KR102056583B1 - Workfloq management apparatus, method, and computer program - Google Patents

Abstract

According to the specification of the present invention, a workflow management method comprises: a step of allowing a workflow management apparatus to store a first project specified for a client included in a meeting schedule by a request from a first user terminal after the meeting schedule included in the first user terminal; a step of allowing the workflow management apparatus to generate one or more tasks corresponding to quality inspection, genome analysis, library generation, and release according to the mission to be executed by the first project; a step of determining the execution condition of the one or more tasks and determining a person in charge of each task in consideration of the execution condition; a step of generating a workspace for a specific task of the first project in the workspace of the person in charge of each task; and a step of executing a task of inspecting the quality of a sample according to one or more tasks included in the first project. The present invention can manage a genome analysis task to be processed to meet the deadline set by a client.

Description

WORKFLOQ MANAGEMENT APPARATUS, METHOD, AND COMPUTER PROGRAM}

The present invention relates to a workflow management apparatus, method, and computer program for genome analysis tasks.

A genome is all the genetic information of a living thing. As a technology for sequencing a genome of an individual, various technologies such as DNA chips, Next Generation Sequencing technology, and Next Next Generation Sequencing technology are being developed. Next-generation sequencing can be used interchangeably with large-scale parallel sequencing or second-generation sequencing.

The genome data generated by next-generation sequencing machines can be as few as tens or hundreds of gigabytes. The analysis of genomic data uses a combination of tools that implement algorithms that perform different functions. In genomic data analysis, each tool is used for each step and each tool is developed individually by different groups. Thus, a genome analysis pipeline is being developed that integrates these individual tools, manages inputs and outputs, and automates all stages of genome data analysis.

The background art described above is technical information possessed by the inventors for the derivation of the present invention or acquired during the derivation process of the present invention, and is not necessarily a publicly known technique disclosed to the general public before the application of the present invention.

(Patent Document 1) Korean Unexamined Patent Publication No. 2017-0065541

According to an embodiment of the present invention, there is provided a workflow management apparatus, method and computer program of a genome analysis task.

According to an embodiment of the present invention, a workflow management method specifies a client included in the meeting schedule by a request from the first user terminal after the meeting schedule included in the first user terminal. Wearing the first project; Generating, by the workflow management device, one or more tasks corresponding to quality inspection, genome analysis, library generation, and release according to a mission to be performed in the first project; Determining an execution condition of the one or more tasks and determining a person in charge of each task in consideration of the execution condition; Creating a workspace for a specific task of the first project in a workspace of a person in charge of each task; And executing a task of checking a quality of a sample according to one or more tasks included in the first project.

In the workflow management method according to the present embodiment, after executing the task of inspecting the quality of the sample, in order to analyze the genome of the sample, an external genome sequencing device is used to inspect the quality of the sample and the sample. Delivering a report, and forwarding the genomic analysis request of the sample; may further include.

The workflow management method according to the present embodiment receives the genome analysis report of the sample from the genome sequence analysis apparatus after the step of transmitting the genome analysis request of the sample, and the quality of the genome analysis report is preset reference condition. Determining whether or not to satisfy, and if the criterion is satisfied, converting the genome analysis report into a library.

In the workflow management method according to the present embodiment, after the step of converting to the library, the library generation result is transmitted to the first user terminal, and when the conform signal is received by the first user terminal, the library The method may further include converting a generation result into a final report of the first project and transferring the final report to a client of the first project.

In the workflow management method according to the present embodiment, after the step of delivering to the client of the first project, the personal information is removed from the information of the object of the sample to generate sample identification information converted and generated, and the by-product of the first project And storing the results of the phosphorus, the quality of the sample, the result of the genome analysis, and the library generation in correspondence with the sample identification information, and managing the search results based on the individual attribute information included in the sample identification information. Further comprising, workflow management method of genomic analysis task.

Workflow management method according to embodiments of the present invention comprises the steps of the workflow management apparatus for wearing the first project generated by the first user terminal; Specifying a mission to be performed by the workflow management apparatus through the first project, and generating at least one task included in the first project in consideration of the first project and the mission; Transmitting, by the workflow management device, a request for checking a quality of a sample received in response to the first project to an account of a first performer, and monitoring whether a quality result of the sample is generated; When the workflow management device receives the quality result of the sample, the workflow management apparatus determines whether the quality of the sample exceeds a preset reference value, and when the quality of the sample exceeds the reference value, Transmitting a signal requesting an experiment to an account of a second performer different from the first performer, and receiving a quality result of the sample through the account of the second performer; The workflow management apparatus compares the quality result of the sample from the first performer and the quality result of the sample from the second performer, selects one quality result, and considers the one quality result. Generating a library using the genome obtained from the sample; Delivering the library to the first user terminal and waiting for a conform signal for the library; And when the conform signal for the library is received from the first user terminal, transferring the library to a terminal of a client of the first project.

Communication unit according to the embodiments of the present invention; And a processor; wherein the processor is configured to generate a first project specified as a client included in the meeting schedule by a request from the first user terminal after the meeting schedule included in the first user terminal. Receive one or more tasks corresponding to the quality inspection, genome analysis, library generation, and release according to the mission to be performed in the first project, determine the execution conditions of the one or more tasks, and consider the execution conditions Determine a person in charge of each task, create a workspace for a specific task of the first project in the work space of the person in charge of each task, and determine the quality of the sample according to one or more tasks included in the first project. It can be characterized in that to execute the task to check the.

A computer program according to an embodiment of the present invention may be stored in a medium to execute any one of the workflow management methods according to an embodiment of the present invention using a computer.

In addition, there is further provided a computer readable recording medium for recording another method for implementing the present invention, another system, and a computer program for executing the method.

Other aspects, features, and advantages other than those described above will become apparent from the following drawings, claims, and detailed description of the invention.

According to embodiments of the present invention, the apparatus, method, and computer program for managing a genome analysis task may manage the genome analysis task to be processed according to a request date of a client using the genome analysis apparatus.

In addition, according to embodiments of the present invention, the apparatus, method, and computer program for managing a genome analysis task may appropriately select a plurality of performers in charge of the genome analysis task so that the genome analysis task may be properly delivered to a client. .

1 is a block diagram of a workflow management system according to embodiments of the present invention.
2 is a view showing a workflow management apparatus according to an embodiment of the present invention.
3 to 6 are flowcharts of a workflow management method according to embodiments of the present invention.
7 and 8 are flowcharts illustrating a method of operating a genetic analysis apparatus according to an embodiment of the present invention.
9 to 12 are exemplary diagrams of user interfaces provided by a workflow management apparatus according to embodiments of the present invention.

As the invention allows for various changes and numerous embodiments, particular embodiments will be illustrated in the drawings and described in detail in the written description. Effects and features of the present invention, and methods of achieving them will be apparent with reference to the embodiments described below in detail together with the drawings. However, the present invention is not limited to the embodiments disclosed below but may be implemented in various forms.

In this specification, a project means one order, and the status is completed after the delivery to the client. If additional work is requested from the same client using the same sample, the project will be created. A project contains a project number and a project name that exist only on the system, and the project number can be identified with an order number or an order number.

An order form exists for each project and is prepared by the sales person, and may include information about the client who requested the project, order amount, service name, details, delivery date, and sample information.

The customer sample number is the number or name assigned by the customer to the sample from the client. The customer sample number is a number assigned by the customer and may not be uniquely assigned to each project.

The specimen number is a number assigned by the system to the work object and may be newly assigned as the work object changes.

The sample name is the sample number that the system attaches to the sample when the sample is received, not the library. The sample name may be set to include a preset character, and for example, may be set to start with 's'.

The sample QC name is quality information that is performed on the sample, that is, identification information of QC (Quality Control).

The library name means information for identifying a library created from a sample or a library received from a customer.

The job number is an identification number on the system that gives a job to be done on the job target.

The sales person refers to the user who creates the project through sales and is ultimately responsible for the whole process from goods receipt to goods issue. The operator refers to the user who is responsible for working in the company from the receipt of the project to the release of the project. The operator is responsible for responding to customers and answering customer questions.

Throughout the specification, “sequence (read)” refers to base pair information on analytical quantities generated from deoxyribonucleic acid (cDNA) or cDNA (complementary DNA) fragments included in a sequencing library. By meaning, it may include fragments of output data, sequences (base sequences), resulting from sequencing. Such sequences may be about 10bp to about 2000bp, about 15bp to about 1500bp, about 20bp to about 1000bp, about 20bp to about 500bp or about 20bp to about 200bp.

Throughout the specification, "paired end read" means that the DNA sequence is obtained at the 5 'end of both of the double strands of the insert, which is generally represented by 2x "y". , “y” may include analytical amounts (lengths) of base sequences that can be read at a time from base pairs (eg, 2 × 100 bp, 2 × 150 bp).

Throughout the specification, “mapping” may include comparing the sequence read of a subject (individual, patient) with a reference genome.

Throughout the specification “baits” may include the generic name of oligonucleotides (ie, probes) responsible for the identification and binding of sites of interest in performing target enrichment.

Throughout the specification, "fastq file" is basic data for analysis and may include sequence ID, nucleotide sequence information, nucleotide sequence quality, and the like.

Throughout the specification, the term "binary alignment / map format file" is a result file in which each sequence of the fastq file is mapped to a standard nucleotide sequence, and is a binary (binary) method of a SAM file (sequence alignment / map format file). In the version, it can be the result obtained in the second stage of data analysis.

Throughout the specification, a “vcf file (variant call format file)” may include a file containing variant information.

Throughout the specification, the term “annotation file” may include a file that describes which genes are included in each variation included in the vcf file.

Throughout the specification, the term “report” may include a final file including sample information and information about each variation.

The workflow management apparatus 100 according to the embodiments of the present invention relates to an analysis apparatus for performing genome analysis, and processes such as receipt of a project generated by a business operator, quality inspection, library production, run, analysis, and release. It is a device implemented to be delivered to the client via.

The workflow management apparatus 100 generates a project by the sales person, and performs a function of managing until the generated project is completed. The workflow management apparatus determines a person in charge of performing each task step of the project in order to complete the project, and determines a detailed deadline for the task by each person in charge to be completed by the deadline.

The workflow management apparatus 100 may manage one or more projects that have been performed and samples received from clients to utilize the newly registered project.

The workflow management apparatus 100 may analyze the results of each work step included in the project and determine the suitability of each work step in order to improve the quality of the result of the project.

1 is a block diagram of a workflow management system according to embodiments of the present invention.

The workflow management apparatus 100 refers to a digital device having a computing power by mounting a processor as a digital device. The workflow management apparatus 100 may be implemented as a web server that provides a service in response to a request of a client terminal.

The workflow management apparatus 100 may communicate with a terminal 300 of a user performing a task and may provide a notification message indicating a deadline for performing a user's task properly, or provide a space for a task. Alternatively, the workflow management apparatus 100 may transmit and receive data between a plurality of performers performing one project. The workflow management apparatus 100 may open a communication channel between the first performer and the second performer performing a project, or may open a communication channel between the manager and the performer of the project.

The workflow management apparatus 100 may communicate with the genome sequencing apparatus 200 as necessary in performing the process of receiving and shipping the project.

The genome sequencing device 200 refers to a digital device having a computing capability by mounting a processor as a digital device. The genome sequence analysis apparatus 200 may be connected to an intranet network, and may analyze the genome sequence according to a request from the workflow management apparatus 100.

The genome sequence analysis apparatus 200 may include a preprocessing step of calculating a quality score for at least one sequence included in the genetic information of the subject, and removing the sequence less than a reference quality score; An extraction step of extracting reliable mutation information by comparing the sequential sequence and the human genome standard sequence after the pretreatment step, calculating a difference, and setting selection criteria; And comparing the similarity with respect to the variation information and the human genome standard sequence, and performing one or more annotations including location information and genetic information about the variation information and interpreting what function is performed. It can be included in the method.

The method of operating the genome sequence analysis apparatus 200 may further include a generation step of generating a report in a format in which a customer can recognize the processing result of the extraction step and the interpretation step.

The preprocessing step may include repeating the removal of the sequence and calculating the quality score until the quality score for the sequence is greater than or equal to the reference quality score.

The extracting step may include: a mapping step of aligning the sequence with the human genome standard sequence by comparing the sequence and the human genome standard sequence passed through the preprocessing step; A removal step of removing duplicate sequences generated at the time of amplification by a polymerase chain reaction (PCR) from the sequence sequences arranged through the mapping step; A rearrangement step of performing local rearrangement on the cleaved sequence that has undergone the removal step that has not been mapped due to insertion or deletion; A recalibration step of generating a recalibration table based on predetermined covariates specified in relation to the nature of the sequence, and recalibrating the base quality score as a score for the estimated error per base; And an excavation step of discovering the variation information based on the degree to which extent is mapped to the human genome standard sequence compared to the sequence of the recalibration.

The genome sequence analysis apparatus 200 may include a preprocessing unit configured to calculate a quality score for at least one sequence included in the genetic information of the subject, and to remove the sequence less than a reference quality score; An extraction unit for comparing the single sequence and the human genome standard sequence passed through the pretreatment step, calculating a difference, and extracting reliable mutation information by setting selection criteria; And an analysis unit that compares similarity between the variation information and the human genome standard sequence, performs one or more annotations including location information and genetic information about the variation information, and interprets a function. It may include.

The genome sequence analysis apparatus 200 may further include a generator configured to generate a report in a format in which a customer can recognize the processing results of the extractor and the interpreter.

The preprocessing unit may repeat the removal of the sequence and the calculation of the quality score until the quality score for the sequence is greater than or equal to the reference quality score.

The extracting unit compares the sequence obtained by the pretreatment step with the human genome standard sequence, aligns the sequence with the human genome standard sequence, and polymerase chain reaction (PCR) from the aligned sequence. Remove the redundant sequence generated at the time of amplification), perform local rearrangement on the removed sequence that has not been mapped due to insertion or deletion, and Generate a recalibration table based on certain covariates specified in relation to the nature of the column, recalibrate the base quality score as a score for speculative errors per base, and perform the recalibration Variation information can be uncovered by comparing the sequence with the human genome standard sequence and to what extent and to what location.

A plurality of users participating in the project may communicate with the workflow management apparatus 100 using the user terminal 300.

The plurality of user terminals 301, 302,..., 30 n, hereinafter 300 refer to a communication terminal capable of using a web service in a wired / wireless communication environment. Here, the user terminal 300 may be a personal computer of the user or may be a portable terminal of the user. In FIG. 1, the portable terminal 3002 is illustrated as a smart phone, but the spirit of the present invention is not limited thereto. As described above, a terminal equipped with an application capable of web browsing may be borrowed without limitation.

In more detail, the user terminal 300 may include a computer (eg, desktop, laptop, tablet, etc.), a media computing platform (eg, cable, satellite set-top box, digital video recorder), a handheld computing device ( PDAs, email clients, etc.), any form of cell phone, or any other type of computing or communication platform, but the invention is not so limited.

Meanwhile, the communication network 400 connects the plurality of user terminals 300 and the workflow management apparatus 100. That is, the communication network 400 refers to a communication network that provides a connection path so that the user terminals 300 may transmit and receive data after connecting to the workflow management apparatus 100. The communication network 400 may be, for example, wired networks such as local area networks (LANs), wide area networks (WANs), metropolitan area networks (MANs), integrated service digital networks (ISDNs), wireless LANs, CDMA, Bluetooth, satellite communications, and the like. Although it may encompass a wireless network, the scope of the present invention is not limited thereto.

2 is a diagram illustrating a workflow management apparatus 100 according to an embodiment of the present invention.

As shown in FIG. 2, the workflow management apparatus 100 may include a processor 110, a communication unit 120, an input / output unit 130, a storage medium 140, and a database 150.

The processor 110 controls the overall operation of the workflow management apparatus 100. The processor 110 may refer to a data processing apparatus embedded in hardware, for example, having a physically structured circuit for performing a function represented by a code or an instruction included in a program. As an example of a data processing device embedded in hardware, a microprocessor, a central processing unit (CPU), a processor core, a multiprocessor, and an application-specific integrated device (ASIC) It may include a processing device such as a circuit, a field programmable gate array (FPGA), etc., but the scope of the present invention is not limited thereto.

The communication unit 120 enables data communication between the workflow management apparatus 100 and the user terminals 300, and the workflow management apparatus 100 and the genome sequence analysis apparatus 100. The communication unit 120 may be a device including hardware and software necessary for transmitting and receiving a signal such as a control signal or a data signal through a wired or wireless connection with another network device.

The input / output unit 130 means a means for inputting data for the user to control the workflow management apparatus 100 and a means for outputting processed data. For example, the input / output unit 130 may include a key pad, a dome switch, a touch pad (contact capacitive type, pressure resistive type, infrared sensing type, surface ultrasonic conduction type, and integral type). Tension measurement method, piezo effect method, etc.), a jog wheel, a jog switch, and the like. In addition, when the input / output unit 130 and the touch pad form a layer structure and constitute a touch screen, the input / output unit 130 may be used as an input device in addition to the output device. The input / output unit 130 may include a liquid crystal display, a thin film transistor-liquid crystal display, an organic light-emitting diode, a flexible display, and a three-dimensional display. 3D display, an electrophoretic display. In addition, the workflow management apparatus 100 may include two or more input / output units 130 according to an implementation form of the workflow management apparatus 100. In this case, the two or more input / output units 130 may be disposed to face each other using a hinge.

The storage medium 140 performs a function of temporarily or permanently storing data processed by the processor 110. Here, the storage medium 140 may include a magnetic storage media or a flash storage media, but the scope of the present invention is not limited thereto.

The storage medium 140 may include instructions implemented to perform an operation of the workflow management apparatus 100.

The storage medium 140 may move to a screen for creating an order form at the request of a business operator and generate a project according to the created order form.

The storage medium 140 may include a program that performs a function of receiving a first project specified by a client included in the meeting schedule by a request from the first user terminal after the meeting schedule included in the first user terminal. Can be stored. Here, the meeting schedule may be obtained through a schedule management program stored in the first user terminal. For example, if a meeting with a client is scheduled on March 22 in the first user terminal, the first project specified as the client of the meeting may be generated on March 29, one week after the meeting. . Through this, a project may be automatically generated only by a meeting schedule with a customer without input through the first user terminal. This eliminates the risk of the first user terminal missing the generation of the project that occurred in the meeting. In another embodiment, a project may be generated by considering a title, content, and sender included in the mail by using the mail received by the first user terminal.

The storage medium 140 subdivides the project into detailed tasks according to missions to be performed through the project. The storage medium 140 may generate tasks such as receipt, quality inspection, genome analysis, library generation, and release for genome analysis, which is a mission to be performed in a project.

The storage medium 140 determines a person in charge of each task in consideration of the nature of each task included in the project, and performs a function of creating a workspace for a project in each person's account. At this time, the decision of the person in charge may consider the schedule of the person in charge as well as the ability and performance of each person. In the case of the first task that must be performed from the first time point, any person in charge is determined among the person in charge whose schedule is empty at the first time point.

It contains commands that create a workspace that keeps up with the release of the project and make it accessible by the project manager. After the project is released, the authority will be changed so that each person in charge cannot read or write.

The storage medium 140 includes instructions for generating and executing a task for checking the quality of a sample received from a customer.

Storage medium 140 includes instructions for delivering a report and a genome analysis request for quality testing of the sample and the sample to an external genome sequencing device for analyzing the genome of the sample.

The storage medium 140 includes instructions for receiving a genome analysis report of the sample from a genome sequence analysis device and determining whether the quality of the genome analysis report satisfies a predetermined reference condition. Instructions included in the storage medium 140 may generate a genome analysis report as a library when the reference condition is satisfied.

After generating the library, the library generation result is transmitted to the first user terminal, and when the conform signal is received by the first user terminal, the library generation result is converted into the final report of the project and the final report is Can be delivered to the client.

After transferring to the client of the project, the storage medium 140 may include instructions for generating sample identification information converted by removing personal information from the object information of the sample.

The storage medium 140 stores the quality results, the genome analysis results, and the library generation results of the samples which are by-products of the project in correspondence with the sample identification information, and manages them to be provided according to a search request based on individual attribute information included in the sample identification information. It may include instructions to.

The database 150 may store and manage the project name, sample identification information, sample information, object information, sample quality test result, genome analysis result, and library generation result for later projects. In this case, personal information may be prevented from being leaked by deleting the personal information included in the quality test result, genome analysis result, and library generation result of the sample.

3 to 6 are flowcharts of a workflow management method according to embodiments of the present invention.

As shown in Figure 3, the workflow management method according to the embodiments of the present invention is a receipt step (S100), manpower management step (S200), quality inspection step (S300), library generation step (S400), shipping step It may include (S500).

In S100, the workflow management apparatus 100 receives a project generated by a sales person in response to a request of a customer after a meeting with a customer. In the receiving step (S100), the project is received through the step of generating an order form including the sample received from the customer and the customer's request.

In S200, the workflow management apparatus 100 may specify a mission to be performed through a project and generate one or more tasks included in the project. The workflow management apparatus 100 determines the performer of each task. Detailed steps of S200 will be described in FIG. 4.

In S300, the workflow management apparatus 100 requests quality control of a sample of the project. The workflow management apparatus 100 measures the quality of the sample received from the customer. The workflow management apparatus 100 determines whether the received sample is suitable for generating a library. If the received sample is not suitable for generating a library, the workflow management apparatus 100 re-executes the quality check on the sample. If the characteristics, conditions, and quality (eg, concentration, volume, etc.) of the sample do not meet the preset library generation conditions (respective reference values), the quality check on the sample may be performed again. Whether to re-execute the quality check can be determined at the request of the person in charge besides the characteristics of the sample itself.

In S400, the workflow management apparatus 100 designs the library using the genome (DNA / RNA) obtained from the sample after the sample quality test is performed. The workflow management apparatus 100 compares the first result with respect to the sample quality and the second result that has been retested, selects a result having a higher quality, condition, characteristic, and the like, and selects higher quality, condition, characteristic, and the like. Uses the results to perform the library design. At this time, the first result and the second result may be selected by a selection input by the person in charge. At this time, the standard for determining the quality varies depending on the sample. For example, in the case of DNA, the quality may be determined according to concentration, quality, purity, gel electrophoresis, and the like. In the case of RNA, concentration, quantity, and purity can be the criteria. Criteria for judging quality for each library may vary for each item.

For example, the sample quality results can be produced in one library, independently or in bundles. When the "Individual Library" button is selected, the sample quality results are produced as a single library independently, and when the "Pulling Library" button is selected, the sample results checked by the user are pooled and generated as a design. Is added to

At this time, the library name is differentially assigned to the previously created library name before generating the library for the project. The values in the library referral information are filled with the values in the order form.

Workflow management method according to embodiments of the present invention performs the function of managing the manpower for the generated project. Workflow management method according to an embodiment of the present invention comprises the steps of receiving an order written from the operator (S110); Registering the first sample received from the customer (S120); Generating a first project based on the order form and the first sample, and receiving the first project into a workflow (S130); Generating tasks corresponding to quality control, library generation, sequencing, and release that are included in the received first project (S210); Determining persons in charge of tasks included in the first project and a completion date (S220); And adding a space corresponding to the first project to an account of persons in charge of tasks included in the first project (S230).

In S110, the workflow management apparatus 100 receives an order form by the sales person. In S120, the workflow management apparatus 100 registers the first sample received from the customer by the operator.

In S130, the workflow management apparatus 100 generates a first project based on the order form and the first sample and allows the first project to be received in the workflow. The workflow management apparatus 100 sets the release target date according to the completion request date of the first project.

In S210, the workflow management apparatus 100 generates one or more tasks included in the first project. In S220, the workflow management apparatus 100 determines the person in charge and completion date information of the tasks, respectively. The workflow management apparatus 100 divides and manages the employees belonging to the experiment team and the research team. If the nature of the tasks belongs to the experiment team, the workflow management apparatus 100 may assign the staff to the operations team. Users belonging to the experiment team can perform tasks such as quality inspection and sequencing results. The operations team can perform quality checks, quality checks such as sequencing results, determine the designed library, and complete the report with the determined library design. The workflow management apparatus 100 may determine a person in charge of each task in consideration of the nature of each task and the work range of the users to which the task belongs.

In S230, the workflow management apparatus 100 adds a space for the first project to the account of each person in charge. Space for the first project can be maintained from receipt to release of the first project. The space for the first project can be deleted after delivery, at the request of the customer. The workflow management apparatus 100 may delete personal information included in the first project and convert the personal information into re-edited data and store the data.

After the manpower of S200 is assigned, processes for confirming once more the status of the first performer in charge of sample quality management may be further performed.

In S311, the workflow management apparatus 100 checks whether the state of the first performer is busy. In operation S313, when the state of the first performer is not busy, the workflow management apparatus 100 transmits a signal for requesting a quality check to an account of the first performer determined first.

In operation S312, when the state of the first performer is busy, the workflow management apparatus 100 may set a different performer than the first performer. At this time, the workflow management apparatus 100 determines one performer from the performer group including the work scope of the first performer. Through this, the workflow management apparatus 100 manages the shipment time of the first project to be performed in accordance with the demand of the customer, and may proceed with the replacement of the representative in consideration of the workload, current status, etc. of the persons in charge of each task.

In S400, the workflow management apparatus 100 checks the sequencing result, analyzes the generated sequencing result, and performs a function of generating a library including the analyzed result.

Analysis of the sequencing results will be described with reference to FIGS. 6 to 9.

Here, the design of the library can be determined as one of the outputs of the projects that have been carried out before. Multiple sample library designs may be determined taking into account the designs of the libraries included in the result report delivered to the customer.

6 is a diagram schematically illustrating a genetic analysis apparatus according to an embodiment of the present invention. Referring to FIG. 6, the genetic analysis apparatus 200 may include a preprocessor 210, an extractor 220, an analyzer 230, and a generator 240.

Genetic analysis apparatus 200 analyzes the sequence of the gene using the genetic information obtained from the subject and the standard gene information obtained from the normal population, and a single nucleotide variation (single) to the test gene of the subject through the sequence analysis of the gene The presence of mutant genes in the genome, such as nucleotide variants (SNV) or copy number variants (CNV), can be identified. Herein, a single nucleotide variant (SNV) ”may refer to a single nucleotide substitution, unlike a copy number variant (CNV) in a gene, in which a relatively large region is deleted or amplified repeatedly. .

Gene information received by the genetic analysis apparatus 200 may correspond to gene information of a fastq file obtained by next generation sequencing (NGS). The fastq file may be in a text-based format that normally stores biological sequences, such as nucleotide sequences, and corresponding quality scores. However, the gene analysis apparatus 200 according to the present embodiment is not limited to the fastq file, and the gene information of another file may also be analyzed. The genetic analysis apparatus 200 may generate a bam file, a SAM file, a vcf file, an annotation file, and a report using the fastq file as an input.

Standard genetic information obtained from a normal population is known in the art, such as the National Center for Biotechnology Information (NCBI), Gene Expression Omnibus (GEO), Food and Drug Administration (FDA), My Cancer Genome, or Food and Drug Administration (KFDA). It may be obtained from a database (DB) already known in the art, or from a biological sample of people recruited for analyzing the test genes of the subject. That is, standard genetic information obtained from a normal population may be obtained from public genomic data or public map data. On the other hand, reference genes included in the standard gene information obtained from the normal population or test genes included in the gene information obtained from the subject, biopsy tissue, formalin-fixed tissue or paraffin-embedded (Formalin-fixed, paraffin-embedded) ) May be obtained from an organization.

In order for the genetic analysis apparatus 200 to generate mutation information of a subject, three processes, namely, filtering a sequence of a subject, finding a variant of the sequence, and analyzing a variant, are required. It may further include a generation process.

The preprocessing unit 210 is the above-described sequence filtering of the subject, in order to obtain accurate mutation information from the genetic information acquired from the subject, that is, one or more sequences obtained from the subject, an adapter of the sequence The part containing the sequence and the base of poor quality can be removed. You can use the cutadapt program to do this. The program identifies and removes adapter sequences that contain each sequence, calculates the average quality score of the sequence, and if the value is below the user-selected quality threshold (for example, quality score <20). We can then repeat this operation starting from the end of the sequence, trimming one by one and calculating the quality score again with the remaining bases until the mean is above the reference quality score. Trimming can start from the 3 'end or the 5' end, depending on the user's choice. When the length of the finally obtained sequence is smaller than the reference value selected by the user (for example, 50bp), the corresponding sequence may be removed, and the filtering of the sequence may be terminated. The preprocessing unit 110 is the above-described sequence filtering of the subject, in order to obtain accurate mutation information from the genetic information acquired from the subject, that is, one or more sequences obtained from the subject, an adapter of the sequence It may include one or more pretreatment modules to remove the portion containing the sequence and a base of poor quality. In response to the analysis request, the preprocessor 210 may select a preprocessing module corresponding to the analysis request from one or more preprocessing modules in consideration of an analysis target, an analysis group, and a client's disposition.

The extraction unit 220 is a process of finding the variant of the above-described sequence, comparing the pre-filtered sequence and the human genome standard sequence, calculating a difference, and then selecting selection criteria to extract reliable mutation information. One or more extraction modules that perform mapping, polymerase chain reaction (PCR) duplication removal, local realignment, base recalibration, variant discovery, and variant filtering. The extractor 120 may select an extraction module corresponding to the analysis request from one or more extraction modules in consideration of the analysis target, the analysis group, the client's disposition, etc. in response to the analysis request.

The extraction unit 220 may use a burrows-wheeler aligner (BWA) to effectively map a subject sequence to a human genomic reference sequence (UCSC build hg19). The data after mapping of the subject sequence and the human genome standard sequence can be immediately sorted in standard sequence order using the Samtools program.

Extraction unit 220 may remove the duplicate sequence generated when amplification by polymerase chain reaction (PCR) from the sequence arranged through the mapping, Samtools 0.1.18 for accurate variant discovery Version of the program can be used to remove duplicate sequences generated during amplification by PCR

The extraction unit 220 may perform local realignment with respect to the above-described removal sequence that is not mapped due to insertion or deletion. The extraction unit 220 may perform local rearrangement using the GATK Lite 2.3.9 version program from the bam file generated in the previous step, and mismatches of the entire sequence through partial rearrangement of the sequence This is to minimize the number of bases to be added and may include the following two detailed procedures.

First we determine a suspicious short interval that seems to require rearrangement. You can then perform partial indel realigner across these intervals, and perform local rearrangement of the sequence sequences that caused misalignment due to indels.

The extraction unit 220 generates a recalibration table based on a predetermined variable (covariate) related to the nature of the sequence using the base recalibrator option provided by the GATK Lite 2.3.9 program. The quality score of the base as a score for can be recalibrated. User-definable variables can include sequence groups, previously reported quality scores, machine cycles, and nucleotide contexts.

Extraction unit 220 may compare the sequence of the recalibration step with the human genome standard sequence to find out the variation information to what extent and how much is mapped. Here, the extraction unit 220 may discover variants using the UnifiedGenotyper option provided by the GATK Lite 2.3.9 program, which may predict the genotype and location of the variant with the highest probability using the Bayesian genotype likelihood model.

The analysis unit 230 compares the similarity between the extracted variation information and the human genome standard sequence, performs one or more annotations including location information and genetic information on the discovered variation information, and performs a certain function. Can be interpreted. That is, the analysis unit 230 may perform annotations to secure positional information and genetic information of the genome of each variation based on the information of the human genome standard sequence NCBI build GRCh37 (hg19). To perform variant annotations, you can use snpEff, one of the commonly used tools. The commenting database used is clinvar, dbsnp, dbnsfp, cosmic DB, and the variant notation can follow the HGVS standard nomenclature. The analysis unit 230 is a process for finding variants of the above-described sequence, comparing the sequences obtained through the preprocessing (filtering) process and the human genome standard sequence, calculating a difference, and then selecting selection criteria to extract reliable mutation information. One or more extraction modules may be used to perform mapping, PCR (polymerase chain reaction) duplication removal, local realignment, base recalibration, variant discovery, and variant filtering. The analysis unit 230 may select an analysis module corresponding to the analysis request from one or more analysis modules in consideration of the analysis target, the analysis group, the client's disposition, etc. in response to the analysis request.

The generation unit 240 may include one or more generation modules for generating a report in a format that can be recognized by a customer of the processing results of the extraction module and the analysis module. In response to the analysis request, the generation unit 240 may select a generation module corresponding to the analysis request from one or more generation modules in consideration of the analysis target, the analysis group, and the propensity of the requested client.

In order to collectively process the same process for a plurality of samples included in one set, an integrated processor and a parallel processor may be further included. The integrated processor (not shown) allocates the first virtual region, which connects the first preprocessing module, the first extraction module, and the first analysis module to the first process, to the storage medium. The parallel processor (not shown) processes each task in parallel to analyze the subjects included in each group included in each of the received one or more analysis requests.

7 and 8 are flowcharts illustrating a method of operating a genetic analysis apparatus according to an embodiment of the present invention. Gene analysis method according to an embodiment of the present invention can be performed in the gene analysis apparatus 200 with the help of the peripheral components as shown in FIG. In the following description, the description overlapping with the description of FIG. 6 will be omitted.

Referring to FIG. 7, in step S310, the genetic analysis apparatus 200 calculates a quality score for at least one sequence included in the genetic information of the subject, and removes the sequence below the reference quality score. Among the one or more pretreatment modules, a first pretreatment module corresponding to the analysis target of the first group is selected. Since the operation of the first preprocessing module is the same as the operation of the preprocessing unit 110, redundant description thereof will be omitted.

The genetic analysis apparatus 200 identifies and removes the adapter sequence containing each sequence, and then calculates an average quality score of the sequence so that the value is less than the quality reference value selected by the user (for example, the quality score). If <20), the sequence can be trimmed one by one from the end and the quality scores are calculated again with the remaining bases and repeated until the mean is above the reference quality score. When the length of the finally obtained sequence is smaller than the reference value selected by the user (for example, 50bp), the corresponding sequence may be removed, and the filtering of the sequence may be terminated.

In step S320, the genetic analysis apparatus 200 compares the pre-processing step sequence with the human genome standard sequence, calculates a difference, sets a selection criterion, and extracts reliable variation information from among one or more extraction modules. The first extraction module corresponding to the analysis target of the group is selected.

After S320, the genetic analysis apparatus 200 compares the similarity with respect to the variation information and the human genome standard sequence, performs one or more annotations including the position information and the genetic information about the variation information, and performs Among the one or more analysis modules for interpreting a function to be performed, a first analysis module corresponding to the analysis target of the first group is selected. The genetic analysis apparatus 200 allocates to the storage medium a first virtual region in which the first preprocessing module, the first extraction module, and the first analysis module are connected in an integrated first process. The genetic analysis apparatus 200 repeatedly performs a first process on each of one or more subjects included in the first group.

8 shows a specific process of the disparity information extraction step (S320). Referring to FIG. 8, in step S321, the genetic analysis apparatus 200 performs a mapping step of aligning the sequences with the human genome standard sequences by comparing the presequenced sequences with the human genome standard sequences.

In step S322, the genetic analysis apparatus 200 performs a removal step of removing the redundant sequence generated in the amplification by the polymerase chain reaction (PCR) from the sequence sequence arranged through the mapping step.

In step S323, a rearrangement step of performing local rearrangement on the sequence sequence having undergone the removal step in which mapping is not performed due to insertion or deletion is performed.

In step S324, the genetic analysis apparatus 200 generates a recalibration table based on a predetermined variable (covariate) specified in relation to the nature of the sequence, and the quality of the base as a score for the estimated error per base. Perform a recalibration step to recalibrate the score.

In step S325, the genetic analysis apparatus 200 performs the excavation step of discovering the variation information in which position and how much is compared to the sequence sequence recalibrated with the human genome standard sequence.

Returning to FIG. 7, in step S330, the genetic analysis apparatus 200 compares the extracted variation information and the similarity with respect to the human genome standard sequence, and includes one or more annotations including location information and genetic information about the variation information. Run the solver and interpret the function to interpret what function it performs.

In operation S340, the gene analysis apparatus 100 performs a generation step of generating a report in a format in which the customer can recognize the processing results of the extraction step S320 and the analysis step S330.

The workflow management method according to the embodiments of the present invention may additionally create a space for a task for a task included in a project. The workflow management method includes searching for one or more samples corresponding to the received first project; Measuring the quality of the first sample; Designing and generating a first library of the first project in consideration of a first sample exceeding a quality criterion and the nature of the first project; Requesting sequencing for the designed first library; In response to the request, receiving a result of the sequencing; Measuring the quality of the results of the sequencing; And when the quality of the result of the sequencing exceeds a preset second reference value, outputting the result of the first project to the account of the seller or the account of the client.

9 to 12 are exemplary diagrams of user interfaces provided by a workflow management apparatus according to embodiments of the present invention.

An administrator of the workflow management apparatus may view a screen 900 that provides a project status.

The screen 900 for providing a project status may provide status information of registered projects. Provides the status of the project in which the goods receipt step was performed in the step 1 area, and provides the status of the project in which the quality inspection step was performed in the step 2 area. Mark as "Waiting" in the Receipt phase for a project that has received a request from a customer but has not yet been formally filed. In the step 2 area related to the quality inspection step, the number of pending projects and the number of projects in progress can also be provided. Project information in the library creation step can be provided in the step 3 area. The project information in the run phase can be provided in the step 4 area. In the run step, a sequence (electronic information) is obtained from the generated library (biochemical material). The library can be loaded into the sequencer, set up the sequencer, and then operated. If the sequencer ends successfully, a sequence (file) is created on the connected storage device. From start to finish the run can be counted as the execution of the run step. The run step may be performed by a person in charge of the experimental unit. Project information in the analysis phase of analyzing the genome can be provided in the step 5 area. After the analysis is completed, project information in the shipping stage can be provided in step 6 area. The number of projects waiting for each step and the number of projects in progress can be provided on the screen.

Information about the projects is project name (R11), service (R12), commissioning agency (R13), customer (R14), log, progress (R15), sales person (R16), operator (R17), order date (R18), customer The signature (R19), the function (R20), etc. can be arranged in one column and provided.

Here, the progress state may be represented by filling as much as performed in the form of a progressive bar.

Client: The agency that commissioned the project

-Customer: The name of the customer belonging to the client

-Log: It shows the log or conversation of the practitioners left in the service. If there is a log, click to check the most recent log entry.

Progress status: show the progress of the entire process as a progress bar

-Operator, operator

-Order date: the date you ordered the project

-Customer Signature: Indicates if the customer signed the order

-Function: You can download or upload the order form of the project.

The screen shown in FIG. 9 may also be provided through terminals of operators of each project. The screen shown in FIG. 9 may be set to be provided to users with the authority of operation and sales of each project. The workflow management apparatus may be implemented such that a screen provided based on a task, role, authority, etc. of each user is changed.

Fig. 10 is a diagram showing the format of an order form created by a sales person.

Order form (ID1), customer's country information (ID2), project type (ID3), order class (ID4), price information (ID5), project creation date (ID6), order date (ID7), delivery date ( ID8), service ID9, order amount Data 1, customer and institution Data 2, contact person Data 3, and the like. In particular, it can provide information about one or more people who work on each project. Clicking on the first contact person in the contact person list establishes a communication channel for communicating with the first contact person and allows a conversation with the first contact person. In addition, the second contact person in the contact person list can be clicked to perform a function of replacing with another contact person.

11 is a diagram showing a log of a project.

The log of the project will show the opinions shared during the project. The log of the project is number (R31), subject (R32), content and creation date (R33), classification (R34), reception (R35), status (R36), project and service (R37), sponsor and customer (R38). ), And so on.

The number R31 may include an identifier assigned to each log. The topic R32 is set by the log creator for each log and is information that briefly expresses the main opinions included in each log.

The classification R34 may include whether a request included in the log is processed when the log includes tasks that a person in charge needs to process, that is, a request. The project and service R37 may include information about the project and the service related to the log.

12 is an example of a sample information list screen managed by a workflow management device.

The sample information list screen provides information about the sample obtained from the customer. The sample information list screen includes sample name (R41), customer sample name (R42), customer sample name (file) (R43), material (R44), goods receipt status (R45), goods receipt status details (R46), major classification (R47). , Usage amount R48, sample CG status R49, internal / external service R50, execution R51, function R52, and the like.

The apparatus described above may be implemented as a hardware component, a software component, and / or a combination of hardware components and software components. For example, the devices and components described in the embodiments are, for example, processors, controllers, arithmetic logic units (ALUs), digital signal processors, microcomputers, field programmable gate arrays (FPGAs). Can be implemented using one or more general purpose or special purpose computers, such as a programmable logic unit (PLU), a microprocessor, or any other device capable of executing and responding to instructions. The processing device may execute an operating system (OS) and one or more software applications running on the operating system. The processing device may also access, store, manipulate, process, and generate data in response to the execution of the software. For ease of understanding, the processing device may be described as one used, but those skilled in the art will appreciate that the processing device includes a plurality of processing elements and / or a plurality of types of processing elements. It can be seen that it may include. For example, the processing device may include a plurality of processors or one processor and one controller. In addition, other processing configurations are possible, such as parallel processors.

The software may include a computer program, code, instructions, or a combination of one or more of the above, and configure the processing device to operate as desired, or process it independently or collectively. You can command the device. Software and / or data may be any type of machine, component, physical device, virtual equipment, computer storage medium or device in order to be interpreted by or to provide instructions or data to the processing device. Or may be permanently or temporarily embodied in a signal wave to be transmitted. The software may be distributed over networked computer systems so that they may be stored or executed in a distributed manner. Software and data may be stored on one or more computer readable recording media.

Method according to the embodiment is implemented in the form of program instructions that can be executed by various computer means may be recorded on a computer readable medium. The computer readable medium may include program instructions, data files, data structures, and the like, alone or in combination. The program instructions recorded on the media may be those specially designed and constructed for the purposes of the embodiments, or they may be of the kind well-known and available to those having skill in the computer software arts. Examples of computer-readable recording media include magnetic media such as hard disks, floppy disks, and magnetic tape, optical media such as CD-ROMs, DVDs, and magnetic disks, such as floppy disks. Magneto-optical media, and hardware devices specifically configured to store and execute program instructions, such as ROM, RAM, flash memory, and the like. Examples of program instructions include machine code, such as produced by a compiler, as well as high-level language code that can be executed by a computer using an interpreter or the like. The hardware device described above may be configured to operate as one or more software modules to perform the operations of the embodiments, and vice versa.

Although the embodiments have been described by the limited embodiments and the drawings as described above, various modifications and variations are possible to those skilled in the art from the above description. For example, the described techniques may be performed in a different order than the described method, and / or components of the described systems, structures, devices, circuits, etc. may be combined or combined in a different manner than the described method, or other components. Or even if replaced or replaced by equivalents, an appropriate result can be achieved.

Therefore, other implementations, other embodiments, and equivalents to the claims are within the scope of the claims which follow.

Claims (6)

In the workflow management method,
After the meeting schedule included in the first user terminal, by the workflow management apparatus, wearing a first project specified as a client included in the meeting schedule by a request from the first user terminal;
Generating, by the workflow management device, one or more tasks corresponding to quality inspection, genome analysis, library generation, and release according to a mission to be performed in the first project;
Determining, by the workflow management apparatus, an execution condition of the one or more tasks and determining a person in charge of each task in consideration of the execution condition;
Generating, by the workflow management apparatus, a workspace for a specific task of the first project in a workspace of a person in charge of each task; And
Executing, by the workflow management apparatus, a task of checking a quality of a sample according to one or more tasks included in the first project;
Forwarding, by the workflow management device, the report on the sample and the quality test of the sample to an external genomic sequencing device to analyze the genome of the sample, and forwarding a genome analysis request of the sample;
The workflow management apparatus receives the genome analysis report of the sample from the genome sequence analysis apparatus, determines whether the quality of the genome analysis report satisfies a predetermined reference condition, and when the reference condition is satisfied, the Converting the genome analysis report into a library; And
And providing, by the workflow management device, a screen for providing a first project status to the first user terminal.
The screen providing the first project status is
The progress step of the first project is expressed as one of a goods receipt step, a quality inspection step, a library generation step, a run step, an analysis step, a delivery step, and is implemented to vary according to the authority of the first user terminal
The project name, service, client, log, progress status, salesperson, operator, order date, customer signature, and function assigned to the first user terminal are provided.
And when the first project is in the run step, the workflow management apparatus loads the library into the sequencer, sets the sequencer of the library, and generates the sequencer in the connected storage device.
delete delete delete A computer program stored in a computer readable storage medium for carrying out the method of claim 1 using a computer.
Communication unit; A workflow management apparatus comprising a;
The processor is
After the meeting schedule included in the first user terminal, the first project specified by the client included in the meeting schedule is received by a request from the first user terminal,
Create one or more tasks corresponding to quality inspection, genome analysis, library generation, and release according to the mission to be performed in the first project,
Determine an execution condition of the one or more tasks, determine a person in charge of each task in consideration of the execution condition,
Create a workspace for a specific task of the first project in the workspace of the person in charge of each task,
Executing a task of checking the quality of a sample according to one or more tasks included in the first project,
To analyze the genome of the sample, send a report on the sample and the quality test of the sample to an external genomic sequencing device, forward a request for genome analysis of the sample,
Receiving a genome analysis report of the sample from the genome sequencing device, determining whether the quality of the genome analysis report satisfies a predetermined reference condition, and if the reference condition is satisfied, converting the genome analysis report to a library. To convert,
Providing a screen for providing a first project status to the first user terminal,
The screen providing the first project status is
The progress step of the first project is represented as one of a receipt step, a quality inspection step, a library generation step, a run step, an analysis step, a delivery step, and is implemented to vary according to the authority of the first user terminal.
The project name, service, client, log, progress status, salesperson, operator, order date, customer signature, and function assigned to the first user terminal are provided.
When the first project is in the run stage, the workflow management apparatus loads the library into the sequencer, sets the sequencer of the library, and generates the sequencer in the connected storage device. Workflow Management Device.

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