Annotation¶

Every compartment, species, parameter and reaction which the PBPK library creates carries an SBO term and ontology terms (#63). The generators annotate an element when they create it, with annotate(element, kind, ...) of pkpdsim.pbpk.annotation: the kind names what the element is (an organ volume, the plasma of an organ, a saturable metabolism) and selects one row of the table KINDS, which holds the SBO term and the ontology terms of the kind. The place of the element adds the terms of where it is:

• the organ: its UBERON, NCIT, FMA and BTO terms (the compartment terms of pkpdsim.annotations) and its PBPKO compartment (LIVER_COMPARTMENT);
• the blood pool: arterial or venous blood, the portal vein;
• the lumen segment of the intestine or the segment of the renal tubule;
• the sampling site of an observer (hepatic vein, arm vein);
• the protein of a process or of its parameters: its UniProt and NCIT terms (the protein table data/proteins.toml);
• the substance of a species: the annotations of its specification (Substance.annotations, ChEBI, PubChem, NCIT).

An input of an organ or of a PD component, which the element of the body replaces in the comp model, takes the annotation of that element, so the comp model and the flat model carry the same terms.

Ontology and qualifiers¶

The PBPKO terms are those of the pinned pymetadata (pymetadata.ontologies.pbpko). A kind takes the organ-specific PBPKO term where PBPKO has one for the organ (VOLUME_OF_LIVER, BLOOD_FLOW_RATE_TO_KIDNEY, LIVER_PLASMA_PARTITION_COEFFICIENT, MAXIMUM_RATE_IN_LIVER); the small and the large intestine take the term of the intestine where PBPKO has none of their own (MAXIMUM_RATE_IN_INTESTINE), adipose tissue is FAT in PBPKO.

The model carries PHYSIOLOGICALLY_BASED_PHARMACOKINETIC_MODEL and WHOLE_BODY_PBPK, the human taxon, the ODE model of MAMO and pharmacokinetics of NCIT. It is a PERFUSION_LIMITED_MODEL when every substance which enters tissue does so flow-limited (Mode.PERFUSION), a PERMEABILITY_LIMITED_PBPK when one has a finite exchange, and neither when no substance enters tissue.

Resource format¶

Every resource of a collection which identifiers.org registers is written as its identifiers.org collection/term, the format of pkpdsim.annotations: uberon/UBERON:0002107, uniprot/P08684; sbmlutils writes the identifiers.org url. identifiers.org does not register PBPKO, so pymetadata cannot parse pbpko/PBPKO:00558 (it logs a MIRIAM error and writes an identifiers.org url which does not resolve). A PBPKO term is therefore written as its bioregistry url, https://bioregistry.io/PBPKO:00558, which resolves and which sbmlutils writes as given (as the apixaban model of pkdb_models does). A build logs no annotation error.

Terms requested upstream¶

PBPKO has no term for some of the quantities, compartments and processes of the library. The library annotates such an element with the nearest PBPKO term which is true for it: the superclass (PHYSIOLOGICAL_PARAMETER, BIOCHEMICAL_PARAMETER, MISCELLANEOUS_PARAMETER, COMPARTMENT), never a specific term whose definition contradicts the element (a fraction per body weight for a fraction of the blood volume, a flow rate for a fraction of the GFR, a clearance (a volume per time) for a clearance per litre of organ). A more specific PBPKO term which the element is a part or a version of is added with BQB.IS_PART_OF or BQB.IS_VERSION_OF (the mucosa is part of the INTESTINAL_TISSUE_COMPARTMENT, the dissolution part of the ABSORPTION). The missing terms are requested from PBPKO:

PBPKO is further not registered at identifiers.org, so its terms are written as bioregistry urls.