Molecular Definition Implementation Guide for Molecular Data Types, published by HL7 International / Clinical Genomics. This guide is not an authorized publication; it is the continuous build for version 1.0.0-ballot1 built by the FHIR (HL7® FHIR® Standard) CI Build. This version is based on the current content of https://github.com/HL7/molecular-definition-data-types/ and changes regularly. See the Directory of published versions

Use Cases

Page standards status: Informative

Implementation Use Cases

This implementation guide, along with its included artifacts, has been meticulously designed and developed to address practical use cases involving the exchange of genomic molecules and their associated data across diverse institutions and systems. By providing standardized frameworks and code systems, the guide facilitates seamless interoperability and accurate data representation. This section presents example use cases that demonstrate how this implementation guide can be leveraged to represent real genomic concepts as FHIR resource instances, thereby illustrating its applicability and effectiveness in real-world genomic data exchange scenarios. The following subsections provides example instances of MolecularDefinition resource and their corresponding profiles.

Representing a Molecular Sequence as a Literal String

The following MolecularDefinitions show examples of a sequence represented as a literal leveraging the Sequence profile. The moleculeType and encoding attributes enable unambiguous interpretation of the sequence value.

• Simple Sequence example DNA A, IUPAC
• Simple Sequence example Amino Acid A, IUPAC

Representing a Molecular Sequence Using Accession Number as a Code

The following MolecularDefinitions show examples of a sequence represented as a code using an accession number leveraging the Sequence profile.

• Example of Sequence profile of CYP2C19 as Accession Number

Molecular Sequence from a Resolvable URL

The following MolecularDefinitions show examples of a sequence represented as a resolvable URL leveraging the Sequence profile. This example shows how the DocumentReference resource is utilized to represent the corresponding URL.

• Sequence example of CYP2C19 as URL

Use Case -4

Use Case -5

Use Case -6

Two Aggregate Use Cases to Represent How Sequence, Allele, Haplotype and Genotype Profiles Can Work Together to Represent various Genotypes

HLA Genotype

To illustrate the interaction of various MolecularDefinition profiles, we begin with a foundational example: an instance of a Sequence profile representing the raw coding sequence of HLA00001.1, which corresponds to the HLA-A01:01:01:01 allele. Building upon this, two distinct sets of Allele profiles are introduced, each encompassing five individual alleles derived from the HLA-A01:01:01:01 and HLA-A*01:02:01:01 groups, respectively. Each Allele set is then aggregated into a corresponding Haplotype instance, capturing the linkage of alleles on a single chromosome. Finally, these two Haplotype instances are integrated into an instance of Genotype profile, representing the combined allelic composition across both chromosomes at the HLA-A locus. This stepwise construction exemplifies how complex genetic information can be systematically modeled from raw sequence data through allelic and haplotypic layers to a comprehensive genotype representation. The following is the set of Molecular Definition instances that represent this use case:

• Genotype of HLA-A01:01:01:01 and HLA-A01:02:01:01 haplotype
  • HLA-A*01:01:01:01 Haplotype instance
    • First Allele, HLA00001.1:c.98T
    • Second Allele, HLA00001.1:c.121C
    • Third Allele, HLA00001.1:c.123C
    • Fourth Allele, HLA00001.1:c.126G
    • Fifth Allele, HLA00001.1:c.144C
  • HLA-A*01:02:01:01 Haplotype instance
    • First Allele, HLA00001.1:c.98C
    • Second Allele, HLA00001.1:c.121A
    • Third Allele, HLA00001.1:c.123T
    • Fourth Allele, HLA00001.1:c.126A
    • Fifth Allele, HLA00001.1:c.144A

CYP2C19 Genotype

The CYP2C19 gene encodes an enzyme essential for metabolizing several medications, including anti-coagulants, anti-depressants, and proton pump inhibitors. Variations in an individual's CYP2C19 genotype can significantly influence drug response, affecting efficacy and risk of adverse effects. In this example, the genotype instance is represented as a composite of two haplotypes, CYP2C191.002](MolecularDefinition-example-haplotype-cyp2c19-1002.html) and [CYP2C193.002, each defined by two alleles located at positions 661 and 1016 within the reference sequence context. This genomic information involves representing these haplotypes and their constituent alleles by leveraging the Molecular Definition profiles, i.e., Genotype, Haplotype, Allele and Sequence, through a series of interconnected profile instances. The following nested list shows this example and corresponding MolecularDefinition instances.

• Genotype of CYP2C19*1.002 and CYP2C19*3.002
  • CYP2C19*1.002:c.[661G; 1016G]
    • First Allele, CYP2C19*1.002:c.661G
    • Second Allele, CYP2C19*1.002:c.1016G
  • CYP2C19*3.002:c.[661A; 1016G]
    • First Allele, CYP2C19*1.002:c.661A
    • Second Allele, CYP2C19*1.002:c.1016G