KR20190023968A - Apparatus and method for clinical genome data set transmitting - Google Patents

Abstract

The invention relates to a method for sharing clinical genome data which shares a series of processes and generation files from the initial generation file of the genomic data to the final generation file in order to obtain the same analysis results by shared institutions. According to the present invention, a method for transmitting a clinical genome data set comprises the steps of: mapping clinical genomic data to generate first data; performing a post-alignment process on the first data to generate second data; detecting a variation from the second data to generate third data; and transmitting all the data and transformation methods of the data.

Description

[0001] APPARATUS AND METHOD FOR CLINICAL GENOME DATA SET TRANSMITTING [0002]

To an apparatus and method for processing genomic data, and more particularly to an apparatus and method for providing processing and transmission for sharing clinical genomic data.

The genomic data was mainly used as research data, not for hospital treatment, but recently it is beginning to be used for medical treatment due to the development of personalized medical care. Recently, conditional screening benefits for gene panel screening have been applied, and interest in analysis of genomic data for clinical use is increasing.

Although it is important to analyze raw data according to NGS (Next Generation Sequencing) test results, it is problematic that the same result can not be obtained when only raw data is shared with other hospitals or institutions. Therefore, a system for smooth sharing of clinical genomic data with other hospitals or institutions is required.

1. U.S. Published Patent US 2015-0095064 (published April 2, 2015) 2. Korean Registered Patent KR 10-12333830 (Registered on February 08, 2013) 3. Korean Patent Publication KR 10-2007-0052673 (Published on May 22, 2007)

According to one embodiment, there is provided a method, at least temporarily implemented by a computer, comprising: mapping clinical genetic data to generate first data; Post-alignment processing the first data to generate second data; Detecting a variation from the second data to generate third data; And transmitting both the data and the methods of transforming the data.

According to another embodiment, the step of mapping the clinical genome data to generate the first data comprises: associating the clinical genome data with the reference genome using an alignment tool; Lt; RTI ID = 0.0 > a < / RTI > set of clinical genomic data.

According to another embodiment, the step of post-alignment processing the first data to generate the second data may include transmitting a set of clinical genome data that rearrange the base sequence in a portion where insertion or deletion occurs according to the mapping A method is disclosed.

According to another embodiment, the step of detecting the mutation from the second data and generating the third data may further comprise the step of generating the third data if the mutation is a single nucleotide variation, insertion or deletion, And information on a chromosomal and genomic coordination information of a breakpoint where the rearrangement occurs in the case of rearrangement. The information on the starting point of the division when the gene copy number is variation, A method of transmitting a set of clinical genomic data including any one of end point position information and copy number change information of a clinical genome.

According to one aspect, there is provided a data processing apparatus comprising: a processing unit for mapping clinical genetic data to generate first data, post-alignment processing the first data to generate second data, and detecting a variation from the second data to generate third data; A storage unit for storing the data; And a transmitter for transmitting both the data and the methods of transforming the data.

According to another aspect, the processor is configured to transmit a clinical genome data set that associates the clinical genome data with a reference genome using an alignment tool and generates first data including positional information of the corresponding reference sequence Lt; / RTI >

According to another aspect of the present invention, there is also provided an apparatus for transmitting a clinical genome data set that generates second data by rearranging a base sequence of a portion where insertion or deletion occurs in the first data according to the mapping.

According to another aspect, the processor is configured to detect a mutation from the second data and to determine whether the mutation is a single nucleotide mutation, an insertion or a deletion, the chromosome, the genomic coordinates, the reference allele, And a chromosome and genome coordination information of a breakpoint where the rearrangement occurs in the case of rearrangement. In case of gene copy number variation, information on the starting point of the division, the end point position information of the division, Or a device that transmits a set of clinical genomic data to generate third data, including any of the change information.

According to one embodiment, there is also provided a computer-readable recording medium embodying a program for performing a method of transmitting the set of clinical genomic data.

FIG. 1 illustrates an existing method of sharing gene data according to an embodiment.
FIG. 2 illustrates a proposed gene data sharing method according to an embodiment.
FIG. 3 illustrates a method of transforming gene data according to an embodiment.
FIG. 4 shows a modification step of gene data according to an embodiment.

Hereinafter, embodiments will be described in detail with reference to the accompanying drawings. However, the scope of the rights is not limited or limited by these embodiments. Like reference symbols in the drawings denote like elements.

The terms used in the following description are chosen to be generic and universal in the art to which they are related, but other terms may exist depending on the development and / or change in technology, customs, preferences of the technician, and the like. Accordingly, the terminology used in the following description should not be construed as limiting the technical thought, but should be understood in the exemplary language used to describe the embodiments.

Also, in certain cases, there may be a term chosen arbitrarily by the applicant, in which case the meaning of the detailed description in the corresponding description section. Therefore, the term used in the following description should be understood based on the meaning of the term, not the name of a simple term, and the contents throughout the specification.

FIG. 1 illustrates an existing method of sharing gene data according to an embodiment. According to one embodiment, a method for sharing clinical genomic data between A and B hospitals is disclosed. In order to share the clinical genome data, NGS raw data (Next Generation Sequencing raw data) is shared as a general method (110). However, if only the NGS raw data is shared, the same analysis result can not be obtained between the A hospital and the B hospital (120).

More specifically, when analysis is performed using NGS raw data, a raw data mapping process, a post-alignment processing process, a variant discovery and annotation process are performed . Since various analysis tools and algorithms are used for each process and the version of each tool may be different, a completely different result is obtained even if the same raw data is used.

Illustratively, but not exclusively, when analyzing NGS data using a product from Illumina, the type of data initially acquired is a FASTQ file. The FASTQ file is a sequence file that records sequence information. However, the same analysis result can not be obtained when only the FASTQ file is shared with another hospital or an institution. Therefore, the proposed gene data sharing method is described below.

FIG. 2 illustrates a proposed gene data sharing method according to an embodiment. According to one embodiment, a method of sharing gene data between the A hospital and the B hospital is disclosed, in which all of the conversion processes of the entire gene data from the FASTQ file to the MAP file are simultaneously shared (210). It is an example only and does not necessarily have the same file extension, but shares the end product including the intermediate product and the process of converting from the raw data that is generated first to the file format that is finally utilized.

When the gene data is shared by the proposed method, the same analysis result (220) can be obtained between the A hospital and the B hospital.

More specifically, the sharing process of 210 is explained. All of the intermediate products and final product data generated through the mapping step of the raw data, the post alignment processing step, the mutation discovery step and the annotation step are all transmitted together with the gene data obtained by the genetic test.

By way of example, but not limitation, the use of the product of Illumina Inc., raw data by genetic analysis can be obtained in the form of a FASTQ file. When raw data mapping is performed using the FASTQ file, a SAM or BAM file can be obtained. The SAM or BAM file is a sequence alignment file mapped to a reference genome. SAM or BAM files are formed depending on which alignment tool or algorithm is used in the raw data mapping process. The SAM or BAM file contains location information of the reference sequence to which each gene fragment is mapped and is used for NGS data analysis. When the post alignment processing is performed using the SAM or BAM file, a VCF or BCF file which is a Variants Call File can be generated. The VCF or BCF file stores information on chromosome and mutation detection and the like. Finally, the VCF or BCF file can be converted into a MAF (Mutation Annotation Format) file. The MAF file contains annotations about the variation, and is the final transformation type.

The FASTQ file is converted into a MAF file through the series of conversion procedures. By sharing the original FASTQ file, SAM or BAM file, VCF or BCF file, MAF file, and conversion tool and algorithm together, the same analysis result can be obtained between A hospital and B hospital.

Although FIG. 1 and FIG. 2 illustrate hospitals, the present invention is not limited thereto, and can be applied to all institutions utilizing dielectric data. More specifically, it can be applied to a case where genomic data is shared with a national research institute or a private gene analysis company in addition to a hospital.

FIG. 3 illustrates a method of transforming gene data according to an embodiment. A raw data mapping step 310, a post-alignment processing step 320, and a variant discovery and annotation step 330.

The primed data mapping step 310 is a step of mapping a base sequence of a short fragment of 50 to 300 bp to a human reference genome. More specifically, base sequences stored in the FASTQ file format can be stored in SAM or BAM file format using an alignment tool.

The post-alignment processing 320 refers to a processing step for reducing false positive variants due to sequencing errors. Except for the case of sequencing the same library to reduce the error caused by the polymerase chain reaction (PCR). In the mapping process, the localization is performed around the insertion or deletion (Indel) because the mapping can not be precisely performed at the positions where the insertion and deletion occur, so that it can be judged as a wrong variant. Since there is no change in the file format (form) in the post alignment processing step, the SAM or BAM file format remains intact and only the contents of the file are changed. The information to be modified may include additional information due to local reordering.

Finally, various mutations can be detected at the stage of 330 (Variant discovery and annotation). Variants can be broadly divided into Single Nucleotide Variant (SNV), Insertion and Deletion, Rearrangement, and Copy Number Variants. And it is detected by using a different kind of program according to the kind of each variation.

In the case of a single nucleotide variation (SNV) or insertion and deletion (Indel), the result is obtained in the form of a VCF file. The VCF file may include information such as chromosome information, genomic coordination, reference allele, variant allele information, and read depth. Also, in case of rearrangement, it does not produce a result in a specific file format, and may include chromosome and genomic coordination information for a breakpoint. In the case of a genetic copy number variation (CNV), it may include information on a starting point of segmentation and information on an end point of the segment, and may include information on the number of replicas as a log value. Each type of mutation may be subjected to annotation together with mutation detection according to a program. In general, in the case of a single nucleotide variation (SNV) or insertion and deletion (Indel), an independent annotation tool can be used to contain information about which gene is located and which variation is reported in another database. have.

FIG. 4 shows a modification step of gene data according to an embodiment. The primary sequencing output may have a BCL (410) file format. And performs conversion into a FASTQ (420) file format, which is a sequence file, using the BCL file. (SAM) or BAM 430 (Sequence Alignment to Reference Genome) information file that is mapped to the reference genome using the FASTQ file. Subsequently, the SAM or BAM file is converted into a VCF or BCF (440) file, which is a Variant Call File (VCF). Finally, an annotated Variant File MAF Annotation File, 450) file.

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 apparatus and components described in the embodiments may be implemented within a computer system, such as, for example, a processor, a controller, an arithmetic logic unit (ALU), a digital signal processor, a microcomputer, a field programmable array (FPA) 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 execution of the software. For ease of understanding, the processing apparatus may be described as being used singly, but those skilled in the art will recognize that the processing apparatus may have a plurality of processing elements and / As shown in FIG. For example, the processing unit may comprise a plurality of processors or one processor and one controller. Other processing configurations are also possible, such as a parallel processor.

The software may include a computer program, code, instructions, or a combination of one or more of the foregoing, and may be configured to configure the processing device to operate as desired or to process it collectively or collectively Device can be commanded. The software and / or data may be in the form of any type of machine, component, physical device, virtual equipment, computer storage media, or device , Or may be permanently or temporarily embodied in a transmitted signal wave. The software may be distributed over a networked computer system and stored or executed in a distributed manner. The software and data may be stored on one or more computer readable recording media.

The method according to an embodiment may be implemented in the form of a program command that can be executed through various computer means and recorded in 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 to be recorded on the medium may be those specially designed and configured for the embodiments or may be available to those skilled in the art of computer software. Examples of computer-readable media include magnetic media such as hard disks, floppy disks and magnetic tape; optical media such as CD-ROMs and DVDs; magnetic media 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 language code such as those 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 devices 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 with reference to the drawings, various modifications and variations may be made by those skilled in the art. For example, it is to be understood that the techniques described may be performed in a different order than the described methods, and / or that components of the described systems, structures, devices, circuits, Lt; / RTI > or equivalents, even if it is replaced or replaced.

Therefore, other implementations, other embodiments, and equivalents to the claims are also within the scope of the following claims.

Claims (9)

In a method at least temporarily implemented by a computer,
Mapping the clinical genomic data to generate first data;
Post-alignment processing the first data to generate second data;
Detecting a variation from the second data to generate third data; And
Transmitting both the data and the data conversion methods
RTI ID = 0.0 > 1, < / RTI >
The method according to claim 1,
Wherein the step of mapping the clinical genome data to generate first data comprises:
And linking the clinical genomic data to a reference genome using an alignment tool and transmitting a set of clinical genomic data comprising positional information of the corresponding reference sequence.
3. The method of claim 2,
Wherein the step of post-alignment processing the first data to generate second data comprises:
And rearranging the nucleotide sequence of the insertion or deletion region according to the mapping.
The method of claim 3,
Wherein the step of detecting the variation from the second data to generate the third data comprises:
Wherein said mutation
A single nucleotide mutation, an insertion or deletion, information on any one of a chromosome, a genome coordination, a reference allele and a mutation allele,
And a chromosome and genome coordination information of a breakpoint at which the rearrangement occurred,
The position information of the start point of the division, the position information of the end point of the division,
How to Transmit a Clinical Genome Data Set
A processing unit for mapping the clinical genome data to generate first data, post-alignment processing the first data to generate second data, and detecting a variation from the second data to generate third data;
A storage unit for storing the data; And
A transmission unit for transmitting both the data and the data conversion methods,
And transmitting the set of clinical genomic data.
6. The method of claim 5,
Wherein,
Associating the clinical genome data with the reference genome using an alignment tool and generating first data including positional information of the corresponding reference sequence
A device for transmitting a clinical genomic dataset.
The method according to claim 6,
Wherein,
And generating a second data by rearranging base sequences of a portion where insertion or deletion occurs in the first data according to the mapping
A device for transmitting a clinical genomic dataset.
8. The method of claim 7,
The processor comprising:
Detecting a variation from the second data,
Wherein said mutation
A single nucleotide mutation, either insertion or deletion, comprises any one of the information of the chromosome, the genomic coordination, the reference allele and the mutation allele,
And a chromosome and genome coordination information of a breakpoint at which the rearrangement occurred,
The third data including any one of the start point information of the division, the end point position information of the division, and the replication number change information in the case of the gene copy number variation
A device for transmitting a clinical genomic dataset.
A method according to any one of claims 1 to 4
A computer-readable medium having embodied thereon a program for performing a method of transmitting a set of clinical genomic data.

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