1、 ISO 2017 Health informatics Data elements and their metadata for describing structured clinical genomic sequence information in electronic health records Informatique de sant lments de donnes et leurs mtadonnes pour dcrire linformation structure de la squence gnomique clinique dans les dossiers de
2、sant lectroniques TECHNICAL SPECIFICATION ISO/TS 20428 Reference number ISO/TS 20428:2017(E) First edition 2017-05 ISO/TS 20428:2017(E)ii ISO 2017 All rights reserved COPYRIGHT PROTECTED DOCUMENT ISO 2017, Published in Switzerland All rights reserved. Unless otherwise specified, no part of this publ
3、ication may be reproduced or utilized otherwise in any form or by any means, electronic or mechanical, including photocopying, or posting on the internet or an intranet, without prior written permission. Permission can be requested from either ISO at the address below or ISOs member body in the coun
4、try of the requester. ISO copyright office Ch. de Blandonnet 8 CP 401 CH-1214 Vernier, Geneva, Switzerland Tel. +41 22 749 01 11 Fax +41 22 749 09 47 copyrightiso.org www.iso.org ISO/TS 20428:2017(E)Foreword v Introduction vi 1 Scope . 1 2 Normative references 1 3 T erms and definitions . 1 4 Abbrev
5、iated terms 5 5 Use case scenario . 6 6 Composition of a clinical sequencing report . 7 6.1 General . 7 6.2 Overall interpretation in summary . 8 6.3 Detailed contents 8 7 Fields and their nomenclature of required data . 9 7.1 General . 9 7.2 Clinical sequencing orders .10 7.2.1 General.10 7.2.2 Cli
6、nical sequencing order code 10 7.2.3 Date and time .10 7.2.4 Specimen information 11 7.3 Information on subject of care .11 7.3.1 General.11 7.3.2 Subject of care identifiers 11 7.3.3 Subject of care name 11 7.3.4 Subject of care birth date .11 7.3.5 Subject of care sex11 7.3.6 Subject of care ethni
7、city .11 7.4 Information on legally authorized person ordering clinical sequencing 11 7.4.1 General.11 7.5 Performing laboratory .12 7.5.1 General.12 7.5.2 Basic information on performing laboratory .12 7.5.3 Information on report generator 12 7.5.4 Information of legally confirmed person on sequenc
8、ing report .12 7.6 Associated diseases and phenotypes 12 7.7 Biomaterial information 12 7.7.1 General.12 7.7.2 Types of sample .12 7.7.3 Genomic source class in biomaterial .12 7.7.4 Conditions of specimen that may limit adequacy of testing .12 7.8 Genetic variations 13 7.8.1 General.13 7.8.2 Gene s
9、ymbols and names 13 7.8.3 Sequence variation information 13 7.9 Classification of variants 14 7.9.1 General.14 7.9.2 Classification of variants based on the pathogeny 14 7.9.3 Classification of variants based on clinical relevance .15 7.10 Recommended treatment .15 7.10.1 General.15 7.10.2 Classific
10、ation of variants based on clinical relevance .15 7.10.3 Clinical trial information 15 7.10.4 Known protocols related to a variant .16 7.10.5 Other recommendation .16 ISO 2017 All rights reserved iii Contents Page ISO/TS 20428:2017(E)7.11 Addendum 16 8 Fields and their nomenclature of optional data
11、.16 8.1 General 16 8.2 Medical history 17 8.3 Family history/Pedigree information 17 8.4 Reference genome version .17 8.5 Racial genomic information 18 8.6 Genetic variation 18 8.7 Detailed sequencing information .18 8.7.1 Clinical sequencing date .18 8.7.2 Quality control metrics 18 8.7.3 Base call
12、ing information 18 8.7.4 Sequencing platform information 19 8.7.5 Analysis platform information 20 8.8 References 20 Annex A (informative) Example structure of clinical sequencing report 21 Annex B (informative) Example layout of clinical sequencing report 28 Bibliography .32 iv ISO 2017 All rights
13、reserved ISO/TS 20428:2017(E) 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 interes
14、ted 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 C
15、ommission (IEC) on all matters of electrotechnical standardization. The procedures used to develop this document and those intended for its further maintenance are described in the ISO/IEC Directives, Part 1. In particular the different approval criteria needed for the different types of ISO documen
16、ts should be noted. This document was drafted in accordance with the editorial rules of the ISO/IEC Directives, Part 2 (see www .iso .org/ directives). 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 responsi
17、ble for identifying any or all such patent rights. Details of any patent rights identified during the development of the document will be in the Introduction and/or on the ISO list of patent declarations received (see www .iso .org/ patents). Any trade name used in this document is information given
18、 for the convenience of users and does not constitute an endorsement. For an explanation on the voluntary nature of standards, the meaning of ISO specific terms and expressions related to conformity assessment, as well as information about ISOs adherence to the World Trade Organization (WTO) princip
19、les in the Technical Barriers to Trade (TBT) see the following URL: w w w . i s o .org/ iso/ foreword .html. The committee responsible for this document is ISO/TC 215, Health informatics. ISO 2017 All rights reserved v ISO/TS 20428:2017(E) Introduction Based on the rapid advancement of sequencing te
20、chnologies, clinical sequencing has been highlighted as one of methods to realize personalized medicine and precision medicine. There are lots of sequencing data in the public domain with clinical information 1 . In addition, genome-scale clinical sequencing is being adopted broadly in medical pract
21、ice 2 . Many hospitals have started to sequence patients whole genome, whole exome, or targeted genes using the next generation sequencing technologies. These genomic data obtained by next generation sequencing technologies can be used for both clinical purposes to diagnose patients and choose the r
22、ight medications and research purposes. Therefore, the management of genomic and clinical data is increasingly highlighted to precision medicine, clinical trial and translational research 3 . However, until now, there is no international standard for representing clinical sequencing results with a s
23、tructured format for electronic health records, in consequence, the necessary genomic test results are not efficiently delivered to the clinicians. There are a few related standards for modelling genetic testing results (i.e. ISO 25720 and several HL7 documents from HL7 clinical genomics working gro
24、up). However, these standards or drafts are mainly focused on the traditional genetic testing results for a single gene test. Based on the rapid development and adoption of next generation sequencing techniques which can detect diverse genetic variants in genome level, there is, therefore, still a n
25、eed to develop a standard to present clinical sequencing data in such a way they become useful for clinicians 4 . To implement a structured clinical sequencing report in electronic health records, all necessary data fields should be defined and the metadata for each chosen field should be defined. F
26、or example, it needs to be determined which vocabulary, in particular gene descriptions and/or disease codes, can be applied in particular fields. In ISO TC 215, GSVML (Genomic Sequence Variation Markup Language) was proposed for interoperability of genomic variants, especially for single nucleotide
27、 polymorphism (SNP) data 5 . HL7 is also developing a domain analysis model for genomics using HL7 version 3 6and fast healthcare interoperability resources (FHIR) 7 . Recently, to facilitate genomic information, SMART on FHIR Genomics has been developed 8,9 . The Clinical Data Interchange Standard
28、Consortium (CDISC) published a study data tabulation model implementation guide: pharmacogenomics/genetics 10 . Several other international organizations such as Global Alliance for Genomics and Health (GA4GH), Actionable Genome Consortium, and Displaying and Integrating Genetic Information Through
29、the EHR (DIGITizE) of Institute of Medicine in US, tried to develop the similar standards. The working group of the American College of Medical Genetics and Genomics Laboratory Quality Assurance Committee published the ACMG clinical laboratory standards for next-generation sequencing 11 . In additio
30、n, web-based tools become available that link genotypic information to phenotypic information, and exchanging information and using it in personalized medicine can be very helpful 12 . In this document, to enable the standard use of patient genomic data from clinical sequencing for healthcare purpos
31、es as well as for clinical trials and research, the metadata for a clinical sequencing report for electronic health records will be developed. It further explains how and where particular appropriate terminological systems that describe the genomes and/or diseases can be applied in these fields. By
32、defining the necessary fields with structured format based on coded data that adhere themselves to terminological principles such as concept representation and governance, this document can help implement clinical decision support service.vi ISO 2017 All rights reserved Health informatics Data eleme
33、nts and their metadata for describing structured clinical genomic sequence information in electronic health records 1 Scope The document defines the data elements and their necessary metadata to implement a structured clinical genomic sequencing report and their metadata in electronic health records
34、 particularly focusing on the genomic data generated by next generation sequencing technology. This document defines the composition of a structured clinical sequencing report (see Clause 5), defines the required data fields and their metadata for a structured clinical sequencing report (see Clause
35、6), defines the optional data (see Clause 7), covers the DNA-level variation from human samples using whole genome sequencing, whole exome sequencing, and targeted sequencing (disease-targeted gene panels) by next generation sequencing technologies. Though whole transcriptome sequencing and other te
36、chnologies are important to provide better patient care and enable precision medicine, this document only deals with DNA-level changes, covers mainly clinical applications and clinical research such as clinical trials and translational research which uses clinical data. However, the necessary steps
37、such as de-identification or consent from patient should be applied. The basic research and other scientific areas are outside the scope of this document, does not cover the other biological species, i.e. genomes of viruses and microbes, and does not cover the Sanger sequencing methods. 2 Normative
38、references There are no normative references in this document. 3 T erms a nd definiti ons For the purposes of this document, the following terms and definitions apply. ISO and IEC maintain terminological databases for use in standardization at the following addresses: ISO Online browsing platform: a
39、vailable at h t t p :/ www .iso .org/ obp IEC Electropedia: available at h t t p :/ www .electropedia .org/ 3.1 allele one of several alternate forms of a gene which occur at the same locus on homologous chromosomes and which become separated during meiosis and can be recombined following fusion of
40、gametes SOURCE: ISO 16577:2016, 3.6 TECHNICAL SPECIFICATION ISO/TS 20428:2017(E) ISO 2017 All rights reserved 1 ISO/TS 20428:2017(E) 3.2 benign alterations with very strong evidence against pathogenicity 3.3 biomaterial materials taken from the human body such as tissue, blood, plasma or urine 3.4 c
41、hromosome structure that comprises discrete packages of DNA and proteins that carries genetic information which condense to form characteristically shaped bodies during nuclear division SOURCE: ISO 19238:2014, 2.7 3.5 clinical sequencing next generation sequencing or later sequencing technologies wi
42、th human samples for clinical practice and clinical trials 3.6 ClinVar freely accessible, public archive of reports of the relationships among human variations and phenotypes, with supporting evidence Note 1 to entry: h t t p:/ www .ncbi .nlm .nih .gov/ clinvar/ . 3.7 copy number variation CNV varia
43、tion in the number of copies of one or more sections of the DNA 3.8 Catalogue of Somatic Mutations in Cancer COSMIC online database of somatically acquired mutations found in human cancer Note 1 to entry: h t t p:/ cancer .sanger .ac .uk/ cosmic. 3.9 dbSNP database of SNPs provided by the US Nationa
44、l Center for Biotechnology Information (NCBI) Note 1 to entry: h t t p s :/ www .ncbi .nlm .nih .gov/ SNP/ . 3.10 deletion mutation in which a part of a chromosome or a sequence of DNA is lost during DNA replication 3.11 deoxyribonucleic acid DNA molecule that encodes genetic information in the nucl
45、eus of cells SOURCE: ISO 25720:2009, 4.7 3.12 DNA sequencing determining the order of nucleotide bases (adenine, guanine, cytosine and thymine) in a molecule of DNA Note 1 to entry: Sequence is generally described from the 5 end.2 ISO 2017 All rights reserved ISO/TS 20428:2017(E) SOURCE: ISO/TS 1782
46、2-1:2014, 3.20 3.13 exome part of the genome formed by exons 3.14 gene basic unit of hereditary material that encodes and controls the expression of a protein or protein subunit SOURCE: ISO 11238:2012, 2.1.16 3.15 gene panel technique for sequencing the targeted genes in a genome 3.16 genomic medici
47、ne medical discipline that involves using genomic information about an individual as part of their clinical care (e.g. for diagnostic or therapeutic decision-making) and the health outcomes and policy implications of that clinical use 3.17 germline series of germ cells each descended or developed fr
48、om earlier cells in the series, regarded as continuing through successive generations of an organism 3.18 indel insertion (3.19) or/and deletion (3.10) 3.19 insertion addition of one or more nucleotide base pairs into a DNA sequence 3.20 inversion chromosome rearrangement in which a segment of a chr
49、omosome is reversed end to end 3.21 large indel insertion or deletion up to 1 kb 3.22 likely benign alterations with strong evidence against pathogenicity Note 1 to entry: Targeted testing of at-risk family members not recommended. 3.23 likely pathogenic alterations with strong evidence in favor of pathogenicity 3.24 pathogenic characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses t
