KR101849879B1 - System and method for genome sequence analysis pipeline - Google Patents

Abstract

The present invention relates to a system and a method for processing a genome sequencing analysis pipeline. The system for processing a genome sequencing analysis pipeline comprises: a user terminal capable of being connected to a web server via the internet or wireless communication with a structure capable of wired/wireless communication; and an execution server (S) accessible via the wires/wireless communication through the user terminal, driving and controlling an application for detailed analysis, newly generating/managing a pipeline for each detailed analysis, and providing the corresponding analysis result in a web reporting form. A customized next generation sequencing (NGS) analysis pipeline for bioinformatics researchers can be composed on the web, and experiments without programming experience can analyze genomic information by using an intuitive user interface (UI) provided in a genome sequencing analysis pipeline processing system.

Description

FIELD OF THE INVENTION [0001] The present invention relates to a genome sequence analysis pipeline system and method,

The present invention relates to a system and a method for processing a genome sequence analysis pipeline. More specifically, the present invention relates to genome sequence analysis pipeline processing systems and methods, in which biotechnology researchers or bioinformatics researchers without programming experience use customized genome information To a system and method for genome sequencing pipeline processing that can be analyzed.

Since the Human Genome Project, Next Generation Sequencing (NGS) has developed rapidly. With the development of IT technology for dealing with large quantities of genetic information at one time (NGS sequencer) and big data (mass information), the cost and time for decrypting individual genome has been dramatically reduced. Thus, the cost of genome sequencing has become very cheap. Inversely, genomic big data is being mass-produced exponentially.

The global NGS market is forecast to grow by 20.5% annually and to USD 12.45 billion by 2022. The genome sector is a rapidly developing field, but Korea has a low level of investment and technology compared to other fields.

With advances in genomic analysis technology, we have been able to go beyond the traditional fractional biotechnology paradigm to study the overall variation of individual genomes and their linkage to disease. It is a field that can generate enormous industrial ripple effect such as customized medical care, microbiological research, and improvement of plant and animal variety.

Currently, there is a shortage of bio information professionals in the domestic genome analysis market, which can analyze large quantities of large genome data. To solve these bottlenecks, collaboration between IT (Information Technology) and BT (Bio Technology) has become indispensable. In the past, if we were focused on hardware (sequencing equipment) that produces large amounts of data through NGS technology, we will need to focus on analytical software to keep pace with the rapid increase in demand for data analysis.

Therefore, it is urgently required to develop a system capable of efficiently processing large-capacity individual genome data based on a high-performance computing infrastructure and integrally analyzing genetic information associated with diseases.

Galaxy in the form of a workflow and tranSMART, DNAnexus, CLC bio, and Illumina's BaseSpace in the precision medical analysis platform (US + Europe), and KT's genome (Bio-Exoress) of National Bio Research Resource Information Center (KOBIC) (shown in FIG. 1 to FIG. 5).

As a result of comparing the above existing platforms, it can be concluded that the conventional platforms have a wide variety of complex workflow forms, which makes it difficult to utilize them for research with various goals, or vice versa, providing researchers with a uniform set of analysis pipelines There has been a problem that it is difficult to attempt analysis with a desired pipeline workflow. In addition, each analysis required a considerable price to pay for data usage, and it was impossible to control the history of analytical data or control the job status of the application because it was not a researcher's server (system). Moreover, public cloud services have many limitations in capitalizing and knowledge of researchers' data. Researchers who need to focus on analytics are spending precious time on simple data processing. These disadvantages were a high stumbling block for researchers who should try various studies.

Accordingly, the present invention is to provide a platform for a Web-based analysis pipeline service capable of efficiently managing and integrating genetic data in order to solve the problems of the conventional platform.

Korean Patent Registration No. 10-1282798 Korean Patent Registration No. 10-1279392

Disclosure of Invention Technical Problem [8] Accordingly, the present invention has been made in view of the above problems, and it is an object of the present invention to provide bio-scientific experiment researchers or bio-informatics researchers who do not have programming experience to perform genome information analysis using an intuitive UI provided by an execution server. The NGS analysis pipeline for bioinformatics researchers can be customized through the web. You can control or check the progress of the analysis from the outside of the laboratory. You can visualize the analysis result by Web reporting method intuitively. And to provide a genome sequencing pipeline processing system and method that enable the genome sequencing analysis pipeline processing system to be provided.

In addition, the present invention reduces unnecessary elements caused by an error occurring in setting environment for script analysis and application execution, facilitates various analysis of the same data, and enables integrated management of previously analyzed data information and history, It is also possible to construct a customized analytical pipeline without the need for a high level of programming skills and to improve the efficiency of research by automating repetitive data analysis processes. And an object of the present invention is to provide a processing system and method.

A genome sequence analysis pipeline processing system using an app system according to an embodiment of the present invention includes a user terminal having a structure capable of wired / wireless communication and being connectable to a web server via the Internet or wireless communication;

It is possible to connect to the user terminal through wired / wireless communication, to run and control the detailed analysis application, to newly create / manage the pipeline for each detailed analysis, and to provide the analysis result in a web reporting format And an execution server (S) for causing the server

In addition, the execution server (S) of the present invention includes a contract agreement processing unit for separately providing a UI provided to each user terminal and business logic;

An application collecting unit for classifying a plurality of data registered in a user terminal into applications and public data and collecting only applications from the classified data;

 A pipeline setting unit for driving and controlling a detailed analysis application collected through the application collecting unit to newly generate and manage a pipeline for each detailed analysis,

And a program providing unit for allowing each component constituting the function of the execution server (S) to be implemented as a screen of a home page in cooperation with a web server.

In addition, the application collected through the application collecting unit of the present invention is analysis software that is published in various academic papers and can be set based on a program that is universally utilized in analysis.

In addition, the pipeline setting unit of the present invention is characterized in that when the public data or the reference data is required in the execution of the pipeline, the reference data can be uploaded in advance and a new pipeline can be constructed.

In addition, the execution server S of the present invention can easily manage the history of the analysis data information and the set values at the analysis by the RDBMS (relational database) interworking process, and apply various data sets to the set pipeline set And it is possible to automate the repetitive data analysis process, thereby improving the efficiency of the research.

The pipeline provided by the execution server S of the present invention includes a QC (Preprocessing, Quality Control and Trimming) analysis, a Genome (Dielectric) analysis, and an RNA-seq / Transcriptome .

Also, according to the simple and intuitive user-oriented UI screen configuration, the execution server S of the present invention allows researchers who are not accustomed to programming to easily access the execution server s, The application can be registered, and the registered application can be combined in the pipeline setting unit to set the pipeline in various forms, and to provide the pipeline through the web page.

In addition, the present invention includes a user registration step (s100) of creating a login or an account so that the "server administrator" can access the execution server (s) using the user terminal;

A data registration step (s200) for registering data through a user terminal registered by the server administrator registered in the user registration step (s100);

An application collecting step (s300) of classifying and collecting only applications among data registered in the data registration step (s200);

And a pipeline setting step (s400) of forming an application collected in the application collection step (s300) into a pipeline.

In the data registration step (s200) of the present invention, the server administrator registers data using a user terminal,

The registered data can be divided into the application and the public data. The application of the classified data is provided to the application collection step (s300), and the published data is the user terminal of the "bio information researcher" The data can be provided as necessary data.

In addition, the pipeline setting step (s400) of the present invention is a step of setting an application collected in the application collection unit as a pipeline,

And further includes a trimming step (s410), an alignment step (s420), and an analysis step (s430) for data analysis.

In addition, the present invention includes a user registration step (S100) of logging in or creating an account so that the user can access the execution server (s) using a user terminal of a "bioinformation researcher" or a user terminal of a "general researcher";

A step S500 of a researcher registered in the user registration step (s100) creating a project through a user terminal and selecting data according to the project;

A step (s600) of selecting a pipeline matching the selected data and providing a set pipeline corresponding thereto;

Driving the provided pipeline (S700) and

And outputting the resultant data and outputting the output data in a report format (s800).

According to the embodiments of the present invention, at least the following effects are obtained.

The present invention constitutes a pipeline for analyzing the next generation genetic sequencing technology (NGS) desired by bioinformatics researchers through the web, and it is possible to control or confirm the progress of analysis from outside the laboratory, The results are presented intuitively on the web.

In addition, the present invention is useful for analyzing methods because it saves unnecessary elements caused by errors in script analysis and environment setting, facilitates various analysis of the same data, and enables integrated management of previously analyzed information data. It is possible to improve the efficiency of the research by automating the repetitive data analysis process.

In addition, the present invention can be configured so that the program provided by the execution server is designed to facilitate the user's convenience, so that the researcher can construct a customized analysis pipeline without having a high level of programming skill, Reporting, and effectively managing data history.

FIG. 1 is a conventional Galaxy CloudMan example screen,
2 is a conventional genome cloud example screen,
3 is a conventional DNAnexus example screen,
4 is a conventional CLC bio example screen,
5 is a conventional CLOSHA (Bio-Exoress) example screen,
6 is a block diagram schematically illustrating a genome sequencing pipeline processing system according to an embodiment of the present invention,
FIG. 7 is a view schematically illustrating application collection using an application collection unit included in a genome sequence analysis pipeline processing system according to an embodiment of the present invention,
8A to 8E illustrate a series of processes designed for a user terminal to access the execution server S and analyze the genome data effectively using a genome sequencing pipeline processing system according to an embodiment of the present invention And is an exemplary screen of the present system,
9 is a flowchart schematically illustrating a process of forming a pipeline by an administrator using a genome sequencing analysis pipeline processing system according to an embodiment of the present invention,
FIG. 10 is a flowchart schematically illustrating a process in which a researcher draws a conclusion using a pipeline using a genome sequencing analysis pipeline processing system according to an embodiment of the present invention.

While the invention is susceptible to various modifications and alternative forms, specific embodiments thereof are shown by way of example in the drawings and will herein be described in detail. It should be understood, however, that the invention is not intended to be limited to the particular embodiments, but includes all modifications, equivalents, and alternatives falling within the spirit and scope of the invention. Like reference numerals are used for like elements in describing each drawing.

The terms first, second, A, B, etc. may be used to describe various elements, but the elements should not be limited by the terms. The terms are used only for the purpose of distinguishing one component from another. For example, without departing from the scope of the present invention, the first component may be referred to as a second component, and similarly, the second component may also be referred to as a first component. And / or < / RTI > includes any combination of a plurality of related listed items or any of a plurality of related listed items.

It is to be understood that when an element is referred to as being "connected" or "connected" to another element, it may be directly connected or connected to the other element, . On the other hand, when an element is referred to as being "directly connected" or "directly connected" to another element, it should be understood that there are no other elements in between.

The terminology used in this application is used only to describe a specific embodiment and is not intended to limit the invention. Many expressions represent plural expressions unless the context clearly dictates otherwise. It is to be understood that the term "comprises" or "having" in the present application does not preclude the presence or addition of features, numbers, steps, operations, components, parts, or combinations thereof described in the specification .

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

Terms such as those defined in commonly used dictionaries are to be interpreted as having a meaning consistent with the contextual meaning of the related art and are to be interpreted as either ideal or overly formal in the sense of the present application Do not.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS In the following, a system and method for processing a genome sequence analysis pipeline according to the present invention will be described in detail with reference to the accompanying drawings.

The dielectric (NGS) analysis pipeline is a well-organized process for effectively analyzing data generated from an experimental equipment called a NGS sequencer (eg Illumina HiSeqX, HiSeq2500, MiSeq, etc.). Bioinformatics researchers utilize various NGS analysis software to analyze genomic data, set up open source based applications (software) for each analysis, and let data flow seamlessly according to the entire analysis process Like software. This is commonly referred to as the NGS analysis pipeline.

To build the analysis pipeline, you need to deploy the application in the corresponding unit analysis, compile and configure it for the server (system) environment. You need to integrate your applications using scripting languages (python, perl, ruby, etc.). At this time, the application of each unit is different from the environment setting and the I / O data format and execution method of the bioinformation analysis tools. Therefore, in order to effectively link them, a flexible integration schema must be implemented considering various exceptions. Professional IT skills and knowledge are essential for this process.

Therefore, the present invention can automate the general research process of a complex genome analysis and make it easy to proceed through the web. In order to solve the secondary problems that may occur when the unit analysis application is executed, To make the study more efficient by not relying on IT any more.

FIG. 5 is a block diagram showing a configuration of a genome sequence analysis pipeline processing system according to an embodiment of the present invention. Referring to FIG.

Referring to FIG. 6, the system includes a user terminal 100 having a structure capable of wired / wireless communication and capable of accessing a web server via the Internet or wireless communication, and a user terminal 100, And an execution server S that can generate and manage a pipeline for each detailed analysis and can provide the analysis result in a web reporting format.

The user terminal 100 includes an integrated unit including a terminal for transmitting data through a wired or wireless Internet network. An input device such as a keyboard and a mouse for inputting various data, an output device such as a monitor and a printer, a transmission / reception device such as a modem or a LAN, a microprocessor or a graphic card And a storage device equipped with various programs for operating or controlling the same, so as to be able to access the Internet network. For example, it is preferable to include at least one personal computer (PC) and / or a notebook computer, and the wireless terminal may be a Personal Communication System (PCS) and / System for mobile communications terminal and / or a personal digital cellular (PDC) and / or a personal handyphone system (PHS) terminal and / or a personal digital assistant (PDA) Phone and / or telematics and / or a wireless data communication terminal and / or a portable Internet terminal.

In the embodiment of the present invention, the user terminal 100 includes a "bio information researcher" user terminal 110 to be used by a "bio information researcher", a "general researcher" user terminal 120 and a server And a "server manager" user terminal 130 for use by the administrator.

This means that the bioinformatic researcher or the system administrator (admin) can access the execution server S and upload data to be referred to in advance when public data (reference data) is required when executing a pipeline (unit analysis application) Line, and allows the general researcher to utilize the set of pipelines set by the administrator.

Therefore, when a general researcher creates a new project to be executed by himself, uploads INPUT DATA, selects a desired analysis pipeline, and executes a job, OUTPUT DATA is obtained as an analyzed result. On the platform, OUTPUT DATA will be provided to the researchers in the form of web reporting.

In the case of the execution server S, a series of processes including mapping, sorting, and reduction are performed in order to analyze data produced in the Next Generation Sequencing (NGS) equipment , "Programmers" who do not have programming experience will be able to work with a pipeline that includes Next Generation Sequencing (NGS) So that it can be analyzed. The execution server S includes a condition agreement processing unit 200, an application collecting unit 300, a pipeline setting unit 400, and a program providing unit 500.

The contract agreement processor 200 determines whether the user terminal 100 connected to the execution server S is the user terminal 110 of the "bio information researcher", the user terminal 120 of the "general researcher" It is possible to determine whether the UI is the user terminal 130 and separately provide the UI and business logic to be provided to each user terminal 100 separately.

Accordingly, the bioinformation researcher user terminal 110 or the server administrator user terminal 130 can upload data to be referred to in advance when public data (reference data) is required when a pipeline (unit analysis application) is executed, Line. The set of pipelines set by admin will be available to general researchers.

 Also, the general researcher user terminal 120 generates a new project to be executed by the user using the pipeline set through the bioinformation researcher user terminal 110 or the server administrator user terminal 130, uploads INPUT DATA, , Select the desired analysis pipeline, and then run the job so that the OUTPUT DATA can be obtained from the analyzed results.

The application collecting unit 300 collects applications to be registered in the bioinformation researcher user terminal 110 or the server administrator user terminal 130. When the public data (reference data) Data can be uploaded in advance, and new pipeline sets can be configured.

Therefore, as shown in FIG. 7, the application collecting unit 300 collects a plurality of open software to apply the same data to various research methods or to reuse the previously analyzed experimental data. Further, the present invention facilitates the management of the history of the analysis data information and the set value at the time of analysis by the RDBMS (relational database) interworking process. Therefore, it is possible to apply various data sets to a set of pipelines once set, so that the efficiency of research can be improved by automating repetitive data analysis processes.

The pipeline setting unit 400 may generate and manage a pipeline for each detailed analysis by driving and controlling the detailed analysis application collected through the application collection unit 300. The pipeline generated by the pipeline setting unit 400 can be provided to the user terminal 100 in a web reporting format through a program providing unit described later.

At this time, the application (analysis software for unit analysis, program) for analyzing system construction is analysis software posted in various academic papers, and it is set based on a program that is universally used for analysis.

The pipeline includes a QC (Preprocessing, Quality Control and Trimming) analysis, a Genome (Analysis) analysis, and an RNA-seq / Transcriptome (Transcriptome) Analysis module.

The QC is the most fundamental step in the dielectric analysis, which removes read errors and maintains a high quality subsequence.

In the trimming stage of the QC analysis, three applications can be selected, and single or multiple selection is possible at this time. In the present invention, the QC analysis is performed separately, and the pipeline is designed by including the genome analysis and the QC analysis step as the preprocessing step in the RNA-Seq analysis.

The genome analysis is divided into de novo assembly and assembly-based variant calling.

The de novo assembly analysis method is a method of assembling a short read to generate a full length sequence without a reference genome. After assembling the genome, the generated sequence can be used as a backbone genome in further studies. The paired-end sequence for constructing the contig and the mate-paired sequence for scaffolding are required as input data. We used SSPACE (Boetzer et al., 2011) open software for scaffolding Platanus (Nishikawa et al., 2015), SOAPdenovo (Luo et al., 2012) and Velvet (Zerbino et al.

The Resequencing (assembly-based variant calling) analysis directly maps to the reference genome or generates a new assembly genome, resulting in SNPs and indels. If the reference genome is deficient or not appropriate, you may get biased results due to mapping errors in finding SNPs. Therefore, in the present invention, a pipeline is constructed as a variant analysis based on a reference genome, and bowtie2 (Langmead et al., 2012), the most widely used mapping tool among alignment software, and BWA (Li et al. ) Was used. Variants calling consisted of GATK (Mckenna et al., 2010) and samtools (Li et al., 2009).

The Transcriptome analysis is one of the important methods for characterizing and understanding phenotype variation in biology, and is also known as RNA-Seq or whole-transcriptome shotgun sequencing, which is used to analyze continuously changing cell transcripts. RNA-Seq can also study alternative splicing, mutation / SNPs, gene fusion, gene alteration, and expression (Maher et al., 2009).

In addition, the pipeline was constructed using the tuxedo pipeline that is currently used in RNA-Seq. After tophat mapping the reads to the reference genome, you can assemble the transcripts with Cufflinks to get FPKM (Fragments per Killobase per transcript in Mapping fragments) values. This is a sequential application of Trinity to sequential processing of large amounts of RNA-Seq readings by combining three independent software modules: Inchworm, Chrysalis, and Butterfly (Grabherr et al. 2011).

8A to 8E are diagrams illustrating a configuration of the program providing unit 500 according to an embodiment of the present invention. Referring to FIGS. 8A to 8E, And is an exemplary screen of the present system for explaining a series of processes designed to connect to the server S and analyze the dielectric data effectively.

The screen of the homepage provided by the web providing method in the program providing unit 500 is composed of an intuitive UI. As shown in FIG. 8B, a menu list is formed in the upper left corner. In the center of the home screen, Statistics, and individual project status.

In addition, it is possible to check the progress of the project in the homepage, to be able to input or output the data including the data area, to confirm the operation of the project and the script in advance when executing the pipeline, So that it can be confirmed.

In addition, as shown in FIG. 8D, a required pipeline is selected from the pipeline provided by the pipeline setting unit 400, and an application of the pipeline can be arbitrarily selected and executed. At this time, application setting is possible and the state of the set application can be displayed.

As described above, according to the simple and intuitive homepage configuration, researchers who are not familiar with programming can easily access the execution server (s), can input data to register an application, and the registered application The pipeline setting unit 400 may be combined to set various types of pipelines and provide them through a web page.

Accordingly, researchers can select various pipelines corresponding to the project through the user terminal 100, input or output data according to the pipelines, and manage various kinds of information such as the progress of the project, list, To be provided or to input data.

6 to 7, the process of setting the pipeline using the system described above and proceeding the project through the set pipeline may be performed as follows.

Specifically, as shown in FIG. 9, a user registration step (SlOO) of creating a login or account for allowing the "server administrator" to access the execution server s using the user terminal 100; A data registration step s200 for registering data through the user terminal 100 by the server administrator registered in the user registration step s100 and the application registration step s200 for collecting and collecting only applications from the data registered in the data registration step s200 An application collection step (s300), and a pipeline setting step (s400) for forming an application collected in the application collection step (s300) into a pipeline.

The user registration step (s100) is a step for accessing the server by logging in through a web page provided by the execution server (s). When the user terminal (130) If the user terminal 110 or 120 of the "bioinformatic researcher" or the "general researcher" is approached, the user can select the project and provide a pipeline corresponding to the project to obtain the result related to the project .

In the data registration step (s200), the server manager registers data using the user terminal 110, and the registered data can be divided into an application and a public data. Among the classified data, the application is provided to the application collection step (s300), and the published data can be provided when the user terminal 110, 120 of the "bio information researcher"

The step of collecting the application (s300) allows various data registered by the server administrator user terminal 130 to be divided into an application and a public data roll, and the application is collected through the application collecting unit 200 of the execution server (s) So that it can be provided to the pipeline setting unit 400.

The pipeline setting step s400 is a step of setting the application collected in the application collecting part 200 as a pipeline. The pipeline setting method includes a trimming step s410, an alignment step s420, And an analysis step (s430).

As shown in Fig. 10, a user who uses a user terminal 110 of a "bio information researcher" or a user terminal 120 of a "general researcher" to log in or make an account so that the user can access the execution server (s) A registration step (SlOO); A step S500 of a researcher registered in the user registration step S100 to create a project through the user terminals 110 and 120 and to select data according to the selected project s500, a pipeline matched to the selected data, A step (s600) of receiving the line, a step (s700) of driving the provided pipeline, and a step (s800) of outputting the data and outputting the output data in a report format.

Therefore, the spirit of the present invention should not be construed as being limited to the above-described embodiments, and all of the equivalents or equivalents of the claims, as well as the following claims, I will say.

100: user terminal
110: "Bioinformatics researcher"
120: "general researcher" user terminal
130: "Server Manager"
S: Execution Server
200: Terms and Conditions Processing Department
300: Application collecting unit
400: Pipeline setting section
500: Program Offering

Claims (1)

A user terminal having a structure capable of connecting to a web server through internet or wireless communication in a structure capable of wired / wireless communication;
It is possible to connect to the user terminal through wired / wireless communication, to run and control the detailed analysis application, to newly create / manage the pipeline for each detailed analysis, and to provide the analysis result in a web reporting format In the execution server (S)
The execution server (S) has a contract agreement processing unit that can separately provide UI and business logic to be provided to each user terminal;
An application collecting unit for classifying a plurality of data registered in a user terminal into applications and public data and collecting only applications from the classified data;
A pipeline setting unit for configuring and managing a new pipeline by driving and controlling trimming, aligning, and analyzing the detailed analysis application collected through the application collecting unit;
A program providing unit for allowing each component constituting the function of the execution server S to be implemented as a screen of a home page in cooperation with a web server
≪ / RTI &
Wherein the pipeline setting unit is configured to upload data to be referred to in advance when public data or reference data is required, and to construct a new pipeline when the pipeline is executed.

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