KR102217060B1 - Apparatus for analysis and management of individual single nucleotide polymorphism - Google Patents

Abstract

Single nucleotide polymorphism (SNP) is a common mutation that appears in one of several DNA bases in a single region of a chromosome. It is predicted that there are about 3 million SNPs in the human genome, and each SNP itself only has a difference in a single base, and the likelihood of disease occurrence and reactivity to specific drugs vary depending on the SNP. It will be said that it is very important to accurately analyze more SNPs.
The present invention relates to an individual single base polymorphism analysis algorithm, a system implementing the same, and a device, and the system implementing the algorithm of the present invention is operated in one step from receiving a test request to outputting a result sheet in an individual single base polymorphism analysis. Since the probe for SNP is systematically managed, it is expected to be widely used in health diagnosis and medical fields.

Description

Apparatus for analysis and management of individual single nucleotide polymorphism}

The present invention relates to an individual base polymorphism analysis and management device.

Single nucleotide polymorphism (SNP) is a common mutation that appears in one of several DNA bases in a single site on a chromosome. SNPs are highly frequent and stable, and are distributed throughout the genome, thereby generating individual genetic diversity. These SNP differences make a difference in susceptibility to different diseases. Therefore, in recent years, based on SNP information, the "Disease Prediction Gene Test, which includes the process of selecting appropriate genes (disease candidate genes) involved in human diseases, discovering their variants, and statistically confirming the association with the disease. Technology" is being developed (US2008-0020484, KR1483284, etc.). However, it is predicted that about 3 million SNPs exist in the human genome, and each SNP itself is only different on a single base, and the likelihood of disease occurrence and reactivity to specific drugs are also different depending on the SNP. Above all, it would be very important to accurately analyze multiple SNPs.

Accordingly, the present invention provides an individual single base polymorphism (SNP) analysis algorithm, a system implementing the same, and an apparatus. The algorithm of the present invention makes it possible to predict the risk and incidence of the test target (disease) by analyzing various SNPs of an individual in a complex manner. In addition, in order to increase the efficiency of analysis, it includes an algorithm that automatically designates the position of the inspection object in the plate by searching for the same probe as the nested probe from the existing OA plate. The system implementing the algorithm of the present invention is operated in one-step from receiving a test request to outputting a result sheet in an individual single-base polymorphism analysis, and systematically managing probes for each SNP, so it is expected to be widely used in health diagnosis and medical fields. do.

The present invention has been devised to solve the problems of the prior art as described above, and relates to an individual single base polymorphism analysis algorithm, a system implementing the same, and an apparatus.

However, the technical problem to be achieved by the present invention is not limited to the problems mentioned above, and other problems that are not mentioned may be clearly understood by those of ordinary skill in the art from the following description.

Hereinafter, various embodiments described herein are described with reference to the drawings. In the following description, for a thorough understanding of the invention, various specific details, such as specific forms, compositions and processes, etc. are set forth. However, certain embodiments may be practiced without one or more of these specific details, or with other known methods and forms. In other instances, well-known processes and manufacturing techniques have not been described in specific details in order not to unnecessarily obscure the present invention. Reference throughout this specification to “one embodiment” or “an embodiment” means that a particular feature, form, composition, or characteristic described in connection with the embodiment is included in one or more embodiments of the invention. Thus, the context of “in one embodiment” or “an embodiment” expressed in various places throughout this specification does not necessarily represent the same embodiment of the invention. Additionally, particular features, shapes, compositions, or properties may be combined in one or more embodiments in any suitable manner.

Unless otherwise defined in the specification, all scientific and technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present invention belongs.

In one embodiment of the present invention, "genetic information" is a broad concept that collectively refers to all information encoded as a nucleotide sequence of DNA, and "genetic information" in the present invention includes nucleotide polymorphism information of an individual. .

In one embodiment of the present invention, "single nucleotide polymorphism (SNP)" is a general mutation that appears in one of several DNA bases in a single site of a chromosome, and about 3 million SNPs in the human genome Is present, and it appears as one per 500 to 1,000 bases, of which about 200,000 are estimated to be cSNPs present in genes that make proteins. SNPs are highly frequent and stable, and are distributed throughout the genome, thereby generating individual genetic diversity. That is, some people have adenine (A) in a specific part of the DNA chain, while others have cytosine (C). These subtle differences (SNPs) can change the function of each gene, and these interact to make people of different shapes and create differences in susceptibility to different diseases. In other words, if you can find the genetic difference between a person who has hepatitis and a person who does not have it, it is possible to find out the function of why the susceptibility to hepatitis is different. If so, the ultimate goal of human genome research is that it will be possible to develop a drug used for the prevention or treatment of hepatitis by using it. Accordingly, world-class pharmaceutical companies and genomic research institutes determined that SNP could provide fundamental information for new drug development in the future, and formed the SNP consortium (TSC), which was the eternal ideal of humanity. Is concentrating on SNP research to advance her dream. However, even if numerous SNPs have been developed, SNPs alone have no meaning. In other words, if there is no object to compare and analyze SNP, this is useless. Therefore, domestic pharmaceutical companies and research institutes secure comparison targets (patient DNA and clinical data) for diseases such as heart disease, dementia, and AIDS, which they have a lot, and determine which SNP is related to which disease. Efforts are being made to build a database.

In one embodiment of the present invention, the "OA plate (open array plate)" refers to a space in which a test/inspection is performed, and a substrate on which a probe reaction occurs from a DNA sample. The OA plate is preferably a microfluidic chip or a microwell array plate, but is not limited thereto.

In one embodiment of the present invention, the "multi well plate" is a space in which a test/inspection is performed like the above OA plate, and may be used by replacing the function of the OA plate. The multi-well plate may be selected from a 1-well to 96-well plate, and a 96-well plate is most preferred, but is not limited thereto.

In one embodiment of the present invention, the term "probe" refers to a nucleic acid fragment corresponding to several to several hundred bases for a specific binding to DNA or RNA, and the presence or absence of specific DNA or RNA because it is labeled Can be probed. The probe of the present invention may be manufactured in the form of an oligonucleotide probe, a single stranded DNA probe, a double stranded DNA probe, an RNA probe, etc., and biotin, FITC, rhodamine, DIG It may be labeled with the like or with a radioactive isotope.

In one embodiment of the present invention, the "disease and drug response-related database" means a data pool for measuring the risk of a specific disease by comparing disease-SNP association results, and of a specific disease associated with a specific SNP. It includes information on symptoms, types of prescription drugs, concentration of prescription drugs, frequency of drug prescription, duration of drug prescription, and side effects."Disease and drug reaction related database" in the present invention refers to domestic and foreign food and drug administrations, medical institutions, and Disease and drug information provided from the health examination center can be included in the data pool, and information on the age and sex of a specific individual and medical history and family tree information on spouses, children, parents, cousins, etc. can be included.

In one embodiment of the present invention, the "research database" refers to a data pool for measuring the risk of a specific disease by comparing disease-SNP association results, but is not limited thereto, but the research data may be a clinical or academic paper. If the data in the data pool is derived from the paper, the data pool is the paper's paper identification number (PMID), research subject, research method, research period, research results, journal information, and research repeatability. Information may be included, and information on the age and sex of an individual subject to the study, and information on the medical history and family tree of spouses, children, parents, cousins, etc. may be included.

In one embodiment of the present invention, the "gene database" refers to a data pool for measuring the risk of a specific disease by comparing disease-SNP association results, and the chromosome number and gene of a specific SNP associated with a specific disease Gene information including gastric and allele information can be included in the data pool. In particular, the race information of an individual to be analyzed may act as an important factor in the data stored in the genetic database, but is not limited thereto.

In one embodiment of the present invention, the "odds ratio" is an index called an estimate of relative risk and is a value estimated in a case-control study. Relative risk is a value estimated from a cohort study and is defined as the ratio of the probability of occurrence of an event when there is a risk factor and the probability of occurrence of an event when there is no risk factor. In the case of a cohort study, since risk factors are set in advance and the occurrence of events is observed over time, the relative risk indicating the association between the presence or absence of an event according to the risk factors is reliable, but a patient-control study in the technical field of the present invention In the case of the case, the relative risk is meaningless because a group is formed according to the occurrence of an event and then the risk factor is classified, so the estimated odds ratio is used.

In one embodiment of the present invention, the term "algorithm" refers to the processes that computer programming must perform to solve a given problem. When the target result can be obtained by mechanically processing it according to a certain sequence, that certain sequence is called an algorithm for the purpose. In general, knowing the algorithm can be converted into a computer program and processed.

In one embodiment of the present invention, "test item (disease)" refers to a disease in which the risk and incidence of disease can be predicted by the algorithm of the present invention, and is largely a chronic disease, cancer disease, drug reaction sensitive disease, and other diseases. In particular, the chronic diseases are type 1 diabetes, type 2 diabetes, hepatitis C, Kawasaki, ankylosing spondylitis, psoriasis, tuberculosis, high blood pressure, osteoarthritis, osteoporosis, coronary artery disease, ulcerative colitis, narcolepsy. , Glaucoma, cerebral aneurysm, stroke, polycystic ovary syndrome, multiple sclerosis, cholelithiasis, Lou Gehrig's disease, lupus, rheumatoid arthritis, rheumatoid heart disease, chronic kidney disease, knee osteoarthritis, pathological myopia (high myopia), Behcet's disease, cataract, vitiligo, Obesity, nonalcoholic fatty liver, myocardial infarction, atrial fibrillation, aspirin hypersensitivity chronic urticaria, atopic dermatitis, allergic reaction to food, gestational diabetes, gestational addiction, triglyceride levels, asthma, intervertebral disc herniation, dementia, Crohn's disease, gout, Parkinson Disease, obstructive pulmonary disease, sebaceous disease, coronary heart disease, migraine and macular degeneration, and the cancer disease is liver cancer, thyroid cancer, testicular cancer, oral cancer, acute myelogenous leukemia, ovarian cancer, biliary tract cancer, colon cancer, It consists of head and neck cancer, diffuse gastric cancer, bladder cancer, childhood leukemia, esophageal cancer, kidney cancer, gastric cancer, breast cancer, cervical cancer, endometrial cancer, prostate cancer, pancreatic cancer, lung cancer, and skin cancer, and the drug reaction-sensitive disease is metaamphetamine-induced It is composed of psychosis, angiotensin converting enzyme inhibitor, warfarin drug sensitivity, and propofol anesthetic sensitivity, and the other diseases are ADHD, panic disorder, nicotine addiction, alcohol dependence, bipolar disorder, depression, autism, and schizophrenia, The present invention is not limited thereto, and there is no limitation to anything that can measure the risk of occurrence by SNP phenotypic analysis.

In the system implementing the individual single-base polymorphism analysis algorithm of the present invention, the probe applied to each test item (disease) is, for example, when predicting skin elasticity phenotype, SNP ID: probe for rs1799750, skin aging SNP ID: rs2070600 for predicting phenotype, SNP ID: rs1800414, or rs74653330 for predicting skin pigmentation phenotype, SNP ID for predicting blood pressure phenotype: rs17249754, rs11191593, or rs3824755 SNP ID: rs560887, rs10830963, or rs4607517 probe for predicting blood sugar phenotype, SNP ID: rs10767664, or probe for rs17782313 for predicting body mass index phenotype, for predicting triglyceride phenotype SNP ID: rs2293571, or probe for rs780092, SNP ID for predicting high-density lipoprotein phenotype: probe for rs3782889, rs3813082, or rs6499861, SNP ID for predicting low-density lipoprotein phenotype: rs3782889, or rs3813082 Probe, it is preferable to use a probe for SNP ID: rs3118470 when predicting a hair loss phenotype, and a probe for SNP ID: rs3827760 when predicting a hair thickness phenotype, but is not limited thereto.

In one embodiment of the present invention, (a) a display for presenting a list of available OA plates; (b) a test position assignment unit connecting the probe contained in the OA plate and the test item waiting to be analyzed; (c) a determination unit for confirming an individual single-base polymorphic genotype based on the probe test result; And, (d) a result unit for predicting the risk of disease occurrence and incidence for each test item; and a single-base polymorphism analysis device for each individual, wherein the OA plate is a microfluidic chip or a microwell array plate. It provides an individual single-base polymorphism analysis device, characterized in that the test position is assigned to the added multi-well plate when the probe contained in the OA plate and the test item waiting to be analyzed are not connected in the step (b). Provides an individual monobasic polymorphism analysis device, wherein the multi-well plate is selected from 1-well to 96-well plates, wherein the device adds or requires a probe necessary for the OA plate It provides a single base polymorphism analysis device, characterized in that it further comprises a; OA plate management unit for removing the probes that are not.

The single base polymorphism analysis apparatus of the present invention is characterized in that it operates as a system consisting of units of business management, inspection management I, inspection management II, and financial management. The sales management unit is characterized in that it is configured to include product management, customer management, and use management modules, and the inspection management unit I is characterized in that it is configured to include reception, output, and other inquiry modules, the The inspection management Ⅱ unit is characterized in that it comprises a DNA extraction, inspection, reagent/equipment management, other inquiry, setting, and result report setting module, and the financial management unit includes a transaction statement and a sales status module. It characterized in that it is configured.

More specifically, the product management module of the sales management unit is characterized in that it is configured to include a sub-module of package generation and package payment, and the customer management module is a requesting agency registration, a requesting agency approval, a requesting agency package registration, and It is characterized in that it is configured to include a sub-module of the requesting agency package payment, and the use management module is configured to include a performance status inquiry, delivery completion, a document return ledger, and a submodule of a new requesting agency.

The acceptance module of the inspection management Ⅰ unit is characterized in that it is configured to include a sub-module of receiving a specimen, waiting for reception, and receiving, and the output module includes a sub-module of creating a result report, outputting a result report, and details of a result report. The other inquiry module is characterized in that it is configured to include a sample re-reception, a document return ledger, and a sub-module of the sample progress status.

The DNA extraction module of the test management Ⅱ unit is characterized in that it comprises a sub-module of DNA extraction instruction, DNA extraction, and DNA concentration determination, and the test module is an analysis instruction, OA plate generation, plate positioning, tester It is characterized by including sub-modules of assignment, genotype reference data, result input, and result review.Reagent/equipment management module includes raw material date deadline, OA plate management, genotype reference data registration, raw material inventory inquiry, raw material use It is characterized by comprising a sub-module of the register, raw material usage status, probe inventory inquiry, probe usage register, probe usage status, and analysis equipment management, and other inquiry modules include sample return register, sample re-reception, and genetic test cancellation. , Specimen disposal, and holiday management, and the setting module includes probe registration, test item registration, test item probe registration, result value analysis algorithm registration for each test item, and a sub-module of reference. It characterized in that it is configured to include, and the result report setting module is characterized in that it is configured to include a sub-module of language management for each test item and judgment/probe language management.

The transaction statement module of the financial management unit is characterized in that it comprises a sub-module of transaction statement management and transaction statement output, and the sales status module is a sales status inquiry by customer, a sales status item inquiry, and a sales status package classification inquiry , Sales status, item inquiry by customer, and sales status and receivables inquiry by customer.

In addition, the single base polymorphism analysis device of the present invention is characterized in that it is operated as a system further including a system environmental condition, a main function, a statistics, and a system management unit.

More specifically, the system environmental condition unit is characterized in that it is configured to include an environment setting and a common usage module, and the main function unit is characterized in that it is configured to include a login, and a main screen module, the The statistical unit is characterized in that it comprises a genome research lab, and a finance/sales module, and the system management unit is characterized in that it comprises a usage management and a log management module.

The genome research module of the statistical unit is characterized in that it comprises a sub-module of the OA plate availability rate and statistical report of the test result, and the finance/sales module is the package usage status, comparison of the same number of points in the same month of the previous year, and It characterized in that it is configured to include a sub-module.

The use management module of the system management unit is characterized in that it comprises a submodule of user management, department management, authority management, menu management, approver management, user authority management, and common code management, and the log management module It is characterized in that it comprises a sub-module of access log management, audit trail, and audit trail experimental information.

Hereinafter, the present invention will be described in detail step by step.

The individual single-base polymorphism (SNP) analysis algorithm of the present invention, and a system implementing the same, allow to predict the risk of occurrence and incidence of a test object (disease) by analyzing various SNPs of an individual in a complex manner. The system implementing the algorithm of the present invention is operated in one-step from receiving a test request to outputting a result sheet in an individual single-base polymorphism analysis, and systematically managing probes for each SNP, so it is expected to be widely used in health diagnosis and medical fields. do.

1 shows an implementation example of the OA plate generation algorithm among the individual single-base polymorphism analysis algorithm of the present invention, a system implementing the same, and an apparatus according to an embodiment of the present invention.
2 is a diagram illustrating an embodiment of an individual single base polymorphism analysis algorithm of the present invention, a system implementing the same, and automatic assignment of a test position on a multi-well plate among devices according to an embodiment of the present invention.

Hereinafter, the present invention will be described in more detail through examples. These examples are only for describing the present invention in more detail, and it will be apparent to those of ordinary skill in the art that the scope of the present invention is not limited by these examples according to the gist of the present invention. .

Throughout the specification, when a part "includes" a certain component, it means that other components may be further included rather than excluding other components unless otherwise stated.

Example 1. System implementing individual single base polymorphism analysis algorithm

The system implementing the individual single-base polymorphism analysis algorithm provided by the present invention is composed of units of sales management, inspection management Ⅰ, inspection management Ⅱ, and financial management, and the sales management unit has the composition of Table 1, inspection management Ⅰ. The unit includes the configuration of Table 2, the inspection management II unit includes the configuration of Table 3, and the financial management unit includes the configuration of Table 4.

Sales management unit 1. Product management 1.1. Create a package 1.2. Package payment 2. Customer management 2.1. Registration of the requesting institution 2.2. Requesting agency payment 2.3. Registering the client package 2.4. Requesting agency package payment 3.3. Usage management 3.1. Performance status inquiry 3.2. Delivery completed 3.3. Document return ledger 3.4. New requesting organization

Specifically explaining the sales management in Table 1,

[One. Product Management], you can create and search packages of services provided, select packages from sorted data, check the list of inspection items included in the selected package, and save them. It is also possible to output the sorted data in Excel, and it is also possible to connect the determined inspection items by payment. [2. Customer Management] provides the function of storing and managing new requesting organizations. By selecting the requesting organization, the information of the requesting organization and the result sheet information can be checked, and it is possible to modify or enter new information. A module that automatically calculates and inputs the supply price and VAT when entering the contract unit price is also provided, and can be linked to payment for this. The requesting agency whose contract period has expired can be marked separately in a specific color. [3. Usage Management], you can search the performance status of the requesting agency by period, and check information on the number of receipts, types, average types, and amounts for the selected period. It is possible to check the delivery information for the result sheet, check the list of documents to be returned and the reason for the return, and separately manage the list of new requesting organizations or requesting organizations that have passed a specific period since the last request.

Inspection Management Ⅰ 1. Reception 1.1. Sample receipt 1.2. Waiting for reception 1.3. Receiving 2. Output 2.1. Result report preparation 2.2. Output report 2.3. Result report details 3. Other inquiry 3.1. Re-reception of samples 3.2. Document return ledger 3.3. Sample progress

When explaining inspection management Ⅰ in Table 2 in detail,

[One. In [Reception], you can manage the list of requesting agencies whose contract period has not expired, and can be linked to the sample receipt data of the requesting agency, and the number of received inspection items and the number of rejected inspection items are provided. It is connected to a module that creates a new submission item of the requesting institution, can input and modify information necessary for reception, and can add information of the doctor in charge. Inspection items can be selected individually or in packages, and if there are duplicate inspection items among the selected inspection items, they are automatically displayed and provided. For received items, only those with approval authority are given the authority to access the data, and they can approve, reject, or cancel the experiment. Extraction can be performed for each inspection item. [2. Output] is a module that creates a result report, and it presents the received items in which the result values of all inspection items are entered. You can select a requesting organization to check the history of the result report, create a new result report, save it, or cancel the experiment. You can check the output history of the result report, search the list for each progress status of the result report, or manage the delivery status. [3. Other Inquiry] allows you to re-submit the items for which samples or documents were re-requested, and it is possible to inquire the progress of the items under test in a list.

Inspection Management Ⅱ 1. DNA extraction 1.1. DNA extraction instruction 1.2. DNA extraction 1.3. DNA concentration determination 2. Inspection 2.1. Analysis instruction 2.2. OA plate creation 2.3. Plate positioning 2.4. Assignment of inspectors 2.5. Genotype reference 2.6. Enter the result 2.7. Review the results 3. Reagent/equipment management 3.1. Raw material deadline 3.2. OA plate management 3.3. Genotype reference data registration 3.4. Raw material inventory inquiry 3.5. Raw material use ledger 3.6. Raw material usage status 3.7. Probe Inventory Inquiry 3.8. Probe ledger 3.9. Probe usage status 3.10. Analysis equipment management 4. Other inquiry 4.1. Sample return book 4.2. Re-reception of samples 4.3. Genetic test cancellation 4.4. Discard the sample 4.5. Holiday management 5. Setting 5.1. Probe registration 5.2. Registration of inspection items 5.3. Registration of inspection item probe 5.4. Registering algorithm for analyzing result value for each test item 5.5. references 6. Result report settings 6.1. Language management for each test item 6.2. Judgment/Probe Language Management

When explaining the inspection management Ⅱ in Table 3 in detail,

[One. DNA extraction], you can assign the person in charge of extraction and equipment for each sample, and you can check the items waiting for extraction. If the extraction result value for the sample already exists, the existing result value can be reused, and items that have been assigned the person in charge and equipment can be assigned to the list during extraction. It is also possible to distribute the authority so that the extracted result value can be entered and only the items in charge of each individual user can be accessed. By grasping the concentration and purity of the DNA extraction result, it is possible to automatically classify it as an analysis instruction screen when it is normal, or as a concentration determination screen when it is not met. [2. [Inspection] is a module in which SNP analysis is performed for each individual test item, and it is possible to inquire items approved for analysis, to create an OA plate, and to automatically designate the test location on the plate. The OA plate generation and the automatic allocation algorithm of positioning will be separately described below. A person in charge and equipment can be designated for the created plate, a reference image for each probe is provided for each inspection item, and an analysis result can be input by selecting a probe list of all analyzed plates, and reviewed. [3. In reagent/equipment management], raw materials can be managed by closing daily, weekly, monthly, or by selected period, and OA plates can be managed. The algorithm for the OA plate management will be separately described below. Reference images for each probe can be newly registered or edited, and stock of raw materials or probes can be inquired, incoming and outgoing details can be inquired, and usage status can be inquired. In addition, it is possible to check the management details of the analysis equipment. [4. Other Inquiry] allows you to search the details of the items received by returning the specimen, and check the report on actions taken when an accident (error) occurs. You can order to discard a specific sample by checking the list of receipts for which samples were re-requested, items for which the experiment has been canceled, or by inquiring the list of all received samples. It is also possible to manage holidays. [5. Setting] In the module, it is possible to search for a probe and register it newly, search for a test item and register it newly, or register a probe by matching the test item (disease). It is also possible to register and search a specific probe test in the test item as an algorithm and the interpretation of the result value. The analysis algorithm for the result value for each test item will be separately described below. References on probes for each test item (disease) can be registered and searched, and references can be managed by genotype. [6. Result Report [Seol]] allows you to manage the contents of the test items for each language, and input and modify the description data for each language. Comprehensive descriptions of judgments can be stored and judgment results and probe data for each language can be managed.

Financial management 1. Transaction Statement 1.1. Transaction Statement Management 1.2. Print transaction statement 2. Sales status 2.1. Sales status inquiry by customer 2.2. Sales status inquiry by item 2.3. View sales status by package classification 2.4. Revenue status Search items by customer 2.5. Revenue status inquiry by customer

Specifically explaining the financial management in Table 4,

[One. Transaction specification], you can search the list of receipts by company and period, the list of transactions, and the list of transactions, and you can search the list of receipts for which financial confirmation is completed by company and period, or you can print the transaction statement and the transaction statement. [2. In [Sales Status], it is possible to search the sales status by customer, item, package, or item by customer, and you can separately search the sales status and receivables by customer. All data can be output to Excel.

In addition to the sales management, inspection management Ⅰ, inspection management Ⅱ, and financial management unit, the system implementing the individual single-base polymorphism analysis algorithm of the present invention further comprises a system environmental condition, main function, statistics, and system management unit. It is possible. The system environmental condition unit includes the configuration of Table 5, the main functional unit includes the configuration of Table 6, the statistical unit includes the configuration of Table 7, and the system management unit includes the configuration of Table 8. When the system environmental condition, main function, statistics, and system management unit are added, the system environmental condition unit and the main function unit are preferably arranged before the inspection management unit, and the statistical unit and the system management unit are arranged after inspection management. However, it is not limited thereto.

System environmental conditions 1. Preferences 2. Common grid usage

If the system environmental conditions in Table 5 are specifically described,

[One. It is possible to connect to'Result Report Output' or'Sample Progress Status' in [Inspection Management I] in Environment Setting]. [2. In Grid Usage Common], the sorted data can be sorted in ascending or descending order, and new data can be entered or modified. Also, sorted data can be output to Excel.

Main function 1. Login 2. Main screen

Specifically describing the main functions in Table 6,

[One. Login], only users who have been approved for use by the system administrator can access the system. Access is controlled by ID and password. [2. In the main screen], the system of the present invention is connected to any unit and can be moved immediately. It is possible to briefly check the progress of work, to understand the status of requests for the entire request period, and to understand the status of receipts by region. In addition, the list of approvals by task is summarized and displayed, and you can move directly.

statistics 1. Genome Research Institute 1.1. OA plate availability 1.2. Statistical report of inspection results 2. Finance/Sales 2.1. Package usage status 2.2. Comparison of the same number of points in the same month of the previous year 2.3. Reception status

To explain the statistics in Table 7 in detail,

[One. Genome Research Institute], you can search the list of OA plates and their availability, and report statistics on the test results. [2. In Finance/Sales], you can inquire the package being used by each requesting agency and the number of monthly receipts for each package, compare the number of receipts by year, month, and day, and view the status of receipts by requesting organization or by date of receipt have. All data can be saved or printed by linking with Excel.

System management 1. Usage management 1.1. User management 1.2. Department management 1.3. Rights management 1.4. Menu management 1.5. Approver Management 1.6. User rights management 1.7. Common code management 2. Log management 2.1. Access log management 2.2. Audit trail 2.3. Audit trail experiment information

Specifically describing the system management in Table 8,

[One. Use Management], you can register users or departments that use the system, register authorization groups that can use the system, and register menus that can be used for each authorization code. In addition, you can register a menu to be used in the system, search a list of approvers and grant approval authority to a specific user, register users who can use each authorization code, or register a common code. [2. In [Log Management], you can search the access records of users who used the system, and the records of events executed in the system. It is also possible to search the history of changed events by inspection item or probe list.

Example 2. OA plate generation and inspection position automatic assignment algorithm

The system for implementing the individual single-base polymorphism analysis algorithm of Example 1 is characterized in that it includes a module that implements an OA plate (open array plate) generation and an automatic test position assignment algorithm.

The OA plate generation, and the automatic test location assignment algorithm comprises: a) presenting a list of available OA plates; b) searching for the same probe as the probe contained in the OA plate among accepted items waiting to be analyzed; And c) generating a plate on which the test is to be performed; and the OA plate is preferably a microfluidic chip or a microwell array plate. A system implementing the OA plate generation algorithm is shown in FIG. 1. In Fig. 1, ① is a tab showing the list of available OA plates, ② is a tab for entering the number of OA plates to be created in the number of grids used, and ③ is a created after finding the same probe as the probe in the OA plate. Plate, ④ indicates a tab for initializing the plate, and ⑤ indicates a tab for storing the finally created OA plate.

In addition, the system implementing the individual single-base polymorphism analysis algorithm of the present invention is characterized in that, when the item to be tested is not in the set value of the OA plate, an additional position is designated using a separate multi-well plate. The position designation may be set automatically/manually with the same disease group, the same gene, or the same probe as a priority according to a preset reference value. It is preferred to designate contiguous locations on a multiwell plate, but it is also possible to configure extra wells that are not contiguous. The multi-well plate may be selected from a 1-well to 96-well plate, and a 96-well plate is most preferred, but is not limited thereto. As an example, when the sample to be tested is a bundle of 3 or less probes and a 96-well plate is used, a method of positioning is shown in FIG. 2. In Fig. 2, ③ indicates confirmation of the test device, ④ indicates a bundle of probes of three or less samples indicated in the spare space, and ⑤ indicates that the user repositions and sets.

In addition, the system implementing the individual single-base polymorphism analysis algorithm of the present invention is characterized in that the test device is selected and set according to a preset rule based on the type of probe used. Binding, amplification, or detection of nucleic acids such as DNA and RNA greatly varies depending on the difference in conditions, so even if the experimental conditions such as probe, reaction time, and reaction temperature are the same, the size of the result depends on the difference of the test device. Can be different. For example, in the case of detecting the SNP rs2046210 of the 6q25.1 gene or the SNP rs4290270 of the TPH2 gene, it is preferable to use the QuantStudio ^TM 6 Flex Real-Time PCR System (4485699, Thermo Fisher Scientific), and the KITLG gene When detecting SNP rs995030, or rs4471514, it is preferable to use the 7500 FAST Real-Time PCR System (4351107, Thermo Fisher Scientific) as a test device. When detecting SNP rs1799752 of the ACE gene, the test device is PCR (Veriti). (4375786, Thermo Fisher Scientific) is preferably used.

Example 3. OA plate management algorithm

The system for implementing the individual single-base polymorphism analysis algorithm of Example 1 is characterized in that it includes a module that implements the OA plate management algorithm.

The OA plate management algorithm includes: a) presenting a list of currently existing OA plates; b) checking the probe information of the presented OA plate; c) adding required probes to the OA plate; And d) removing unneeded probes from the OA plate.

Example 4. Algorithm for interpreting result values for each test item

The system for implementing the individual single-base polymorphism analysis algorithm of the first embodiment is characterized in that it includes a module that implements the result value analysis algorithm for each test item.

The algorithm for analyzing result values for each test item may include: a) checking a registered probe for each test item; b) confirming the probe-genotypic result; c) applying weights for each test item; And d) predicting the risk and incidence of disease for each test item.

The weight in step c) may be different depending on the test item (disease), and the prevalence according to age or sex ratio, prevalence according to race, medical history of a specific individual from disease and drug reaction related databases, research databases, and genetic databases. An estimate of the relative risk calculated by taking into account family tree information, disease-SNP association results, etc. can be applied.

As the specific parts of the present invention have been described in detail above, it is obvious that these specific techniques are only preferred embodiments for those of ordinary skill in the art, and thus the scope of the present invention is not limited thereto. Therefore, it will be said that the practical scope of the present invention is defined by the appended claims and their equivalents.

Claims (15)

(a) a display for presenting a list of available OA plates;
(b) a test position assignment unit connecting the probe contained in the OA plate and the test item waiting to be analyzed;
(c) a determination unit for confirming an individual single-base polymorphic genotype based on the probe test result; And,
(d) a result unit for predicting the risk of disease occurrence and incidence for each test item; comprising, a single-base polymorphism analysis device for each individual,
The OA plate is characterized in that it is a microfluidic chip or a microwell array plate,
The single-base polymorphic genotype includes the TPH2 gene, and the polymorphic genotype of the KITLG gene,
When the polymorphism of the TPH2 gene is rs4290270, the test device is automatically set up with QuantStudio ^TM 6 Flex Real-Time PCR System (Catalog number: 4485699, Thermo Fisher Scientific),
When the polymorphism of the KITLG gene is rs995030, or rs4471514, the test device is automatically set to 7500 FAST Real-Time PCR System (Catalog number: 4351107, Thermo Fisher Scientific).
delete The method of claim 1,
In step (b), when the probe contained in the OA plate and the test item waiting for analysis are not connected, the test position is assigned to the added multi-well plate.
The method of claim 3,
The multi-well plate is characterized in that any one selected from 1-well to 96-well plate, individual single base polymorphism analysis device.
The method of claim 1,
The apparatus further comprises an OA plate management unit for adding probes necessary to the OA plate or removing probes that are not required. A device for analyzing individual single base polymorphisms.
The method of claim 1,
The device is characterized in that it is operated as a system consisting of units of sales management, inspection management I, inspection management II, and financial management, individual single base polymorphism analysis device.
The method of claim 6,
The sales management unit is characterized in that configured to include product management, customer management, and use management modules, individual single base polymorphism analysis device.
The method of claim 6,
The inspection management I unit is characterized in that configured to include a reception, output, and other inquiry module, individual single base polymorphism analysis device.
The method of claim 6,
The test management Ⅱ unit is characterized in that it comprises a DNA extraction, test, reagent / equipment management, other inquiry, setting, and result report setting module, the individual single base polymorphism analysis device.
The method of claim 6,
The financial management unit, characterized in that configured to include a transaction statement and a sales status module, individual single base polymorphism analysis device.
The method of claim 6,
The system further comprises a system environmental condition, a main function, a statistics, and a system management unit.
The method of claim 11,
The system environmental condition unit is configured to include an environment setting, and a common usage module.
The method of claim 11,
The main function unit is characterized in that configured to include a login, and a main screen module, individual single base polymorphism analysis device.
The method of claim 11,
The statistical unit, characterized in that consisting of a genome research institute, and a finance/sales module, individual single base polymorphism analysis device.
The method of claim 11,
The system management unit is characterized in that configured to include a use management, and a log management module, individual single base polymorphism analysis device.

Images