Biomarker Ontology

[Astghik-S]

Title

Biomarker Ontology

Short Description

The Biomarker Ontology comprises a comprehensive knowledge involving a variety of fields of medical and biological aspects.

Description

The Biomarker Ontology (BMONT) is a comprehensive knowledge representation involving a variety of fields of medical and biological aspects. BMONT is built in line with Basic Formal Ontology (BFO) and Open Biological and Biomedical Ontology (OBO) principles.
Entities and definitions are added by reviewing the old biomarker terminology that was created by Fraunhofer SCAI 10 years ago and was used for mining biomarker information in biomedical literature. In addition, related terms were collected from scientific publications and books capturing various disease fields.

The ontology is proposed to be used for improving biomarker identification tasks, as well as a supportive integratable tool for abundant AI techniques, such as Machine Learning (ML) and Large Learning Model (LLM).

Identifier Space

BMO

License

CC-BY 4.0

Domain

health

Source Code Repository

OBOFoundry.github.io

Homepage

https://github.com/SCAI-BIO/BiomarkerOntology

Issue Tracker

https://github.com/SCAI-BIO/BiomarkerOntology/issues

Contribution Guidelines

https://github.com/SCAI-BIO/BiomarkerOntology/blob/main/CONTRIBUTING.md

Ontology Download Link

https://github.com/SCAI-BIO/BiomarkerOntology

Contact Name

Alpha Tom Kodamullil

Contact Email

alpha.tom.kodamullil@scai.fraunhofer.de

Contact GitHub Username

akodamullil

Contact ORCID Identifier

https://orcid.org/0000-0001-9896-3531

Formats

• OWL RDF/XML (.owl)
• OBO (.obo)
• OBO Graph JSON (.json)

Dependencies

-doid -chebi -mondo -cto -efo

Related

DOID
MONDO
CHEBI
CTO
EFO

Usages

No response

Intended Use Cases and/or Related Projects

A biomedical ontology to classify biomarkers and apply semantic technologies in the domain of various diseases, analyse biomarker discovery workflows. Annotation of medical texts.

Data Sources

Several sources from domain experts assembled by Fraunhofer SCAI.

Additional comments or remarks

No response

OBO Foundry Pre-registration Checklist

• I have read and understood the registration process instructions and the registration checklist.
• There is no other ontology in the OBO Foundry which would be an appropriate place for my terms. If there were, I have contacted the editors, and we decided in mutual agreement that a separate ontology is more appropriate.
• My ontology has a specific release file with a version IRI and a dc:license annotation, serialised in RDF/XML.
• My identifiers (classes and properties IRIs) are formatted according to the OBO Foundry Identifier Policy
• My term labels are in English and conform to the OBO Foundry Naming Conventions
• I understand that term definitions are key to understanding the intentions of a term, especially when the ontology is used in curation. I made sure that a reasonable majority of terms in my ontology--and all top level terms--have definitions, in English, using the IAO:0000115 property.
• For every term in my ontology, I checked whether another OBO Foundry ontology has one with the same meaning. If so, I re-used that term directly (not by cross-reference, by directly using the IRI).
• For all relationship properties (Object and Data Property), I checked whether the Relation Ontology (RO) includes an appropriate one. I understand that aligning with RO is an essential part of the overall alignment between OBO ontologies!
• For the selection of appropriate annotation properties, I looked at OMO first. I understand that aligning ontology metadata and term-level metadata is essential for cross-integration of OBO ontologies.
• If I was not sure about the meaning of any of the checkboxes above, I have consulted with a member of the OBO Foundry for advice, e.g., through the obo-discuss Google Group.
• The requested ID space does not conflict with another ID space found in other registries such as the Bioregistry and BioPortal, see here for a complete list.

[nlharris]

@matentzn @pfabry did you see this New Ontology request?

[pfabry]

Dear @Astghik-S ,

Thank you for your submission. The review will be executed as a two stage process:

First, you will have to pass OBO NOR Dashboard. Pass means that no check apart from Users and Versioning may be red. In addition, a new check is currently implemented: it consists in a lexical match of your original terms with those already existing in OBO Foundry published ontologies. The goal is to prevent the duplication of terms with similar meanings (cf. Review SOP). A list of terms that are potential duplicates will be provided soon.

After you have successfully passed the Dashboard you will be assigned an OBO Operations committee member to review the ontology. The assigned reviewer is to be considered the final arbiter of requirements; look to that reviewer's guidance regarding which suggestions made by other reviewers must be done, which suggestions are simply good to do but not required, and which should not be done.

Usually, the review will result in an opportunity for you to improve the ontology. When the reviewer believes the ontology is ready for presentation to the OBO Operations Committee, they will present your ontology during an OBO Operations Call. This gives other members of the committee the opportunity to assess your work.

When a decision is reached by the committee you will be informed here on the issue tracker. The process can take any number of weeks or months, depending on the case at hand.
Please let us know about any reasons you might have for increased urgency.

You will be informed once your ontology is loaded in the OBO NOR Dashboard.

Good luck!

[Astghik-S]

Dear @pfabry thank you very much for the detailed information. I am looking forward to checking the Dashboard and proceeding with further steps.

[pfabry]

@Astghik-S
Your ontology has been added to the OBO NOR Dashboard.
In addition, the lexical matching hasn't find any duplicate in your ontology.

[pfabry]

@Astghik-S
Your ontology has passed the OBO NOR Dashboard and has been assigned to @deepakunni3 for reviewing.

[deepakunni3]

Manual review of Biomarker Ontology

1. Ontology scope

The submitter describes Biomarker Ontology (BMO) as an ontology for classifying biomarkers, improving biomarker identification and facilitating tools used in machine learning and large language models. Upon closer inspection of the ontology, it looks like the ontology adds new terms and extends existing terms from CHEBI, CTO, CMO, OMIT, PR with additional axioms. The domain is 'health' which is consistent with the description and the terms defined within BMO.

The submitter states that several domain experts from Fraunhofer SCAI were involved in the development of BMO. But it is not clear who they are. The terms in BMO do not have any attribution so as to who contributed it. In addition, there are 36 terms in the ontology that have IAO:0000119 definition source as "ChatGPT". This seems to indicate some level of automated term extraction and creation. The submitter does make a reference to an older "biomarker ontology" developed 10 years ago by Fraunhofer SCAI. That means this iteration of BMO is meant to be an updated version which has been prepared for open-source sharing and contribution.

2. Terms with the new ontology prefix ❗

Do the terms follow the OBO identifier scheme?❗

The Base IRI for terms in BMO is http://purl.obolibrary.org/obo/bmo.owl/BMO_. It would be appropriate to remove the bmo.owl from the IRI to match the OBO identifier scheme.

Are there terms with the same meaning available in another OBO Foundry ontology? Yes❗

Yes, after reviewing terms from BMO, there are cases where a term from another ontology could be used instead. Following are some of the terms that could be replaced with an existing term:

• The term BMO:0000060 d-dimer can be replaced with PR:000050369 D-dimer (human)
• The term BMO:0000061 Growth Differentiation Factor 15 can be replaced with OMIT:0026290 Growth Differentiation Factor 15
• The termBMO:0000092 blood glucose level can be replaced with CMO:0000046 blood glucose level

Is there another OBO Foundry ontology whose scope covers any of the new terms? ❗

Yes, after reviewing terms from BMO, there are cases where another ontology would cover some of the new terms. Following are BMO terms that could be added to another OBO Foundry ontology:

Clinical Measurement Ontology (CMO)

CMO contains terms that are specific to clinical measurements and thus could cover the following terms defined within BMO:

• BMO:0000110 cerebral blood volume
• BMO:0000113 gray matter volume
• BMO:0000131 N-Terminal Pro-B-Type Natriuretic Peptide
• BMO:0000103 blood lipid level

Protein Ontology (PRO)

PRO contains terms that represent proteins and thus could cover the following terms defined within BMO:

• BMO:0000062 lipoprotein a
• BMO:0000063 fibrinogen
• BMO:0000064 Creatine Kinase-MB

Ontology of Precision Medicine and Investigation (OPMI)

OPMI already defines several biomarkers and thus could cover the following terms defined within BMO:

• BMO:0000076 therapeutic biomarker
• BMO:0000075 parmacodynamic biomarker
• BMO:0000077 digital biomarker

Ontology for Biomedical Investigations (OBI)

OBI already defines several terms for devices and thus could cover the following terms defined in BMO:

• BMO:0000078 digital device

Note: The ontology submitter must make efforts to coordinate and add these terms to the suggested ontologies. If the terms are rejected or deemed as out of scope by the target ontologies then an exception can be made for those terms.

3. Correct use of imported terms ❗

If the ontology reuses terms from other OBO ontologies, are they used accurately? ✅

The BMO ontology imports several terms from CHEBI, OBI, SIO, EFO, OMIT and extends these terms using object properties to indicate whether the terms are a predictive, prognostic, diagnostic biomarker for a disease (via OWL restrictions). The imported terms have sufficient metadata.

Are imported terms in appropriate hierarchies, and do they preserve the term’s upper-level alignment? ❗

There are certain cases where an imported term does not have the parent class from the upstream ontology as its parent. Rather it is an ancestral class which is ambiguous.

• For example, in BMO, CHEBI:17855 Triglyceride is a subclass of CHEBI:23367 Molecular Entity when in reality CHEBI:17855 Triglyceride is subclass of CHEBI:35741 glycerolipid

Are any additional axioms used for these terms correct in both a technical (e.g. passes reasoning) and substantive sense? ❗

There are other cases where an imported term is defined as a subclass of a term from an entirely different ontology.

• For example, BMO imports MONDO:0007915 systemic lupus erythematosus and states that this term is subclass of DOID:417 autoimmune disease even though according to MONDO, MONDO:0007915 is subclass of MONDO:0004670. It is not clear why a new subClassOf axiom was added to an imported term.

4. Basic review of axiomatic patterns ✅

Are axioms generally stated simply or are they highly complex? (Highly complex axioms will require extra scrutiny.) ✅

The axioms are simply and appropriately constructed.

Are existential restrictions used correctly? ✅

Yes, existential restrictions are used correctly.

5. Appropriate use of object properties ✅

BMO defines 7 BMO-specific object properties and they are used in a consistent manner throughout the ontology.

One thing to note is that the object properties have a label but no additional information such as definition, domain or range that further describe these properties and their usage.

BMO also re-uses object properties from RO and their usage are consistent as well.

6. Responsiveness to suggested changes ❔

This is the first iteration of feedback. Will evaluate the responsiveness in the next iteration.

Additional Questions/Suggestions

• The BMO repository (https://github.com/Astghik-S/BMO) is located within a GitHub user account. Ideally, this should be moved to a GitHub organization to ensure sustainability.
• It looks like the repository itself is fairly new (2 months since creation). There is no community interaction or history to see. If this is a new ontology then that is expected. But there does seem to references to a historical version of BMO.
• The README (https://github.com/Astghik-S/BMO?tab=readme-ov-file#maintenance) has a statement that indicates that BMO will be maintained for at least 3 years. It would be good for the submitters to set up their repository for better community engagement to empower open-source contributors to continue the development and maintenance of BMO.
• Favoring PATO (an OBO Foundry ontology) over SIO for terms that represent quality such as 'normal', 'abnormal', 'increased', 'decreased', etc.
• There are terms in BMO that do not have a parent class. It would be clearer to give these an appropriate parent class:
  • BMO:0000070
  • BMO:0000072
  • BMO:0000073
  • BMO:0000098
  • BMO:0000100
  • BMO:0000132

Lexical Matching

After running lexical match on term labels in BMO with terms from OBO Foundry ontologies (excluding NCIT), following are the results:

• BMO:0000009 monitoring biomarker
• BMO:0000012 safety biomarker
• BMO:0000015 surrogate biomarker
• BMO:0000016 context of use
• BMO:0000020 clinical sensitivity
• BMO:0000022 probability of false negatives
  • stato:0000220 false negative rate (0.778)
• BMO:0000025 companion diagnostics
  • chebi:3479 cefadroxil (0.521)
• BMO:0000037 kidney injury molecule-1
• BMO:0000038 urine total potein
• BMO:0000050 human epidermal growth factor receptor 2
• BMO:0000060 d-dimer
• BMO:0000061 Growth Differentiation Factor 15
  • ogg:3000009518 GDF15 (0.778)
• BMO:0000063 fibrinogen
  • dron:00018213 Fibrinogen (0.762)
  • go:0005577 fibrinogen complex (0.556)
  • go:0008001 obsolete fibrinogen (0.556)
• BMO:0000064 Creatine Kinase-MB
  • go:0004111 creatine kinase activity (0.556)
• BMO:0000075 pharmacodynamic biomarker
• BMO:0000083 augmentation index
  • ncbitaxon:8831 Aix (0.743)
  • vto:0030587 Aix (0.743)
• BMO:0000091 sleep stage
• BMO:0000092 blood glucose level
  • cmo:0000046 blood glucose level (0.778)
  • vt:0000188 blood glucose amount (0.556)
• BMO:0000104 total cholesterol
• BMO:0000120 amyloid deposition
  • mpath:34 amyloid deposition (0.778)
• BMO:0000130 gait unsteadiness
  • hp:0002066 Gait ataxia (0.549)
  • hp:0002317 Unsteady gait (0.772)
  • mp:0001393 ataxia (0.556)
• BMO:0000131 N-Terminal Pro-B-Type Natriuretic Peptide

Note: The above list is a suggestion and it is up to the discretion of the ontology submitter to check for consistency before considering a term as a potential replacement.

Robot Report

After running the robot report command on BMO:

java -jar robot.jar report --input BMO-merged.owl

Following are BMO-specific issues as reported by robot:

Rule Name	Subject	Property	Value
duplicate_exact_synonym	obo:bmo.owl/BMO_0000015	oboInOwl:hasExactSynonym	
duplicate_label_synonym	obo:bmo.owl/BMO_0000063	oboInOwl:hasExactSynonym	fibrinogen
equivalent_class_axiom_no_genus	obo:bmo.owl/BMO_0000070	obo:bmo.owl/BMO_0000066	DOID:4
equivalent_class_axiom_no_genus	obo:bmo.owl/BMO_0000072	obo:bmo.owl/BMO_0000067	DOID:4
equivalent_class_axiom_no_genus	obo:bmo.owl/BMO_0000073	obo:bmo.owl/BMO_0000065	DOID:4
equivalent_class_axiom_no_genus	obo:bmo.owl/BMO_0000074	obo:bmo.owl/BMO_0000071	DOID:4
equivalent_class_axiom_no_genus	obo:bmo.owl/BMO_0000098	obo:bmo.owl/BMO_0000097	DOID:4
equivalent_class_axiom_no_genus	obo:bmo.owl/BMO_0000100	obo:bmo.owl/BMO_0000099	DOID:4
equivalent_class_axiom_no_genus	obo:bmo.owl/BMO_0000132	obo:bmo.owl/BMO_0000057	DOID:4
missing_definition	obo:bmo.owl/BMO_0000048	IAO:0000115	
missing_definition	obo:bmo.owl/BMO_0000057	IAO:0000115	
missing_definition	obo:bmo.owl/BMO_0000065	IAO:0000115	
missing_definition	obo:bmo.owl/BMO_0000066	IAO:0000115	
missing_definition	obo:bmo.owl/BMO_0000067	IAO:0000115	
missing_definition	obo:bmo.owl/BMO_0000070	IAO:0000115	
missing_definition	obo:bmo.owl/BMO_0000071	IAO:0000115	
missing_definition	obo:bmo.owl/BMO_0000072	IAO:0000115	
missing_definition	obo:bmo.owl/BMO_0000073	IAO:0000115	
missing_definition	obo:bmo.owl/BMO_0000074	IAO:0000115	
missing_definition	obo:bmo.owl/BMO_0000097	IAO:0000115	
missing_definition	obo:bmo.owl/BMO_0000098	IAO:0000115	
missing_definition	obo:bmo.owl/BMO_0000099	IAO:0000115	
missing_definition	obo:bmo.owl/BMO_0000100	IAO:0000115	
missing_definition	obo:bmo.owl/BMO_0000132	IAO:0000115	
missing_superclass	obo:bmo.owl/BMO_0000070	rdfs:subClassOf	
missing_superclass	obo:bmo.owl/BMO_0000072	rdfs:subClassOf	
missing_superclass	obo:bmo.owl/BMO_0000073	rdfs:subClassOf	
missing_superclass	obo:bmo.owl/BMO_0000074	rdfs:subClassOf	
missing_superclass	obo:bmo.owl/BMO_0000098	rdfs:subClassOf	
missing_superclass	obo:bmo.owl/BMO_0000100	rdfs:subClassOf	
missing_superclass	obo:bmo.owl/BMO_0000132	rdfs:subClassOf	

Checklist

• MUST change the term IRI from http://purl.obolibrary.org/obo/bmo.owl/BMO_ to http://purl.obolibrary.org/obo/BMO_ to match the OBO identifier scheme
• SHOULD replace BMO:0000060 d-dimer with PR:000050369 D-dimer (human)
• SHOULD replace BMO:0000061 Growth Differentiation Factor 15 with OMIT:0026290 Growth Differentiation Factor 15
• SHOULD replace BMO:0000092 blood glucose level with CMO:0000046 blood glucose level
• SHOULD look into the lexical match results and evaluate possible replacement terms from existing OBO Foundry ontologies
• MUST add terms that overlap in scope to the respective ontologies (CMO, PRO, OPMI, OBI)
• MUST look into the rdfs:subClassOf axioms added to imported terms to ensure that they are consistent with upstream ontologies
• SHOULD add definition, rdfs:domain and rdfs:range information to BMO-specific object properties for better readability, interpretation and usage
• CONSIDER moving BMO repository from a GitHub user account to a GitHub organization
• SHOULD set up their repository for better community engagement to empower open-source contributors to continue the development and maintenance of BMO
• SHOULD add an appropriate parent class to BMO terms that are missing a parent class

@Astghik-S Please take time to go through the above review and the subsequent checklist. You can use this issue thread to keep us up to date regarding progress. If you have any questions or concerns then please don't hesitate to reach out.

[Astghik-S]

@deepakunni3 Thank you for the review and comments. I shall check all mentioned points, address all, and come back to you!

[Astghik-S]

@deepakunni3 sorry for the late reply. We checked all comments and below I am addressing all of those.

• First of all , I would like to mention that we changed the acronym to BMONT in order to to avoid ambiguity, and corrected the base IRI for it. As well as, upon your suggestion we have stored the ontology.

• Names of contributed people are added.

• For the completeness of the ontology we added definitions for the newly defined terms. In cases when no other definition source was found we manually checked and added the definitions suggested by ChatGPT. Meaning, that no automated term extraction and creation is done.

• The submitter does make a reference to an older "biomarker ontology" developed 10 years ago by Fraunhofer SCAI. That means this iteration of BMO is meant to be an updated version which has been prepared for open-source sharing and contribution.

-- We changed the ontology description as 10 years ago our colleagues created not an ontology but rather a terminology and we have only used it to extract relevant terms. The BMONT was built from scratch. I hope this resolves the ambiguity.

• Following are some of the terms that could be replaced with an existing term

-- The mentioned terms that were mistakenly defined as new ones despite the fact they already exist are replaced.

• Following are BMO terms that could be added to another OBO Foundry ontology:

-- Trying to guess which OBO ontology could include the suggested term is very demotivating and time consuming. If the term is not in other ontologies then simply we should define it as we are applying for OBO approval.
We can of course check if BMONT terms that could be added to another OBO Foundary ontology, for example CMO, PRO, and OBI asking them to check if they are willing to have the terms in their ontology. But why are we making efforts to create a valuable ontology?

Moreover, we do not think that "BMO:0000076 therapeutic biomarker", "BMO:0000075 parmacodynamic biomarker"
"BMO:0000077 digital biomarker" are more in scope of Ontology of Precision Medicine and Investigation (OPMI) than of our BMONT.

• Considering your comment that there are certain cases where an imported term does not have the parent class from the upstream ontology as its parent. Rather it is an ancestral class which is ambiguous. We would like to consider the example yo provided: In BMO, CHEBI:17855 C is a subclass of CHEBI:23367 Molecular Entity when in reality CHEBI:17855 Triglyceride is subclass of CHEBI:35741 glycerolipid.

We would like to mention that, it is not ambiguous at all and we do not have to include all ancestral classes if it is not necessary otherwise we will include the whole CHEBI which is nonsense. “Triglyceride” is a “molecular entity” so “is a” relationship is there so no obligation or violation.

• Considering another cmment of you mentioning that there are other cases where an imported term is defined as a subclass of a term from an entirely different ontology: For example, BMO imports MONDO:0007915 systemic lupus erythematosus and states that this term is subclass of DOID:417 autoimmune disease even though according to MONDO, MONDO:0007915 is subclass of MONDO:0004670. It is not clear why a new subClassOf axiom was added to an imported term.
  Here we would like to note that the class "autoimmune disease" is in both MONDO and DOID OBO ontologies, so if it is already imported from DOID practically it is not possible to rearrange, remove and add classes each time. So if there is a term with exactly the same name we just took it as appropriate upper class.

-As you mentioned there are terms in BMO that do not have a parent class. It would be clearer to give these an appropriate parent class:
BMO:0000070, BMO:0000072, BMO:0000073, BMO:0000098, BMO:0000100, BMO:0000132

The mentioned classes do not have parent classes because they are for text mining purposes which also is given in their name to avoid confusions.