ISO/TS 23357:2023

Genomics informatics - Clinical genomics data sharing specification for next-generation sequencing

This document specifies clinical sequencing information generated by massive parallel sequencing technology for sharing health information via massively parallel sequencing. This document covers the data fields and their metadata from the generation of sequence reads and base calling to variant evaluation and assertion for archiving reproducibility during health information exchange of clinical sequence information. However, the specimen collection, processing and storage, DNA extraction and DNA processing and library preparation, and the generation of test report are not in the scope of this document. This document hence defines the data types, relationship, optionality, cardinalities and bindings of terminology of the data. In essence, this document specifies: - the required data fields and their metadata from generation of sequence reads and base calling to variant evaluation and assertion for sharing clinical genomic sequencing data files generated by massively parallel sequencing technology, as shown in Figure 1; - the sequencing information from human samples using DNA sequencing by massively parallel sequencing technologies for clinical practice.

Informatique génomique — Spécification du partage des données de génomique clinique pour le séquençage de nouvelle génération

General Information

• Status: Published
• Publication Date: 02-Jul-2023
• 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: 6060 - International Standard published
• Start Date: 03-Jul-2023
• Due Date: 05-Feb-2023
• Completion Date: 03-Jul-2023

Overview

ISO/TS 23357:2023 - Genomics informatics: Clinical genomics data sharing specification for next-generation sequencing defines a standardized data specification for sharing clinical sequencing information produced by massively parallel (next‑generation) sequencing (NGS). The technical specification covers the required data fields and metadata from the generation of sequence reads and base calling through read alignment, variant calling, annotation, evaluation and assertion to support reproducibility and interoperable health information exchange. It applies to human DNA sequencing in clinical practice and addresses layered sequencing files (e.g., FASTQ, SAM/BAM/CRAM, VCF, MAF) and associated metadata. Specimen collection, DNA extraction, library preparation and final test‑report generation are explicitly out of scope.

Key topics and requirements

• Scope of data coverage: Metadata and data fields from sequence reads/base calling to variant evaluation/assertion for clinical NGS.
• Data model elements: Definitions of data types, relationships, optionality, cardinalities and bindings to terminologies to ensure consistent exchange and archiving.
• Derived data formats: Support and mapping for common NGS file types - FASTQ (reads), SAM/BAM/CRAM (alignments), VCF (variant calls), MAF (aggregated mutation data).
• Analysis provenance: Capture of sequencing instrumentation, base calling, read alignment, post‑processing, variant calling and annotation metadata required for reproducibility.
• Quality and reproducibility: Fields to represent quality control and processing steps so receiving sites can reproduce analytic results.
• Clinical focus: Specifically designed for clinical sequencing workflows (human DNA) and health information exchange requirements.

Applications

• Clinical interoperability: Exchange clinical genomic data between hospitals, labs and EHR systems when patients transfer care or request their data.
• Reproducible diagnostics: Allow receiving laboratories or clinicians to reproduce variant calls by providing alignment, variant calling and annotation metadata.
• Health IT integration: Guide health IT vendors and EHR integrators on data structures and terminology bindings needed to store and transmit clinical NGS results.
• Translational research: Facilitate multi‑institutional studies that combine clinical and genomic datasets while preserving processing provenance.

Who should use this standard

• Clinical genomics laboratories and bioinformatics teams
• Health IT vendors, EHR and HIE integrators
• Clinical molecular diagnostics developers
• Translational researchers and multi‑site study coordinators
• Standards bodies and implementers seeking interoperable genomic data exchange

Related standards

• ISO/TS 20428:2017 (referenced for clinical sequencing terminology)
• Work prepared by ISO/TC 215 (Health informatics), Subcommittee SC1 (Genomics informatics)

Keywords: ISO/TS 23357:2023, genomics informatics, clinical genomics, next‑generation sequencing, NGS, data sharing, FASTQ, BAM, CRAM, VCF, MAF, reproducibility, health IT.

Standards Content (Sample)

TECHNICAL ISO/TS
SPECIFICATION 23357
First edition
2023-07
Genomics informatics — Clinical
genomics data sharing specification
for next-generation sequencing
Informatique génomique — Spécification du partage des données de
génomique clinique pour le séquençage de nouvelle génération
Reference number
© ISO 2023
All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may
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ISO copyright office
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Phone: [phone]
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Published in Switzerland
ii
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 2
4 Abbreviated terms . 4
5 Summary of the clinical genomic information model . 4
5.1 General . 4
5.2 Patient . 5
5.2.1 General . 5
5.2.2 Identifiers . 5
5.2.3 Name . 5
5.2.4 Sex . 5
5.2.5 Birth data . 5
5.2.6 Ethnicity . 5
5.2.7 List of diagnosis . 5
5.2.8 Treatment . 6
5.3 Specimen . 6
5.3.1 General . 6
5.3.2 Tissue or organ of origin . 6
5.3.3 Collection date . 6
5.3.4 Type of specimen . 7
5.4 Experimental equipment . 7
5.4.1 General . 7
5.4.2 Quality control . 7
5.4.3 Base calling information . 7
5.5 Analysis equipment . 9
5.5.1 General . 9
5.5.2 Read alignment . 10
5.5.3 Alignment post processing . 11
5.5.4 Variant calling . 11
5.5.5 Variant annotation .12
5.6 Derived data .12
5.6.1 General .12
5.6.2 FASTAQ FASTQ . 13
5.6.3 Sequence alignment map (SAM) . . 13
5.6.4 Binary alignment map (BAM) . 13
5.6.5 Compressed reference-oriented alignment map (CRAM) .13
5.6.6 Variant cell format (VCF) . 13
5.6.7 Mutation annotation format (MAF) . 13
Bibliography .14
iii
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
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electrotechnical standardization.
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described in the ISO/IEC Directives, Part 1. In particular, the different approval criteria needed for the
different types of ISO document 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).
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www.iso.org/iso/foreword.html.
This document was prepared by Technical Committee ISO/TC 215, Health informatics, Subcommittee SC
1, Genomics informatics.
Any feedback or questions on this document should be directed to the user’s national standards body. A
complete listing of these bodies can be found at www.iso.org/members.html.
iv
Introduction
Owing to the rapid advancement of next-generation sequencing technologies, the human genome is
[7]
being adopted in clinical settings to realize precision medicine . Massive parallel sequencing or next-
generation sequencing (NGS) is any of several high-throughput approaches to DNA sequencing using
the concept of massively parallel processing. These technologies use miniaturized and parallelized
platforms for sequencing of 1 million to 43 billion short reads (50-400 bases each) per instrument run.
The data obtained in a clinical setting should be shared with another institution when patients move or
shared with the patient if requested.
The clinical application steps based on clinical sequence information consist of:
a) specimen collection, processing and storage;
b) DNA extraction;
c) DNA processing and library preparation;
d) generation of sequence reads and base calling;
e) sequencing alignment/mapping;
f) variant calling;
g) variant annotation and filtering;
h) variant evaluation and assertion;
[8]
i) generation of test report .
It is required to share clinical sequencing information at a level that can reproduce the results of the
institution that obtained the initial clinical sequencing information. In addition, the shared clinical
genomic sequencing data should be interoperable.
This document proposes a data specification to integrate multi-layered sequencing files and related
parameters and clinical data for achieving the reproducibility of genomic data in clinical practice.
This document will assist health IT companies by proposing new system requirements to deal with
genomic data.
This document can be used to store and share clinical genomic data in electronic health records. In
addition, it will be helpful in translational research, which requires genomic and clinical data from
multiple institutes.
v
TECHNICAL SPECIFICATION ISO/TS 23357:2023(E)
Genomics informatics — Clinical genomics data sharing
specification for next-generation sequencing
1 Scope
This document specifies clinical sequencing information generated by massive parallel sequencing
technology for sharing health information via massively parallel sequencing. This document covers
the data fields and their metadata from the generation of sequence reads and base calling to variant
evaluation and assertion for archiving reproducibility during health information exchange of clinical
sequence information. However, the specimen collection, processing and storage, DNA extraction and
DNA processing and library preparation, and the generation of test report are not in the scope of this
document.
This document hence defines the data types, relationship, optionality, cardinalities and bindings of
terminology of the data.
In essence, this document specifies:
— the required data fields and their metadata from generation of sequence reads and base calling to
variant evaluation and assertion for sharing clinical genomic sequencing data files generated by
massively parallel sequencing technology, as shown in Figure 1;
— the sequencing information from human samples using DNA sequencing by massively parallel
sequencing technologies for clinical practice.
NOTE The grey shaded text indicates the scope of this document.
Figure 1 — Clinical application processes based on next-generation sequencing (NGS) data
2 Normative references
There are no normative references in this document.
3 Terms and definitions
For the purposes of this document, the terms and definitions given in [external document reference
xxx] and the following apply.
ISO and IEC maintain terminology databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at https:// www .iso .org/ obp
— IEC Electropedia: available at https:// www .electropedia .org/
3.1
clinical sequencing
next generation sequencing or future sequencing technologies using human samples for clinical practice
and clinical trials
[SOURCE: ISO/TS 20428:2017, 3.5, modified — "later" has been replaced with "future" in the definition.]
3.2
deoxyribonucleic acid
DNA
molecule that encodes the genetic information in the nucleus of cells
[SOURCE: ISO 25720:2009, 4.7]
3.3
DNA sequencing
determination of the order of nucleotide bases (adenine, guanine, cytosine, and thymine) in a molecule
of DNA (3.4)
Note 1 to entry: Sequence is generally described from the 5’ end.
[SOURCE: ISO 17822:2020, 3.19]
3.4
exome
part of the genome that corresponds to the complete complement of the exons of a cell
3.7
FASTQ
text-based format for storing both the biological sequence (typically nucleotide sequence) and its
corresponding quality scores
3.8
gene
category of nucleic acid sequences that functions as a unit of heredity and codes for the basic instructions
for the development, reproduction, and maintenance of organisms
3.9
germline
series of germ cells, each descended or developed from earlier cells in the series, regarded as continuing
through successive generations of an organism
[SOURCE: ISO/TS 20428:2017, 3.17]
3.10
indel
insertion (3.15) or/and deletion (3.7)
[SOURCE: ISO/TS 20428:2017, 3.18]
3.12
mutation annotation format
MAF
tab-delimited text file with aggregated mutation information from variant call format (3.21) files and
generated on a project-level
3.13
next-generation sequencing
massive parallel sequencing
NGS
technology that can sequence millions of small fragments of DNA (3.4) in parallel
3.14
sequence read
read
fragmented nucleotide sequences which are used to reconstruct the original sequence for next
generation sequencing technologies
[SOURCE: ISO/TS 20428:2017, 3.26]
3.15
read type
type of implementation 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 (3.14) implements the sequencing instrument reads from one end of a
fragment to the other end.
Note 3 to entry: Paired-end: Paired end implements a read from one end to the other end and then starts another
round of reading from the opposite end.
[SOURCE: ISO/TS 20428:2017, 3.27, modified — "run" has been replaced with "implementation" in the
definition and the notes to entry.]
3.16
reference sequence
sequence file that is used as a reference to describe the variants that are present in the analyzed
sequence
3.18
specimen
biospecimen
sample of a tissue, body fluid, food, or other substance collected or acquired to support the assessment,
diagnosis, treatment, mitigation or prevention of a disease, disorder or abnormal physical state, or its
symptoms
[SOURCE: ISO/TS 20428:2017, 3.34, modified — the term "biological specimen" has been removed.]
3.19
subject of care
person who uses or is a potential user of a health care service
[SOURCE: ISO/TS 22220:2011, 3.2, modified — "Note 1 to entry" and the abbreviated term "SOC" have
been deleted.]
3.20
target capture
method to capture genomic regions of interest from a DNA (3.4) sample prior to sequencing
[SOURCE: ISO/TS 20428:2017, 3.36]
3.21
variant call format
VCF
format of the text file used in bioinformatics for storing gene (3.8) sequence variations
4 Abbreviated terms
BAM binary alignment map
bp base pair
COSMIC Catalogue of Somatic Mutations in Cancer
CRAM compressed reference-oriented alignment map
EBI European Bioinformatics Institute
HGNC HUGO Gene Nomenclature Committee
HGVS Human Genome Variation Society
HUGO Human Genome Organization
MAF mutation annotation format
NCBI National Center for B
...