Unified Biomedical Knowledge Graph (UBKG)
Building sets of assertions
The Unified Biomedical Knowledge Graph (UBKG) is an organized collection of assertions–relationships between things, or entities.
Entities, Relationships, and Ontologies, and Assertions
Entities
Because the UBKG is a knowledge graph of biomedical information, its entities will be relevant to biomedical research. Examples include:
- genetic characteristics–structure, variation, methods of interaction
- gene products
- protein characteristics
- diseases
- chemical compounds
- body structures
Many of these entities will be relatively well known, to the extent that they can be identified by codes (encoded) in vocabularies (e.g., HGNC ids for genes; transcript IDs in Ensembl). Other entities may be the products of new research–e.g., newly identified structures, compounds, or other forms of signal.
Relationships
Although entities are important in the UBKG, the UBKG’s promise is greatest in how it identifies relationships between entities. The UBKG can not only summarize a set of relationships in a particular domain (e.g., relationships between genes and gene products, or relationships between gene products and diseases); it may be able to foster the discovery of relationships that span domains (e.g., relationships between genes and diseases mediated by gene products).
Types of relationships
Relationships in the UBKG are one of two types.
- Hierarchical or taxonomic relationships that characterize entities of the same type. For example, a B cell is a kind of lymphocyte, as is a T cell. The B cell and T cell entities have an is a kind of hierarchical relationship with lymphocyte.
- Non-hierarchical relationships, often between entities of different types. For example, a B cell produces antibodies and a T cell produces cytokines. produces is a non-hierarchical relationship.
Ontologies and Assertions
For the purposes of the UBKG, an ontology is a collection of relationships that can be identified between the entities of a particular domain of knowledge. Each relationship in an ontology is part of an assertion.
An assertion includes two entities and a relationship. The two entities are usually described as the subject and the object. The relationship is expressed as a verb, and is also known as the predicate of the assertion.
An assertion is thus a statement in the form: subject predicate object
An ontology is equivalent to a set of assertions, at least for the purposes of the UBKG. The terms ontology and set of assertions will be used interchangeably.
(Formal definitions of ontologies involve characteristics that are not represented in knowledge graphs.)
Domains, Namespaces, and SABs
An ontology is a model of a particular state of nature, and is limited to a particular domain. A particular entity may be part of more than one ontology–e.g., genes figure in a number of biomedical ontologies.
The domain for an ontology is also known as its namespace. A namespace can also refer to a vocabulary used to encode entities.
Domains are identified with acronymns called Source Abbreviations (SABs). Examples of SABs are SNOMEDCT_US, PATO, and UBERON.
Example
Consider the following set of assertions from the Phenotypic Quality Ontology (PATO).
(The assertions are represented as they would appear in an edges.tsv file. Predicates have been translated from their labels in Relations Ontology.)
| subject | predicate | object |
|---|---|---|
| UBERON:0000457 | branching part of | UBERON:0001532 |
| PATO:0001776 | subClassOf | PATO:0001544 |
| CL:0000101 | capable of | GO:0050906 |
| PATO:0001894 | subClassOf | UBERON:0000061 |
For this set of assertions:
- The domain is PATO.
- Entities are from the UBERON, CL, GO, and PATO vocabularies.
In other words, PATO is the SAB both for the entire ontology and for some entities in the ontology.
Cross-references
As shown in the preceding example, many ontologies use the same identifiers for entities. Many entities, however, are represented with different codes in different vocabularies. Identifiers from different vocabularies that refer to the same entity are considered equivalent.
The UBKG represents equivalent identifiers by means of cross-reference relationships. Cross-referenced entities allow for synonomy, or links between vocabularies.
Synonomy increases the possibility of identifying assertions that span ontological domains. If, for example, ontology A asserts a relationship between two entities and one of the entities is cross-referenced to an entity in another ontology, it may be possible to link the assertion in the first ontology to assertions in the second ontology.
When building a set of assertions, it is important to determine whether any of the entities in assertions can be cross-referenced to other entities. Cross-references are listed in the dbxrefs column of the nodes.tsv file.
Bringing it all together
To add information to the UBKG, it is necessary to model a domain of information as a set of assertions.
Modeling includes the following tasks:
- Identify the ontology domain with an appropriate SAB.
- Identity the entities in the ontology.
- If the entities are encoded in a vocabulary, identify both the codes and the SAB for the vocabulary.
- If the entities are not encoded in a vocabulary, define both the SAB and codes.
- Identify the types of relationships that can exist between entities. Where possible, describe the relationships using properties from the Relationship Ontology.
- Identify applicable cross-references for entities.
The information obtained from these tasks can be used to build the edges and nodes files that are described on the Formats page.
Example
You wish to add baking data to the UBKG. You have information on:
- different types of flours
- grains used to make flours
- mills that grind grains into flours
- breads baked from flours
You have vocabularies by which you identify flours, grains, breads, and mills. For example, GRAIN 001 in your GRAIN vocabulary identifies wheat flour. You have developed a model that relates elements as follows:
Finally, although you have your own vocabularies, you know that at least some of your data are represented by codes in other vocabularies. For example, your GRAIN vocabulary includes an entry for “rye”, but you know that code 412068007 in SNOMED_CT also refers to rye.
To integrate this data in to the UBKG, you do the following:
- Define an SAB for your domain–e.g., BAKING. UBKG will assingn this SAB to the relationships that you define in your edges.tsv file.
- Organize your codes for grains, breads, flours, and mills. For example,
| Vocabulary | Code | Item |
|---|---|---|
| FLOUR | 001 | Wheat flour |
| FLOUR | 002 | Rye flour |
| FLOUR | 003 | Corn flour |
| GRAIN | 001 | Wheat |
| GRAIN | 002 | Rye |
| GRAIN | 003 | Corn |
| MILL | 001 | Water mill |
| MILL | 002 | Ox mill |
| MILL | 003 | Metate |
| BREAD | 001 | Sourdough |
| BREAD | 002 | Marble rye |
| BREAD | 003 | Tortilla |
- Identify suitable relationships from RO, where applicable. For example, although your model originally stated that a flour comes_from a grain, you rename the relationship derives_from, which corresponds to RO_0001000. You cannot find anything in RO to represent baked_into or product_of, so those relationships remain unchanged.
- Build your edges.tsv file, using codes from your vocabularies to represent the entities and the relationships that you defined:
| subject | predicate | object |
|---|---|---|
| FLOUR:001 | RO_0001000 | GRAIN:001 |
| FLOUR:001 | product_of | MILL:001 |
| FLOUR:001 | baked_into | BREAD:001 |
| FLOUR:002 | RO_0001000 | GRAIN:002 |
| FLOUR:002 | product_of | MILL:001 |
| FLOUR:002 | baked_into | BREAD:002 |
| FLOUR:003 | RO_0001000 | GRAIN:003 |
| FLOUR:003 | product_of | MILL:003 |
| FLOUR:003 | baked_into | BREAD:003 |
- Build your nodes.tsv file, including cross-references for grains that you identified.
| node_id | node_label | node_definition | node_synonyms | node_dbxrefs |
|---|---|---|---|---|
| FLOUR:001 | Wheat flour | Flour made from wheat | ||
| GRAIN:001 | Wheat | Wheat | Triticum asetivum | SNOMEDCT_US:65256004 |
| MILL:001 | Ox Mill | Mill driven by oxen | ||
| FLOUR:002 | Rye flour | Flour made from rye | ||
| GRAIN:002 | Rye | SNOMEDCT_US:412068007 |