National foreword

This British Standard is the UK implementation of ISO 4454:2022.

The UK participation in its preparation was entrusted to Technical Committee IST/35, Health informatics.

A list of organizations represented on this committee can be obtained on request to its committee manager.

Contractual and legal considerations

This publication has been prepared in good faith, however no representation, warranty, assurance or undertaking (express or implied) is or will be made, and no responsibility or liability is or will be accepted by BSI in relation to the adequacy, accuracy, completeness or reasonableness of this publication. All and any such responsibility and liability is expressly disclaimed to the full extent permitted by the law.

This publication is provided as is, and is to be used at the recipient’s own risk.

The recipient is advised to consider seeking professional guidance with respect to its use of this publication.

This publication is not intended to constitute a contract. Users are responsible for its correct application.

Compliance with a British Standard cannot confer immunity from legal obligations.

This British Standard was published under the authority of the Standards Policy and Strategy Committee on 31 July 2022.

Foreword

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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 https://www.iso.org/directives).

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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.

Introduction

While great strides have been made in exchange formats for sequence and variation data (e.g. Variant Call Format), the majority of genotype formats do not include a means to share corresponding phenotypic (e.g. observable characteristics, signs/symptoms of disease) information. While some genomic databases have defined their own formats for representing phenotypic information, the lack of uniformity amongst these organizations hinders communication and limits the ability to perform analysis across organizations. For individuals with rare and undiagnosed disease, broad adoption and utilization of uniform, machine-readable, phenotypic descriptions could improve the speed and accuracy of diagnosis by promoting quicker, more comprehensive and cost-effective information acquisition and exchange relevant for research and medical care.

Phenotypic abnormalities of individuals are currently described in diverse places in diverse formats, such as journal/publications databases, laboratory systems, patient registries, health records, and even in social media. The structure of the data in the phenopackets exchange standard will be optimized for integration and efficient data flow across these distributed contexts. Increasing the volume of computable data across a diversity of systems will support large-scale computational disease analysis of combined genotype and phenotype data. Studies of well over 100 000 patients are thought to be required to effectively assess the role of rare variation in common disease or to discover the genomic basis for a substantial portion of diseases. Phenopackets can help integrate geographically distributed cases to build such virtual cohorts and remove the time burden on resources that need to integrate information manually.

Medical coding systems and clinical exchange standards have not to date included rich phenotypic descriptions, as they are largely focused on supporting billing and clinical encounter documentation, rather than the documenting and sharing of the biologically relevant phenotypic information needed for computational use, mechanism discovery, and precision classification. From a clinical perspective, the integration of a standard for phenotypic description and exchange into and out of EHRs would improve disease diagnosis and management, especially for genomic health and precision medicine applications.

Phenopackets enable clinicians, biologists, and disease and drug researchers to build more complete models of disease. It is designed to encourage wide adoption and synergy between the people, organizations and systems that comprise the joint effort to address human disease and biological understanding. The phenopacket proposed in this document is designed to support deep phenotyping, a process wherein individual components of each phenotype are observed and documented. The phenotypes can be constitutional or those related to a sample (such as from a biopsy).

1 Scope

This document specifies a uniform, machine-readable, phenotypic description of an individual, patient or sample in the context of rare disease, common/complex disease or cancer.

It is applicable to academic, clinical and commercial research, as well as clinical diagnostics. While intended for human data collection, it can be used in other areas (e.g. mouse research). It does not define the phenotypic information that needs to be collected for a particular use but represents that information in an appropriately descriptive manner that allows it to be computationally exchanged between systems.

2 Normative references

3 Terms and definitions

4 Abbreviated terms

5 Phenopackets Schema and Requirements

5.1 Phenopacket Schema

5.2 Requirement Levels

5.3 Ontology Use

6 Phenopacket Schema Top-Level Elements

6.1 Phenopacket

6.2 Family

6.3 Cohort

7 Phenopackets Building Blocks

7.1 General

7.2 Age

7.3 AgeRange

7.4 Biosample

7.5 ComplexValue

7.6 Disease

7.7 DoseInterval

7.8 DrugType

7.9 Evidence

7.10 ExternalReference

7.11 File

7.12 GeneDescriptor

7.13 GenomicInterpretation

7.14 GestationalAge

7.15 Individual

7.16 Interpretation

7.17 KaryotypicSex

7.18 Measurement

7.19 MedicalAction

7.20 MetaData

7.21 OntologyClass

7.22 Pedigree

7.23 PhenotypicFeature

7.24 Procedure

7.25 Quantity

7.26 RadiationTherapy

7.27 ReferenceRange

7.28 Resource

7.29 Sex

7.30 TherapeuticRegimen

7.31 TimeElement

7.32 TimeInterval

7.33 Timestamp

7.34 Treatment

7.35 Update

7.36 Value

7.37 VariationDescriptor

7.38 VariantInterpretation

7.39 VitalStatus

Bibliography

BS ISO 4454:2022

Genomics informatics. Phenopackets: A format for phenotypic data exchange

Current

Published:

31 Jul 2022