ISO 25720:2009

Health informatics - Genomic Sequence Variation Markup Language (GSVML)

ISO 25720:2009 is applicable to the data exchange format that is designed to facilitate the exchange of the genomic sequence variation data around the world, without forcing change of any database schema. From an informatics perspective, GSVML defines the data exchange format based on XML. The scope of ISO 25720:2009 is the data exchange format, but the database schema itself is outside the scope of this International Standard. From a biological point of view, all genetic sequence variations are taken into consideration and are within the scope of this International Standard, while polymorphisms, especially SNP, are the main focus of this International Standard. In other words, the annotations of variation as clinical concerns and -omics concerns are within the scope of ISO 25720:2009. Though SNPs exist in various biological species, the scope of this International Standard covers the human health associated species as human, cell line, and preclinical animals. The other biological species are outside the scope of ISO 25720:2009. The clinical field is within the scope of this International Standard, but the basic research fields and other scientific fields are outside the scope of ISO 25720:2009. Here, clinical research including drug discovery is within the scope of this International Standard. As for supposed application fields, our main focus is in human health including clinical practice, preventive medicine, translational research and clinical researches.

Informatique de santé — Langage de balisage de la variation de séquence génomique

General Information

• Status: Published
• Publication Date: 16-Aug-2009
• ICS: 35.240.80 - IT applications in health care technology
• Technical Committee: ISO/TC 215/SC 1 - Genomics Informatics
• Drafting Committee: ISO/TC 215/SC 1/WG 1 - Genomics data sharing
• Current Stage: 9060 - Close of review
• Completion Date: 04-Jun-2029

Overview

ISO 25720:2009 - Genomic Sequence Variation Markup Language (GSVML) defines an interoperable XML-based data exchange format for genomic sequence variation data in human health. The standard targets the representation and interchange of genetic variation annotations - with a primary focus on single nucleotide polymorphisms (SNPs) and short tandem repeat polymorphisms (STRPs) - while allowing expandability to other variation types. ISO 25720:2009 addresses the data exchange format and messaging; database schemas and internal storage models are explicitly outside its scope.

Key topics and requirements

• XML foundation: GSVML is specified using XML, with normative DTD and XML Schema definitions provided as annexes (for machine-readable validation and consistent parsing).
• Scope of biological content: Covers human health–related species (human, cell lines, preclinical animals); non–human species and basic bench research outside scope.
• Variation coverage: All sequence variations are considered; SNPs and STRPs are the core, with annotations for clinical and -omics contexts included.
• Conformance & extensibility: Defines conformance rules for message exchange and is designed to be extensible so implementations can incorporate additional variation types and annotations without changing existing database schemas.
• Clinical focus: Intended primarily for clinical applications (clinical practice, preventive medicine, translational and clinical research, including drug discovery and pharmacogenomics).

Applications

• Standardized exchange of SNP/STRP datasets between laboratories, clinical sites, and research centers.
• Integration of genomic variation data into electronic health records (EHRs) and clinical decision support workflows.
• Interoperable reporting for clinical genomics, pharmacogenomics, and translational research pipelines.
• Data sharing for multicenter clinical studies, variant annotation services, and regulatory submissions where consistent XML encoding is required.
• Enabling downstream analytics, variant interpretation, and cross-database aggregation without forcing changes to local database schemas.

Who should use this standard

• Clinical informaticians and health IT architects implementing genomic data exchange.
• Bioinformaticians and genomic data engineers formatting and validating variation datasets.
• EHR vendors, laboratory information systems (LIS) suppliers, and diagnostic labs exchanging clinical variant data.
• Translational researchers, pharmacogenomics teams, and public-health genomics programs that require interoperable variant messaging.

Related standards

• HL7 (Clinical Genomics use cases and messaging)
• EN 13606 (electronic healthcare record communication)
• DICOM / imaging standards (contextual interoperability)
• Other bio‑markup efforts referenced in the standard: BSML, SBML, Neuro‑ML, dbSNP, JSNP

Keywords: ISO 25720:2009, GSVML, Genomic Sequence Variation Markup Language, SNP, STRP, health informatics, XML, data exchange format, clinical genomics, pharmacogenomics, interoperability.

Standards Content (Sample)

INTERNATIONAL ISO
STANDARD 25720
First edition
2009-08-15
Health informatics — Genomic Sequence
Variation Markup Language (GSVML)
Informatique de santé — Langage de balisage de la variation de
séquence génomique
Reference number
©
ISO 2009
PDF disclaimer
PDF files may contain embedded typefaces. In accordance with Adobe's licensing policy, such files may be printed or viewed but shall
not be edited unless the typefaces which are embedded are licensed to and installed on the computer performing the editing. In
downloading a PDF file, parties accept therein the responsibility of not infringing Adobe's licensing policy. The ISO Central Secretariat
accepts no liability in this area.
Adobe is a trademark of Adobe Systems Incorporated.
Details of the software products used to create the PDF file(s) constituting this document can be found in the General Info relative to
the file(s); the PDF-creation parameters were optimized for printing. Every care has been taken to ensure that the files are suitable for
use by ISO member bodies. In the unlikely event that a problem relating to them is found, please inform the Central Secretariat at the
address given below.
IMPORTANT — The electronic file of this document contains colours which are considered to be
useful for the correct understanding of the document. Users should therefore consider printing this
document using a colour printer.

This CD contains the publication ISO 25720:2009 in portable document format (PDF), which can be viewed
using Adobe® Acrobat® Reader.
Adobe and Acrobat are trademarks of Adobe Systems Incorporated.

©  ISO 2009
All rights reserved. Unless required for installation or otherwise specified, no part of this CD-ROM/DVD may be reproduced, stored in a
retrieval system or transmitted in any form or by any means without prior permission from ISO. Requests for permission to reproduce this
product should be a
...

INTERNATIONAL ISO
STANDARD 25720
First edition
2009-08-15
Health informatics — Genomic Sequence
Variation Markup Language (GSVML)
Informatique de santé — Langage de balisage de la variation de
séquence génomique
Reference number
©
ISO 2009
PDF disclaimer
This PDF file may contain embedded typefaces. In accordance with Adobe's licensing policy, this file may be printed or viewed but
shall not be edited unless the typefaces which are embedded are licensed to and installed on the computer performing the editing. In
downloading this file, parties accept therein the responsibility of not infringing Adobe's licensing policy. The ISO Central Secretariat
accepts no liability in this area.
Adobe is a trademark of Adobe Systems Incorporated.
Details of the software products used to create this PDF file can be found in the General Info relative to the file; the PDF-creation
parameters were optimized for printing. Every care has been taken to ensure that the file is suitable for use by ISO member bodies. In
the unlikely event that a problem relating to it is found, please inform the Central Secretariat at the address given below.

©  ISO 2009
All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized in any form or by any means,
electronic or mechanical, including photocopying and microfilm, without permission in writing from either ISO at the address below or
ISO's member body in the country of the requester.
ISO copyright office
Case postale 56 • CH-1211 Geneva 20
Tel. + 41 22 749 01 11
Fax + 41 22 749 09 47
E-mail [e-mail]
Web www.iso.org
Published in Switzerland
ii © ISO 2009 – All rights reserved

Contents Page
Foreword .iv
Introduction.v
1 Scope.1
2 Conformance .1
2.1 Purpose .1
2.2 Needs and general requirements.1
3 Normative references.2
4 Terms and definitions .2
5 GSVML specification.5
5.1 Specification requirements and GSVML positioning .5
5.2 GSVML structure .5
5.3 GSVML DTD and XML schema.5
6 GSVML development process.5
Annex A (normative) DTD of GSVML .22
Annex B (normative) XML schema of GSVML .46
Annex C (informative) Basic reference works.105
Bibliography.131

Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards bodies
(ISO member bodies). The work of preparing International Standards is normally carried out through ISO
technical committees. Each member body interested in a subject for which a technical committee has been
established has the right to be represented on that committee. International organizations, governmental and
non-governmental, in liaison with ISO, also take part in the work. ISO collaborates closely with the
International Electrotechnical Commission (IEC) on all matters of electrotechnical standardization.
International Standards are drafted in accordance with the rules given in the ISO/IEC Directives, Part 2.
The main task of technical committees is to prepare International Standards. Draft International Standards
adopted by the technical committees are circulated to the member bodies for voting. Publication as an
International Standard requires approval by at least 75 % of the member bodies casting a vote.
Attention is drawn to the possibility that some of the elements of this document may be the subject of patent
rights. ISO shall not be held responsible for identifying any or all such patent rights.
ISO 25720 was prepared by Technical Committee ISO/TC 215, Health informatics.
iv © ISO 2009 – All rights reserved

Introduction
In the current electronic world, there are multiple different types of data for healthcare, as shown in Figure 1.
Besides clinical data and image data, as we move into this post genomic era, we are creating, internationally,
overwhelming amounts of genomic data. The International Standards developing organizations are developing
standards for these data; Health Level Seven develops standards for clinical data, DICOM and JPEG develop
standards for image data. Genomic Sequence Variation Markup Language (GSVML) defines a standard for
genomic data, especially human-related DNA variation data. The core target for the GSVML is the Single
Nucleotide Polymorphism (SNP).
Clinical dataClinical data
HL7HHL7L7
Image data
Genomic data
GSVML
DICOM,JPEG
HL7CG
Figure 1 — Major data types of health care
In this post genomic era, the management of health-related data is becoming increasingly important to both
genomic research and genome-based medicine (see reference [1]). Informational approaches to the
management of clinical, image and genomic data are beginning to have as much worth as basic, bench top
research. Nowadays there are many kinds of -omics data around the world awaiting effective utilization for
human health. The hurdle that must be overcome to achieve this goal is the development of data format and
message standards to support the interchange of -omics data. Genomic data include genome sequence, DNA
sequence variation and other genome-based data such as expression data, proteomics data, molecular
network, etc. As an entry point, this International Standard focuses on the DNA sequence variation. Among
the DNA sequence variation, the SNP is selected as the core object because of the following three reasons.
a) SNP is the most researched sequence variation for human health.
b) In the current context, vast amounts of SNP data exist around the world in various types of data formats.
As a result of the recent explosion in SNP research, the vast amounts of experimental data have been
accumulating in many databases in various types of data formats. These data await utilization in drug
discovery, clinical diagnosis and clinical research.
c) SNP data already have a great impact for human applications such as gene-based medicine and
pharmacogenomics.
With a view to this context, the international community requires an interoperable format for the interchange of
SNP data. Prior to the standardization development, we elucidated the need for data exchange among the
human health-related facilities that have various types of data formats.
In the present circumstances, SNP is expected to be a key to understanding human response to external
stimuli such as any kind of alien invasions, therapies, and the environmental interactions (see reference [2]).
Bacterial infection is an example of alien invasion, and the responses to the infections are different amongst
individuals. According to the therapy, the side effects to a drug are different amongst the patients. These
responses are also different in various environments.
The Markup Language is a set of symbols and rules for their use when doing a markup of a document (see
reference [3]). The first standardized markup language was Standard Generalized Markup Language
[4]
(SGML), which has strong similarities with troff and nroff text layout languages supplied with Unix systems.
[5]
Hypertext Markup Language (HTML) is based on SGML . Extensible Markup Language (XML) is a
pared-down version of SGML, designed especially for Web documents (see reference [6]). XML acts as the
[7]
basis for Extensible HTML (XHTML) and Wireless Markup Language (WML) (see reference [8]) and for
[9]
standardized definitions of system interaction such as Simple Object Access Protocol (SOAP) . By contrast,
text layout or semantics are often defined in a purely machine-interpretable form, as in most word processor
file formats (see reference [10]).
Markup Language for the biomedical field, based on XML, has been in development for several decades to
enhance the exchange data among researchers. Bioinformatic Sequence Markup Language (BSML) (see
[12] [13]
reference [11]), Systems Biology Markup Language (SBML) , Cell Markup Language (Cell ML) , and
[14]
Neuro Markup Language (Neuro-ML) are examples of markup languages. Polymorphism Mining and
[15]
Annotation Programs (PolyMAPr) is centric on SNP and tries to achieve mining, annotation and functional
[16]
analysis of public databases such as dbSNP , the Cancer Gene Anatomy Project (CGAP) (see reference
[17]), and Japanese single nucleotide polymorphisms (JSNP) (see reference [18]) through programming.
To utilize the accumulated SNP data among many facilities around the world, standards for the interchange of
SNP data must be defined. The required standards include defining a data format and exchange messages.
Markup Language is the reasonable choice to address this need. As for genomic data message handling,
[19]
Health Level Seven Clinical Genomics Special Interest Group has summarized clinical use cases for
general genomic data. The GSVML project has contributed to these efforts. Additionally, this work
[20]
incorporated use cases based on the Japanese Millennium Project . Based on these contexts and
investigations, this International Standard elucidates the needs and the requirements for GSVML and then
proposes the specification of GSVML for the international standardization.

vi © ISO 2009 – All rights reserved

INTERNATIONAL STANDARD ISO 25720:2009(E)

Health informatics — Genomic Sequence Variation Markup
Language (GSVML)
IMPORTANT — The electronic file of this document contains colours which are considered to be
useful for the correct understanding of the document. Users should therefore consider printing this
document using a colour printer.
1 Scope
This International Standard is applicable to the data exchange format that is designed to facilitate the
exchange of the genomic sequence variation data around the world, without forcing change of any database
schema. From an informatics perspective, GSVML defines the data exchange format based on XML. The
scope of this International Standard is the data exchange format, but the database schema itself is outside the
scope of this International Standard. From a biological point of view, all genetic sequence variations are taken
into consideration and are within the scope of this International Standard, while polymorphisms, especially
SNPs, are the main focus of this International Standard. In other words, the annotations of variation as clinical
concerns and -omics concerns are within the scope of this International Standard. Though SNPs exist in
various biological species, the scope of this International Standard covers the human health associated
species as human, cell line, and preclinical animals. The other biological species are outside the scope of this
International Standard. The clinical field is within the scope of this International Standard, but the basic
research fields and other scientific fields are outside the scope of this International Standard. Here, clinical
research, including drug discovery, is within the scope of this International Standard. As for supposed
application fields, the main focus is in human health, including clinical practice, preventive medicine,
translational research and clinical researches.
2 Conformance
2.1 Purpose
This International Standard provides a data exchange format for genomic sequence variation data in human
health. This International Standard provides the GSVML specification mainly for the case of SNP and Short
Tandem Repeat Polymorphism (STRP). Considering that SNP and STRP are the major and simple
polymorphisms in human health research, centering on them and expanding the specification to the other
sequence variation data seems reasonable. This International Standard allows for the expandability of
GSVML from SNP and STRP to other sequence variation data.
2.2 Needs and general requirements
The vast volume of experimental data from the recent explosion of genomic sequence variation research has
produced an overwhelming amount of data stored in many databases with various types of format worldwide.
Standardization of data exchange is urgent for managing, analysing, and utilizing these data. Standardizing
the interoperable format is necessary for easy and convenient genomic sequence variation data exchange.
Considering that genomic sequence variation, especially SNP and STRP, has its significant meaning in the
gene-based medicine and the pharmacogenomics for human health, the data exchange format is the key to
enhancing the gene-based clinical research and the gene-based medicine.
The management of genomic data is as critical as the basic research data in this new era. There are many
kinds of -omics data around the world, and the time has come to effectively use these genomic data for
human health. In order to use these data effectively and efficiently, standards must be developed to permit the
interoperable interchange of genomic data globally. These standards must define the data format as well as
the messages to be used to interchange and share this data globally. This International Standard addresses
those requirements, using a Markup Language.
3 Normative references
The following referenced documents are indispensable for the application of this document. For dated
references, only the edition cited applies. For undated references, the latest edition of the referenced
document (including any amendments) applies.
EN 13606 (all parts), Health informatics — Electronic healthcare record communication
4 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
4.1
actor
something or someone who supplies a stimulus to the system
NOTE Actors include both humans and other quasi-autonomous things, such as machines, computer tasks and
systems.
4.2
Bioinformatic Sequence Markup Language
BSML
extensible language specification and container for bioinformatic data
4.3
Cell Markup Language
Cell ML
Extensible Markup Language to provide a standard method for representing and exchanging computer-based
biological models
4.4
Cancer Gene Anatomy Project
CGAP
database containing genomic expression data collected for various tumorgenic tissues in both humans and
mice and also providing information on methods and reagents used in deriving the genomic data
4.5
dbSNP
database of SNPs provided by the US National Center for Biotechnology Information (NCBI)
4.6
Digital Imaging and Communications in Medicine
DICOM
standard in the field of medical informatics for exchanging digital information between medical imaging
equipment (such as radiological imaging) and other systems, ensuring interoperability
4.7
deoxyribonucleic acid
DNA
molecule that encodes genetic information in the nucleus of cells
4.8
DNA sequence variation
differences of DNA sequence among individuals in a population
NOTE DNA sequence variation implies polymorphism (4.20).
2 © ISO 2009 – All rights reserved

4.9
Document Type Definition
DTD
separate document that contains formal definitions of all of the data elements in a particular type of HTML,
SGML or XML document
4.10
entry point
reference point that designate the class(es) from which the messages begin for the particular domain
4.11
gene-based medicine
medicine based on genes or genetic science
4.12
Hypertext Markup Language
HTML
set of markup symbols or codes inserted in a file intended for display on a World Wide Web browser page
4.13
Joint Photographic Experts Group
JPEG
compression technique for images
4.14
Japanese single nucleotide polymorphisms
JSNP
database of Japanese single nucleotide polymorphisms
4.15
markup language
ML
set of symbols and rules for their uses when doing a markup of a document
4.16
Neuro Markup Language
Neuro-ML
markup language for describing models of neurons and networks of neurons
4.17
nroff
unix text-formatting program that is a predecessor of the Unix troff document processing system
4.18
pharmacogenomics
branch of pharmaceutics aiming to develop rational means to optimize drug therapy, with respect to the
patient's genotype
4.19
Polymorphism Mining and Annotation Programs
PolyMAPr
programs for polymorphism database mining, annotation and functional analysis
4.20
polymorphism
variation in the sequence of DNA among individuals
NOTE Polymorphism implies SNP (4.23) and STRP (4.26).
4.21
Systems Biology Markup Language
SBML
markup language for simulations in systems biology
4.22
Standard Generalized Markup Language
SGML
standard for defining description of the structure of different types of electronic documents
4.23
Single Nucleotide Polymorphism
SNP
single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population
4.24
Systematized Nomenclature of Medicine – Clinical Terms
SNOMED CT
dynamic, scientifically validated clinical health care terminology and infrastructure
4.25
Simple Object Access Protocol
SOAP
lightweight protocol for exchange of information in a decentralized, distributed environment
4.26
Short Tandem Repeat Polymorphism
STRP
variable segments of DNA that are two to five bases long with numerous repeats
4.27
troff
document processing system developed by AT&T for the Unix operating system
4.28
variable number of tandem repeat
VNTR
class of polymorphism characterized by the highly variable copy number of identical or closely related
sequences
4.29
Wireless Markup Language
WML
XML language used to specify content and user interface for WAP (wireless application protocol) devices
4.30
Extensible HTML
XHTML
hybrid between HTML and XML specifically designed for net device displays
4.31
Extensible Markup Language
XML
pared-down version of SGML, designed especially for web documents
4.32
XML schema
language for describing the structure and constraining the contents of XML documents
4 © ISO 2009 – All rights reserved

5 GSVML specification
5.1 Specification requirements and GSVML positioning
In the current context, annotative information about genomic sequence variation is increasing, which is filling
in the gaps in information. The genomic sequence variation data themselves are also increasing but are
stored in various databases. This trend is typical of SNP data. The pitfall of genomic sequence variation data
handling is the lack of standardization of the data formats for the genomic sequence variation. Historically, the
markup languages listed in Clause 4 have been used, and programs are developed to handle the genomic
information. However, there have been no genomic sequence variation centric markup languages so far.
GSVML is the first genomic sequence variation centric markup language and is human health centric.
Considering that SNP is a highly researched polymorphism and has a great impact, especially for human
health and response, we can say that GSVML has the greatest potential to be the designated markup
language for human healthcare. On the other hand, setting the applications to practical human health means it
must handle direct or indirect SNP annotations. Here the direct SNP annotation indicates general annotative
information such as SNP associated genes and experimental preparations. The indirect SNP annotation
indicates all of the -omics data and clinical data that result from SNP variation. To understand the gene-based
clinical situation of each patient, we need this kind of additional information. Considering the requirement to
add many kinds of additional information, the development and standardization of GSVML cannot stand alone
and need harmonization with the other international standardization organizations such as Health Level Seven.
GSVML is intended to be used in data exchange messages related to human health. In the development and
standardization of GSVML in this application domain, we must always keep an eye on the patient's safety,
clinical efficiency and medical costs. For the patient's safety, from an informational viewpoint, the conservation
and the protection of patient information are important. For the enhancement of clinical efficiency, simplicity
and ease of understanding are important. For medical cost reduction, the adaptation ability and ease of
installation are important. GSVML tries to respond to these basic requirements by providing the sharable XML
based data exchanging format. GSVML can be used for the clinically genomic sequence variation data
exchange among various types of data formats. In the greater framework of clinical data standardization,
GSVML plays the part of describing the genomic sequence variation data and their necessary information.
5.2 GSVML structure
The outlined structure of GSVML is shown in Figure 3. GSVML consists of three data criteria, viz. variation
data, direct annotation and indirect annotation. The variation data criterion describes the straightforward
variation data as allele, type, position, length, region, etc. The direct annotation criterion describes the
attached data of variation data as experiment analysis, epidemiology or associated gene, etc. The indirect
annotation criterion describes the explanatory/higher-level information of variation data such as the -omics
data, the clinical information and the environmental data. These data criteria have internal relations to each
other. The detailed structure of GSVML is shown in Figures 4 to 21.
5.3 GSVML DTD and XML schema
The DTD of GSVML is shown in Annex A. The XML schema of GSVML is shown in Annex B.
6 GSVML development process
The development of GSVML followed eight steps:
⎯ Step 1: Set the elements and needs according to the investigated use cases.
We prepared six use cases for three typical criteria. Four use cases concerned the clinical practice, and one
use case for each clinical trial and translational research.
⎯ Step 2: Construct the basic structure and DTD.
⎯ Step 3: Investigate the existing biological ML, and its applicability to the needs (comparison with MAGE-
[21]
ML, BSML, SBML, RNAML , ProML, CellML, PolyMAPr).
⎯ Step 4: Refine the basic structure and DTD, construct the XML Schema (XSD).
⎯ Step 5: Investigate the existing SNP databases (their data format comparison).
⎯ Step 6: Check the interface ability to the Health Level Seven Genotype Model.
⎯ Step 7: Redefine the needs of GSVML and its demanded elements.
⎯ Step 8: Refine the basic structure, DTD, and XML Schema.
Figure 2 shows the outline of the process of the development. We did design work in harmony with HL7
Clinical Genomics SIG. There were “to and fro” processes between design work and the standardization
process.
Additionally, we analysed the interface between GSVML and EN 13606, SNOMED-CT.
Use case analysis
Needs and requirement analysis
Data format diversity investigation
Requirement analysis and needs definition
Messaging case analysis
Database schema analysis
Future vision (extensibility)
Sharable format extraction
Additional data format consideration
Messaging design
Application supposition
Collaboration with HL7 CG SIG
GSVML design
Design work
Feedback
ISO standardization process
(verification and justification)

Figure 2 — Outline of the process of GSVML development
6 © ISO 2009 – All rights reserved

Epidemiology
Clinical
Mendelian
Disease
observations Experimental
segregate
analysis
Phenotype
Homozygote
Omics Clinical
detect
annotation
annotation
Variation
annotation
GSVML
Indirect annotation
miscellaneous
Direct annotation
HL7 CG models(DSTU)*
(root)
Environmental
condition
Whole
genome
Variation
sequence
Somatic mutation
Variation data
Personal
type reference
information
Location
Source
Variation
Variation database reference
attribute
information
* HL7 CG models (DSTU) will be used instead of indirect annotation criterion.
Figure 3 — The outlined structure of GSVML
GSVML root
Figure 4 — Detailed structure of GSVML
variation_data 1 - 1
1 - 2
1 - 3
*1…_dbref structure
Figure 5 — Detailed structure of GSVML
8 © ISO 2009 – All rights reserved

1 - 1
1 - 3
1 - 1 - 1
*1
*1
1 - 2
Figure 6 — Detailed structure of GSVML
ass_gene
1 - 1 - 1
Figure 7 — Detailed structure of GSVML
GSVML root
Figure 8 — Detailed structure of GSVML
10 © ISO 2009 – All rights reserved

direct_annotation
2 - 1
2 - 2
2 - 3
*1
Figure 9 — Detailed structure of GSVML
experiment_analysis
variation_identify
*1
2 - 1
2 - 1 - 1
2 - 1 - 2
Figure 10 — Detailed structure of GSVML
12 © ISO 2009 – All rights reserved

publication and submitter
2 - 1 - 1 2 - 1 - 2
*1
*1
Recursive reference allowed
Figure 11 — Detailed structure of GSVML
experiment_analysis
variation_characterize
2 - 2
Figure 12 — Detailed structure of GSVML
14 © ISO 2009 – All rights reserved

1 - 1 - 1
epidemiology
2 - 3 - 1
(Statistical data section)
2 - 3
*1
Figure 13 — Detailed structure of GSVML
disease_epidemiology
2 - 3 - 1
Figure 14 — Detailed structure of GSVML
GSVML root
Figure 15 — Detailed structure of GSVML
16 © ISO 2009 – All rights reserved

3 - 2
indirect_annotation
*1
3 - 3
*1
*1
3 - 1
Figure 16 — Detailed structure of GSVML
3 - 1 - 1
clinical_annotation 2 - 3 - 1
*1
3 - 1 - 2
3 - 1 - 3
3 - 1 - 4
3 - 1
3 - 1 - 5
3 - 1 - 6
*1
3 - 1 - 7
*1
*1
Figure 17 — Detailed structure of GSVML
18 © ISO 2009 – All rights reserved

disease_description
3 - 1 - 3
3 - 1 - 1
3 - 1 - 4
3 -1 -2
3 -1 -7
3 -1 -5
Figure 18 — Detailed structure of GSVML
3 - 1 - 2
3 - 1 - 4
3 - 1 - 3
3 -1 -5
Figure 19 — Detailed structure of GSVML
family_history
3 - 2
3 - 3
3 - 1 - 6
recursive
description
*1
allowed
3 - 1
Figure 20 — Detailed structure of GSVML
20 © ISO 2009 – All rights reserved

therapy
3 - 1 - 7
Figure 21 — Detailed structure of GSVML
Annex A
(normative)
DTD of GSVML