]> Molecular Entity Ontology This module contains terms and relations necessary for representing selected molecular entities in biopharmaceutical manufacturing, including molecular entity populations, molecular entity roles, chemical residues and moieties, biological sequences, proteins, glycans, glycoproteins, and glycosylation- and glycation-related residues. Many molecular entity terms are adapted from ChEBI and represented using IOF annotation conventions and modeling patterns to support consistent description of molecular structure, composition, and role. http://opensource.org/licenses/MIT BMIC Molecular Entity Ontology

acid-base indicator role https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Phenol red bearing an acid-base indicator role when its color indicates the pH range of cell culture medium; Bromothymol blue bearing an acid-base indicator role when its color change indicates a shift from acidic to neutral or basic pH; Methyl orange bearing an acid-base indicator role during an acid-base titration; Phenolphthalein bearing an acid-base indicator role when its color change indicates the endpoint of a titration.

http://purl.obolibrary.org/obo/CHEBI_50407

Acid-base indicators are typically weak acids or weak bases whose conjugate forms differ in color over a characteristic pH transition range. In titration applications, the indicator is selected so that its color change occurs at or near the equivalence point. In cell culture or process contexts, an acid-base indicator may be used to provide a visual indication that the medium, buffer, or solution has shifted into a different pH range.

AcidBaseIndicatorRole(x) → MolecularColorIndicatorRole(x)

true

molecular color indicator role held by a molecular entity when it is used or planned to be used so that its color indicates the pH range of a material entity

There are insufficient constructs present to create a set of necessary and sufficient conditions

if x is an 'acid-base indicator role' then x is a 'molecular color indicator role'

acidic charge variant population https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ deamidated monoclonal antibody population; sialylated antibody glycoform-enriched population; acidic peak population detected by cation-exchange chromatography; lower-pI protein population detected by capillary isoelectric focusing

AcidicChargeVariantPopulation(x) ↔ ProteinChargeVariantPopulation(x) ∧ ∃c(ProteinAcidicChargeVariantClassifier(c) ∧ classifiedBy(x, c))

protein charge variant population classified by a protein acidic charge variant classifier

every instance of 'acidic charge variant population' is defined as exactly an instance of 'protein charge variant population' that is 'classified by' some 'protein acidic charge variant classifier'

amino acid https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Alanine; Glycine; Lysine; Glutamic acid

https://www.ebi.ac.uk/chebi/CHEBI:33709

AminoAcid(x) → OrganicMolecularEntity(x)

true

organic molecular entity that contains a carboxyl group and one or more amino groups

See the primitive rationale under molecular entity

if x is an 'amino acid' then x is an 'organic molecular entity'

amino acid residue https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Alanine residue in a peptide; Glycine residue in a synthetic peptide; Lysine residue in a monoclonal antibody heavy chain; Cysteine residue participating in a disulfide bond in a protein; Serine residue in a phosphorylated protein.

http://purl.obolibrary.org/obo/CHEBI_33708

During peptide-bond formation, each amino acid loses the atoms corresponding to one molecule of water. The remaining portion constitutes the amino-acid residue within the polypeptide chain.

AminoAcidResidue(x) → ChemicalMoiety(x) ∧ ∃y (properContinuantPartOfAtAllTimes(x, y) ∧ (Peptide(y) ∨ Protein(y)))

true

chemical moiety that is a proper part of a peptide or protein and that is the remaining portion of an amino acid resulting from peptide-bond formation

This term is expected to remain primitive as the detailed treatment of chemical bonds, structure and formation is outside of the current scope of IOF. Other biological and chemical ontologies should be used for these purposes

if x is an 'amino acid residue' then x is a 'chemical moiety' and x is a 'proper continuant part of at all times' some 'peptide' or 'protein'

amino acid sequence https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ peptide sequence primary structure sequence The amino acid sequence of a monoclonal antibody heavy chain; The amino acid sequence of a monoclonal antibody light chain; The amino acid sequence of a recombinant enzyme; The amino acid sequence of a synthetic peptide; The amino acid sequence of a peptide impurity detected during product characterization

http://purl.obolibrary.org/obo/SO_0000104 and https://www.codamono.com/biointerchange/gfvo#PeptideSequence and https://www.ema.europa.eu/en/documents/scientific-guideline/ich-q-6-b-test-procedures-and-acceptance-criteria-biotechnologicalbiological-products-step-5_en.pdf

AminoAcidSequence(x) → BiologicalSequence(x) ∧ ∀y (genericallyDependsOnAtSomeTime(x, y) → (Peptide(y) ∨ Protein(y)))

true

biological sequence that is the ordered pattern of amino-acid residues that constitute a particular continuous peptide or protein molecule

There are insufficient constructs to create a set of necessary and sufficient conditions

if x is an 'amino acid sequence' then x is a 'biological sequence' and x 'generically depends on at some time' only on some 'peptide' or 'protein'

anion https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Sulfate ion (SO₄²⁻); Nitrate ion (NO₃⁻); Acetate ion (CH₃COO⁻)

https://www.ebi.ac.uk/chebi/CHEBI:22563

Anion(x) → Ion(x)

true

ion that is a monoatomic or polyatomic species having one or more elementary charges of the electron

See the primitive rationale under molecular entity

if x is an 'anion' then x is an 'ion'

antibody https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ A monoclonal antibody that binds a therapeutic target antigen; An IgG antibody that binds a viral surface protein; A recombinant antibody that binds a cell-surface receptor; A neutralizing antibody that binds an antigen and blocks its biological activity; An antibody used as a capture reagent in an immunoassay.

https://tools.thermofisher.com/content/sfs/brochures/1601975-Antibody-Production-Purification-Guide.pdf

Antibody(x) → Protein(x)

true

protein that has the function to selectively bind some antigen

There are insufficient constructs to define a set of necessary and sufficient conditions.

if x is an 'antibody' then x is a 'protein'

antimicrobial agent role https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ role held by Gentamicin added to cell culture media to prevent bacterial contamination; role held by Benzalkonium chloride included in formulations as a preservative.

https://www.ebi.ac.uk/chebi/CHEBI:33281

AntimicrobialAgentRole(x) → MolecularEntityRole(x)

true

role held by a molecular entity when it is used or planned to be used to kill, inactivate, or inhibit the growth, proliferation, or replication of microorganisms or viruses

There are insufficient constructs to create a set of necessary and sufficient conditions

if x is an 'antimicrobial agent role' then x is a 'molecular entity role'

antioxidant role https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ role held by ascorbic acid (vitamin C) added to media or formulations to prevent oxidation of sensitive components; role held by α-Tocopherol (vitamin E) used to inhibit lipid peroxidation and maintain stability of cell culture supplements or product formulations

http://purl.obolibrary.org/obo/CHEBI_22586

Some molecules have antioxidant activity because of their chemical structure. In manufacturing contexts, this role is typically asserted when that activity is intentionally used, for example when a compound is added to a medium, buffer, or formulation to protect materials, nutrients, or products from oxidation during processing or storage. Antioxidant agents may be used to maintain the stability of media components, extend product shelf life, or prevent loss of potency during storage. The role may be realized through mechanisms such as scavenging reactive oxygen species, reducing oxidized molecules, chelating pro-oxidant metal ions, or inhibiting reactions initiated by dioxygen molecule or peroxides.

AntioxidantRole(x) → MolecularEntityRole(x)

true

role held by a molecular entity when it is used or planned to be used to counteract oxidation or inhibit reactions initiated by dioxygen molecule, peroxides, or other oxidizing species

There are insufficient constructs to create a set of necessary and sufficient conditions

if x is an 'antioxidant role' then x is a 'molecular entity role'

basic charge variant population https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ C-terminal lysine-containing monoclonal antibody population; an amidated protein population; a basic peak population detected by cation-exchange chromatography; higher-pI protein population detected by capillary isoelectric focusing;

BasicChargeVariantPopulation(x) ↔ ProteinChargeVariantPopulation(x) ∧ ∃c(ProteinBasicChargeVariantClassifier(c) ∧ classifiedBy(x, c))

protein charge variant population classified by a protein basic charge variant classifier

every instance of 'basic charge variant population' is defined as exactly an instance of 'protein charge variant population' that is 'classified by' some 'protein basic charge variant classifier'

biantennary complex N-glycan moiety https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ G0F biantennary complex N-glycan moiety in a monoclonal antibody Fc glycan; G1F biantennary complex N-glycan moiety with one terminal galactose residue; G2F biantennary complex N-glycan moiety with two terminal galactose residues; Sialylated biantennary complex N-glycan moiety on a recombinant glycoprotein.

https://www.sigmaaldrich.com/RS/en/technical-documents/technical-article/protein-biology/protein-labeling-and-modification/n-glycans

BiantennaryComplexNGlycanMoiety(x) → CorePentasaccharideNGlycanMoiety(x)

true

core pentasaccharide N-glycan moiety that has N-acetylglucosamine residues attached to both the α-3 and α-6 mannose branches and contains no mannose residues beyond those in the conserved core

if x is a 'biantennary complex N-glycan moiety' then x is a 'core pentasaccharide N-glycan moiety'

biological sequence https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ The nucleotide sequence of a plasmid DNA molecule; The nucleotide sequence of an mRNA transcript; The amino acid sequence of a monoclonal antibody heavy chain; The amino acid sequence of a synthetic peptide; The RNA sequence of a viral genome segment; The DNA sequence of a gene coding region.

https://www.ncbi.nlm.nih.gov/IEB/ToolBox/SDKDOCS/BIOSEQ.HTML#:~:text=A%20biological%20sequence%20is%20a,DNA%2C%20RNA%2C%20or%20protein. and http://purl.obolibrary.org/obo/SO_0000001

BiologicalSequence(x) → GenericallyDependentContinuant(x) ∧ ∀y (genericallyDependsOnAtSomeTime(x, y) → (DeoxyribonucleicAcid(y) ∨ Peptide(y) ∨ Protein(y) ∨ RibonucleicAcid(y)))

true

generically dependent continuant that is the ordered pattern of residues that constitute a particular continuous DNA, RNA, peptide, or protein molecule

There are insufficient constructs to create a set of necessary and sufficient conditions

if x is a 'biological sequence' then x is a 'generically dependent continuant' and x 'generically depends on at some time' only on some 'deoxyribonucleic acid', 'peptide', 'protein', or 'ribonucleic acid'

biological sequence variant https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ recombinant protein molecule with an amino acid substitution detected by peptide mapping; truncated monoclonal antibody heavy-chain molecule detected in a drug substance lot

BiologicalSequenceVariant(x) ↔ (DeoxyribonucleicAcid(x) ∨ RibonucleicAcid(x) ∨ Peptide(x) ∨ Protein(x)) ∧ ∃r(BiologicalSequenceVariantClassifier(r) ∧ classifiedBy(x, r))

DNA or RNA or protein or peptide classified by a biological sequence variant classifier

every instance of 'biological sequence variant' is defined as exactly an instance of 'deoxyribonucleic acid', 'ribonucleic acid', 'peptide', or 'protein' that is 'classified by' some 'biological sequence variant classifier'

biological sequence variant classifier https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ a classifier grounded in a specified BRCA1 reference sequence that classifies a BRCA1 DNA molecule containing the c.68_69delAG deletion as a biological sequence variant; a classifier grounded in a specified monoclonal-antibody heavy-chain reference sequence that classifies a heavy-chain molecule containing an amino-acid substitution as a biological sequence variant; a classifier grounded in the intended full-length protein sequence that classifies a truncated heavy-chain molecule as a biological sequence variant; a classifier grounded in a specified RNA reference sequence that classifies an RNA molecule containing an insertion as a biological sequence variant; a classifier grounded in a specified peptide reference sequence that classifies a clipped peptide as a biological sequence variant

http://purl.obolibrary.org/obo/SO_0001060 and https://www.cancer.gov/publications/dictionaries/genetics-dictionary/def/variant and https://www.rapidnovor.com/sequence-variant-analysis-monoclonal-antibodies/#:~:text=Variant%20Analysis%20Service-,Introduction,variants%20and%20their%20associated%20risks.

A biological sequence variant classifier is grounded in comparison with a specified reference biological sequence. Classification by such a classifier indicates that the classified molecular entity is treated as a sequence variant relative to that reference sequence. It does not imply that the molecular entity is intrinsically a variant independently of the selected reference. Different classifiers may classify the same molecular entity differently when they are grounded in different reference sequences or comparison criteria

BiologicalSequenceVariantClassifier(x) → Classifier(x) ∧ ∃s(BiologicalSequence(s) ∧ isAbout(x, s)) ∧ ∃m((DeoxyribonucleicAcid(m) ∨ RibonucleicAcid(m) ∨ Peptide(m) ∨ Protein(m)) ∧ classifies(x, m))

true

classifier that classifies a DNA molecule, RNA molecule, peptide, or protein which has a biological sequence that differs from a specified reference biological sequence by one or more substitutions, insertions, deletions, truncations, or extensions

There are insufficient constructs to create necessary and sufficient conditions.

if x is a 'biological sequence variant classifier', then x is a 'classifier' that 'is about' some 'biological sequence' and 'classifies' some 'deoxyribonucleic acid', 'ribonucleic acid', 'peptide', or 'protein'

carbohydrate https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Glucose; Sucrose; Fructose; Lactose; Mannose

https://www.ebi.ac.uk/chebi/CHEBI:16646

Carbohydrates include simple sugars (monosaccharides) such as glucose and fructose, and compounds formed by their condensation, such as disaccharides, oligosaccharides, and polysaccharides. They can also occur in reduced (alditols) or oxidized (acids, aldehydes, ketones) forms, or as modified derivatives in which one or more hydroxy groups are replaced or substituted. Carbohydrates serve as energy sources, structural materials, and signaling molecules in living organisms.

Carbohydrate(x) → OrganicMolecularEntity(x)

true

organic molecular entity that is a polyhydroxy aldehyde, polyhydroxy ketone, derivative of such an entity, or condensation product of such entities

See the primitive rationale under molecular entity

if x is a 'carbohydrate' then x is an 'organic molecular entity'

cation https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Potassium ion (K⁺); Calcium ion (Ca²⁺); Ammonium ion (NH₄⁺)

https://www.ebi.ac.uk/chebi/CHEBI:36916

Cation(x) → Ion(x)

true

ion that is a monoatomic or polyatomic species having one or more elementary charges of the proton

See the primitive rationale under molecular entity

if x is a 'cation' then x is an 'ion'

charge variant classifier https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ classifier that classifies a group of monoclonal antibody molecules detected as an acidic peak in cation-exchange chromatography as a charge variant relative to a reference monoclonal antibody molecule; a classifier that classifies a group of recombinant protein molecules detected as a basic peak by imaged capillary isoelectric focusing as a charge variant relative to a reference recombinant protein molecule; a classifier that classifies a group of antibody-drug conjugate molecules according to charge-related analytical properties under a product-specific charge variant method; a classifier that classifies a group of lipid nanoparticles according to surface-charge-related analytical properties relative to a reference lipid nanoparticle

A charge variant classifier is a broad parent for classifiers that group material entities by charge-related analytical properties. It is intended to support different material domains, including molecular products and particle-based products. More specific subclasses should be used when the charge-related terminology, analytical methods, or reference comparisons are domain-specific, such as protein charge variants, molecular charge variants, or lipid nanoparticle surface-charge variants. The reference material entity is the material entity prescribed by the relevant design specification as the basis for comparison.

ChargeVariantClassifier(x) → Classifier(x) ∧ ∃s (DesignSpecification(s) ∧ isAbout(x, s) ∧ ∃r (MaterialEntity(r) ∧ prescribes(s, r))) ∧ ∃g (ObjectAggregate(g) ∧ classifies(x, g))

true

classifier that classifies a population of material entities according to charge-related analytical properties relative to a reference material entity

There are insufficient constructs to create necessary and sufficient conditions.

if x is a 'charge variant classifier' then x is a 'classifier' that 'is about' some 'design specification' that 'prescribes' some 'material entity', and x 'classifies' some 'object aggregate'

chelating agent role https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Role held by ethylenediaminetetraacetic acid (EDTA) acting as a chelating agent in buffers to remove trace metal ions; ethyleneglycol-bis(beta-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA) bearing a selective calcium chelating agent role in calcium-sensitive assays; citric acid bearing a chelating agent role and regulating the presence of iron in culture media; nitrilotriacetate groups immobilized on an affinity resin and bearing a chelating agent role during metal-ion coordination

http://purl.obolibrary.org/obo/CHEBI_38161 and https://www.sigmaaldrich.com/RS/en/technical-documents/technical-article/protein-biology/protein-purification/chelators?srsltid=AfmBOooXIbg6UbKJhWf8NjXdHt19Ktk2E5gud8zwrHR5iuqvICV2jrN8 and https://www.merckmillipore.com/CH/en/products/chemistry-and-biochemicals/biochemicals/chelating-reducing-agents

Histidine added as a buffering component rather than for chelation; citrate added to adjust pH or provide a carbon source rather than to bind metals; magnesium ions acting as cofactors

1) The environment may be a solution, resin, gel, or other medium in which a metal ion can form coordination bonds. 2) Chelating agents are used for different purposes, such as preventing metal-catalyzed degradation, removing or masking trace metals, maintaining metal ion availability, or supporting analytical and purification steps where metal ions or metal ion bound biomolecules are captured, removed, or released.

ChelatingAgentRole(x) → MolecularEntityRole(x)

true

role held by a molecular entity when it is used or planned to be used to bind a metal ion through two or more coordination sites

There are insufficient constructs to create a set of necessary and sufficient conditions

if x is a 'chelating agent role' then x is a 'molecular entity role'

chemical moiety https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Fc N-glycan; Phosphate group on serine; Ubiquitin moiety; PEG chain on therapeutic protein; Carboxylate group; Methyl group

http://purl.obolibrary.org/obo/CHEBI_24433

Free‐standing molecules (e.g., methane, water); Unbound ions or radicals not attached to a larger entity

ChemicalMoiety(x) → MaterialEntity(x) ∧ ∃y (properContinuantPartOfAtAllTimes(x, y) ∧ MolecularEntity(y))

true

material entity consisting of a linked collection of atoms or a single atom and that is a proper continuant part of a molecular entity

This term is expected to remain primitive.

if x is a 'chemical moiety' then x is a 'material entity' and x is a 'proper continuant part of at all times' some 'molecular entity'

complex afucosylated N-glycan moiety https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ G0 biantennary complex N-glycan moiety with no fucose residue; G1 biantennary complex N-glycan moiety with no fucose residue; G2 biantennary complex N-glycan moiety with no fucose residue.

https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-development-production-characterisation-and-specification-monoclonal-antibodies-and-related-products-revision-1_en.pdf and http://www.jbiomed.com/v04p0035.htm and https://pmc.ncbi.nlm.nih.gov/articles/PMC4634315/

ComplexAFucosylatedNGlycanMoiety(x) ↔ BiantennaryComplexNGlycanMoiety(x) ∧ ¬∃y (hasProperContinuantPartAtAllTimes(x, y) ∧ FucoseResidue(y))

biantennary complex N-glycan moiety that has no fucose residues as parts

every instance of 'complex afucosylated N-glycan moiety' is defined as exactly an instance of 'biantennary complex N-glycan moiety' that 'has proper continuant part at all times' no 'fucose residue'

complex agalactosylated N-glycan moiety https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ G0 biantennary complex N-glycan moiety with no galactose residues; G0F biantennary complex N-glycan moiety with core fucose but no galactose residues; Agalactosylated Fc N-glycan moiety detected in monoclonal antibody glycan profiling.

ComplexAGalactosylatedNGlycanMoiety(x) ↔ BiantennaryComplexNGlycanMoiety(x) ∧ ¬∃y (hasProperContinuantPartAtAllTimes(x, y) ∧ GalactoseResidue(y))

biantennary complex N-glycan moiety that has no galactose residues as parts

every instance of 'complex agalactosylated N-glycan moiety' is defined as exactly an instance of 'biantennary complex N-glycan moiety' that 'has proper continuant part at all times' no 'galactose residue'

complex asialylated N-glycan moiety https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ G0 biantennary complex N-glycan moiety with no sialic acid residues; G1F biantennary complex N-glycan moiety with no sialic acid residues; Asialylated Fc N-glycan moiety detected during monoclonal antibody glycan profiling.

ComplexASialylatedNGlycanMoiety(x) ↔ BiantennaryComplexNGlycanMoiety(x) ∧ ¬∃y (hasProperContinuantPartAtAllTimes(x, y) ∧ SialicAcidResidue(y))

biantennary complex N-glycan moiety that has no sialic acid residues as parts

every instance of 'complex asialylated N-glycan moiety' is defined as exactly an instance of 'biantennary complex N-glycan moiety' that 'has proper continuant part at all times' no 'sialic acid residue'

complex fucosylated N-glycan moiety https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ G0F biantennary complex N-glycan moiety with a core fucose residue; G1F biantennary complex N-glycan moiety with one galactose residue and one fucose residue; G2F biantennary complex N-glycan moiety with two galactose residues and one fucose residue;

ComplexFucosylatedNGlycanMoiety(x) ↔ BiantennaryComplexNGlycanMoiety(x) ∧ ∃y (hasProperContinuantPartAtAllTimes(x, y) ∧ FucoseResidue(y))

biantennary complex N-glycan moiety that has as part one or more fucose residues

every instance of 'complex fucosylated N-glycan moiety' is defined as exactly an instance of 'biantennary complex N-glycan moiety' that 'has proper continuant part at all times' some 'fucose residue'

complex galactosylated N-glycan moiety https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ G1F biantennary complex N-glycan moiety with one galactose residue; G2F biantennary complex N-glycan moiety with two galactose residues; G1 biantennary complex N-glycan moiety with one galactose residue and no fucose residue; Galactosylated Fc N-glycan moiety detected during monoclonal antibody glycan profiling

In biopharmaceutical analysis, ‘galactosylation’ commonly refers to the presence of galactose residues on the antennae of complex biantennary N-glycans. Complex biantennary glycans have two N-acetylglucosamine–initiated antennae that can receive galactose, and galactosylation levels are routinely reported through the relative abundance of mono-galactosylated (G1) and di-galactosylated (G2) complex species. Hybrid glycans may carry a galactose residue on a GlcNAc-extended arm, but they are not typically categorized as G1/G2 complex species and are usually not included in percent galactosylation calculations for complex Fc glycan profiles. High-mannose glycans do not contain complex-type antennae and are not treated as galactosylated complex N-glycans. Accordingly, this class applies to complex N-glycan moieties that contain one or more galactose residues

ComplexGalactosylatedNGlycanMoiety(x) ↔ BiantennaryComplexNGlycanMoiety(x) ∧ ∃y (hasProperContinuantPartAtAllTimes(x, y) ∧ GalactoseResidue(y))

biantennary complex N-glycan moiety that has as part one or more galactose residues

every instance of 'complex galactosylated N-glycan moiety' is defined as exactly an instance of 'biantennary complex N-glycan moiety' that 'has proper continuant part at all times' some 'galactose residue'

complex N-glycolylneuraminic acid containing N-glycan moiety https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Complex sialylated N-glycan moiety containing a terminal N-glycolylneuraminic acid residue; NGNA-containing complex N-glycan moiety detected during glycan profiling of a recombinant glycoprotein; Biantennary complex N-glycan moiety with one branch terminating in an N-glycolylneuraminic acid residue.

complex NGNA containing N-glycan moiety

https://pmc.ncbi.nlm.nih.gov/articles/PMC4634315/

ComplexNGlycolylneuraminicAcidContainingNGlycanMoiety(x) ↔ ComplexSialylatedNGlycanMoiety(x) ∧ ∃y (hasProperContinuantPartAtAllTimes(x, y) ∧ NGlycolylneuraminicAcidResidue(y))

complex sialylated N-glycan moiety that has as part one or more N-glycolylneuraminic acid (NGNA) residues

every instance of 'complex N-glycolylneuraminic acid containing N-glycan moiety' is defined as exactly an instance of 'complex sialylated N-glycan moiety' that 'has proper continuant part at all times' some 'N-glycolylneuraminic acid residue'

complex sialylated N-glycan moiety https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Sialylated biantennary complex N-glycan moiety with one terminal sialic acid residue; Disialylated biantennary complex N-glycan moiety with two terminal sialic acid residues;

ComplexSialylatedNGlycanMoiety(x) ↔ BiantennaryComplexNGlycanMoiety(x) ∧ ∃y (hasProperContinuantPartAtAllTimes(x, y) ∧ SialicAcidResidue(y))

biantennary complex N-glycan moiety that has as part one or more sialic acid residues

every instance of 'complex sialylated N-glycan moiety' is defined as exactly an instance of 'biantennary complex N-glycan moiety' that 'has proper continuant part at all times' some 'sialic acid residue'

core pentasaccharide N-glycan moiety https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Core pentasaccharide N-glycan moiety in a monoclonal antibody Fc N-glycan; Core Man₃GlcNAc₂ moiety shared by G0F, G1F, and G2F Fc glycoforms; Core pentasaccharide N-glycan moiety in a high-mannose glycan on a recombinant glycoprotein.

https://www.sigmaaldrich.com/RS/en/technical-documents/technical-article/protein-biology/protein-labeling-and-modification/n-glycans and https://pmc.ncbi.nlm.nih.gov/articles/PMC9781892/

1) This class represents the canonical core structure of N-glycan moieties commonly encountered in biopharmaceutical glycoproteins, including monoclonal antibodies and other recombinant proteins. These moieties share the conserved chitobiose core and branched mannose structure that define common N-glycan families, including high-mannose, hybrid, and complex glycoforms routinely monitored in industry analytics. This structural pattern underlies standard glycan annotations such as G0F, G1F, G2F, and high-mannose species. 2) In canonical eukaryotic protein N-glycosylation, core pentasaccharide N-glycan moieties are attached to L-asparagine residues. This is reflected in the necessary condition that this moiety is a proper continuant part of some N4-glycosyl-L-asparagine.

CorePentasaccharideNGlycanMoiety(x) → NGlycanMoiety(x) ∧ ∃y (properContinuantPartOfAtAllTimes(x, y) ∧ N4GlycosylLAsparagine(y))

true

N-glycan moiety that contains the core pentasaccharide Man₃GlcNAc₂, consisting of a di-N-acetyl-chitobiose unit extended by a branched mannose trisaccharide

if x is a 'core pentasaccharide N-glycan moiety' then x is an 'N-glycan moiety' and x is a 'proper continuant part of at all times' some 'N4-glycosyl-L-asparagine'

deamidated residue https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Deamidated asparagine residue in a monoclonal antibody; Deamidated glutamine residue in a recombinant protein; Aspartate-like residue formed by deamidation of an asparagine residue within a peptide; Glutamate-like residue formed by deamidation of a glutamine residue within a protein.

http://purl.obolibrary.org/obo/MOD_00400

This modification corresponds to deamidation of an amino acid residue such as asparagine or glutamine. The reaction converts the side-chain amide to a carboxyl group, typically yielding aspartate or glutamate within the peptide.

DeamidatedResidue(x) → ModifiedAminoAcidResidue(x)

true

modified amino acid residue in which a carboxamide group has been converted to a carboxyl group, involving a net gain of oxygen and loss of nitrogen and hydrogen

if x is a 'deamidated residue' then x is a 'modified amino acid residue'

deoxyribonucleic acid https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Plasmid DNA used as a vector in recombinant protein expression; Host cell DNA detected as a process-related impurity in a drug substance sample; Genomic DNA extracted from a production cell line; DNA primer used in a PCR assay; Residual DNA fragment measured during biologics process clearance testing

DNA

http://purl.obolibrary.org/obo/CHEBI_16991

DeoxyribonucleicAcid(x) → NucleicAcid(x)

true

nucleic acid that is composed of nucleotides containing deoxyribose

See the primitive rationale under molecular entity

if x is 'deoxyribonucleic acid' then x is a 'nucleic acid'

dioxygen molecule https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ dissolved oxygen in cell culture medium; oxygen present in the headspace of a culture vessel; oxygen transferred from the gas phase into the liquid phase of a bioreactor; oxygen consumed by aerobic cells during cultivation

http://purl.obolibrary.org/obo/CHEBI_15379

Dioxygen Molecule is the molecular form O₂. In common laboratory, bioprocess, and manufacturing usage, it is often referred to simply as oxygen, for example when discussing dissolved oxygen, oxygen sparging, or oxygen transfer.

DioxygenMolecule(x) → InorganicMolecularEntity(x)

true

inorganic molecular entity consisting of two oxygen atoms covalently bonded to each other

See the primitive rationale under molecular entity

if x is 'dioxygen molecule' then x is an 'inorganic molecular entity'

endotoxin https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Lipopolysaccharide impurity from Gram-negative bacterial material in a buffer sample; Lipopolysaccharide detected in a purification pool; Lipopolysaccharide associated with a single-use component rinse or extract sample;

See the expanded definition under the corresponding role class.

Endotoxin(x) ↔ Lipopolysaccharide(x) ∧ ∃r (hasRole(x, r) ∧ EndotoxinRole(r))

lipopolysaccharide with an endotoxin role

every instance of 'endotoxin' is defined as exactly an instance of 'lipopolysaccharide' that 'has role' some 'endotoxin role'

endotoxin role https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Lipopolysaccharide from Gram-negative bacterial contamination bearing an endotoxin role in a buffer sample; Lipopolysaccharide impurity bearing an endotoxin role in a purification pool; Lipopolysaccharide residue bearing an endotoxin role on a single-use component extractable or rinse sample; Lipopolysaccharide impurity bearing an endotoxin role in a final drug substance sample.

https://www.thermofisher.com/rs/en/home/life-science/protein-biology/protein-purification-isolation/protein-purification/endotoxin-quantitation-removal.html” and https://www.biophorum.com/download/cvp-case-study-interactive-version/ and https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-industry-pyrogen-and-endotoxins-testing-questions-and-answers”

1) This role excludes protein exotoxins, viral agents, inorganic poisons, non-microbial pyrogens, ions, and non-viable particulate matter that is not lipopolysaccharide-derived. 2) In biologics manufacturing, the endotoxin role identifies lipopolysaccharide impurities originating from Gram-negative bacteria that must be quantified and limited in material samples, single-use parts, buffers, purification pools, in-process holds, or final product samples based on pyrogen-safety acceptance thresholds. Endotoxin control is assessed through corresponding sample-level measurable attributes, such as endotoxin load or endotoxin content, and supports contamination risk mitigation, process comparability, in-process hold and filtration decisions, and product release decisions.

EndotoxinRole(x) → MolecularToxinRole(x) ∧ ∃y (roleOf(x, y) ∧ Lipopolysaccharide(y))

true

molecular toxin role held by a lipopolysaccharide (LPS) that originates from Gram-negative bacterial cellular material

There are insufficient constructs to create a set of necessary and sufficient conditions

if x is an 'endotoxin role' then x is a 'molecular toxin role' and x is a 'role of' some 'lipopolysaccharide'

enzyme activator role https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Enzyme activator role held by magnesium ions that enhance the activity of DNA and RNA polymerases; Enzyme activator role held by chloride ions that activate salivary amylase; Enzyme activator role held by potassium ions that increase pyruvate kinase activity; Enzyme activator role held by calcium ions that promote protease and phospholipase activation

https://www.ebi.ac.uk/chebi/CHEBI:195252

EnzymeActivatorRole(x) → EnzymeRegulatorRole(x)

true

role held by a molecular entity when it increases the catalytic activity of an enzyme without covalently modifying the enzyme

This term is expected to remain primitive as the detailed treatment of molecular activity modulation is outside of the current scope of IOF. Other biological and chemical ontologies should be used for these purposes

if x is an 'enzyme activator role' then x is an 'enzyme regulator role'

enzyme cofactor role https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Role held by magnesium ions stabilizing ATP in kinase reactions; Role held by zinc ions required for the catalytic activity of alcohol dehydrogenase; Role held by flavin adenine dinucleotide (FAD) acting as an electron carrier in redox enzymes; Role held by a heme group supporting oxidation reactions within cytochrome oxidase

https://www.ebi.ac.uk/chebi/CHEBI:23357

EnzymeCofactorRole(x) → MolecularEntityRole(x)

true

role held by a molecular entity that is realized in an enzymatic reaction through enabling the catalytic activity of a particular enzyme

if x is an 'enzyme cofactor role' then x is a 'molecular entity role'

enzyme inhibitor role https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Inhibitor role held by aprotinin when added to cell culture media to inhibit serine proteases and prevent product degradation; Role held by sodium fluoride when inhibiting enolase in glycolytic pathways; Inhibitor role held by cyanide when binding to cytochrome oxidase and blocking electron transport

https://www.ebi.ac.uk/chebi/CHEBI:23924

EnzymeInhibitorRole(x) → EnzymeRegulatorRole(x)

true

role held by a molecular entity that is realized in an enzyme catalyzed reaction through decreasing or preventing the catalytic activity of the enzyme

if x is an 'enzyme inhibitor role' then x is an 'enzyme regulator role'

enzyme regulator role https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ ATP bearing an enzyme regulator role when it allosterically inhibits phosphofructokinase; A small-molecule bearing a competitive inhibitor role when binding to an enzyme active site; Calcium ion bearing an enzyme regulator role when it non-covalently activates a calcium-dependent enzyme; Role held by an allosteric activator that increases enzyme catalytic activity by stabilizing an active conformation

http://purl.obolibrary.org/obo/TXPO_0003722 and http://purl.obolibrary.org/obo/GO_0030234

EnzymeRegulatorRole(x) → MolecularActivityRegulatorRole(x)

true

role held by a molecular entity when it binds to an enzyme and modulates its catalytic activity

if x is an 'enzyme regulator role' then x is a 'molecular activity regulator role'

fucose residue https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Fucose residue attached to the core N-acetylglucosamine of an N-linked glycan; Fucose residue in a core-fucosylated monoclonal antibody Fc glycan; Fucose residue in a Lewis-type glycan epitope.

FucoseResidue(x) → MonosaccharideResidue(x)

true

monosaccharide residue that is the remaining portion of fucose after formation of a glycosidic bond

if x is a 'fucose residue' then x is a 'monosaccharide residue'

galactose residue https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Galactose residue in a complex N-linked glycan; Galactose residue attached to N-acetylglucosamine in a monoclonal antibody Fc glycan; Terminal galactose residue in a biantennary glycan.

GalactoseResidue(x) → MonosaccharideResidue(x)

true

monosaccharide residue that is the remaining portion of galactose after formation of a glycosidic bond

if x is a 'galactose residue' then x is a 'monosaccharide residue'

glycated residue https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Glycated lysine residue in a monoclonal antibody formed by non-enzymatic reaction of the lysine side-chain amino group with glucose; N-terminal glycated residue in a recombinant protein formed by non-enzymatic reaction of the N-terminal amino group with a reducing sugar;

http://purl.obolibrary.org/obo/MOD_00767

GlycatedResidue(x) → GlycoconjugatedResidue(x)

true

glycoconjugated residue that is formed by non-enzymatic covalent attachment of a reducing sugar to an amino group of an amino acid residue, producing a Schiff-base or Amadori-type ketosamine adduct

if x is a 'glycated residue' then x is a 'glycoconjugated residue'

glycoconjugated residue https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ N-glycosylated asparagine residue in a monoclonal antibody; O-glycosylated serine residue in a glycoprotein; O-glycosylated threonine residue in a mucin-like domain; Glycated lysine residue in a protein; Amadori-modified lysine residue formed by non-enzymatic glycation.

http://purl.obolibrary.org/obo/MOD_00764

GlycoconjugatedResidue(x) → ModifiedAminoAcidResidue(x)

true

modified amino acid residue that has a covalently attached carbohydrate or carbohydrate-derived group, formed either through enzymatic glycosidic bond formation or through non-enzymatic glycation involving a Schiff-base or Amadori-type ketosamine adduct

if x is a 'glycoconjugated residue' then x is a 'modified amino acid residue'

glycoprotein https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Monoclonal antibody with an N-glycosylated asparagine residue in its Fc region; Recombinant erythropoietin containing N-glycosylated and O-glycosylated residues; Fc-fusion protein containing an N-glycosylated residue; Viral envelope protein containing glycosylated residues; Host cell glycoprotein detected as a process-related impurity.

http://purl.obolibrary.org/obo/PR_000037069

Glycoprotein(x) ↔ Protein(x) ∧ ∃y (hasProperContinuantPartAtAllTimes(x, y) ∧ GlycosylatedResidue(y))

protein that includes at least one glycosylated residue

every instance of 'glycoprotein' is defined as exactly an instance of 'protein' that 'has proper continuant part at all times' some 'glycosylated residue'

glycosylated residue https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ N-glycosylated asparagine residue in a monoclonal antibody Fc region; O-glycosylated serine residue in a glycoprotein; O-glycosylated threonine residue in a mucin-like domain; Glycosylated asparagine residue carrying an N-linked glycan produced through enzymatic glycosylation.

http://purl.obolibrary.org/obo/MOD_00693

This class differs from glycation-derived glycoconjugated residues because the carbohydrate group is attached through an enzymatically formed glycosidic bond. In biopharmaceutical proteins, glycosylated residues commonly arise through regulated enzymatic glycosylation pathways, such as N-linked glycosylation of asparagine or O-linked glycosylation of serine or threonine. For many secreted mammalian proteins, these pathways occur through the endoplasmic reticulum and Golgi apparatus. In contrast, glycated residues arise through non-enzymatic reactions during manufacturing, formulation, or storage, such as reactions with reducing sugars that form Schiff-base or Amadori-type ketosamine adducts.

GlycosylatedResidue(x) → GlycoconjugatedResidue(x)

true

glycoconjugated residue that results from replacement of a hydrogen atom with a carbohydrate-like group through formation of a glycosidic bond

if x is a 'glycosylated residue' then x is a 'glycoconjugated residue'

growth factor https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Vascular endothelial growth factor (VEGF) promoting endothelial proliferation; Insulin-like growth factor 1 (IGF-1) enhancing recombinant protein production in mammalian cells

http://purl.obolibrary.org/obo/GO_0008083

See the expanded definition under the corresponding role class.

GrowthFactor(x) ↔ (Peptide(x) ∨ Protein(x)) ∧ ∃r (hasRole(x, r) ∧ GrowthFactorRole(r))

protein or peptide with a growth factor role

every instance of 'growth factor' is defined as exactly an instance of 'peptide' or 'protein' that 'has role' some 'growth factor role'

growth factor role https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Role held by vascular endothelial growth factor (VEGF) that promotes endothelial proliferation; Role held by insulin-like growth factor 1 (IGF-1) that enhances recombinant protein production in mammalian cells

http://purl.obolibrary.org/obo/GO_0008083

In culture media and biomanufacturing formulations, this role is typically asserted when a protein or peptide is intentionally added to support cell proliferation, maintain viability, promote differentiation, or enhance productivity.

GrowthFactorRole(x) → MolecularMessengerRole(x) ∧ ∃y (roleOf(x, y) ∧ (Peptide(y) ∨ Protein(y)))

true

role held by a peptide or protein that is realized in receptor-mediated signaling processes that stimulate cellular growth, proliferation, survival, or differentiation

This term is expected to remain primitive as the detailed treatment of molecular messaging is outside of the current scope of IOF. Other biological and chemical ontologies should be used for these purposes

if x is a 'growth factor role' then x is a 'molecular messenger role' and x is a 'role of' some 'peptide' or 'protein'

heterodimeric antibody https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Bispecific IgG-like antibody with two different heavy chains; Heterodimeric monoclonal antibody engineered with knob-into-hole heavy-chain pairing; Antibody containing one heavy chain specific for antigen A and another heavy chain specific for antigen B.

https://www.cytivalifesciences.com/en/us/insights/capture-of-bispecific-antibodies-and-removal-of-product-related-impurities

HeterodimericAntibody(x) → Antibody(x)

true

antibody consisting of two heavy chains and two light chains in which the two heavy chains differ in amino acid sequence, the two light chains differ in amino acid sequence, or both

There are insufficient constructs to define a set of necessary and sufficient conditions.

if x is a 'heterodimeric antibody' then x is an 'antibody'

high mannose N-glycan moiety https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Man5 N-glycan moiety detected on a monoclonal antibody Fc glycan; Man8 N-glycan moiety on a recombinant glycoprotein; High mannose N-glycan moiety observed as an elevated Man5 species during glycan profiling; Oligomannose N-glycan moiety containing terminal mannose residues without complex-type antenna extensions.

https://www.sigmaaldrich.com/RS/en/technical-documents/technical-article/protein-biology/protein-labeling-and-modification/n-glycans

HighMannoseNGlycanMoiety(x) → CorePentasaccharideNGlycanMoiety(x)

true

core pentasaccharide N-glycan moiety whose branches are extended only by mannose residues and whose total mannose count is commonly between five and nine

if x is a 'high mannose N-glycan moiety' then x is a 'core pentasaccharide N-glycan moiety'

homodimeric antibody https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Conventional monoclonal IgG antibody with two identical heavy chains and two identical light chains; IgG1 monoclonal antibody produced from a single antibody clone; Homodimeric Fc-containing antibody with matched heavy-chain pairing; Standard monospecific therapeutic antibody with two equivalent antigen-binding arms.

https://www.cytivalifesciences.com/en/us/insights/capture-of-bispecific-antibodies-and-removal-of-product-related-impurities

HomodimericAntibody(x) → Antibody(x)

true

antibody consisting of two heavy chains and two light chains in which the two heavy chains have the same amino acid sequence and the two light chains have the same amino acid sequence

There are insufficient constructs to define a set of necessary and sufficient conditions.

if x is a 'homodimeric antibody' then x is an 'antibody'

hormone https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Insulin acting as a regulator of glucose metabolism and anabolic activity; Hydrocortisone included in formulations to maintain epithelial cell differentiation and reduce stress responses; Triiodothyronine (T₃) supplemented to stimulate protein synthesis and enhance metabolic activity; Estradiol incorporated to regulate gene expression in hormone-responsive production cell lines

http://purl.obolibrary.org/obo/CHEBI_24621

See the expanded definition under the corresponding role class.

Hormone(x) ↔ OrganicMolecularEntity(x) ∧ ∃r (hasRole(x, r) ∧ HormoneRole(r))

organic molecular entity with a hormone role

every instance of 'hormone' is defined as exactly an instance of 'organic molecular entity' that 'has role' some 'hormone role'

hormone role https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Hormone role held by insulin when acting as a regulator of glucose metabolism and anabolic activity; Hormone role held by hydrocortisone when included in formulations to maintain epithelial cell differentiation and reduce stress responses; Hormone role held by a triiodothyronine (T₃) supplement to stimulate protein synthesis and enhance metabolic activity; Hormone role held by estradiol when incorporated to regulate gene expression in hormone-responsive production cell lines

http://purl.obolibrary.org/obo/CHEBI_24621

1) Some molecules naturally act as hormones in living systems by binding to receptors and influencing cell metabolism, growth, differentiation, or gene expression. In formulation and culture contexts, this role is typically asserted when that activity is intentionally used, for example when a compound is added to a medium, buffer, or formulation to promote cell proliferation, maintain differentiation, or regulate metabolic balance. 2) Although hormones were originally understood as endogenous substances synthesized by specialized cells or glands and transported to target sites, the term may also include semi-synthetic or fully synthetic compounds that mimic, replace, or modify natural hormonal activity

HormoneRole(x) → MolecularMessengerRole(x) ∧ ∃y (roleOf(x, y) ∧ OrganicMolecularEntity(y))

true

role held by an organic molecular entity that is realized in receptor-mediated signaling or regulatory processes that modulate the activity, metabolism, growth, or differentiation of cells or tissues

if x is a 'hormone role' then x is a 'molecular messenger role' and x is a 'role of' some 'organic molecular entity'

hybrid N-glycan moiety https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Hybrid N-glycan moiety on a recombinant glycoprotein with one arm retaining terminal mannose residues and another arm extended with N-acetylglucosamine; Hybrid N-glycan moiety detected during glycan profiling of a therapeutic glycoprotein; Hybrid N-glycan moiety in which one branch has high-mannose character while another branch has complex-type extension.

https://www.sigmaaldrich.com/RS/en/technical-documents/technical-article/protein-biology/protein-labeling-and-modification/n-glycans

HybridNGlycanMoiety(x) → CorePentasaccharideNGlycanMoiety(x)

true

core pentasaccharide N-glycan moiety that contains both unsubstituted terminal mannose residues and at least one mannose residue substituted by an N-acetylglucosamine unit

if x is a 'hybrid N-glycan moiety' then x is a 'core pentasaccharide N-glycan moiety'

inorganic molecular entity https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Water (H₂O); Ammonia (NH₃); Nitric oxide (NO)

https://www.ebi.ac.uk/chebi/CHEBI:24835

This class follows the ChEBI-style distinction between inorganic and organic molecular entities.

InorganicMolecularEntity(x) → MolecularEntity(x)

true

molecular entity that contains no carbon

See the primitive rationale under molecular entity

if x is an 'inorganic molecular entity' then x is a 'molecular entity'

ion https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Hydrogen ion (H⁺); Chloride ion (Cl⁻); Sodium ion (Na⁺); Ammonium ion (NH₄⁺)

https://www.ebi.ac.uk/chebi/CHEBI:24870

Ion(x) → MolecularEntity(x)

true

molecular entity having a net electric charge

See the primitive rationale under molecular entity

if x is an 'ion' then x is a 'molecular entity'

lipid https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Phosphatidylcholine; Cholesterol; Triglyceride; Sphingomyelin

http://purl.obolibrary.org/obo/CHEBI_18059

Lipid(x) → OrganicMolecularEntity(x)

true

organic molecular entity belonging to a structurally diverse class of hydrophobic or amphipathic entities that includes fats, oils, waxes, phospholipids, steroids, and related entities

See the primitive rationale under molecular entity

if x is a 'lipid' then x is an 'organic molecular entity'

lipid precursor role https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Role held by ethanolamine serving as a precursor for phosphatidylethanolamine synthesis in mammalian cells; Role held by choline functioning as a precursor for phosphatidylcholine

https://pub.uni-bielefeld.de/record/2943695 and https://clinref.com/data/uploads/books/LehningerBiochemistry6thed.pdf

Lipid precursors are molecular entities that serve as starting materials or metabolic inputs for lipid biosynthesis. Their availability can influence the rate and composition of lipid formation, affecting membrane structure, energy storage, and signaling balance. In cell culture and biomanufacturing, sufficient lipid precursor supply supports membrane biogenesis, cell growth, and product secretion.

LipidPrecursorRole(x) → MolecularEntityRole(x)

true

role of a molecular entity that provides carbon or functional groups required for the biosynthetic formation of complex lipids such as fatty acids, phospholipids, or sterols

This term is expected to remain primitive as the detailed treatment of biochemical processes is outside of the current scope of IOF. Other biological and chemical ontologies should be used for these purposes

if x is a 'lipid precursor role' then x is a 'molecular entity role'

lipopolysaccharide https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Lipopolysaccharide from Escherichia coli detected as an endotoxin-related impurity in a process sample; E. coli O111:B4 lipopolysaccharide used as a reference or challenge material in endotoxin-related testing; Salmonella enterica lipopolysaccharide used as a representative Gram-negative bacterial LPS;

http://purl.obolibrary.org/obo/CHEBI_16412

Lipopolysaccharide(x) → OrganicMolecularEntity(x)

true

organic molecular entity that consists of lipid A covalently linked to a core oligosaccharide and, where present, an O-antigen polysaccharide

See the primitive rationale under molecular entity

if x is a 'lipopolysaccharide' then x is an 'organic molecular entity'

main charge variant population https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ main monoclonal antibody peak population in cation-exchange chromatography; protein population with pI comparable to the reference protein form in capillary isoelectric focusing

MainChargeVariantPopulation(x) ↔ ProteinChargeVariantPopulation(x) ∧ ∃c(ProteinMainChargeVariantClassifier(c) ∧ classifiedBy(x, c))

protein charge variant population classified by a protein main charge variant classifier

every instance of 'main charge variant population' is defined as exactly an instance of 'protein charge variant population' that is 'classified by' some 'protein main charge variant classifier'

mannose residue https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Mannose residue in the core structure of an N-linked glycan; Mannose residue in a high-mannose glycan on a recombinant glycoprotein; Terminal mannose residue in an oligomannose-type N-glycan.

MannoseResidue(x) → MonosaccharideResidue(x)

true

monosaccharide residue that is the remaining portion of mannose after formation of a glycosidic bond

if x is a 'mannose residue' then x is a 'monosaccharide residue'

modified amino acid residue https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Oxidized methionine residue in a monoclonal antibody; Deamidated asparagine residue in a protein; Phosphorylated serine residue in a peptide; Glycated lysine residue in a protein; Alkylated cysteine residue in a peptide.

http://purl.obolibrary.org/obo/PR_000025513

This class includes amino acid residues that have undergone a covalent change such as oxidation, reduction, alkylation, acylation, or other modification to their side-chain or backbone atoms while remaining part of an intact peptide or protein. The class does not include moieties that result from cleavage of the peptide backbone or from replacement of the original amino acid at that position

ModifiedAminoAcidResidue(x) → AminoAcidResidue(x)

true

amino acid residue that has undergone covalent modification of side-chain or backbone atoms while remaining part of an intact peptide or protein

if x is a 'modified amino acid residue' then x is an 'amino acid residue'

molecular activity regulator role https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Allosteric inhibitor role held by a small molecule that reduces enzyme activity through non-covalent binding; Competitive inhibitor role held by a molecule that competes with a substrate for an enzyme active site; Receptor antagonist role held by a molecule that blocks receptor activation; Enzyme activator role held by a molecule that stabilizes an active enzyme conformation.

http://purl.obolibrary.org/obo/GO_0098772 and http://purl.obolibrary.org/obo/TXPO_0003713

MolecularActivityRegulatorRole(x) → MolecularEntityRole(x)

true

role held by a molecular entity when it modulates the activity of another molecular entity

if x is a 'molecular activity regulator role' then x is a 'molecular entity role'

molecular color indicator role https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Phenol red bearing a molecular color indicator role when its color change indicates pH in cell culture medium; Bromothymol blue bearing a molecular color indicator role when its color change indicates acidity or alkalinity; Resazurin bearing a molecular color indicator role when its color change indicates cellular metabolic activity; Iodine bearing a molecular color indicator role when color formation indicates the presence of starch.

http://purl.obolibrary.org/obo/CHEBI_50410

MolecularColorIndicatorRole(x) → MolecularVisualIndicatorRole(x)

true

molecular visual indicator role held by a molecular entity when it is used or planned to be used so that a change in its color indicates the presence, amount, or condition of a particular material entity or quality

There are insufficient constructs present to create a set of necessary and sufficient conditions

if x is a 'molecular color indicator role' then x is a 'molecular visual indicator role'

molecular entity https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ ion; salt; amino acid; protein; antibody

http://purl.obolibrary.org/obo/CHEBI_23367

MolecularEntity(x) → MaterialEntity(x)

true

material entity that is a constitutionally or isotopically distinct atom, molecule, ion, ion pair, radical, radical ion, complex, conformer, or other chemically distinguishable entity

This term is expected to remain primitive. Entities under this term are predominantly adapted from CHEBI and can be used interchangeably with the IRI of the corresponding CHEBI entity.

if x is a 'molecular entity' then x is a 'material entity'

molecular entity population https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ A population of monoclonal antibody molecules in a drug substance sample; A population of host cell protein molecules in a process intermediate; A population of product-related protein variant molecules in a recombinant protein batch; A population of released N-glycan molecules in a glycan profiling sample; A population of residual host cell DNA molecules in a drug substance sample; A population of peptide molecules generated during peptide mapping.

MolecularEntityPopulation(x) ↔ ObjectAggregate(x) ∧ ∃y (hasMemberPartAtSomeTime(x, y) ∧ MolecularEntity(y)) ∧ ∀z (hasMemberPartAtSomeTime(x, z) → MolecularEntity(z))

object aggregate that has one or more molecular entities as member parts and has only molecular entities as member parts

every instance of 'molecular entity population' is defined as exactly an instance of 'object aggregate' that 'has member part at some time' some 'molecular entity' and 'has member part at some time' only 'molecular entity'

molecular entity role https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Role held by ethylenediaminetetraacetic acid (EDTA) acting as a chelating agent in buffers to remove trace metal ions; Role held by vitamin C acting as an antioxidant in media or formulations to prevent oxidation of sensitive components

http://purl.obolibrary.org/obo/CHEBI_50906

This role represents context-dependent behaviors of molecules, such as binding, catalysis, inhibition, or signaling. The specified conditions may include factors such as sufficient concentration, presence of a binding partner, enzyme, receptor, substrate, cofactor, or competing molecule, as well as relevant pH, temperature, solvent, compartment, or process environment. The same molecular entity may bear different molecular entity roles in different chemical or biological contexts. This class corresponds to the use of “role” in ChEBI and is used to describe realizable molecular behaviors in chemical or biological environments.

MolecularEntityRole(x) → Role(x) ∧ ∃y (roleOf(x, y) ∧ MolecularEntity(y))

true

role of a molecular entity that reflects a chemical or biochemical behavior it may exhibit under specified conditions

There are insufficient constructs to create a set of necessary and sufficient conditions

if x is a 'molecular entity role' then x is a 'role' and x is a 'role of' some 'molecular entity'

molecular indicator role https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Phenol red bearing a molecular indicator role when its color change indicates pH in cell culture medium; Fluorescein-labeled molecule bearing a molecular indicator role when its fluorescence indicates binding or localization; Resazurin bearing a molecular indicator role when its reduction indicates cellular metabolic activity; pH indicator dye bearing a molecular indicator role when its color change indicates acidity or alkalinity; Redox indicator molecule bearing a molecular indicator role when its color change indicates oxidation-reduction state.

http://purl.obolibrary.org/obo/CHEBI_47867

The observable change is often visual (e.g., color change), but may also be a non-visual detectable signal (e.g., change in absorbance, change in electrical signal, or change in emitted or absorbed radiation)

MolecularIndicatorRole(x) → MolecularEntityRole(x)

true

role held by a molecular entity when it is used or planned to be used so that an observable change in that molecular entity indicates the presence, amount, or condition of a particular material entity or quality

There are insufficient constructs present to create a set of necessary and sufficient conditions

if x is a 'molecular indicator role' then x is a 'molecular entity role'

molecular messenger role https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Molecular messenger role held by insulin when added to cell culture medium to promote glucose uptake and anabolic metabolism; Molecular messenger role held by epidermal growth factor (EGF) when added to serum-free media to stimulate cell proliferation

http://purl.obolibrary.org/obo/CHEBI_33280 and https://www.ncbi.nlm.nih.gov/books/NBK538154/

MolecularMessengerRole(x) → MolecularEntityRole(x)

true

role held by a molecular entity that participates in transmitting biological signals between or within cells, tissues, or organs to support coordination of biological processes

if x is a 'molecular messenger role' then x is a 'molecular entity role'

molecular toxin https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ A mycotoxin molecule that has a toxin role; A bacterial lipopolysaccharide molecule that has a toxin role; A cytotoxic small molecule that has a toxin role under a specified exposure condition;

See the expanded definition under the corresponding role class.

MolecularToxin(x) ↔ MolecularEntity(x) ∧ ∃r (hasRole(x, r) ∧ MolecularToxinRole(r))

molecular entity with a molecular toxin role

every instance of 'molecular toxin' is defined as exactly an instance of 'molecular entity' that 'has role' some 'molecular toxin role'

molecular toxin role https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Lipopolysaccharide molecule bearing a toxin role when present as a process-related impurity that can trigger harmful biological responses; Lipid A moiety bearing a toxin role in a context where it induces inflammatory activity; A mycotoxin molecule bearing a toxin role when contaminating a raw material;

http://purl.obolibrary.org/obo/CHEBI_27026 and http://purl.obolibrary.org/obo/IDO_0000426

1) A molecular entity bearing a toxin role is distinguished by its capacity to cause damage or dysfunction when introduced or absorbed in sufficient quantity. This may include: (i) malfunction of cells; (ii) damage to the extracellular matrix; or (iii) cell damage to a degree that can lead to cell loss or cell death. 2) An entity bearing a molecular toxin role has a corresponding toxic disposition. This disposition is not modeled in the current version of the ontology and will be reconsidered in the future.

MolecularToxinRole(x) → MolecularEntityRole(x)

true

molecular entity role held by a molecular entity in a biological exposure setting in which its chemical or biochemical activity is treated as capable of causing damage or dysfunction to a cell or organism

This term is expected to remain primitive as the detailed treatment of toxicity is outside of the current scope of IOF. Other biological and chemical ontologies should be used for these purposes

if x is a 'molecular toxin role' then x is a 'molecular entity role'

molecular visual indicator role https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Phenol red bearing a molecular visual indicator role when its color change indicates pH in cell culture medium; Bromothymol blue bearing a molecular visual indicator role when its color change indicates acidity or alkalinity; Fluorescein bearing a molecular visual indicator role when its fluorescence indicates the presence or localization of a labeled material entity;

http://purl.obolibrary.org/obo/CHEBI_50408

MolecularVisualIndicatorRole(x) → MolecularIndicatorRole(x)

true

molecular indicator role held by a molecular entity when it is used or planned to be used so that a visible change in that molecular entity indicates the presence, amount, or condition of a particular material entity or quality

There are insufficient constructs present to create a set of necessary and sufficient conditions

if x is a 'molecular visual indicator role' then x is a 'molecular indicator role'

monosaccharide https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ glucose; fructose; galactose

http://purl.obolibrary.org/obo/CHEBI_35381

Monosaccharide(x) → Carbohydrate(x)

true

carbohydrate that consists of a single polyhydroxy aldehyde or polyhydroxy ketone unit with three or more carbon atoms and is not glycosidically linked to another carbohydrate unit

See the primitive rationale under molecular entity

if x is a 'monosaccharide' then x is a 'carbohydrate'

monosaccharide residue https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Glucose residue in a cellulose chain; Mannose residue in an N-linked glycan; Galactose residue in an oligosaccharide; N-acetylglucosamine residue in a glycoprotein glycan; Sialic acid residue in a complex N-glycan.

http://purl.obolibrary.org/obo/CHEBI_78848

MonosaccharideResidue(x) → ChemicalMoiety(x)

true

chemical moiety that is a proper part of an oligosaccharide, polysaccharide, or glycoconjugate and that is the remaining portion of a monosaccharide after formation of a glycosidic bond

if x is a 'monosaccharide residue' then x is a 'chemical moiety'

N4-glycosyl-L-asparagine https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ N-Glycosyl-L-asparagine N4-glycosyl-L-asparagine residue in the Fc region of a monoclonal antibody; N4-glycosyl-L-asparagine residue carrying a complex N-linked glycan in a recombinant glycoprotein

http://purl.obolibrary.org/obo/MOD_00160 and http://purl.obolibrary.org/obo/CHEBI_59108

The term “N4-glycosyl-L-asparagine” follows the classical IUPAC atom-numbering scheme, in which the side-chain amide nitrogen of L-asparagine is designated as N4. This nitrogen is the site of N-linked glycosylation.

N4GlycosylLAsparagine(x) → NGlycosylatedResidue(x)

true

N-glycosylated residue in which a glycan is covalently attached to the side-chain nitrogen of an L-asparagine residue

if x is an 'N4-glycosyl-L-asparagine' then x is an 'N-glycosylated residue'

N-glycan moiety https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ N-glycan moiety attached to an asparagine residue in a monoclonal antibody Fc glycan; N-linked glycan moiety attached to an asparagine residue in a recombinant glycoprotein

http://purl.obolibrary.org/obo/CHEBI_59520

NGlycanMoiety(x) → ChemicalMoiety(x)

true

chemical moiety that is the remaining portion of a glycan resulting from its covalent attachment to the side-chain nitrogen of an asparagine or arginine residue

if x is an 'N-glycan moiety' then x is a 'chemical moiety'

N-glycolylneuraminic acid residue https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ N-glycolylneuraminic acid residue at the terminal position of a glycoprotein glycan; N-glycolylneuraminic acid residue attached to galactose in a sialylated N-linked glycan;

NGNA residue

NGlycolylneuraminicAcidResidue(x) → SialicAcidResidue(x)

true

sialic acid residue that is the remaining portion of N-glycolylneuraminic acid after formation of a glycosidic bond

if x is an 'N-glycolylneuraminic acid residue' then x is a 'sialic acid residue'

N-glycosylated residue https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ N-glycosylated asparagine residue in the Fc region of a monoclonal antibody; Asparagine residue carrying an N-linked glycan in a recombinant glycoprotein; N-glycosylated asparagine residue within an N-X-S/T consensus sequon of a therapeutic protein

http://purl.obolibrary.org/obo/MOD_00006

This class includes amino acid residues, most commonly asparagine, that have a covalently attached carbohydrate group through an N-glycosidic linkage. In biopharmaceutical proteins, N-glycosylation is typically generated by enzymatic glycosylation pathways involving the endoplasmic reticulum and Golgi apparatus and yields N-linked glycans with characteristic core structures.

NGlycosylatedResidue(x) ↔ GlycosylatedResidue(x) ∧ ∃y (hasProperContinuantPartAtAllTimes(x, y) ∧ NGlycanMoiety(y))

glycosylated residue in which a carbohydrate or carbohydrate-derived group is attached to a nitrogen atom through formation of an N-glycosidic bond

every instance of 'N-glycosylated residue' is defined as exactly an instance of 'glycosylated residue' that 'has proper continuant part at all times' some 'N-glycan moiety'

non-proteinogenic amino acid https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Ornithine; Citrulline; β-alanine; 4-hydroxyproline

https://www.ebi.ac.uk/chebi/CHEBI:83820

NonProteinogenicAminoAcid(x) → AminoAcid(x)

true

amino acid that is not normally incorporated into polypeptide chains by ribosomal translation

See the primitive rationale under molecular entity

if x is a 'non-proteinogenic amino acid' then x is an 'amino acid'

nucleic acid https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ DNA; RNA

http://purl.obolibrary.org/obo/CHEBI_33696

NucleicAcid(x) → OrganicMolecularEntity(x)

true

organic molecular entity composed of two or more nucleotides linked by phosphodiester bonds

See the primitive rationale under molecular entity

if x is a 'nucleic acid' then x is an 'organic molecular entity'

nucleoside https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Adenosine; Cytidine; Guanosine; Uridine

https://www.ebi.ac.uk/chebi/CHEBI:33838

The nucleobase is typically adenine, guanine, cytosine, thymine, uracil, or xanthine. The sugar component is usually ribose or deoxyribose, forming an N-glycosidic bond.

Nucleoside(x) → OrganicMolecularEntity(x)

true

organic molecular entity that consists of a nucleobase linked through a nitrogen atom to a sugar such as ribose or deoxyribose

See the primitive rationale under molecular entity

if x is a 'nucleoside' then x is an 'organic molecular entity'

nucleotide https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Adenosine triphosphate (ATP); Guanosine monophosphate (GMP); Cytidine triphosphate (CTP)

https://www.ebi.ac.uk/chebi/CHEBI:36976

A nucleotide includes three structural components: a nitrogen-containing base, a pentose sugar (ribose or deoxyribose), and one or more phosphate groups linked to the sugar, typically at the 5′ position.

Nucleotide(x) → OrganicMolecularEntity(x)

true

organic molecular entity that consists of a nucleoside having one or more phosphate groups attached to its sugar moiety

See the primitive rationale under molecular entity

if x is a 'nucleotide' then x is an 'organic molecular entity'

nucleotide sequence https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ The nucleotide sequence of a plasmid DNA molecule; The nucleotide sequence of an mRNA transcript; The nucleotide sequence of a viral RNA genome segment; The nucleotide sequence of a gene coding region; The nucleotide sequence of an RNA guide molecule; The nucleotide sequence of a DNA primer.

http://purl.obolibrary.org/obo/NCIT_C45374

NucleotideSequence(x) → BiologicalSequence(x) ∧ ∀y (genericallyDependsOnAtSomeTime(x, y) → (DeoxyribonucleicAcid(y) ∨ RibonucleicAcid(y)))

true

biological sequence that is the ordered pattern of nucleotide residues that constitute a particular continuous DNA or RNA molecule

There are insufficient constructs to create a set of necessary and sufficient conditions

if x is a 'nucleotide sequence' then x is a 'biological sequence' and x 'generically depends on at some time' only on some 'deoxyribonucleic acid' or 'ribonucleic acid'

O-glycan moiety https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ O-glycan moiety attached to a serine residue in a glycoprotein; O-glycan moiety attached to a threonine residue in a mucin-like domain; O-linked glycan moiety attached to hydroxylysine in a collagen-like protein

http://purl.obolibrary.org/obo/CHEBI_59521

OGlycanMoiety(x) → ChemicalMoiety(x)

true

chemical moiety that is the remaining portion of a glycan resulting from its covalent attachment to the side-chain hydroxyl oxygen of a serine, threonine, hydroxylysine, or hydroxyproline residue

if x is an 'O-glycan moiety' then x is a 'chemical moiety'

O-glycosylated residue https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ O-glycosylated serine residue in a glycoprotein; O-glycosylated threonine residue in a mucin-like domain; Serine residue carrying an O-linked glycan in a recombinant therapeutic protein; Threonine residue carrying an O-linked glycan introduced through enzymatic glycosylation

http://purl.obolibrary.org/obo/MOD_00396

This class includes amino acid residues, most commonly serine and threonine, that have a covalently attached carbohydrate group through an O-glycosidic linkage. O-glycosylation may occur on hydroxyl-containing residues and should be distinguished from N-glycosylation, where the glycan is attached through a nitrogen atom, and from glycation, where sugar attachment arises through non-enzymatic reaction with amino groups.

OGlycosylatedResidue(x) ↔ GlycosylatedResidue(x) ∧ ∃y (hasProperContinuantPartAtAllTimes(x, y) ∧ OGlycanMoiety(y))

glycosylated residue in which a carbohydrate or carbohydrate-derived group is attached to an oxygen atom through formation of an O-glycosidic bond

every instance of 'O-glycosylated residue' is defined as exactly an instance of 'glycosylated residue' that 'has proper continuant part at all times' some 'O-glycan moiety'

organic molecular entity https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Ethanol; Acetic acid; Glucose; Lactic acid; Albumin; Estradiol

https://www.ebi.ac.uk/chebi/CHEBI:50860

This class follows the ChEBI-style distinction between inorganic and organic molecular entities.

OrganicMolecularEntity(x) → MolecularEntity(x)

true

molecular entity that contains carbon

See the primitive rationale under molecular entity

if x is an 'organic molecular entity' then x is a 'molecular entity'

oxidized residue https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Oxidized methionine residue in a monoclonal antibody; Oxidized tryptophan residue in a recombinant protein; Oxidized cysteine residue formed during protein handling or storage; Methionine sulfoxide residue formed by oxidation of a methionine residue.

http://purl.obolibrary.org/obo/MOD_00675

OxidizedResidue(x) → ModifiedAminoAcidResidue(x)

true

modified amino acid residue that results from covalent changes involving loss of hydrogen atoms or addition of oxygen atoms to the residue

if x is an 'oxidized residue' then x is a 'modified amino acid residue'

peptide https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Glutathione; Oxytocin; Bradykinin; Angiotensin II

https://www.ebi.ac.uk/chebi/CHEBI:16670

A peptide is formed through condensation reactions between amino acids, producing amide linkages known as peptide bonds. After peptide-bond formation, the peptide contains amino acid residues rather than free amino acid molecules as parts. The term generally refers to molecules composed of α-amino acid residues, but may also include peptides containing residues derived from other amino acid types.

Peptide(x) → OrganicMolecularEntity(x)

true

organic molecular entity consisting of two or more amino acid residues linked by peptide bonds

See the primitive rationale under molecular entity

if x is a 'peptide' then x is an 'organic molecular entity'

polyamine https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Putrescine; Spermidine; Spermine

https://www.ebi.ac.uk/chebi/CHEBI:88061

Polyamine(x) → OrganicMolecularEntity(x)

true

organic molecular entity that contains two or more amino groups

See the primitive rationale under molecular entity

if x is a 'polyamine' then x is an 'organic molecular entity'

polypeptide https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Casein; Collagen fragment; Insulin chain A; β-lactoglobulin

https://www.ebi.ac.uk/chebi/CHEBI:15841

Polypeptide(x) → Peptide(x)

true

peptide containing ten or more amino acid residues

See the primitive rationale under molecular entity

if x is a 'polypeptide' then x is a 'peptide'

polysaccharide https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ cellulose; glycogen; dextran; levan

http://purl.obolibrary.org/obo/CHEBI_18154

This term is commonly used only for those containing more than ten monosaccharide residues.

Polysaccharide(x) → Carbohydrate(x)

true

carbohydrate consisting of large numbers of monosaccharide residues linked glycosidically

See the primitive rationale under molecular entity

if x is a 'polysaccharide' then x is a 'carbohydrate'

protein https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Albumin; Monoclonal antibody (IgG); Recombinant human growth hormone

http://purl.obolibrary.org/obo/CHEBI_36080 and https://www.fda.gov/media/122985/download and Lehninger Principles of biochemistry and https://goldbook.iupac.org/terms/view/P04898

1) From FDA Definition of the Term “Biological Product” : “protein” means any alpha amino acid polymer with a specific, defined sequence that is greater than 40 amino acids in size. 2) Per IUPAC, proteins are naturally occurring or synthetic polypeptides with molecular weights greater than about 10,000, while the boundary is acknowledged to be imprecise. 3) The expression “sufficient length or molecular mass” is used to capture the fact that the protein–peptide boundary is not fixed by a single universally accepted criterion. The FDA criterion provides a regulatory threshold based on amino acid count, while the IUPAC criterion reflects a broader chemical convention based on molecular weight. 4) Ribosomal synthesis is not included as a necessary condition in the definition because it describes one way in which many naturally occurring proteins are produced, rather than what the molecular entity is. Since both FDA and IUPAC definitions allow classification based on the structure and composition of the polymer, and IUPAC explicitly includes synthetic polypeptides, requiring ribosomal synthesis would make the class too narrow. Ribosomally synthesized proteins can therefore be represented as a more specific subclass where the production history is relevant.

Protein(x) → OrganicMolecularEntity(x) ∧ ∃p (hasContinuantPartAtAllTimes(x, p) ∧ Polypeptide(p))

true

organic molecular entity that consists of one or more polypeptide chains of sufficient length or molecular mass to be distinguished from peptides

See the primitive rationale under molecular entity

if x is a 'protein' then x is an 'organic molecular entity' and x 'has continuant part at all times' some 'polypeptide'

protein acidic charge variant classifier https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ a classifier that classifies a deamidated monoclonal antibody population as an acidic charge variant; a classifier that classifies a sialylated antibody glycoform-enriched population as an acidic charge variant; a classifier that classifies an acidic peak population detected by cation-exchange chromatography; a classifier that classifies a lower-pI protein population detected by capillary isoelectric focusing

https://pmc.ncbi.nlm.nih.gov/articles/PMC5392216/ and https://www.chromatographyonline.com/view/charge-variant-profiling-biopharmaceuticals and https://www.agilent.com/cs/library/applications/compendium-chargevariant-advancebio-5994-0034EN-us-agilent.pdf?srsltid=AfmBOorRMu0dQH4wotghCeKwXSMCdNuuNsAEkA06EkLXupvMO6SBKJaN

The term acidic is used in the conventional charge-variant sense, typically reflecting lower isoelectric point, lower net electric charge, or corresponding behavior in methods such as ion-exchange chromatography or capillary isoelectric focusing.

ProteinAcidicChargeVariantClassifier(x) → ProteinChargeVariantClassifier(x)

true

protein charge variant classifier that classifies a molecular entity population composed of proteins or protein fragments as differing from a reference protein form by having a lower isoelectric point or lower net electric charge under the relevant analytical conditions

There are insufficient constructs to create a set of necessary and sufficient conditions.

if x is a 'protein acidic charge variant classifier' then x is a 'protein charge variant classifier'

protein aggregate https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Soluble antibody HMW clusters observed by SEC; freeze-stress induced protein dimers tethered by disulfides;

https://pmc.ncbi.nlm.nih.gov/articles/PMC5392216/ and http://id.nlm.nih.gov/mesh/D066329 and http://biomodels.net/SBO/SBO_0000543 and https://www.fda.gov/media/85017/download

mAb monomer; ribosome; nucleosome

1) Aggregates can form through diverse mechanisms including non-covalent self-association, misfolding, interfacial, environmental, or mechanical stresses, or via covalent links that are not peptide bonds. 2) The class includes assemblies formed from any mixture of folded, partially folded, misfolded, or unfolded proteins. 3) Aggregates may appear intracellularly or extracellularly. 4) The term is neutral with respect to function, or lack thereof, and solubility, which are modeled separately when relevant. 5) The term includes molecular-scale and supramolecular protein assemblies, including heterogeneous, non-stoichiometric, or reversibly associated high-molecular-weight species. Proteinaceous particles, inclusion bodies, bulk precipitates, and other larger material aggregates are not instances of this class.

ProteinAggregate(x) → OrganicMolecularEntity(x) ∧ ∃y∃z((Protein(y) ∨ ProteinFragment(y)) ∧ (Protein(z) ∨ ProteinFragment(z)) ∧ y ≠ z ∧ hasProperContinuantPartAtAllTimes(x,y) ∧ hasProperContinuantPartAtAllTimes(x,z))

true

organic molecular entity that consists of two or more protein molecules or protein fragments associated through non-covalent interactions, covalent bonds other than peptide bonds, or both

There are insufficient constructs to define a set of necessary and sufficient conditions.

if x is a 'protein aggregate' then x is an 'organic molecular entity' that 'has proper continuant part at all times' at least two distinct entities, each of which is a 'protein' or a 'protein fragment'

protein basic charge variant classifier https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ classifier that classifies a C-terminal lysine-containing monoclonal antibody population as a basic charge variant; a classifier that classifies an amidated protein population as a basic charge variant; a classifier that classifies a basic peak population detected by cation-exchange chromatography; a classifier that classifies a higher-pI protein population detected by capillary isoelectric focusing;

The term basic is used in the conventional charge-variant sense, typically reflecting higher isoelectric point, higher net electric charge, or corresponding behavior in methods such as ion-exchange chromatography or capillary isoelectric focusing. It does not mean that the classified population acts as an alkalizing (basifying) agent.

ProteinBasicChargeVariantClassifier(x) → ProteinChargeVariantClassifier(x)

true

protein charge variant classifier that classifies a molecular entity population composed of proteins or protein fragments as differing from a reference protein form by having a higher isoelectric point or higher net electric charge under the relevant analytical conditions

There are insufficient constructs to create a set of necessary and sufficient conditions.

if x is a 'protein basic charge variant classifier' then x is a 'protein charge variant classifier'

protein charge variant classifier https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ a classifier that classifies the acidic peak population of a monoclonal antibody in cation-exchange chromatography as a protein charge variant; a classifier that classifies a basic peak population of a recombinant protein by imaged capillary isoelectric focusing; a classifier that classifies deamidated antibody-related molecular populations as acidic charge variants under a product-specific charge variant method

A protein charge variant classifier classifies populations of protein or protein-fragment molecules by charge-related analytical behavior, such as net electric charge, isoelectric point, ion-exchange retention behavior, capillary isoelectric focusing behavior, or electrophoretic mobility. The classified population may contain multiple molecular forms grouped together by the analytical method, rather than one structurally uniform molecular species. The reference protein form is specified by the relevant design specification.

ProteinChargeVariantClassifier(x) → ChargeVariantClassifier(x) ∧ ∃s(DesignSpecification(s) ∧ isAbout(x,s) ∧ ∃r(Protein(r) ∧ prescribes(s,r))) ∧ ∃p(MolecularEntityPopulation(p) ∧ classifies(x,p) ∧ ∃m((Protein(m) ∨ ProteinFragment(m)) ∧ hasMemberPartAtSomeTime(p,m)) ∧ ∀n(hasMemberPartAtSomeTime(p,n) → (Protein(n) ∨ ProteinFragment(n))))

true

charge variant classifier that classifies a molecular entity population composed of proteins or protein fragments according to charge-related analytical behavior relative to a reference protein form

There are insufficient constructs to create a set of necessary and sufficient conditions.

if x is a 'protein charge variant classifier' then x is a 'charge variant classifier' that classifies some 'molecular entity population' whose members are proteins or protein fragments, and x is about some 'design specification' that prescribes some protein

protein charge variant population https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ acidic peak population of a monoclonal antibody; a basic peak population of a recombinant protein;

ProteinChargeVariantPopulation(x) → ∀m(hasMemberPartAtSomeTime(x,m) → (Protein(m) ∨ ProteinFragment(m)))

ProteinChargeVariantPopulation(x) ↔ MolecularEntityPopulation(x) ∧ ∃c(ProteinChargeVariantClassifier(c) ∧ classifiedBy(x, c))

molecular entity population classified by a protein charge variant classifier

if x is a 'protein charge variant population' and x 'has member part at some time' m, then m is a 'protein' or 'protein fragment'

every instance of 'protein charge variant population' is defined as exactly an instance of 'molecular entity population' that is 'classified by' some 'protein charge variant classifier'

protein fragment https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Fab fragment generated by cleavage of an antibody; Fc fragment generated by cleavage of an antibody; Peptide fragment generated during proteolytic digestion for peptide mapping; Clipped monoclonal antibody fragment detected during product characterization; Protein fragment formed during storage-related degradation; Host cell protein fragment detected as a process-related impurity

https://www.bioprocessintl.com/formulation/stability-considerations-for-biopharmaceuticals-overview-of-protein-and-peptide-degradation-pathways and https://pmc.ncbi.nlm.nih.gov/articles/PMC5392216/ and https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-development-production-characterisation-and-specification-monoclonal-antibodies-and-related-products-revision-1_en.pdf

1) The phrase ‘was a proper part of a protein’ indicates that the fragment existed as part of a larger protein molecule before cleavage. After the bond-breaking event, it may persist as an independent molecular entity. 2) Protein fragments may be generated by spontaneous, chemically induced, environmentally induced, mechanically associated, or enzyme-mediated peptide-bond cleavage. Examples include hydrolysis under stress conditions, fragmentation during storage or processing, and proteolytic cleavage.

ProteinFragment(x) → Peptide(x) ∨ Protein(x)

true

peptide or protein that was a proper part of a protein molecule and resulted from cleavage of one or more peptide bonds within that protein

There are insufficient constructs to define a set of necessary and sufficient conditions.

if x is a 'protein fragment' then x is a 'peptide' or 'protein'

protein high molecular weight population https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ high-molecular-weight species peak; antibody dimer and oligomer populations detected during aggregate analysis; soluble protein aggregate material observed as high-molecular-weight species relative to the monomer peak;

ProteinHighMolecularWeightPopulation(x) → ∀m(hasMemberPartAtSomeTime(x,m) → (Protein(m) ∨ ProteinAggregate(m)))

ProteinHighMolecularWeightPopulation(x) ↔ ProteinSizeVariantPopulation(x) ∧ ∃c(ProteinHighMolecularWeightVariantClassifier(c) ∧ classifiedBy(x, c))

protein size variant population classified by a protein high molecular weight variant classifier

if x is a 'protein high molecular weight population' and x 'has member part at some time' m, then m is a 'protein' or 'protein aggregate'

every instance of 'protein high molecular weight population' is defined as exactly an instance of 'protein size variant population' that is 'classified by' some 'protein high molecular weight variant classifier'

protein high molecular weight variant classifier https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ a classifier that classifies the population corresponding to a high-molecular-weight species peak in a monoclonal antibody size exclusion chromatography-high performance liquid chromatography (SEC-HPLC) assay; a classifier that classifies antibody dimer and oligomer populations detected during aggregate analysis; a classifier that classifies soluble protein aggregate material observed as high-molecular-weight species relative to the monomer peak; a classifier that classifies covalent or non-covalent antibody aggregate populations detected in a drug substance lot;

https://pmc.ncbi.nlm.nih.gov/articles/PMC3564875/ and https://pmc.ncbi.nlm.nih.gov/articles/PMC9980510/ and https://www.biopharminternational.com/view/protein-impurities-pose-challenges

A protein high molecular weight variant classifier classifies protein-related molecular populations whose molecular size or molecular weight is greater than the reference protein form under the relevant analytical method. The classified population may include aggregates, dimers, oligomers, covalently linked forms, non-covalent associated forms, or other high-molecular-weight product-related material.

ProteinHighMolecularWeightVariantClassifier(x) → ProteinSizeVariantClassifier(x) ∧ ∃p (MolecularEntityPopulation(p) ∧ classifies(x, p) ∧ ∃m ((Protein(m) ∨ ProteinAggregate(m)) ∧ hasMemberPartAtSomeTime(p, m)) ∧ ∀m (hasMemberPartAtSomeTime(p, m) → (Protein(m) ∨ ProteinAggregate(m))))

true

protein size variant classifier that classifies a molecular entity population composed of proteins or protein aggregates as having greater molecular size or molecular weight than a reference protein form

There are insufficient constructs to create a set of necessary and sufficient conditions.

if x is a 'protein high molecular weight variant classifier' then x is a 'protein size variant classifier' that classifies some 'molecular entity population' whose members are proteins or protein aggregates

protein low molecular weight population https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ low-molecular-weight species peak; clipped antibody fragment populations detected by Capillary Electrophoresis-Sodium Dodecyl Sulfate (CE-SDS); protein fragments formed during stability testing

ProteinLowMolecularWeightPopulation(x) → ∀m(hasMemberPartAtSomeTime(x,m) → (Protein(m) ∨ ProteinFragment(m)))

ProteinLowMolecularWeightPopulation(x) ↔ ProteinSizeVariantPopulation(x) ∧ ∃c(ProteinLowMolecularWeightVariantClassifier(c) ∧ classifiedBy(x, c))

protein size variant population classified by a protein low molecular weight variant classifier

if x is a 'protein low molecular weight population' and x 'has member part at some time' m, then m is a 'protein' or 'protein fragment'

every instance of 'protein low molecular weight population' is defined as exactly an instance of 'protein size variant population' that is 'classified by' some 'protein low molecular weight variant classifier'

protein low molecular weight variant classifier https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ a classifier that classifies the population corresponding to a low-molecular-weight species peak in a monoclonal antibody size exclusion chromatography-high performance liquid chromatography (SEC-HPLC) assay; a classifier that classifies clipped antibody fragment populations detected by Capillary Electrophoresis-Sodium Dodecyl Sulfate (CE-SDS); a classifier that classifies protein fragments formed during stability testing as low-molecular-weight species; a classifier that classifies a half-antibody population as lower molecular weight than the reference antibody form;

https://www.agilent.com/cs/library/applications/application-intact-protein-analysis-1290-bio-5994-3021en-agilent.pdf?srsltid=AfmBOord0gYpA_izWG5ho6VxaMiEr6N9eFGWe1h-RuEb88akGHX2gVrA and https://www.biopharminternational.com/view/protein-impurities-pose-challenges and https://www.sciencedirect.com/science/article/pii/S0022354922003392

A protein low molecular weight variant classifier classifies protein-related molecular populations whose molecular size or molecular weight is lower than the reference protein form under the relevant analytical method. The classified population may include fragments, clipped forms, truncated forms, partially degraded chains, light-chain or heavy-chain fragments, half-antibody species, or other low-molecular-weight product-related material.

ProteinLowMolecularWeightVariantClassifier(x) → ProteinSizeVariantClassifier(x) ∧ ∃p (MolecularEntityPopulation(p) ∧ classifies(x, p) ∧ ∃m ((Protein(m) ∨ ProteinFragment(m)) ∧ hasMemberPartAtSomeTime(p, m)) ∧ ∀m (hasMemberPartAtSomeTime(p, m) → (Protein(m) ∨ ProteinFragment(m))))

true

protein size variant classifier that classifies a molecular entity population composed of proteins or protein fragments as having lower molecular size or molecular weight than a reference protein form

There are insufficient constructs to create a set of necessary and sufficient conditions.

if x is a 'protein low molecular weight variant classifier' then x is a 'protein size variant classifier' that classifies some 'molecular entity population' whose members are proteins or protein fragments

protein main charge variant classifier https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ a classifier that classifies the main monoclonal antibody peak population in cation-exchange chromatography; a classifier that classifies the protein population with pI comparable to the reference protein form in capillary isoelectric focusing; a classifier that classifies the main electrophoretic band population under a product-specific charge variant method;

A main charge variant classifier classifies the protein or protein-fragment population whose charge-related analytical behavior is comparable to the reference protein form specified by the relevant product or design specification. In many charge-variant methods, this population corresponds to the main analytical peak, band, or region. The term main does not imply that the classified population is chemically homogeneous, nor does it imply that all non-main charge variants are impurities.

ProteinMainChargeVariantClassifier(x) → ProteinChargeVariantClassifier(x)

true

protein charge variant classifier that classifies a molecular entity population composed of proteins or protein fragments as having charge-related analytical behavior comparable to the reference protein form under the relevant analytical conditions

There are insufficient constructs to create a set of necessary and sufficient conditions.

if x is a 'protein main charge variant classifier' then x is a 'protein charge variant classifier'

protein size variant classifier https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ a classifier that classifies a monoclonal antibody aggregate population as a protein size variant by size-exclusion chromatography; a classifier that classifies a clipped antibody fragment population as a protein size variant by CE-SDS; a classifier that classifies a low-molecular-weight fragment population relative to the reference protein form; a classifier that classifies a high-molecular-weight oligomer population relative to the reference protein form;

https://pmc.ncbi.nlm.nih.gov/articles/PMC3564875/ and https://pmc.ncbi.nlm.nih.gov/articles/PMC9980510/ and https://www.biopharminternational.com/view/protein-impurities-pose-challenges and https://link.springer.com/article/10.1186/s41120-024-00096-x and https://www.fda.gov/media/182387/download

ProteinSizeVariantClassifier(x) → SizeVariantClassifier(x) ∧ ∃s (DesignSpecification(s) ∧ isAbout(x, s) ∧ ∃r (Protein(r) ∧ prescribes(s, r))) ∧ ∃p (MolecularEntityPopulation(p) ∧ classifies(x, p) ∧ ∃m ((Protein(m) ∨ ProteinFragment(m) ∨ ProteinAggregate(m)) ∧ hasMemberPartAtSomeTime(p, m)) ∧ ∀m (hasMemberPartAtSomeTime(p, m) → (Protein(m) ∨ ProteinFragment(m) ∨ ProteinAggregate(m))))

true

size variant classifier that classifies a molecular entity population composed of proteins, protein fragments, or protein aggregates according to molecular size or molecular weight relative to a reference protein form

There are insufficient constructs to create a set of necessary and sufficient conditions.

if x is a 'protein size variant classifier' then x is a 'size variant classifier' that 'is about' some 'design specification' that 'prescribes' some 'protein', and x 'classifies' some 'molecular entity population' whose members are proteins, protein fragments, or protein aggregates

protein size variant population https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ monoclonal antibody aggregate population; clipped antibody fragment population

ProteinSizeVariantPopulation(x) → ∀m(hasMemberPartAtSomeTime(x,m) → (Protein(m) ∨ ProteinFragment(m) ∨ ProteinAggregate(m)))

ProteinSizeVariantPopulation(x) ↔ MolecularEntityPopulation(x) ∧ ∃c(ProteinSizeVariantClassifier(c) ∧ classifiedBy(x, c))

molecular entity population classified by a protein size variant classifier

if x is a 'protein size variant population' and x 'has member part at some time' m, then m is a 'protein', 'protein fragment', or 'protein aggregate'

every instance of 'protein size variant population' is defined as exactly an instance of 'molecular entity population' that is 'classified by' some 'protein size variant classifier'

proteinogenic amino acid https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Glycine; L-alanine; L-lysine; L-methionine; L-serine; L-tryptophan; L-glutamic acid; L-cysteine.

https://www.ebi.ac.uk/chebi/CHEBI:83813

ProteinogenicAminoAcid(x) → AminoAcid(x)

true

amino acid that is normally incorporated into polypeptide chains by ribosomal translation

See the primitive rationale under molecular entity

if x is a 'proteinogenic amino acid' then x is an 'amino acid'

ribonucleic acid https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ mRNA transcript used as an expression intermediate; Guide RNA used in a gene-editing process; Ribosomal RNA present as part of a ribosome; Transfer RNA involved in translation; Viral RNA detected in a process or analytical sample; RNA molecule measured during gene-expression analysis.

RNA

http://purl.obolibrary.org/obo/CHEBI_33697

RibonucleicAcid(x) → NucleicAcid(x)

true

nucleic acid that is composed of nucleotide units containing ribose

See the primitive rationale under molecular entity

if x is 'ribonucleic acid' then x is a 'nucleic acid'

ribonucleoside https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Adenosine molecule; Guanosine molecule; Cytidine molecule; Uridine molecule.

https://www.ebi.ac.uk/chebi/CHEBI:18254

Ribonucleoside(x) → Nucleoside(x)

true

nucleoside where the sugar component is D-ribose

See the primitive rationale under molecular entity

if x is a 'ribonucleoside' then x is a 'nucleoside'

salt https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ sodium chloride; sodium monophosphate; potassium acetate

https://www.ebi.ac.uk/chebi/CHEBI:24866

Salt(x) → MolecularEntity(x) ∧ ∃a (hasContinuantPartAtAllTimes(x, a) ∧ Anion(a)) ∧ ∃c (hasContinuantPartAtAllTimes(x, c) ∧ Cation(c))

true

molecular entity that is an assembly of cations and anions

See the primitive rationale under molecular entity

if x is a 'salt' then x is a 'molecular entity', x 'has continuant part at all times' some 'anion', and x 'has continuant part at all times' some 'cation'

sialic acid residue https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Sialic acid residue at the terminal position of a complex N-linked glycan; Sialic acid residue attached to a galactose residue in a glycoprotein glycan; N-acetylneuraminic acid residue in a sialylated monoclonal antibody glycan.

SialicAcidResidue(x) → MonosaccharideResidue(x)

true

monosaccharide residue that is the remaining portion of sialic acid after formation of a glycosidic bond

if x is a 'sialic acid residue' then x is a 'monosaccharide residue'

size variant classifier https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ a classifier that classifies a group of monoclonal antibody molecules detected as a high molecular weight fraction by size-exclusion chromatography as a size variant relative to a reference monoclonal antibody; a classifier that classifies a group of recombinant protein fragments detected as a low molecular weight fraction by capillary electrophoresis as a size variant relative to a reference recombinant protein; a classifier that classifies a group of antibody-drug conjugate molecules according to size-related analytical properties under a product-specific size variant method;

A size variant classifier is a broad parent for classifiers that group material entities by size-related analytical properties. It is intended to support different material domains, including molecular products and particle-based products. More specific subclasses should be used when the size-related terminology, analytical methods, or reference comparisons are domain-specific, such as protein size variants, molecular size variants, aggregate variants, fragment variants, or lipid nanoparticle particle-size variants. The reference material entity is the material entity prescribed by the relevant design specification as the basis for comparison.

SizeVariantClassifier(x) → Classifier(x) ∧ ∃s (DesignSpecification(s) ∧ isAbout(x, s) ∧ ∃r (MaterialEntity(r) ∧ prescribes(s, r))) ∧ ∃g (ObjectAggregate(g) ∧ classifies(x, g))

true

classifier that classifies a population of material entities according to size-related analytical properties relative to a reference material entity

There are insufficient constructs to create necessary and sufficient conditions.

if x is a 'size variant classifier' then x is a 'classifier' that 'is about' some 'design specification' that 'prescribes' some 'material entity', and x 'classifies' some 'object aggregate'

steroid https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Estradiol; Testosterone; Cortisol

https://www.ebi.ac.uk/chebi/CHEBI:35341

1) Additional side chains or functional groups may be attached to the core rings, and the rings may be hydrogenated or slightly modified by rearrangement. 2) Steroids include naturally occurring compounds and synthetic analogues. This class encompasses sterols (e.g., cholesterol), bile acids, and steroid hormones, as well as numerous synthetic derivatives with medicinal applications. 3) Chemically, steroids are compounds derived from the cyclopenta[a]phenanthrene skeleton, typically with methyl groups at C-10 and C-13 and often an alkyl side chain at C-17. Natural steroids arise from squalene and may show partial hydrogenation or minor ring modifications.

Steroid(x) → Lipid(x)

true

lipid that has a core structure of four fused carbon rings, consisting of three six-membered rings and one five-membered ring

See the primitive rationale under molecular entity

if x is a 'steroid' then x is a 'lipid'

trace element role https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Trace element role held by Fe²⁺ from an iron salt that was added to media as part of a trace element supplement; Trace element role held by Cu²⁺ from CuSO₄·5H₂O (copper sulfate pentahydrate) added to support oxidative enzyme function

https://aiche.onlinelibrary.wiley.com/doi/full/10.1002/btpr.3368 and https://pubmed.ncbi.nlm.nih.gov/30290072/ and https://pub.uni-bielefeld.de/record/2943695 and https://evsexplore.semantics.cancer.gov/evsexplore/concept/ncit/C896

1) Entities bearing a trace element role support biological processes through activities such as catalysis, electron transfer, or structural stabilization of biomolecules. They are commonly introduced through inorganic salts, oxoanions, chelates, or other molecular entities that make the relevant element bioavailable. Examples include iron, zinc, copper, manganese, cobalt, and selenium supplied through compounds such as ferrous salts, zinc salts, copper salts, manganese salts, cobalt salts, or selenite. 2) Trace elements are often intentionally introduced through culture-medium or feed components, but may also originate from raw material impurities, equipment leachables, or process water. In such cases, an elemental molecular entity may bear both a trace element role and an impurity role, depending on its origin, amount, and contribution to biological processes. Mere presence in a small amount is insufficient for bearing a trace element role.

TraceElementRole(x) → MolecularEntityRole(x)

true

role held by a molecular entity composed of a single chemical element that originates from a source external to cells, is present in a small amount, and supports biological processes in those cells

if x is a 'trace element role' then x is a 'molecular entity role'

vitamin https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Thiamine (vitamin B₁) supporting carbohydrate metabolism; Riboflavin (vitamin B₂) serving as precursor of flavin cofactors (FAD, FMN); Biotin acting in carboxylation reactions.

http://purl.obolibrary.org/obo/CHEBI_33229

See the expanded definition under the corresponding role class.

Vitamin(x) ↔ OrganicMolecularEntity(x) ∧ ∃r (hasRole(x, r) ∧ VitaminRole(r))

organic molecular entity with a vitamin role

every instance of 'vitamin' is defined as exactly an instance of 'organic molecular entity' that 'has role' some 'vitamin role'

vitamin role https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ Vitamin role held by thiamine (vitamin B₁) when supporting carbohydrate metabolism; Vitamin role held by riboflavin (vitamin B₂) when serving as precursor of flavin cofactors (FAD, FMN); Vitamin role held by biotin when acting in carboxylation reactions

http://purl.obolibrary.org/obo/CHEBI_33229

Vitamins are organic compounds that support or regulate metabolic and physiological processes, often by serving as cofactors, coenzyme precursors, or regulatory metabolites. They are required only in small amounts but may not be synthesized, supplied, or activated in sufficient quantity without external inputs such as nutrient supplementation or relevant environmental conditions. In human and animal nutrition, vitamins are obtained through dietary intake; in biomanufacturing, they may be incorporated into culture media or feed formulations to support cell viability, growth, and productivity

VitaminRole(x) → MolecularEntityRole(x) ∧ ∃y (roleOf(x, y) ∧ OrganicMolecularEntity(y))

true

role held by an organic molecular entity that is used in small amounts to support metabolic or physiological functions and whose adequate availability depends on external supply or environmental activation

if x is a 'vitamin role' then x is a 'molecular entity role' and x is a 'role of' some 'organic molecular entity'

water molecule https://spec.industrialontologies.org/ontology/biopharma/MolecularEntity/ H₂O (ordinary water); D₂O (heavy water); HDO (semi-heavy water)

http://purl.obolibrary.org/obo/CHEBI_15377

1) Water molecule refers to the molecular entity H₂O, not to a bulk water material, aqueous solution, or other water-containing mixture. In laboratory and biomanufacturing usage, ‘water’ often refers to materials composed primarily of water molecules, such as Purified Water, Water for Injection, buffers, media, or other aqueous materials. These bulk materials and mixtures should be modeled separately from the water molecule itself. 2) Water molecules may occur in isotopic variants, such as heavy water (D₂O) or semi-heavy water (HDO). These variants have the same atom-connectivity pattern as H₂O but differ in hydrogen isotope composition.

WaterMolecule(x) → InorganicMolecularEntity(x)

true

inorganic molecular entity consisting of an oxygen atom that is covalently bonded to two hydrogen atoms

See the primitive rationale under molecular entity

if x is a 'water molecule' then x is an 'inorganic molecular entity'