Profiles

Important

This overview is meant to provide a conceptual understanding of how profiling works. The technical details behind how profiles are specified and used are described in the Developer Guide section.

Profiling Tasks

As noted, the VA-Spec provides Statement, Study Result, Evidence Line, and Proposition Profiles that specialize these core classes to support a specific domain of variant knowledge (e.g. pathogenicity), and/or support conventions of a particular community guideline (e.g. ACMG-2015).

The table below describes the different profiling tasks supported in v1.0 of the VA-Spec, with examples based on definition of ACMG-aligned Variant Pathogenicity profiles. These are illustrated graphically in the figure that follows.

Profiling Task	Example
Define a domain- or community-specific version of a Core Model class	Specialization of the `Proposition` class to create the `VariantPathogenicityProposition` profile
Import and reference classes for domain entities that variant knowledge is about	The `VariantPathogenicityProposition` profile uses `MolecularVariation` and `CategoricalVariation` classes imported from VRS and CatVRS, and a minimal `Condition` class defined in the VA-Spec itself.
Constrain attributes to take a more specific type of value (possible renaming them in the process)	The `VariantPathogenicityProposition` profile renames the `object` attribute to `objectCondition`, and restricts it to take a `Condition` as its value
Define value sets and binding them to select attributes.	The `ACMG 2015 Variant Pathogenicity Statement` profile restricts its `classification` attribute to take values based on ACMG 2015 criterion codes and terminology.
Define a new attribute to capture domain-specific information in a profiled class	The `VariantPathogenicityProposition` profile defines `geneContextQualifier` and `alleleOriginQualifier` attributes.
Refine cardinality of select attributes	The `ACMG 2015 Variant Pathogenicity Statement` profile makes `Statement.classification` a required field.

Profiling Example

The diagram below illustrates at a conceptual level some of the profiling steps applied to the core Statement and Proposition classes, to create models supporting ACMG-based Variant Pathogenicity Statements.

../_images/profiling-methodology.png — ACMG-based Variant Pathogenicity Profiles.

(A) Core Proposition and Statement classes, showing a subset of their attributes. (B) ACMG-based Variant Pathogenicity profiles derived from these core classes, with profiling specializations in green. Text in curly braces are enumerations, which in some cases are nested inside fields of a MappableConcept. The actual VA-Spec v1.0 schema for these profiles are here and here.

This data example illustrates application of these two profiles to represent a simple Variant Pathogenicity Statement.

Future versions of the VA-Spec will include a more formal specification and tooling support for executing these tasks and validating they were performed correctly.