ISO/TS 20428:2017
(Main)Health informatics — Data elements and their metadata for describing structured clinical genomic sequence information in electronic health records
Health informatics — Data elements and their metadata for describing structured clinical genomic sequence information in electronic health records
ISO/TS 20428:2017 defines the data elements and their necessary metadata to implement a structured clinical genomic sequencing report and their metadata in electronic health records particularly focusing on the genomic data generated by next generation sequencing technology. ISO/TS 20428:2017 - 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 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 technologies 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 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.
Informatique de santé — Éléments de données et leurs métadonnées pour décrire l'information structurée de la séquence génomique clinique dans les dossiers de santé électroniques
General Information
Standards Content (Sample)
TECHNICAL ISO/TS
SPECIFICATION 20428
First edition
2017-05
Health informatics — Data elements
and their metadata for describing
structured clinical genomic sequence
information in electronic health
records
Informatique de santé — Éléments de données et leurs métadonnées
pour décrire l’information structurée de la séquence génomique
clinique dans les dossiers de santé électroniques
Reference number
ISO/TS 20428:2017(E)
©
ISO 2017
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ISO/TS 20428:2017(E)
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ISO/TS 20428:2017(E)
Contents Page
Foreword .v
Introduction .vi
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Abbreviated 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 Clinical 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 sex.11
7.3.6 Subject of care ethnicity .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 sequencing 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 symbols 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 Classification 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
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ISO/TS 20428:2017(E)
7.11 Addendum .16
8 Fields and their nomenclature of optional data .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 calling 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
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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 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.
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 documents 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 responsible 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 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 ISO’s adherence to the
World Trade Organization (WTO) principles 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.
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ISO/TS 20428:2017(E)
Introduction
Based on the rapid advancement of sequencing technologies, clinical sequencing has been highlighted
as one of methods to realize personalized medicine and precision medicine. There are lots of sequencing
[1]
data in the public domain with clinical information . In addition, genome-scale clinical sequencing
[2]
is being adopted broadly in medical practice . 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 right medications and research purposes. Therefore, the
management of genomic and clinical data is increasingly highlighted to precision medicine, clinical trial
[3]
and translational research .
However, until now, there is no international standard for representing clinical sequencing results with
a structured 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 group).
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 need to develop a
[4]
standard to present clinical sequencing data in such a way they become useful for clinicians .
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. For 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 polymorphism (SNP)
[5] [6]
data . HL7 is also developing a domain analysis model for genomics using HL7 version 3 and fast
[7]
healthcare interoperability resources (FHIR) . Recently, to facilitate genomic information, SMART on
[8],[9]
FHIR Genomics has been developed . The Clinical Data Interchange Standard Consortium (CDISC)
[10]
published a study data tabulation model implementation guide: pharmacogenomics/genetics .
Several other international organizations such as Global Alliance for Genomics and Health (GA4GH),
Actionable Genome Consortium, and Displaying and Integrating Genetic Information Through 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
[11]
published the ACMG clinical laboratory standards for next-generation sequencing . In addition,
web-based tools become available that link genotypic information to phenotypic information, and
[12]
exchanging information and using it in personalized medicine can be very helpful .
In this document, to enable the standard use of patient genomic data from clinical sequencing for
healthcare purposes 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 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.
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TECHNICAL SPECIFICATION ISO/TS 20428:2017(E)
Health informatics — Data elements 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 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 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 technologies 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 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 references
There are no normative references in this document.
3 Terms and definitions
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: available at http:// www .iso .org/ obp
— IEC Electropedia: available at http:// 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 gametes
[SOURCE: ISO 16577:2016, 3.6]
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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
chromosome
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 with 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: http:// www .ncbi .nlm .nih .gov/ clinvar/ .
3.7
copy number variation
CNV
variation 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: http:// cancer .sanger .ac .uk/ cosmic.
3.9
dbSNP
database of SNPs provided by the US National Center for Biotechnology Information (NCBI)
Note 1 to entry: https:// 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 nucleus 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.
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ISO/TS 20428:2017(E)
[SOURCE: ISO/TS 17822-1:2014, 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 medicine
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 from 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 chromosome 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 to a therapeutic intervention
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ISO/TS 20428:2017(E)
3.25
prenatal/fetal
biomaterial sample of fetuses before birth
Note 1 to entry: Prenatal/fetal DNA sequencing: Reading the DNA of foetuses to diagnose Mendelian disease of
unborn child.
3.26
sequence read
read
fragmented nucleotide sequences which are used to reconstruct the original sequence for next
generation sequencing technologies
3.27
read type
type of run in the sequencing instrument
Note 1 to entry: It can be either single-end or paired-end.
Note 2 to entry: Single-end: Single read runs the sequencing instrument reads from one end of a fragment to the
other end.
Note 3 to entry: Paired-end: Paired end runs read from one end to the other end, and then start another round of
reading from the opposite end.
3.28
reference sequence
digital nucleic acid sequence database, assembled by scientists as a representative example of
human genome
3.29
ribonucleic acid
RNA
polymer of ribonucleotides occurring in a double-stranded or single-stranded form
[SOURCE: ISO 22174:2005, 3.1.3]
3.30
sequence variation
DNA sequence variation
variation
differences of DNA sequence among individuals in a population
Note 1 to entry: Variation implies CNV (3.7), deletion (3.10), insertion (3.19), indel (3.18), small indel (3.32), large
indel (3.20), and SNP (3.31).
[SOURCE: ISO 25720:2009, 4.8]
3.31
single nucleotide polymorphism
SNP
single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population
Note 1 to entry: Pronounced “snip”.
[SOURCE: ISO 25720:2009, 4.23]
3.32
small indel
insertion or deletion of 2 ~100 nucleotides
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3.33
somatic cell
cells of the body in contrast to the germ line cells
3.34
biological specimen
biospecimen
specimen
sample of tissue, body fluid, food, or other substance that is collected or acquired to support the
assessment, diagnosis, treatment, mitigation or prevention of a disease, disorder or abnormal physical
state, or its symptoms
3.35
subject of care
any person who uses, or is a potential user of, a health care service
[SOURCE: ISO/TS 22220:2011, 3.2]
3.36
target capture
method to capture genomic regions of interest from a DNA sample prior to sequencing
3.37
uncertain significance
alterations with limited and/or conflicting evidence regarding pathogenicity
3.38
whole exome sequencing
WES
technique for sequencing all the protein-coding genes in a genome
3.39
whole genome sequencing
WGS
technique that determines the complete DNA sequence of an organism’s genome at a single time
4 Abbreviated terms
This list of abbreviated terms includes all abbreviations used in this document.
ACMG the American College of Medical Genetics and Genomics
COSMIC the Catalogue of Somatic Mutations in Cancer
CPIC the Clinical Pharmacogenetics Implementation Consortium
EBI the European Bioinformatics Institute
FHIR Fast Healthcare Interoperability Resources
HGNC the HUGO Gene Nomenclature Committee
HGVS the Human Genome Variation Society
HUGO the Human Genome Organization
IARC International Agency for Research on Cancer
LOINC Logical Observation Identifiers Names and Codes
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ISO/TS 20428:2017(E)
NCBI National Center for Biotechnology Information
NCCN National Comprehensive Cancer Network
NGS Next Generation Sequencing
SNP Single Nucleotide Polymorphism
SPREC Standard Preanalytical Code
WES Whole Exome Sequencing
WGS Whole Genome Sequencing
5 Use case scenario
The abstracted use case for generating a clinical genomic sequencing report is demonstrated in
Figure 1. At first, the clinician will place a clinical sequencing order using the electronic health records
system (step 1 in Figure 1). After the order, a responsible department will request DNA sequencing
to the sequencing facility (step 2). This sequencing facility can be located inside of the hospital or
be an independent sequencing facility outside the hospital (step 3). When confirming the order, the
sequen
...
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