Specification for genetic conditions and haplotypes

[cookeac]

Proposal or request provided by an ICAR ADE specification user:

I am trying to determine the appropriate ICAR API schemas to use for genomic test results and disease test results.

I can see how we can use the diagnoses schema for milk culture result entry. However, for disease testing, users tend to want to set a permanent flag on animals showing their status. This is used especially for those needing to export a report for traceability upon shipping the animal to another location.

The standard data fields are:
Date of test
Test type
Result (positive, negative, or inconclusive)
Result Value (numeric)
I can also see the need to include values for the source of the result and test method.

[cookeac]

Discussed 2024-08-08
We could see a few options for this:

1. Implement one of the existing clinical laboratory or testing laboratory data standards. These already exist (often in XML, but are transferrable). They are likely more complex than our requirements but the tools exist to specify a concrete subset.
2. Implement a test result event that captured the animal/location/date, laboratory identifier, sample Id, and then an array of results (for instance Andrew's team had implemented one with an array of these items).
3. Implement a test result event as above, but have it contain an array of icarDiagnosisType.

We ask all members to talk to their teams who deal with test results or geneticists who deal with genetic tests whether they have sample data and/or what data fields they capture. This would help us decide on an approach.

[cvigorsICBF]

Some things to consider:

Test type - Assuming this is the kind of test carried out, e.g. mystatinV1, mystatinV2, micro satellites, BVD (Virus) Elisa etc. This is likely to be an ever changing list. Suggest renaming to 'Test Name'
Sample type - e.g. blood, hair, ear punch etc.
Result - possibly too simple with just 3 fields. BVD lab test, for example could be "positive" or "dam positive" and more. Might be better as a string, suggest rename to 'Interpreted result', or something similar?
Result value - possible scenario where the value is not numeric is a genetic test on animal coat colour.
Lab - Identifier for the lab carrying out the test.
Lab reference number.

Suggestion is to get some sample scenarios of laboratory tests for disease and genetic conditions that need to be handled by this feature.

A lot of the fields in this does seem more applicable, especially the inclusion of unit.

[cookeac]

Discussed in the US/Canada time zone meeting on 2024-10-02.

Potential confusion between lab tests (general) and genetic condition test results (the target of this).

• Outcome: I have renamed the issue to be more specific.

Is there a standardised list of genetic conditions and haplotypes? Check with ICAR Interbull specs.

• There doesn't seem to be a global list, though individual breed societies and national breed organisations each have a list that they focus on.
• The Interbull specs don't include this. GenoEx has specifications for sharing SNPs and genomes, but not these results.

Examples include:

• https://uscdcb.com/haplotypes/
• https://www.angusaustralia.com.au/education/breeding-and-genetics/genetic-conditions-in-angus
• https://hereford.org/member-services/herd-management-tools/genetic-abnormalities/
• https://www.icbf.com/wp-content/uploads/2014/06/Farmer-Genetic-Disease-and-Trait-Information-for-IDB-Genotyped-Animals-in-Ireland_9_20_16.pdf (see page 10)
• https://www.holsteinusa.com/programs_services/genomics.html

And extracts from the following list:

NAME	CARRIER_CODE	FREE_CODE	SUFFERER_CODE
Achondrodysplasie	AC+	AC-	AC*
Arthrogrypose	AS+	AS-	AS*
Axonopathy	AX+	AX-	AX*
Holstein Haplotype 1	H1+	H1-	H1*
Holstein Haplotype 2	H2+	H2-	H2*
Holstein Haplotype 3	H3+	H3-	H3*

Most lists seem to use a name, a 2-3 character abbreviation, and then an indicator or additional character for free, carrier, or affected.

Should this be an event with a date?

• A test is definitely an event that occurs at a specific date and likely involves sampling and a specific laboratory.
• However, by the time these have passed back through an organisation for reporting, the date and laboratory may not be available.
• The genetic conditions themselves don't change over time unless the test prediction was incorrect.

Proposed model

An API call that can return data for all animals at a location, or be filtered to a specific animal.
Each resource is identified to the animal, and may have the processing organisation (or laboratory) and (analysis) eventDate.
Each resource also has an array of results, each with:

• identifier - a scheme and ID identifying the condition or haplotype. Ideally ICAR would build a database of unique conditions.
• name - a descriptive name of the condition (e.g. "Holstein Haplotype 1")
• status - the status of the condition, an enumerated value comprising "Free", "Carrier", "Affected"
• copyCount - optional, but a few genetic conditions such as double-muscling can have multiple copies of the gene.

[cookeac]

Discussed at 2025-05-14 meeting:

• Distinguished between a test result which may be momentary and a lifetime indicator
• Would need to handle genomic, proteonomic, or metagenomics markers
• Might be best constructed as either a resource that can be fetched for an animal with a list of marker strings OR an array within icarAnimalCoreResource which has a list of marker strings.
• Noted also the proposed model above which has slightly more information (free, carrier, affected and copy count).

[cookeac]

An advantage of making this a separate resource rather than in icarAnimalCoreResource might be control of access to sensitive information.

As these are permanent conditions, we don't need an event date - so a resource is better.
If you were documenting the process of determining the state (e.g. laboratory tests) then that would be an event.

[cookeac]

2025-07-09 Meeting:

• We would prefer that this is an event with a date, because changes can happen over time - even baseline changes
• Add certified lab identifier
• Add the scheme or methodology and the marker/indicator/test id within that scheme
• Have a name for those who need it
• Look at the CDCB list for how they express the data associated with results - define the data components from this.
• Sample type - blood, hair, etc
• Analysis type
• Sample Id

Lab tests would have a similar structure but might be best in a different API

Note: often genomic results with have multiple values per trait: parent average, genomic value, reliability