+
+ +
+

Validate phenotypic features

+

One of the most convenient benefits of using ontology concepts for annotation of items with features and properties +is that one can leverage the information encoded in the semantic relationships of the ontology hierarchy. +Among other things, the semantic relationships empower fuzzy searches and similarity measures that have found +broad usage in many fields, such as biomedicine.

+

HPO became a de facto standard for representing phenotypic features - the signs and symptoms of an individual. +However, unlike in the case of other ontologies, several unique rules should be followed to maximize the benefits +of HPO annotations. In the sections below, we describe the rules and show how HPO toolkit can reveal their violations.

+

For the sake of this guide, let’s assume we have an individual annotated with the following four phenotypic features:

+
    +

  • Arachnodactyly

    • +

  • Seizure

    • +

  • Focal clonic seizure

    • +

  • Enuresis nocturna

    • +
+
>>> curies = [
+...   'HP:0001505',  # Arachnodactyly
+...   'HP:0001250',  # Seizure
+...   'HP:0002266',  # Focal clonic seizure
+...   'HP:0010677'   # Enuresis nocturna
+... ]
+
+
+

Let’s convert the CURIEs into term ids:

+
>>> import hpotk
+>>> term_ids = [hpotk.TermId.from_curie(curie) for curie in curies]
+
+
+

and let’s finish the setup by loading the toy HPO shipped with the documentation.

+
>>> hpo = hpotk.load_minimal_ontology('data/hp.toy.json')
+
+
+
+

Do not use obsolete term ids

+

As the first rule, the annotations should always use the current identifier. During ontology development, +some concepts may become obsolete and later be removed from the ontology altogether. +Most of the time, however, the removed concepts have a straightforward replacement.

+

The hpotk.validate.ObsoleteTermIdsValidator points out the usage of obsolete term ids +and suggests the replacement.

+

Let’s create the validator and check if the phenotypic features are OK:

+
>>> from hpotk.validate import ObsoleteTermIdsValidator
+>>> obs_val = ObsoleteTermIdsValidator(hpo)
+
+>>> vr = obs_val.validate(term_ids)
+
+
+

The validator returns back an instance of hpotk.validate.ValidationResults with the validation output. +We can check for presence of issues in the input:

+
>>> vr.is_ok()
+False
+
+
+

The input is not OK, so we should look at the issues in greater detail:

+
>>> for validation_result in vr.results:
+...   print(validation_result)
+ValidationResult(level=<ValidationLevel.WARNING: 1>, category='obsolete_term_id_is_used', message='Using the obsolete HP:0001505 instead of HP:0001166 for Arachnodactyly')
+
+
+

We see that the HP:0001505 is obsolete and HP:0001166 should be used as the new Arachnodactyly identifier.

+
+
+

Phenotypic features should be descendants of Phenotypic abnormality

+

HPO hierarchy has several major branches to uniquely represent concepts such as clinical modifiers, modes of inheritance, +and past medical medical history. However, the signs and symptoms should be encoded into descendants +of Phenotypic abnormality.

+

hpotk.validate.PhenotypicAbnormalityValidator checks that all identifiers correspond to descendants +of Phenotypic abnormality:

+

Let’s test that this is valid for the patient features:

+
>>> from hpotk.validate import PhenotypicAbnormalityValidator
+>>> pa_val = PhenotypicAbnormalityValidator(hpo)
+
+>>> vr = pa_val.validate(term_ids)
+>>> vr.is_ok()
+True
+
+
+

Yes, the all term ids represent the descendants of Phenotypic abnormality.

+
+
+

Phenotypic features should not violate the annotation propagation rule

+

Last and most importantly, let’s discuss the concept of annotation redundancy. +HPO uses is_a to represent the edges of the ontology hierarchy graph. The edges model the “parent-child” +relationships between two ontology concepts (the object subsumes the subject).

+

When using HPO concepts to encode clinical features of an individual, presence of a concept implies presence +of all ancestral concepts. This is also known as the “True path rule”, where the annotation “propagates” across +the concept ancestors.

+

In general, using the same annotation more than once is considered an error (e.g. annotate the subject with Focal clonic seizure +and Focal clonic seizure). However, thanks to the True path rule, using a concept and its ancestor is an offender +of a similar kind.

+

hpotk.validate.AnnotationPropagationValidator checks if a set of terms violate the annotation propagation rule +- if a collection of concepts contains a term and its ancestor.

+
>>> from hpotk.validate import AnnotationPropagationValidator
+>>> ap_val = AnnotationPropagationValidator(hpo)
+
+>>> vr = ap_val.validate(term_ids)
+>>> vr.is_ok()
+False
+
+
+

There seems to an issue. Let’s break it down:

+
>>> for validation_result in vr.results:
+...   print(validation_result.level)
+...   print(validation_result.category)
+...   print(validation_result.message)
+ValidationLevel.ERROR
+annotation_propagation
+Terms should not contain both present Focal clonic seizure [HP:0002266] and its present or excluded ancestor Seizure [HP:0001250]
+
+
+

The validator points out that Seizure is an ancestor of Focal clonic seizure and should, therefore, not be used +as an annotation of the individual.

+

That’s it for now. There are more validators to come!

+
+
+ + +
+