel information. Due to this aspect, when genes are analyzed by use of various gene panels, a user who performs a panel test can obtain an output according to the gene panel that is used. Thus, convenience for the user is improved.
The controller (11) may select, on the basis of the obtained gene panel information, reference sequence information with which the read sequence information should be compared, and may output, to the output unit (13), the analysis result based on comparison between the read sequence information and the selected reference sequence information.
The controller (11) may output, to the output unit (13), an analysis result that includes information related to a mutation associated with the obtained gene panel information, among mutations identified through analysis of the read sequence information.
On the basis of the obtained gene panel information, the controller (11) may output, to the output unit (13), drug information related to a mutation identified through analysis of the read sequence information, as the analysis result of the read sequence information.
On the basis of the obtained gene panel information, the controller (11) may output an evaluation result of a quality of a gene panel test, to the output unit (13).
In order to solve the above problem, a management server (3) according to an aspect of the present invention is configured to receive, from a gene analysis apparatus (1), information that includes information for specifying a user who performs analysis of a sequence of a gene, gene panel information related to a gene panel having been used, and information related to an analysis state of sequence information.
The “information related to an analysis state of sequence information” may be the number of times of sequence analysis an analysis using a predetermined gene panel has been performed in the gene analysis apparatus 1, may be the number of genes that have been analyzed, or may be the accumulated total of the number or the like of mutations that have been identified. Alternatively, the “information related to an analysis state of sequence information” may be information related to the amount of data that has been processed in the analysis.
The management server (3) may receive, from the gene analysis apparatus (1), information related to an analysis state of sequence information of the gene.
For each piece of the gene panel information, the management server (3) may receive, from the gene analysis apparatus (1), information related to an analysis state of sequence information of the gene.
For each piece of the gene panel information, the management server (3) may receive, from the gene analysis apparatus (1), the number of times of the analysis of the sequence of the gene.
For each piece of the gene panel information, the management server (3) may receive, from the gene analysis apparatus (1), the number of the genes having been analyzed.
For each piece of the gene panel information, the management server (3) may receive, from the gene analysis apparatus (1), information related to an amount of data having been processed in the analysis of the sequence of the gene.
On the basis of information related to an analysis state of sequence information of the gene, the management server (3) may calculate a consideration for a case where the user has performed analysis of a sequence using the gene analysis apparatus (1).
The management server (3) may receive, from the gene analysis apparatus (1), an update request for the gene panel information.
In order to solve the above problem, a gene analysis system (100) according to an aspect of the present invention includes a gene analysis apparatus (1) and a management server (3). The gene analysis apparatus (1) includes a controller (11) configured to obtain read sequence information read by a sequencer (2) and gene panel information related to a gene panel including a plurality of genes to be analyzed; and an output unit (13) configured to output an analysis result of the read sequence information based on the gene panel information obtained by the controller (11). The management server (3) is configured to receive, from the gene analysis apparatus (1) via a network (4), information that includes information for specifying a user who performs analysis of a sequence of a gene, gene panel information related to a gene panel having been used, and information related to an analysis state of the sequence of the gene.
According to this aspect, the gene analysis apparatus (1) outputs an analysis result of the read sequence information on the basis of the obtained gene panel information. Meanwhile, the management server (3) receives, from the gene analysis apparatus (1), information that includes information for specifying a user who performs analysis of a sequence of a gene, gene panel information related to a gene panel having been used, and information related to an analysis state of the sequence of the gene.
According to this aspect, for example, when genes in various combinations are analyzed by use of various gene panels, a user who performs a panel test can obtain an output according to the gene panel that is used. Thus, convenience is improved. Further, the management server (3) can confirm/manage the record of analysis performed by the user using the gene analysis apparatus (1). Therefore, for example, a consideration such as usage fee for the gene analysis system (100) can be appropriately determined, and can be charged on the user.
A consideration for a case where the user has performed analysis of a sequence using the gene analysis apparatus may be calculated on the basis of information related to an analysis state of sequence information of the gene.
The gene analysis apparatus (1) according to each aspect of the present invention may be realized by a computer. In this case, a program that realizes the gene analysis apparatus (1) in the form of a computer by causing the computer to operate as units (software elements) of the gene analysis apparatus (1), and a computer readable storage medium having stored therein the program, are also included in the scope of the present invention.
In order to solve the above problem, a program according to an aspect of the present invention is configured to analyze gene sequence information. The program causes a computer to execute obtaining read sequence information read by a sequencer and gene panel information related to a gene panel including a plurality of genes to be analyzed; and outputting an analysis result of the read sequence information on the basis of the obtained gene panel information.
According to this aspect, effects similar to those obtained by the gene analysis method according to one aspect of the present invention are exhibited.
A storage medium according to an aspect of the present invention is a computer readable storage medium having stored therein the program according to one aspect of the present invention.
A gene analysis method according to an aspect of the present invention is for analyzing gene sequence information. The gene analysis method includes obtaining read sequence information read by a sequencer (2) and gene panel information related to a gene panel including a plurality of genes to be analyzed; and outputting an analysis result of the read sequence information on the basis of the obtained gene panel information. When the obtained gene panel information does not match gene panel information that has been registered, an error is displayed.
A gene analysis method according to an aspect of the present invention is for analyzing gene sequence information. The gene analysis method includes obtaining read sequence information read by a sequencer (2) and gene panel information related to a gene panel including a plurality of genes to be analyzed; and outputting an analysis result of the read sequence information on the basis of the obtained gene panel information. When the obtained gene panel information does not match gene panel information that has been designated by a medical institution (210), an error is displayed.
According to the present invention, when analysis target genes in various combinations are measured by use of various gene panels, convenience for the user can be improved.
Hereinafter, an embodiment of the present invention is described in detail.
In a gene analysis method according to an embodiment of the present invention, gene panel information related to a gene panel is obtained, and on the basis of the obtained gene panel information, an analysis result of a read sequence having been read by a sequencer is outputted. Accordingly, when analysis target genes in various combinations are analyzed by use of various gene panels, appropriate analysis results according to the gene panels can be outputted without the need of selectively using an analysis program for each gene panel, and thus, convenience for the user is improved.
First, the outline of a gene analysis system 100 according to an embodiment of the present invention is described with reference to
The gene analysis system 100 shown in
The test institution 120 is an institution that tests/analyzes a sample provided from the medical institution 210, that creates a report based on an analysis result, and that provides the report to the medical institution 210. The test institution 120 is provided with, but not limited to, a sequencer 2, the gene analysis apparatus 1, and the like.
The analysis system management institution 130 is an institution that manages analyses in general performed in each test institution 120 that uses the gene analysis system 100. For example, the analysis system management institution 130 is a business entity that allows a gene analysis apparatus 1 to be installed in a test institution 120 and that provides gene analysis services that correspond to various gene panels. The analysis system management institution 130 performs management of the gene analysis system 100 such that information stored in databases of the gene analysis apparatus 1 is updated; and gene analysis is performed on the basis of the latest information. The analysis system management institution 130 may obtain the state of gene analysis in the gene analysis apparatus 1, and may obtain consideration from the test institution 120 in accordance with the performance of gene analysis.
The medical institution 210 is an institution in which doctors, nurses, pharmacists and the like perform medical activities such as providing diagnoses, therapies, and preparation of medicines to patients, and examples of the medical institution 210 include hospitals, clinics, pharmacies, and the like.
Next, the flow of a process performed in an application example of the gene analysis system 100 shown in
First, a test institution 120 that is going to use the gene analysis system 100 introduces the gene analysis apparatus 1. Then, the test institution 120 files an application for use of the gene analysis system 100 to the analysis system management institution 130 (step S101).
The test institution 120 and the analysis system management institution 130 can conclude in advance a desired contract with regard to use of the gene analysis system 100, out of a plurality of contract types. For example, service contents provided from the analysis system management institution 130 to the test institution 120, a method of determination of a system usage fee charged on the test institution 120 by the analysis system management institution 130, a method of payment of a system usage fee, and the like may be selected from a plurality of different contract types. The management server 3 of the analysis system management institution 130 specifies the content of the contract concluded with the test institution 120, in response to the application filed from the test institution 120 (step S102).
Next, the management server 3, which is managed by the analysis system management institution 130, provides a test institution ID to the gene analysis apparatus 1 of the test institution 120 that has concluded the contract, and starts providing various types of services (step S103).
The gene analysis apparatus 1 receives various types of services from the management server 3. Such various types of services include provision of programs and information for controlling analysis results of gene sequences that can be outputted from the gene analysis apparatus 1, and reports and the like based on the analysis results. Accordingly, the gene analysis apparatus 1 can output an analysis result, a report, and the like that match gene panel information having been inputted.
In the medical institution 210, a doctor or the like collects a sample such as blood and a tissue of a lesion site of a subject, as necessary. When analysis of the collected sample is requested to the test institution 120, an analysis request is transmitted from a communication terminal 5 provided in the medical institution 210, for example (step S105). When requesting analysis of samples to a test institution 120, the medical institution 210 transmits the analysis request and provides the test institution 120 with sample IDs provided to the respective samples. The sample ID provided to each sample associates the sample with information and the like of the subject from which the sample has been collected.
A “subject” herein denotes a human subject, or a subject that is not human such as a mammal, an invertebrate, a vertebrate, a fungus, a yeast, a bacterium, a virus, or a plant. The embodiments herein relate to a human subject, but the concept of the present invention can be applied to a genome derived from an organism such as any animal other than human or any plant, and is useful in fields such as medical care, veterinary medicine, and zoological science.
In the following, an example case in which the medical institution 210 requests a panel test analysis to the test institution 120 is described. The panel test is not limited to a laboratory test, but also includes tests for research use.
When a gene panel test is requested form the medical institution 210, a desired gene panel may be designated. Thus, gene panel information can be included in the analysis request transmitted from the medical institution 210 in step S105 shown in
The gene analysis apparatus 1 receives the analysis request from the medical institution 210 (S106). Further, the gene analysis apparatus 1 receives a sample from the medical institution 210, which is the transmit source of the analysis request.
There are a plurality of gene panels that can be used in analysis that the test institution 120 is requested to perform by the medical institution 210, and a gene group to be analyzed is fixed for each gene panel. The test institution 120 can selectively use a plurality of gene panels so as to suit the purpose of the analysis. That is, with respect to a first sample provided from the medical institution 210, a first gene panel can be used to analyze a first analysis target gene group, and with respect to a second sample, a second gene panel can be used to analyze a second analysis target gene group.
The gene analysis apparatus 1 receives, from a user, an input of gene panel information related to a gene panel that is to be used for analyzing the sample (step S107).
In the test institution 120, pretreatment of the received sample is performed, and sequencing using the sequencer 2 is performed (step S108).
Here, the pretreatment can include processes from fragmentation of genes such as DNA contained in the sample to collection of the fragmented genes. The sequencing includes a process of reading the sequence of one or a plurality of DNA fragments to be analyzed that have been collected in the pretreatment. Sequence information read in the sequencing performed by the sequencer 2 is outputted as read sequence information to the gene analysis apparatus 1.
Subsequently, the gene analysis apparatus 1 obtains the read sequence information from the sequencer 2, and performs gene sequence analysis (step S109).
The gene analysis apparatus 1 creates a report on the basis of the analysis result obtained in step S109 (step S110), and transmits the created report to the communication terminal 5 (step S111).
As described above, in the test institution 120, a sample is analyzed in response to the analysis request from the medical institution 210, and a report based on the analysis result is created. The medical institution 210 receives the report from the test institution 120 (step S112). The test institution 120 may charge the medical institution 210 for an analysis fee as a consideration for performing the analysis of the sample and providing the report based on the analysis result to the medical institution 210, which is the source of the analysis request.
The analysis system management institution 130 provides various types of information and services in accordance with the content of the contract with each test institution 120 as described above, and may charge the test institution 120 for a consideration such as a system usage fee.
The gene analysis apparatus 1 of the test institution 120 using the gene analysis system 100 notifies the management server 3 of the gene panel information related to the gene panel used in the analysis, information related to the analyzed genes, an analysis record, and the like (step S113). Specifically, the gene analysis apparatus 1 sends a test institution ID, a gene panel ID, gene IDs, an analysis record, and the like, to the management server 3.
The management server 3 stores the obtained test institution ID, gene panel ID, gene IDs, analysis record, and the like in association with one another (step S114).
The test institution ID is information that specifies a user who performs gene sequence analysis. The test institution ID may be a user ID, which is identification information provided to each user that uses the gene analysis apparatus 1.
The gene panel ID is identification information provided in order to specify a gene panel that is used in analysis of target genes. The gene panel ID provided to a gene panel is associated with the gene panel name, the name of the company that provides the gene panel, and the like.
The gene ID is identification information provided for each gene in order to specify an analysis target gene.
The analysis record is information related to the analysis state of gene sequence information. For example, the analysis record may be the number of times of sequence analysis an analysis using a predetermined gene panel has been performed in the gene analysis apparatus 1, may be the number of genes that have been analyzed, or may be the accumulated total of the number or the like of mutations that have been identified. Alternatively, the analysis record may be information related to the amount of data that has been processed in the analysis.
The management server 3 aggregates, for each test institution 120, the analysis records in a predetermined period (for example, any period such as day, week, month, or year), and determines a system usage fee according to the aggregation result and the contract type (step S115). The analysis system management institution 130 may charge the determined system usage fee on the test institution 120, and request payment of the system usage fee to the analysis system management institution 130.
The gene analysis system 100 is a system for analyzing gene sequence information, and includes the gene analysis apparatus 1 and the management server 3 at least. The gene analysis apparatus 1 is connected to the management server 3 via a network 4 such as an intranet and the internet.
The sequencer 2 is a base sequence analysis apparatus used for reading base sequences of genes contained in a sample.
Preferably, the sequencer 2 according to the present embodiment is a next-generation sequencer that performs sequencing using a next-generation sequencing technology, or a third-generation sequencer. The next-generation sequencer denotes one of base sequence analysis apparatuses which have been developed in recent years. The next-generation sequencer has a significantly improved analytical capability by performing, in a flow cell, parallel processing of a large amount of a single DNA molecule or a DNA template having been clonally amplified.
The sequencing technology usable in the present embodiment can be a sequencing technology that obtains a plurality of reads by reading the same region multiple times (deep sequencing).
Examples of the sequencing technology usable in the present embodiment include sequencing technologies that can obtain a large number of reads per run, on the basis of a sequencing principle other than that of the Sanger's method, such as ionic semiconductor sequencing, pyrosequencing, sequencing-by-synthesis using a reversible dye terminator, sequencing-by-ligation, and sequencing by use of probe ligation of oligonucleotide.
A sequence primer to be used in sequencing is not limited in particular, and is set as appropriate on the basis of a sequence that is suitable for amplifying the target region. Also, with respect to reagents to be used in sequencing, suitable reagents may be selected in accordance with the sequencing technology and the sequencer 2 to be used. The procedure from pretreatment to sequencing will be described later with reference to a specific example.
Next, data stored in the management server 3 is described with reference to
In data 3A shown in
For example, in a case where a test institution “Institution P” has concluded a contract of “Plan 1” with the analysis system management institution 130, the analysis system management institution 130 charges the test institution P for a usage fee that corresponds to the number of times of operation. “The number of times of operation” is the number of times a panel test has been performed by the gene analysis apparatus 1, for example.
Data 3C to 3E shown in
When the analysis system management institution 130 determines a system usage fee, the system usage fee may be varied depending on whether the gene panel that was used in the test is from a company that provides (for example, produces or sells) the gene panel. In this case, it is sufficient that data 3F shown in
An example case in which “Institution P” concluded a contract of “Plan 1” with the analysis system management institution 130 and the analysis records are those shown in
The storage unit 12 also has stored therein a program for sequence analysis, a program for generating a single reference sequence, and the like. The output unit 13 includes a display, a printer, a speaker, and the like. An input unit 17 includes a keyboard, a mouse, a touch sensor, and the like. Alternatively, an apparatus may be used that has both of the functions of an input unit and an output unit, such as a touch panel in which a touch sensor and a display are integrated. A communication unit 14 is an interface through which the controller 11 performs communication with an external apparatus.
The gene analysis apparatus 1 includes the controller 11 which comprehensively controls the units of the gene analysis apparatus 1; the storage unit 12 which has stored therein various types of data used by an analysis execution unit 110; the output unit 13; the communication unit 14; a display unit 16; and the input unit 17. The controller 11 includes the analysis execution unit 110 and a management unit 116. Further, the analysis execution unit 110 includes a sequence data reading unit 111, an information selection unit 112, a data adjustment unit 113, a mutation identification unit 114, and a report creation unit 115. A gene-panel-related information database 121, a reference sequence database 122, a mutation database 123, and an analysis record log 151 are stored in the storage unit 12.
Even when a different gene panel is used for each analysis, the gene analysis apparatus 1 creates a report including an analysis result that corresponds to the gene panel that has been used. Thus, the user who uses the gene analysis system 100 can analyze the result of a panel test by use of a common analysis program irrespective of the type of the gene panel, and create a report. This eliminates inconvenience such as when a panel test is performed, an analysis program to be used needs to be selected for each gene panel; and special setting needs to be made for the analysis program that is used for the gene panel. Thus, convenience for the user is improved.
When the user of the gene analysis apparatus 1 has inputted gene panel information through the input unit 17, the information selection unit 112 refers to the gene-panel-related information database 121, and controls the algorithms in the analysis program such that the analysis program performs analysis of the analysis target genes in accordance with the inputted gene panel information. That is, the gene analysis apparatus 1 selects an analysis algorithm in accordance with the inputted gene panel information.
Here, the gene panel information may be any information that specifies the gene panel used in the measurement performed by the sequencer 2. For example, the gene panel information is the gene panel name, the names of analysis target genes of the gene panel, the gene panel ID, and the like.
On the basis of the gene panel information inputted through the input unit 17, the information selection unit 112 selects an analysis algorithm for performing analysis so as to correspond to the analysis target genes of the gene panel indicated by the gene panel information. Specific examples of selecting an analysis algorithm in the present embodiment include: (1) a reference sequence; and (2) a region of the mutation database 123 to be referred to for identifying a mutation.
The information selection unit 112 outputs an instruction based on the gene panel information, to at least one of the data adjustment unit 113, the mutation identification unit 114, and the report creation unit 115. With this configuration, the gene analysis apparatus 1 can output an analysis result of the read sequence information on the basis of the inputted gene panel information.
That is, the information selection unit 112 is a function block that performs control so as to obtain gene panel information related to a gene panel including a plurality of genes to be analyzed, and cause the output unit 13 to output an analysis result of the read sequence information on the basis of the obtained gene panel information.
In a case where genes contained in various samples are analyzed by the user who performs a panel test, various gene panels are used in accordance with the analysis target gene group for each sample.
That is, the gene analysis apparatus 1 can obtain first read sequence information read by use of a first gene panel for analyzing a first analysis target gene group from a first sample; and second read sequence information read by use of a second gene panel for analyzing a second analysis target gene group from a second sample.
Even when analysis target genes in various combinations have been analyzed by use of various gene panels, the gene analysis apparatus 1 can appropriately output analysis results obtained through analysis of read sequence information because the gene analysis apparatus 1 is provided with the information selection unit 112.
That is, if the user merely selects gene panel information, without setting an analysis program to be used in analysis of read sequence information and performing analysis for each analysis target gene, an analysis result of each piece of read sequence information can be appropriately outputted.
For example, when the information selection unit 112 outputs an instruction based on gene panel information to the data adjustment unit 113, the data adjustment unit 113 performs an alignment process and the like reflecting the gene panel information.
In accordance with the gene panel information, the information selection unit 112 issues an instruction so that the reference sequence (reference sequences in which wild type genome sequences and mutation sequences are incorporated) to be used by the data adjustment unit 113 when mapping the read sequence information is limited only to the reference sequence for genes that correspond to the gene panel information.
In this case, since the gene panel information is already reflected in the result of the process performed by the data adjustment unit 113, the information selection unit 112 need not output an instruction based on the gene panel information to the mutation identification unit 114 which subsequently performs a process following the process performed by the data adjustment unit 113.
For example, in a case where the information selection unit 112 outputs an instruction based on the gene panel information to the mutation identification unit 114, the mutation identification unit 114 performs a process reflecting the gene panel information.
For example, in accordance with the gene panel information, the information selection unit 112 issues an instruction so that the region of the mutation database 123 referred to by the mutation identification unit 114 is limited to only mutations related to the genes that correspond to the gene panel information. As a result, the gene panel information is reflected in the result of the process performed by the mutation identification unit 114.
gene panel cannot be used (step S205), and prohibits the analysis from being performed by the gene analysis apparatus 1.
In this case, instead of the message to the effect that the gene panel cannot be used, a message that indicates an error may be displayed. The message may be, for example, “The selected gene panel is not registered.” and may further include a message that Here, a process for receiving an input of gene panel information shown in step S107 in
Here, an example configuration is described in which the controller 11 causes the display unit 16 to display a GUI for inputting gene panel information, thereby allowing the user to input gene panel information.
In this case, the input unit 17 can be a device (for example, a mouse, a keyboard, etc.) that allows the user to perform an input operation on the presented GUI. In a case where a touch panel is overlaid on the display unit 16, the display unit 16 has a function of the input unit 17. That is, in a case where a touch panel is used as the display unit 16, the display unit 16 also serves as the input unit 17.
First, the controller 11 of the gene analysis apparatus 1 causes the display unit 16 to display a GUI for allowing the user to select gene panel information. On the basis of the input operation on the GUI by the user, the controller 11 obtains the gene panel information (step S201).
On the basis of the information selected by the user in the information displayed as the GUI, the information selection unit 112 searches the gene-panel-related information database 121 and reads gene panel information that corresponds to the selected information.
In addition, the gene analysis apparatus 1 reads gene panel information that is included in the analysis request received from the medical institution 210.
When a gene panel corresponding to the selected information is already registered in the gene-panel-related information database 121 (YES in step S202) and the gene panel matches the gene panel included in the analysis request received from the medical institution 210 (YES in step S203), the information selection unit 112 receives the input. Then, the information selection unit 112 causes the display unit 16 to display a message to the effect that the inputted gene panel can be used (step S204).
Meanwhile, when the gene panel corresponding to the selected information is not registered in the gene-panel-related information database 121, i.e., when an unregistered gene panel has been selected (NO in step S202), the information selection unit 112 causes the display unit 16 to display a message to the effect that the inputted urges re-input, such as “Please input gene panel information again”.
When the gene panel corresponding to the selected information does not match the gene panel included in the analysis request received from the medical institution 210 (NO in step S203), the information selection unit 112 causes the display unit 16 to display a message to the effect that the inputted gene panel cannot be used (step S205), and prohibits analysis from being performed by the gene analysis apparatus 1.
Also in this case, instead of the message to the effect that the gene panel cannot be used, a message that indicates an error may be displayed. The message may be, for example, “The selected gene panel is different from that in the order.” and may further include a message that urges re-input, such as “Please input gene panel information again”.
This process can prevent performing sequencing by use of an inappropriate gene panel and performing unnecessary analysis operation, and can eliminate wasteful use of gene panels and wasteful operation of the gene analysis system 100.
Next, some examples of an input screen for allowing the user to input gene panel information is described with reference to
As shown in
The list of gene panel names on the GUI is displayed on the basis of gene panel names of gene panels that are provided with gene panel IDs and that are already registered in the gene-panel-related information database 121.
In the GUI shown in
Next, data stored in the gene-panel-related information database 121 referred to by the information selection unit 112 when gene panel information has been inputted through the input unit 17 is described with reference to
In the gene-panel-related information database 121, as shown in data 121A in
In addition, in the gene-panel-related information database 121, as shown in data 121B in
As shown in
When analysis target genes have been selected out of the gene names presented on the GUI as shown in
In the gene-panel-related information database 121, as shown in data 121C in
When a gene panel related to a disease of interest has been selected from a list of the gene panel names for respective diseases presented on the GUI (i.e., a case as shown in
Here, update of information stored in the gene-panel-related information database 121 is described with reference to
Update of information stored in the gene-panel-related information database 121 can be performed by use of an update patch provided from the analysis system management institution 130 to the test institution 120. For example, in such a case where an analysis target gene of a gene panel has been changed, or where a new gene panel has been added, information stored in the gene-panel-related information database 121 is updated to the latest information.
Provision of the update patch from the analysis system management institution 130 may be targeted to test institutions 120 that have paid the system usage fee. For example, the analysis system management institution 130 may notify each test institution 120 that the condition for providing an update patch is existence of an update patch that can be provided and payment of the system usage fee. Such a notification can appropriately urge each test institution 120 to pay the system usage fee.
As shown in
When a “register” button is pressed after the file name has been inputted, a request for updating the information related to the genes that correspond to the gene names included in the file is associated with the test institution ID, and the request is transmitted to the management server 3 via the communication unit 14. The generation of the update request and the association of the update request with the test institution ID may be performed by the controller 11 shown in
The analysis system management institution 130 permits the gene analysis apparatus 1 to download information that includes the gene IDs provided to the gene names included in the update request received by the management server 3; and the gene panel ID provided to the gene panel that has the genes as the analysis target genes.
Alternatively, as shown in
When a “register” button is pressed after the gene name has been inputted, a request for updating the information related to the gene that corresponds to the gene name is associated with the test institution ID, and the request is transmitted to the management server 3 via the communication unit 14. The analysis system management institution 130 permits the gene analysis apparatus 1 to download information that includes the gene ID provided to the gene name included in the update request received by the management server 3; and the gene panel ID provided to the gene panel that has the gene as the analysis target gene.
The field for inputting a “registration file name” in
For example, information of input candidates to be displayed is provided in advance from the management server 3 to the gene analysis apparatus 1, and is stored in the storage unit 12. Then, when a click operation onto the GUI in the input field has been detected, all of the gene names that can be updated may be presented as input candidates to allow selection by the user therefrom, or a gene name that can be updated and that matches the character string inputted by the user may be presented as an input candidate. Alternatively, for example, at the time point when the user has inputted “E” in the field for inputting a “gene name” in
The gene-panel-related information database 121 may store each gene name, the gene ID of the gene, and the name of protein coded by the gene in association with one another.
In this case, even when the inputted character string is not a gene name but a protein coded by the gene, the information selection unit 112 can obtain a gene name and a gene ID that are associated with the inputted protein name, by referring to the gene-panel-related information database 121.
When a protein name has been inputted in the field for inputting a “gene name” and the register button has been pressed, a GUI may be displayed that shows a gene name associated with the protein name to allow the user to confirm that the gene name is the correct one.
The management unit 116 stores, in the analysis record log 151, as appropriate, an analysis record that includes the number of times of operation performed by the analysis execution unit 110, the number of analyzed genes, the total number of identified mutations, and the like, in association with the gene panel IDs and the gene IDs. At a desired frequency (for example, each day, each week, or each month), the management unit 116 reads data including the analysis record and the like from the analysis record log 151, and transmits the data in association with the test institution ID, to the management server via the communication unit 14.
The communication unit 14 allows the gene analysis apparatus 1 to communicate with the management server 3 via the network 4. Data transmitted from the communication unit 14 to the management server 3 can include the test institution ID, gene panel IDs, gene IDs, analysis records, update requests, and the like. Data received from the management server 3 can include gene panel information, gene names that can be updated, and the like.
Here, the procedure of sequencing shown in S108 in
The type of the sequencer 2 that can be used in the present embodiment is not limited in particular, and any sequencer that can analyze a plurality of analysis targets in one run can be suitably used. In the following, an example case in which a sequencer of Illumina, Inc. (San Diego, Calif.) (for example, MySeq, HiSeq, NextSeq, or the like), or an apparatus that employs a method similar to that of the sequencer of Illumina, Inc. is used.
Through a combination of a Bridge PCR method and a Sequencing-by-synthesis technique, the sequencer of Illumina, Inc. can perform sequencing, with a target DNA being amplified and synthesized to a huge number on a flow cell.
(a. Pretreatment)
First, as shown in
Next, as shown in
The adapter sequence is a sequence to be used for performing sequencing in a later step. In one embodiment, the adapter sequence in Bridge PCR can be a sequence that is hybridized with an oligo DNA immobilized on the flow cell.
In one aspect, as shown in the upper part of
In another aspect, as shown in the lower part of
The index sequence is a sequence for distinguishing data of each sample. The index sequence is unique to each sample, each gene panel, and each company that provides gene panels. For example, a base sequence used as the index sequence has, but not limited to a given length; and a sequence pattern such as 10 to 14 consecutive adenines, or 5 to 7 consecutive adenines followed by 5 to 7 consecutive guanines.
The index sequence can be used for identifying, on the basis of the sequence pattern and the length thereof, information related to the following with respect to the sequence of the DNA fragment having the index sequence added thereto, which sample is the source of the read sequence information, which gene panel was used, which company provides the gene panel having been used, and the like. A configuration for identifying information related to a panel by use of the index sequence will be described later in detail (see embodiment 4).
For example, the index sequence in an analysis using a gene panel A may have a sequence pattern of 14 consecutive adenines, and the index sequence in an analysis using a gene panel B may have a sequence pattern of 7 consecutive adenines followed by 7 consecutive guanines. Alternatively, the index sequence in an analysis using the gene panel A may have a sequence of 14 consecutive adenines (i.e., the length of the index sequence is 14), and the index sequence in an analysis using a gene panel C may have a sequence of 10 consecutive adenines (i.e., the length of the index sequence is 10).
The index sequence and the adapter sequences can be added to the DNA fragment by using a known technique in this technical field. For example, the DNA fragment may be blunted and ligated with the index sequence, and then, further ligated with the adapter sequence.
Next, as shown in
In a panel test using the sequencer 2 in the present embodiment, a large number of genes (for example, 100 or more) are analyzed. The reagent to be used in the panel test includes a set of RNA baits that respectively correspond to the large number of genes. When a different panel is used, the number and the types of genes to be tested are different. Thus, the set of RNA baits included in the reagent to be used in the panel test is also different.
Then, as shown in
Then, as shown in the lower part of
Further, as shown from the left part to the center part of
(b. Sequencing)
First, as shown in the right section of
That is, each DNA fragment to be analyzed (for example, Template DNA in
Then, as shown in
First, to the single-stranded DNA immobilized on the flow cell (the upper left part of
After the sequence primer is added, one base elongation is caused by the DNA polymerase, using dNTP labeled with fluorescence and having the 3′ end blocked. Since the dNTP having the 3′ end side blocked is used, the polymerase reaction stops when one base elongation has been realized. Then, the DNA polymerase is removed (the right middle part of
According to the technique described above, the length of the chain that can be analyzed reaches 150 bases×2, and analysis in a unit much smaller than the unit of a picotiter plate can be performed. Thus, due to the high density, a huge amount of sequence information of 40 to 200 Gb can be obtained in one analysis.
(c. Gene Panel)
The gene panel to be used for reading the read sequences by the sequencer 2 means an analysis kit for analyzing a plurality of analysis targets in one run as described above. In one embodiment, the gene panel can be an analysis kit for analyzing a plurality of gene sequences related to a specific disease.
When used herein, the term “kit” is intended to mean a package that includes containers (for example, bottles, plates, tubes, and dishes) each containing a specific material. Preferably, the kit includes instructions for using each material. When used in the context of a kit herein, “include (is included)” is intended to mean a state of being included in any of individual containers that form a kit. The kit can be a single package of a plurality of different compositions, and the forms of the compositions can be those described above. In the case of a solution form, the solution may be contained in a container. The kit may include a substance A and a substance B that are mixed in one container, or that are in separate containers. The “instructions” indicate the procedure of applying each component in the kit to a therapy and/or diagnosis. The “instructions” may be written or printed on paper or any other medium, or may be stored in a magnetic tape, or an electronic medium such as a computer readable disk or tape or a CD-ROM. The kit can include a container that contains a diluent, a solvent, a washing liquid, or another reagent. Further, the kit may also include an apparatus that is necessary for the kit to be applied to a therapy and/or diagnosis.
In one embodiment, the gene panel may be provided with one or more of reagents such as the reagent for fragmenting nucleic acid, the ligation reagent, the washing liquid, and the PCR reagent (dNTP, DNA polymerase, etc.); and magnetic beads, which have been described above. The gene panel may be provided with one or more of oligonucleotides for adding the adapter sequences to the fragmented DNA; oligonucleotides for adding the index sequence to the fragmented DNA; the RNA bait library; and the like.
In particular, the index sequence provided to each gene panel can be a sequence that is unique to the gene panel and that identifies the gene panel. The RNA bait library provided to each gene panel can be a library that is unique to the gene panel and that includes RNA baits that correspond to the test genes of the gene panel.
Next, the processes performed by the sequence data reading unit 111, the data adjustment unit 113, and the mutation identification unit 114 of the analysis execution unit 110 are described, while following the process flow shown in
First, in step S11 in
The read sequence information is data that indicates a base sequence read by the sequencer 2. The sequencer 2 performs sequencing on a large number of nucleic acid fragments obtained by use of a specific gene panel, reads sequence information thereof, and provides the sequence information as read sequence information, to the gene analysis apparatus 1.
In one aspect, the read sequence information may include the sequence having been read and a quality score of each base in the sequence. Both of read sequence information obtained by subjecting an FFPE sample from a lesion site of a subject to the sequencer 2, and read sequence information obtained by subjecting a blood sample of the subject to the sequencer 2 are inputted to the gene analysis apparatus 1.
Q=−10 log10E
In this equation, E represents an estimated value of the probability of incorrect base assignment. The greater the value of Q is, the lower the probability of the error is. The smaller the value of Q, the greater the portion of the read that cannot be used is. In addition, false-positive mutation assignment also increases, which could result in lowered accuracy of the result. “False-positive” means that the read sequence is determined as having a mutation although the read sequence does not have a true mutation as a determination target. “Positive” means that the read sequence has a true mutation as a determination target, and “negative” means that the read sequence does not have any mutation as a determination target.
Next, in step S12 in
The data adjustment unit 113 performs alignment for both of read sequence information obtained by subjecting an FFPE sample from a lesion site of a subject to the sequencer 2, and read sequence information obtained by subjecting a blood sample of the subject to the sequencer 2.
The reference sequence information is information indicating the reference sequence name (reference sequence ID), the sequence length of the reference sequence, and the like in the reference sequence database 122. Preferably, the reference sequence information can identify the reference sequence, and includes the reference sequence name and the reference sequence ID, for example. The read sequence name is information indicating the name (read sequence ID) of each read sequence for which the alignment has been performed.
The position information is information indicating the position (leftmost mapping position) on the reference sequence at which the leftmost base of the read sequence has been mapped. The map quality is information indicating the quality of mapping that corresponds to the read sequence. The sequence is information indicating the base sequence (example: GTAAGGCACGTCATA . . . ) that corresponds to each read sequence.
Further, each reference sequence in the reference sequence database 122 is provided with metadata that indicates gene panel information. For example, the gene panel information provided to each reference sequence can be information that directly or indirectly indicates an analysis target gene that corresponds to the reference sequence.
In one embodiment, the information selection unit 112 may perform control such that, when the data adjustment unit 113 obtains a reference sequence from the reference sequence database 122, the data adjustment unit 113 refers to the inputted gene panel information and the metadata of each reference sequence, and selects a reference sequence that corresponds to the gene panel information. For example, in one aspect, the information selection unit 112 may control the data adjustment unit 113 so as to select a reference sequence that corresponds to an analysis target gene that is specified by the inputted gene panel information. This allows the data adjustment unit 113 to perform mapping only on the reference sequence related to the gene panel having been used, and thus, efficiency of the analysis can be improved.
In another embodiment, the information selection unit 112 may not necessarily perform the above-described control. In this case, the information selection unit 112 only needs to control the mutation identification unit 114 or the report creation unit 115 as described later.
The known mutations are mutations registered in external databases (for example, COSMIC, ClinVar, etc.), and the chromosome position, the gene name, and the mutation have been identified as shown in
In the example shown in
In step S401 in
In one aspect, the data adjustment unit 113 calculates a score that indicates the degree of matching between the read sequence and the reference sequence. The score indicating the degree of matching can be, for example, a percentage identity between two sequences.
For example, the data adjustment unit 113 specifies the positions at which bases of the read sequence and bases of the reference sequence are the same, obtains the number of the matched positions, and divides the number of the matched positions by the number (the number of bases in the comparison window) of bases of the read sequence compared with the reference sequence, thereby calculating the percentage.
In the calculation of the score indicating the degree of matching between a read sequence and a reference sequence, the data adjustment unit 113 may perform calculation such that, when the read sequence includes a predetermined mutation (for example, Indel: Insertion/Deletion) with respect to the reference sequence, a score lower than that calculated in the normal calculation is obtained.
In one aspect, for a read sequence that includes at least one of insertion and deletion with respect to a reference sequence, the data adjustment unit 113 may correct the score by, for example, multiplying the score calculated in the above-described normal calculation, by a weighting factor according to the number of bases corresponding to the insertion/deletion. The weighting factor W may be calculated as, for example, W={1−(1/100)×(the number of bases corresponding to insertion/deletion)}.
The score of the degree of matching between a read sequence R4 and the reference sequence is 81% in the normal calculation because 17 bases out of 21 bases of the read sequence match the bases of the reference sequence. The corrected score is 77.8%=81%×0.96.
The data adjustment unit 113 calculates the score of the degree of matching while changing the mapping position of the read sequence with respect to each reference sequence, thereby specifying a position on the reference sequence at which the degree of matching with the read sequence satisfies a predetermined criterion. At this time, an algorithm known in this technical field, such as dynamic programming, the FASTA method, and the BLAST method, may be used.
With reference back to
When all the read sequences included in the read sequence information obtained by the sequence data reading unit 111 have not been aligned (NO in step S405), the data adjustment unit 113 returns to step S401. When all the read sequences included in the read sequence information have been aligned (YES in step S405), the data adjustment unit 113 completes the process of step S12.
The data adjustment unit 113 may output, as an analysis result of the read sequence information, a comparison result obtained by comparing the read sequence information with sequence information of an analysis target gene of the gene panel associated with the obtained gene panel information.
The sequence information of an analysis target gene of the gene panel can include the sequence of the gene to be analyzed (for example, exon), and an index sequence added to the sequence of the gene to be analyzed.
For example, in the cases of (1) and (2) below, the data adjustment unit 113 may cause the display unit 16 to display an error as an analysis result of the read sequence information.
(1) When mapping of a read sequence is performed, the index sequence included in the read sequence information read by the sequence data reading unit 111 is different from the index sequence (see
(2) The read sequence information includes not less than a predetermined number of sequences of genes that are not analysis target genes of the gene panel corresponding to the gene panel information obtained by the information selection unit 112; or the read sequence information only includes less than a predetermined number of sequences of analysis target genes of the gene panel indicated by the gene panel information obtained by the information selection unit.
These cases are highly likely to be caused by an erroneous input of gene panel information by the user. Thus, the data adjustment unit 113 may cause the display unit 16 to display an error such as “Analysis cannot be performed” and “There is an error in gene panel information”, and the like.
Alternatively, the data adjustment unit 113 may cause the display unit 16 to further display a message such as “Please input gene panel information again”, to urge the user to input the gene panel name, the name of the analysis target gene, and the like again.
The display unit 16 may display an error only when the number of pieces of read sequence information that include the sequences of genes that are not analysis target genes of the gene panel corresponding to the gene panel information is not less than a predetermined number. Alternatively, an error may be displayed only when pieces of read sequence information include not less than a predetermined number of pieces of read sequence information for which mapping has been performed with respect to genes that are not analysis target genes of the gene panel corresponding to the gene panel information.
An example has been described in which the display unit 16 is used as the destination to which an error is outputted. However, the configuration for outputting an error is not limited thereto. For example, an error content may be outputted as sound from a speaker. Alternatively, an error may be indicated to the user by lighting or blinking a lamp or the like.
Next, with reference back to
Then, in step S14 in
In one aspect, the mutation identification unit 114 generates a result file on the basis of the extracted mutation.
As shown in
In
With reference back to
“Annotation” indicates information related to the mutation. For example, “Annotation” may be information that indicates a mutation of an amino acid such as “EGFR C2573G”, “EGFR L858R”, or the like. For example, “EGFR C2573G” indicates a mutation in which cysteine at the 2573rd residue of protein “EGFR” is substituted by glycine.
As in the example described above, “Annotation” of mutation information may be information for converting a mutation according to base information into a mutation according to amino acid information. In this case, on the basis of the information of “Annotation” that has been referred to, the mutation identification unit 114 can convert a mutation according to base information into a mutation according to amino acid information.
Using the information that specifies each mutation included in the result file as a key (for example, base information corresponding to the mutation position information and the mutation), the mutation identification unit 114 searches the mutation database 123. For example, using any one of pieces of information “CHROM”, “POS”, “REF”, and “ALT” as a key, the mutation identification unit 114 may search the mutation database 123. When a mutation extracted by comparing the alignment sequence derived from the blood specimen and the alignment sequence derived from the lesion site has been registered in the mutation database 123, the mutation identification unit 114 identifies the mutation as a mutation existing in the sample, and provides annotation (for example, “EGFR L858R”, “BRAF V600E”, etc.) to the mutation included in the result file.
In one embodiment, before the mutation identification unit 114 searches the mutation database 123 on the basis of the result file, the information selection unit 112 may mask (exclude), in the result file, mutations that do not correspond to the gene panel information inputted to the mutation identification unit 114.
For example, in one aspect, the mutation identification unit 114 having been notified of the gene panel information from the information selection unit 112 may refer to a table indicating the correspondence relationship between each analysis target gene and the position information (for example, “CHROM” and “POS”) as shown in
In one embodiment, the information selection unit 112 may perform control such that, when the mutation identification unit 114 refers to mutation information in the mutation database 123 in order to provide annotation, the mutation identification unit 114 refers to the inputted gene panel information and the metadata of each piece of mutation information, and selectively refers to mutation information that corresponds to the gene panel information.
For example, in one aspect, the information selection unit 112 may control the mutation identification unit 114 such that the mutation identification unit 114 refers to mutation information that corresponds to the analysis target genes specified by the inputted gene panel information. Accordingly, the mutation identification unit 114 only has to refer to the mutation information, in the mutation database 123, that is related to the gene panel having been used. Thus, annotation providing efficiency can be improved.
It should be noted that, from all the identified mutations, a mutation that corresponds to the inputted gene panel information may be selected on the basis of the gene panel information, and information that is related to the selected mutation may be outputted as an analysis result of the read sequence information.
In this case, for example, it is sufficient that metadata of each piece of mutation information stored in the mutation database includes the gene ID of the analysis target gene, and, for each mutation of the gene, information as to whether or not the mutation is an analysis target of the gene panel.
According to this configuration, the mutation identification unit 114 may be controlled to refer to the gene panel information from the information selection unit 112 and metadata of each piece of mutation information, and to select, from all the identified mutations, only mutation information that corresponds to the gene panel information. For example, there may be cases where different gene panels have analysis target genes having the same gene ID, but mutations to be analyzed are different between the gene panels.
Even in such a case, if the above-described configuration is employed, the mutation identification unit 114 can output, to the report creation unit 115, only the mutation information that corresponds to the gene panel information inputted by the user. As the analysis result of the read sequence information, mutation information may be outputted from the output unit 13 or may be displayed on the display unit 16.
When the entire exon region is analyzed by a panel test, many mutations are detected in genes of a subject. Here, mutations include those of which the clinical significance has not been confirmed or for which therapeutically effective drugs have not been established. Thus, such mutations provide information other than information that can be utilized by doctors for actual therapies. Doctors trying to apply the result of a genetic test to an actual therapy for a subject desire to selectively know mutations that can be utilized in the actual therapy among many detected mutations.
The report creation unit 115 creates a report on the basis of the information outputted by the mutation identification unit 114 and the gene panel information provided from the information selection unit 112 (corresponding to step S110 in
On the basis of the gene panel information from the information selection unit 112, the report creation unit 115 selects the target to be included in the report and deletes, from the report, the information that has not been selected. Alternatively, the information selection unit 112 may control the report creation unit 115 such that information related to genes that correspond to the gene panel information inputted through the input unit 17 is selected as the target to be included in the report, and information that has not been selected is deleted from the report.
The report created by the report creation unit 115 may be transmitted in the form of data, as an analysis result of the read sequence information, from the output unit 13 to the terminal device 5 provided at the medical institution 210 (corresponding to step S111 in
Another embodiment of the present invention is describe below. For convenience of description, the members having the same functions as those of the members described in the above embodiment are denoted by the same reference characters, and description thereof is not repeated.
Here, a gene analysis apparatus 1a capable of creating a report that includes information related to drugs (drug information) that are related to mutations identified by the mutation identification unit 114 is described with reference to
The flow of a process in which the drug search unit 117 generates a list that includes information related to drugs is described with reference to
Using the mutation ID provided to each mutation identified by the mutation identification unit 114 as a key, the drug search unit 117 searches the drug database 124 (step S15a). On the basis of the search result, the drug search unit 117 generates a list that includes information related to drugs that are related to mutations (step S16a). The generated list is incorporated into the report created by the report creation unit 115.
Data 124A stored in the drug database 124 and used when the drug search unit 117 searches the drug database 124 and generates a drug list is described with reference to
As shown in
Each mutation ID in the drug database 124 may be provided with “metadata about gene-panel-related information”, which is metadata related to gene panel information. The drug search unit 117 refers to the “metadata about gene-panel-related information” in accordance with an instruction from the information selection unit 112.
Then, the drug search unit 117 changes the range in which the drug database 124 is searched, to a range indicated by the metadata. Accordingly, in accordance with “metadata about gene-panel-related information” provided to each drug and the inputted gene panel information, the drug search unit 117 can narrow the drugs that should be referred to in the drug database, and can generate a list that includes information related to drugs according to the gene panel information.
The drug search unit 117 may search the drug database 124 having the data structure shown in
The drug search unit 117 searches the drug database 124 storing the data shown in
On the basis of the search result, the drug search unit 117 generates a list that includes the mutation, the related drug corresponding to the mutation, information related to approval of the related drug, and the like (step S16b).
The drug search unit 117 may search the drug database 124 having the data structure shown in
The drug search unit 117 searches the drug database 124 storing data 124B shown in
When the searched drug has been approved (YES in step S21), the drug search unit 117 determines whether the disease of the subject from whom the sample has been collected, and the disease (for example, “target disease” shown in
When the disease of the subject and the “target disease” match each other (YES in step S22), the drug search unit 117 associates the drug of the search result, as an approved drug, with the mutation (step S24), and generates a list that includes the mutation, the related drug corresponding to the mutation, information related to the approval of the related drug, and the like (step S16a).
Meanwhile, when the disease of the subject and the “target disease” is different from each other (NO in step S22), the drug search unit 117 determines that the searched related drug is a drug having a possibility of off-label use, associates the determination result with the mutation (step S25), and generates a list that includes the mutation, the related drug corresponding to the mutation, information related to approval of the related drug, and the like (step S16a).
The information related to the disease of the subject can be inputted through the input unit 17 by an operator or the like when performing gene analysis, for example. In addition, for example, a header region of the read sequence information may include the disease ID which is identification information corresponding to the disease of the subject.
The drug search unit 117 may search the drug database 124 having the data structure shown in
The drug search unit 117 searches the drug database 124 storing data 124C shown in
It should be noted that the data 124A shown in
Another embodiment of the present invention is described below. For convenience of description, the members having the same functions as those of the members described in the above embodiments are denoted by the same reference characters, and description thereof is not repeated.
Here, a gene analysis apparatus 1b that can create a report including various types of reference information related to each mutation identified by the mutation identification unit 114 is described with reference to
Using the mutation ID provided to each mutation identified by the mutation identification unit 114 as a key, the reference search unit 118 searches the reference database 125. On the basis of the search result, the reference search unit 118 extracts reference information related to the mutation. The extracted reference information is incorporated into a report created by the report creation unit 115.
Data stored in the reference database 125 searched by the reference search unit 118 is described with reference to
As shown in
Each of mutation ID in the reference database 125 may be provided with “metadata about gene-panel-related information” (not shown) which is metadata related to gene panel information. In this case, in accordance with an instruction from the information selection unit 112, the reference search unit 118 refers to the “metadata about gene-panel-related information” and changes the range in which the reference database 125 is searched, to a range indicated by the metadata. Accordingly, in accordance with the “metadata about gene-panel-related information” associated with each mutation and the inputted gene panel information, the reference search unit 118 can narrow the reference information that should be referred to in the drug database, and can extract reference information according to the gene panel information.
The report creation unit 115 may create a report on the basis of information outputted by the drug search unit 117, or may create a report on the basis of information outputted by the reference search unit 118. Further, the report creation unit 115 may create a report on the basis of both of information outputted by the drug search unit 117 and information outputted by the reference search unit 118.
Information related to each identified mutation, information of a drug related to the mutation, reference related to the mutation (including, for example, molecular biological findings of the mutation, information related to documents, and the like), or information in which these types of information are combined as desired can be included in the report created by the report creation unit 115.
The information selection unit 112 performs control such that, for example, information related to each target gene that corresponds to the inputted gene panel information is selected as a target to be included in a report; and the report creation unit 115 creates a report in which the selected information is included.
The column “clinical study list” includes a list of information related to clinical trials of drugs generated on the basis of search results obtained by the drug search unit 117 searching the drug database 124.
Another embodiment of the present invention is described below. For convenience of description, the members having the same functions as those of the members described in the above embodiments are denoted by the same reference characters, and description thereof is not repeated.
Here, a gene analysis apparatus 1c is described in which an information selection unit 112c also has a function of obtaining gene panel information on the basis of the index sequence included in the read sequence information, in addition to the function of allowing the user to input gene panel information. In the following, a gene-panel-related information database 121c, a data adjustment unit 113c, and the information selection unit 112c shown in
The index sequence may be inserted only in a sequence of a specific gene among the analysis target genes of the gene panel. In the case of read sequence information having no index sequence inserted therein, the user may be caused to input gene panel information as shown in
<Gene-Panel-Related Information Database 121c>
First, data 121D stored in the gene-panel-related information database 121c referred to by the information selection unit 112c is described with reference to
The example in
<Data Adjustment Unit 113c>
The data adjustment unit 113c analyzes read sequence information read by the sequence data reading unit 111, and determines whether or not the sequences include an index sequence “pppppppppp”, “qqqqqqqqqq”, or the like stored in the gene-panel-related information database 121c. When the index sequence is not included, the data adjustment unit 113c notifies the information selection unit 112c that the index sequence is not included. Meanwhile, when the index sequence is included, the data adjustment unit 113c outputs the detected index sequence (for example, “pppppppppp”) to the information selection unit 112c.
<Information Selection Unit 112c>
When the information selection unit 112c has been notified by the data adjustment unit 113c that the index sequence is not included, the information selection unit 112c causes the display unit 16 to display the GUI shown in
As described above, when an index sequence is inserted in the read sequence information, it is possible to specify gene-panel-related information without causing the user to input gene-panel-related information. Therefore, enhanced convenience can be provided to the user.
The present invention is not limited to the embodiments described above, and various modifications can be made without departing from the scope of the claims. Embodiments obtained by combining as appropriate technological means disclosed in different embodiments are also included in the technological scope of the present invention.
For example, one medical institution 210 and one test institution 120 are shown in
In
The gene analysis system 100 can be suitably applied also to an institution that has the functions of both of the medical institution 210 and the test institution 120 (for example, research institutes that have both a clinical facility and a test facility, university hospitals, and the like). This is not limited to the gene analysis system 100. The gene analysis method performed by the gene analysis apparatus 1, a program for controlling the gene analysis apparatus 1 implemented by a computer that realizes the gene analysis method, and a computer readable storage medium having stored therein the program are also suitably applied to an institution that has functions of both of the medical institution 210 and the test institution 120.
The analysis using the gene panel may be used in analysis of polymorphism such as Single Nucleotide Polymorphism (SNP) and Copy Number Variation (CNV, Copy Number Polymorphism). The gene panel may be used for obtaining an output of information related to the amount of mutations in the entire genes that are analyzed (also referred to as Tumor Mutation Burden), or may be used for calculating the methylation frequency.
As means for allowing the user to input gene panel information, an example of displaying a GUI for inputting has been shown. However, the present invention is not limited thereto. For example, the input unit 17 may be a bar code reader that allows the user to read a bar code. In a case where a bar code is provided on, for example, a label of a container of each reagent of each gene panel and the surface of a box housing a set of reagents of the gene panel, if the bar code is read by use of the bar code reader, gene panel information is inputted.
When the controller 11 causes the display unit 16 to display a GUI for inputting gene panel information, the user may be caused to select an analysis target gene. In this case, as shown in
The gene names displayed on the GUI are based on the gene names of genes provided with gene IDs and registered in the gene-panel-related information database 121. The gene names on the list shown as alternatives are displayed on the basis of gene panel information registered in the gene-panel-related information database 121.
Alternatively, as shown in
In this case, on the basis of the selected disease name, the information selection unit 112 specifies a gene panel ID associated with the disease name, and searches the gene-panel-related information database 121, to obtain gene panel information that corresponds to the selected disease name.
The gene names displayed on a GUI as the alternatives that allow selection of a gene panel related to the selected disease are based on the information registered in the gene-panel-related information database 121.
The gene panel name of a gene panel related to a disease may be a reagent kit name. The gene panel includes a set of reagents such as various types of buffers, enzymes, and primers that are used in target sequencing which is performed by the sequencer 2 in order to read the sequences of the analysis target genes. The set of reagents is provided with a reagent kit name or a gene panel name.
Here, another example of the flow of a process for receiving an input of gene panel information, shown in step S107 in
The flow of a process shown in
When the gene panel that corresponds to the selected information does not match the gene panel included in the analysis request received from the medical institution 210 (NO in step S203), the information selection unit 112 causes the display unit 16 to display an indication that the inputted gene panel is different from the designated gene panel, and a message asking whether or not to use the inputted gene panel (step S206). When the information selection unit 112 has received an input for asking permission to use the inputted gene panel (YES in step S207), the information selection unit 112 receives the input. Then, the information selection unit 112 causes the display unit 16 to display a message to the effect that the inputted gene panel can be used (step S204).
Meanwhile, when the information selection unit 112 has not received an input for asking permission to use the inputted gene panel (NO in step S207), the information selection unit 112 causes the display unit 16 to display a message to the effect that the inputted gene panel cannot be used (step S205), and prohibits the analysis from being performed by the gene analysis apparatus 1.
A configuration may be employed in which, when the gene analysis apparatus 1 receives an input of gene panel information, either the input mode shown in
Another embodiment of the present invention is described below. For convenience of description, the members having the same functions as those of the members described in the above embodiments are denoted by the same reference characters, and description thereof is not repeated.
In a gene analysis method according to the present embodiment, gene panel information is obtained, and on the basis of the obtained gene panel information, an analysis algorithm for evaluating the quality of a panel test is selected. Accordingly, when analysis target genes in various combinations are analyzed by use of various gene panels, appropriate quality control according to the gene panel can be performed.
Examples of the quality evaluation process selected in accordance with the gene panel include: (1) selecting the quality evaluation index to be used in quality evaluation of a panel test; (2) selecting the criterion to be used in determination as to whether a sufficient reliability is obtained when the same quality evaluation index is used; and (3) selecting the number of quality evaluation indexes to be used in quality evaluation of a panel test.
Examples of the quality evaluation index include indexes such as the reading quality included in read sequence information outputted by the sequencer 2; the proportion of bases read by the sequencer 2, to bases included in a plurality of genes as analysis targets; the depth of reading of read sequence information; the variation of the depth of reading of read sequence information; and whether or not all of mutations of each standard gene included in a quality control sample have been detected.
Here, a gene analysis apparatus 1d having a function of evaluating the quality of a panel test on the basis of a quality evaluation index is described with reference to
An analysis execution unit 110d of the gene analysis apparatus 1d is different from the gene analysis apparatus 1 shown in
The quality evaluation criteria database 126 stores criterion values which each specify whether or not the reliability of the analysis result in a panel test reaches a certain level. Here, the certain level is used in determining whether or not a reliability required for applying an analysis result of a panel test to a therapy or a diagnosis has been attained.
The information selection unit 112 according to the present embodiment selects the criterion value of the quality evaluation index on the basis of gene panel information inputted through the input unit 17.
Examples of the quality evaluation index generated by the quality control unit 119 for a measurement include indexes such as the reading quality included in read sequence information outputted by the sequencer 2; the proportion of bases read by the sequencer 2, to bases included in a plurality of genes as analysis targets; the depth of reading of read sequence information; the variation of the depth of reading of read sequence information; and whether or not all of mutations of each standard gene included in a quality control sample have been detected.
The examples of the quality evaluation index above are described in detail.
The quality score is an index that indicates the correctness of each base in a gene sequence read by the sequencer 2.
For example, when read sequence information is outputted in a FASTQ file from the sequencer 2, the quality score is included in the read sequence information (see
The cluster concentration is an index that indicates reading quality included in read sequence information outputted by the sequencer 2. The sequencer 2 locally amplifies and immobilizes a large number of single-stranded DNA fragments on a flow cell, to form clusters (see 9 in
For example, when the densities of clusters are excessively increased, and the clusters are excessively close to each other or overlap each other, the contrast, i.e., the S/N ratio, of the image of the flow cell is reduced, and the fluorescence microscope is less likely to focus. Thus, fluorescence cannot be accurately detected, and as a result, the sequence reading accuracy could be reduced.
Quality Evaluation Index (3): Index that Indicates the Proportion of Base Sequences in the Target Region Read by the Sequencer 2, to Base Sequences Read by the Sequencer 2.
This index is an index that indicates how many bases in the target region have been read, among bases including bases in the region other than the target region read by the sequencer 2. The index is calculated as a ratio between the total number of bases that have been read and the total number of bases in the target region.
Quality Evaluation Index (4): Index that Indicates the Reading Depth of Read Sequence Information.
This index is an index, with respect to each base included in a gene as an analysis target, that is based on the total number of read sequences in which the base has been read. The index is calculated as a ratio between the total number of bases, among bases having been read, that have depth greater than or equal to a predetermined value, and the total number of bases having been read.
The reading depth means the total number of pieces of read sequence information read with respect to the same base, and is also referred to as coverage, or depth of coverage.
Quality Evaluation Index (5): Index that Indicates the Variation of Reading Depth of Read Sequence Information.
This index is an index that indicates uniformity of the depth. When the number of pieces of read sequence information having been read in a certain portion in the region having been read is extremely great, uniformity of the depth is low. Meanwhile, when pieces of read sequence information are evenly present over the entirety of the region having been read, the uniformity of the depth is high. For example, the uniformity of the depth can be represented as numbers by use of the interquartile range (IQR). The greater the IQR is, the lower the uniformity is. The less the IQR is, the higher the uniformity is.
Quality Evaluation Index (6): Index that Indicates Whether or not all the Mutations in Each Standard Gene Included in the Quality Control Sample have been Detected.
This index is an index indicating that the mutation in each standard gene included in the quality control sample has been detected and accurately identified when the quality control sample and a sample collected from a subject have been measured. For example, whether or not the position of a known mutation in each standard gene included in the quality control sample, the type of the mutation, and the like have been accurately identified, is used as the quality evaluation index. The quality control sample is prepared by mixing a plurality of standard genes.
The flow of a process of performing quality evaluation of a panel test is described with reference to
First, in step S31 in
The quality control sample includes at least two of a standard gene including SNV, a standard gene including Insertion, a standard gene including Deletion, a standard gene including CNV, and a standard gene including Fusion. For example, the quality control sample includes, as standard genes, a partial sequence of gene A including “SNV” with respect to the wild type and a partial sequence of gene B including “Insertion” with respect to the wild type.
Next, in step S32, the sequencer 2 reads base sequences of DNA contained in the pretreated sample.
Subsequently, in step S33, a controller 11d of the gene analysis apparatus 1d causes the input unit 17 to display a GUI for allowing the user to select gene panel information. On the basis of the input operation on the GUI by the user, the gene panel information is obtained. The gene panel information may not necessarily be obtained through an input on the GUI by the user. For example, the gene panel information may be obtained by use of an identifier such as a bar code attached to the gene panel, or may be identified by reading an index sequence.
The controller 11d of the gene analysis apparatus 1d determines the type of the gene panel on the basis of the obtained gene panel information. The gene analysis apparatus 1d selects an analysis algorithm so as to perform quality control of the panel test in accordance with the obtained type of the gene panel.
In S34, the gene analysis apparatus 1d analyzes a gene sequence in accordance with the type of the gene panel, and identifies the presence or absence of a mutation in the base sequence, the position of a mutation, the type of the mutation, and the like. Through the analysis of the read gene sequence, the detected mutation is identified.
The gene analysis apparatus 1d evaluates the quality of the panel test on the basis of the generated quality evaluation index. The quality control unit 119 obtains the quality score (quality evaluation index 1) and the cluster concentration (quality evaluation index 2) from the sequence data reading unit 111. In addition, the quality control unit 119 obtains the proportion (quality evaluation index 3) of the bases in the target region read by the sequencer 2, the reading depth of the read sequence information (quality evaluation index 4), and the variation of the reading depth of the read sequence information (quality evaluation index 5), from the data adjustment unit 113. Further, the quality control unit 119 obtains whether or not all the mutations in each standard gene included in the quality control sample have been detected (quality evaluation index 6), from the mutation identification unit 114. The quality control unit 119 need not obtain all of the quality evaluation indexes, and may obtain one or a plurality of desired indexes.
The quality control unit 119 compares the obtained quality evaluation index with the criterion value of the quality evaluation index stored in the quality evaluation criteria database 126, and determines whether the analysis result has sufficient reliability. Here, in the quality evaluation criteria database 126, each criterion value of a corresponding quality evaluation index is stored in association with information that specifies a gene panel.
For example, when the type of the gene panel is panel A in S35, determination is performed by use of a criterion value a with respect to a quality evaluation index A, and determination is performed by use of a criterion value b with respect to a quality evaluation index B. Meanwhile, when the type of the gene panel is panel B in S35, determination is performed by use of a criterion value c with respect to the quality evaluation index A, and determination is performed by use of the criterion value b with respect to the quality evaluation index B. In this manner, in the analysis of panel A and the analysis of panel B, the same quality control index A is used, whereas different criteria are used for the evaluations. In the analysis of panel A, the quality control indexes A and B are used, whereas in the analysis of panel B, the quality control indexes A and C are used, and quality control indexes different from each other are used.
When the type of the gene panel is panel C in S35, determination is performed by use of a criterion value e with respect to a quality evaluation index D. In this manner, in the analysis of panel A, quality evaluation is performed on the basis of two indexes, i.e., the quality evaluation indexes A and B, but in the analysis of panel C, quality evaluation is performed by use of only the quality evaluation index D. In this manner, the number of quality evaluation indexes to be used may be changed in accordance with the gene panel.
Lastly, in S36, the gene analysis apparatus 1d creates a report that includes the identified mutation and the evaluation result of the quality of the panel test determined in step S34.
Below these items, the gene panel name “panel A” is also included as gene panel information. Further, the quality evaluation index “QC index”, which is information related to the quality of the panel test, is outputted in the report.
When the quality evaluation index is less than a predetermined criterion, the detected gene mutation may be marked with *. In addition, or instead, a comment for indicating that the reliability is low can be added.
The present invention is not limited to the above-described embodiments. Various modifications can be made without departing from the scope of claims. Embodiments obtained by combining as appropriate technological means disclosed in different embodiments are also included in the technical scope of the present disclosure.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2017-208651 | Oct 2017 | JP | national |
| 2018-201317 | Oct 2018 | JP | national |
This application is a continuation of International Application PCT/2018/039963 filed on Oct. 26, 2018, which claims benefit of Japanese patent application JP 2017-208651 filed on Oct. 27, 2017, and Japanese patent application JP 2018-201317 filed on Oct. 25, 2018, all of which are incorporated herein by reference in their entireties.
| Number | Date | Country | |
|---|---|---|---|
| Parent | PCT/JP2018/039963 | Oct 2018 | US |
| Child | 16855239 | US |
