We show use of the FHIR design we are proposing for these cases:

1. Specimen Identification
   1. Get references to all variants obtained from germline analysis.
   2. Explore antibacterial drug resistance over time (non-patient DNA)
2. Clinical Sequencing – Germline Testing
3. Cancer Profiling
4. Decision Making Tools – Family History and Drug Dosage Calculators
   1. Today clinicians translate (i.e. manually re-enter) genetic data into tools for decision making. This includes family history tools and drug dosage calculators. In the future, this data will automatically be incorporated into clinical decision making tools.
   2. Get pharmacogenomic reporting and disease risk or diagnosis associated with variant
5. Public Health
6. Clinical and Research Data Warehouses

3.1 Specimen Identification

• Germline testing for biomarkers/mutations (usually inherited)
• Tumor testing for biomarkers/mutations (somatic / tumor specific)
• Pediatric Testing
• Infectious Disease Testing

3.1 Get references to all variants obtained from germline analysis

GET /Observation?component-code-value=http://loinc.org|LA6683-2

*Return a bundle of genetics-profile-based Observation instances

3.2 Clinical Sequencing – Germline Testing

For a chart review, get references to all DNA sequences related to mutations with an interpretation “Unknown Significance”

GET /Observation?subject=123&component-code-value=http://loinc.org|53037-8$LA6682-4

53037-8: LOINC code for “Genetic disease sequence variant interpretation”

LA6682-4: LOINC answer code for “Unknown Significance”.

3.3 Cancer Profiling

The goal of this profile methodology is to get references from all variants obtained from somatic analysis. Changes in the population of cells with particular mutations will change overtime as well as in conjunction with events such as therapy. For instance, targeted chemotherapy may kill a specific population of cancer cells with specific mutations and other cancer cell populations may survive and continue to divide. Therefore, clearly annotating these specimens as somatic variants and capturing annotations related to a time relevant to a treatment timeline may be critical for analysis.

GET /Observation?_profile=http://hl7.org/fhir/StructureDefinition/observation-genetics&component-code-value=http://loinc.org|LA6684-0&date=2015-07-04&subject=123

3.4 Decision Making Tools - Family History and Drug Dosage Calculators

Today clinicians translate (i.e. manually re-enter) genetic data into tools for decision making. This includes family history tools and drug dosage calculators. In the future, this data will automatically be incorporated into clinical decision making tools.

Get family history related to one observation:

GET /DiagnosticReport?_profile=http://hl7.org/fhir/StructureDefinition/diagnosticreport-genetic&subject=123

GET /Observation?_profile=http://hl7.org/fhir/StructureDefinition/observation-genetics&subject=123&component-code-value= http://loinc.org|51963-7

51963-7 : LOINC code for “Medication Assessed ”

3.5 Public Health

Today Registrars manually translate clinical data into public health reporting systems. This data is used to monitor and improve public health (e.g. surveillance and clinical research). In the future, this data will be extracted from the EHR in an automated (or semi-automated) fashion.

For a breast cancer clinical genomic study, get all genetic-profile-based observations of patients with breast cancer:

GET /DiagnosticReport?_profile=http://hl7.org/fhir/StructureDefinition/diagnosticreport-genetic&component-code-value=http://snomed.info/sct|254837009

3.6 Clinical and Research Data Warehouse

Health data warehousing should persist data in its standardized formats, while allowing users to export subsets of the data in the warehouse into multiple ‘data marts’, optimized for specific use cases, analysis type or reporting needs.

Get all genetic-profile-based observations of patients with the variant c.181T>G

GET /Observation?_profile=http://hl7.org/fhir/StructureDefinition/observation-genetics&
    component-code-value=http://www.ncbi.nlm.nih.gov/projects/SNP|rs58238560

3.2 Other Genomics Use Case

During the development of the FHIR Genomics design, CGWG participants have commented on the earlier use cases and/or proposed new use cases. In this section, we list describe of these new cases and demonstrate how the proposed design will address them.

3.2.1 Get a Patient's Family members' genetics report

This example is proposed by Kevin Hughes. Family history is useful for clinicians to know more about the condition of the patient.

GET /FamilyMemberHistory?_profile=http://hl7.org/fhir/StructureDefinition/familymemberhistory-genetic&patient=123

3.2.2 Panel

Search for results from nephrotic syndrome panel

GET /DiagnosticReport&_profile=http://hl7.org/fhir/StructureDefinition/diagnosticreport-genetic&code=N0336&patient=123

3.2.3 Basic Queries

Find patients by condition and affected status

GET /Condition?component-code-value-[x]=http://snomed.info/sct|439401001

Find patients by phenotypical attribute

GET /Observation?_profile=http://hl7.org/fhir/StructureDefinition/observation-geneticsGene&CodeableConcept=http://loinc.org|79716-7

79716-7: LOINC code for “CYP2C9 gene product metabolic activity interpretation”

Find patients by molecular data type available

GET /Observation?_profile=http://hl7.org/fhir/StructureDefinition/observation-genetics&DNARegionName=NC_000017.10:g.497469T>A

53035-2: LOINC code for “DNA marker assessed"

Find mutation by mutation type and position

GET /Observation?_profile=http://hl7.org/fhir/StructureDefinition/observation-geneticsVariant&Name=NM_000059.3:c.706C;A&Type=http://loinc.org|81289-1

Find patients based on mode of inheritance (genomic region, position, gene, SNP)

GET /FamilyMemberHistory?_profile=http://hl7.org/fhir/StructureDefinition/familymemberhistory-genetic&reasonCode=http://snomed.info/sct|272398008

7272398008: SNOMED code for “ Inheritance types "

Search for patient by ID

GET /Patient?subject=123

Search for diagnostic reports with a given variant

GET /DiagnosticReport?_profile=http://hl7.org/fhir/StructureDefinition/diagnosticreport-genetics&component-code-value=http://www.ncbi.nlm.nih.gov/projects/SNP|rs58238560

Given diagnostic report, return associated family history information

GET /DiagnosticReport?_profile=http://hl7.org/fhir/StructureDefinition/diagnosticreport-geneticsFamilyMemberHistory&_Id=123

Search for variants given gene and variant classification

GET /Observation?_profile=http://hl7.org/fhir/StructureDefinition/observation-genetics&component-code-value=http://www.genenames.org|3236&component-code-value=http://loinc.org|LA6684-0

Search for patients based on genetic ancestry

GET /Observation?_profile=http://hl7.org/fhir/StructureDefinition/observation-genetics&component-code-value=http://www.genenames.org|186044009&component-code-value=http://snomed.info/sct|LA6684-0

3.2.4 Boolean Queries

Find all patients with a set of variants

GET /Observation?_profile=http://hl7.org/fhir/StructureDefinition/observaiton-genetics&component-code-value=http://www.ncbi.nlm.nih.gov/projects/SNP|rs58238560$rs58238559$rs58238565

rs58238560: variant: NC_000017.10:g.497469T>A rs58238559: variant: NC_000007.13:g.87082273T>C rs58238565: variant: NC_000005.10:g.131929452C>A

3.2.5 Specimen-based Queries

Find specimens collected from specific specimen body sites

GET /Specimen?component-code-value=http://snomed.info/sct|85151006

Find specimens from this patient's pedigree

GET /FamilyMemberHistory?_profile=http://hl7.org/fhir/StructureDefinition/familymemberhistory-genetic&patient=123

Find specimens based on patient disease status

GET /DiagnosticReport?_ptofile=http://hl7.org/fhir/StructureDefinition/diagnosticreport-genetic&component-code-value=http://snomed.info/sct|254837009&patient=123

Find specimens based on specimen disease status

GET /Specimen?status=available

Find specimens based on technology platform

GET /Specimen?_profile=http://hl7.org/fhir/StructureDefinition/shareablecodesystem&code=Information Technology

Find specimens based on instrument identifier

GET /Specimen?container.identifier=48736-15394-75465

3.2.6 Time-Based Queries

Find specimens collected within an absolute date range

GET /Specimen?receivedTime=2011-03-04T07:03:00Z

Find specimens collected within a relative date range

GET /Specimen?_profile=http://hl7.org/fhir/StructureDefinition/specimen-treatmentTime&duration=quot