CHEBI IDs used by HPO and other phenotype ontologies do not match those used by GO, RHEA, UniProt

[cmungall]

The phenotype ontologies make the same classic mistake used by GO originally, in assuming CHEBI follows a biologist-friendly nomenclature. It does not. We are now undergoing an expensive refactor.

protonation states

See ebi-chebi/ChEBI#4482

• HP uses calcium atom, RHEA/GO uses calcium(2+) (uniprot synonym: "calcium")
• HP uses ammonia, RHEA/GO uses ammonium (uniprot synonym: "NH4+")
• HP uses carnosine, RHEA/GO uses carnosine zwitterion (uniprot synonym: "carnosine")

L vs D forms

In a mammal, it's usually obvious that

• glucose means D-glucose
• amino acid means L-amino acid

There may be some exceptions (e.g. some D amino acids may be synthesized in the brain but it's not clear if this is a distinct pathway or just racemization of the L pathway), but in general it's always a specific form

CHEBI always provides a triad of stereochemical-agnostic plus L and D (and sometimes racemized forms..). Really the agnostic form should never be annotated to. You always know the form.

In GO we are slowly moving to committing to the specific form

[cmungall]

Example from MP:

• abnormal calcium ion homeostasis: ... 'inheres in part of' some 'calcium ion homeostasis'
  • abnormal circulating calcium level: ... 'inheres in' some ('calcium atom' and ('part of' some blood))

In GO:

id: GO:0055074 ! calcium ion homeostasis
intersection_of: GO:0048878 ! chemical homeostasis
intersection_of: RO:0002332 CHEBI:29108 ! calcium(2+)

The MRCA of the two CHEBI terms is "molecular entity"

This isn't causing any real problems since HP, MP are asserting the hierarchy and aren't particularly dependent on logical definitions, in particular between process phenotypes and "amount" phenotypes (other than for matching between ontologies, for which just agreeing on an arbitrary CHEBI term is needed), but it does limit how we use CHEBI as a linkage

[cmungall]

Another oddity of the current situation

• [] HP:0000118 ! Phenotypic abnormality
  • [i] HP:0001939 ! Abnormality of metabolism/homeostasis
    • [i] HP:0032180 ! Abnormal circulating metabolite concentration
      • [i] HP:0003111 ! Abnormal blood ion concentration <-- uses chebi ion
        • [i] HP:0010929 ! Abnormal blood cation concentration <-- uses chebi cation
          • [i] HP:0011030 ! Abnormal blood transition element cation concentration
            • [i] HP:0010836 ! Abnormal circulating copper concentration
              • [i] HP:0032254 ! Increased circulating copper concentration
          • [i] HP:0010930 ! Abnormal blood monovalent inorganic cation concentration
            • [i] HP:0010931 ! Abnormal blood sodium concentration <-- uses chebi atom
          • [i] HP:0010927 ! Abnormal blood inorganic cation concentration <-- uses chebi cation
            • [i] HP:0004921 ! Abnormal magnesium concentration <-- uses chebi atom
        • [i] HP:0011422 ! Abnormal blood chloride concentration <-- uses chebi atom