This document discusses building a repository of biomedical ontologies using Neo4j. It describes loading over 140 ontologies with over 4.5 million terms and 11 million relations into Neo4j. This allows complex ontology queries and navigation of relationships. The repository is accessed through a REST API and is being used by over 2000 users for tasks like exploring disease relationships and taxonomic classification. Maintaining and improving the system is an ongoing effort.

1. Building a repository of biomedical
ontologies with Neo4j
Simon Jupp jupp@ebi.ac.uk, @simonjupp
Samples, Phenotypes and Ontologies Team
European Bioinformatics Institute
Cambridge, UK.

2. Biological data heavily interlinked
Proteome
Metabolome
Genome
tissue
CE-MS
antibody array LC-MS/MS
m/z
600 800 1000 1200 1400 1600
10
20
30
40
50
60
70
80
90
100
Intensity
609.256
b6
755.422
y8
882.357
b9
852.476
y9
995.435
b10
1092.506
b11
1181.252
y12
1318.578
b13
1587.759
b16
1715.817
b18
858.408
b18 ++
794.380
b16 ++
0
miRNA
array
mRNA
array
PathwaysProtein Interaction
Drug targets

3. We need terminology standards
Dyschromatopsia

4. Search PubMed for “color blindness”

5. Search PubMed for “Dyschromatopsia”

6. Search PubMed for "abnormality of the eye"

7. The ontology of color blindness
HP:0011518 (Dichromacy )HP:0011518 (Eye)
HP:0000551 (Abnormality of color vision )
HP:0007641 (Dyschromatopsia)
Is-a
Is-a
Disease-location

8. The ontology of color blindness
HP:0011518 (Dichromacy )HP:0011518 (Eye)
HP:0000551 (Abnormality of color vision )
HP:0007641 (Dyschromatopsia)
Is-a
Is-a
Disease-location
“Colorblindness”
“A form of colorblindness in
which only two of the three
fundamental colors can be
distinguished due to a lack of
one of the retinal cone
pigments.”
synonym
definition

9. 9
Genotype Phenotype
Sequence
Proteins
Gene products Transcript
Pathways
Cell type
BRENDA tissue /
enzyme source
Development
Anatomy
Phenotype
Plasmodium
life cycle
-Sequence types
and features
-Genetic Context
- Molecule role
- Molecular Function
- Biological process
- Cellular component
-Protein covalent bond
-Protein domain
-UniProt taxonomy
-Pathway ontology
-Event (INOH pathway
ontology)
-Systems Biology
-Protein-protein
interaction
-Arabidopsis development
-Cereal plant development
-Plant growth and developmental stage
-C. elegans development
-Drosophila development FBdv fly
development.obo OBO yes yes
-Human developmental anatomy, abstract
version
-Human developmental anatomy, timed version
-Mosquito gross anatomy
-Mouse adult gross anatomy
-Mouse gross anatomy and development
-C. elegans gross anatomy
-Arabidopsis gross anatomy
-Cereal plant gross anatomy
-Drosophila gross anatomy
-Dictyostelium discoideum anatomy
-Fungal gross anatomy FAO
-Plant structure
-Maize gross anatomy
-Medaka fish anatomy and development
-Zebrafish anatomy and development
-NCI Thesaurus
-Mouse pathology
-Human disease
-Cereal plant trait
-PATO PATO attribute and value.obo
-Mammalian phenotype
- Human phenotype
-Habronattus courtship
-Loggerhead nesting
-Animal natural history and life history
eVOC (Expressed
Sequence Annotation
for Humans)
Ontologies for life sciences

10. Ontology Lookup Service
• Ontology search engine (Solr)
• Graph database of terms (Neo4j)
• Powerful RESTful API (Built with Spring data neo4j / rest)
• Open source project
• Generic infrastructure (can load any ontology represented in OWL)
https://github.com/EBISPOT/OLS
Repository of over 140 biomedical ontologies (4.5 million terms, 11 million relations)
http://www.ebi.ac.uk/ols/beta

11. Web Ontology Language – (OWL)
• W3C standard vocabulary for describing
ontologies
• Powerful knowledge representation
However
• OWL ontologies aren’t graphs, but…
… can be represented as an RDF graph
… people want to use them as graphs
• Plenty of RDF databases around
• But incomplete w.r.t. OWL semantics
• SPARQL is an acquired taste

12. OWL to Neo4j schema
• Each node label one of {Class, Property, Individuals} AND {Ontology name}
• All OWL annotations become properties (labels, id, descriptions etc)
• Superclass of (named and simple existentials) become edges in Neo4j
• E.g. In OWL “heart” subclassOf (part-of some “cardiovascular system”)
In Neo4j “heart” part-of “cardiovascular system”

13. What are the sub types of “colorblindess”?
MATCH (n:Class {obo_id: 'HP:0007641'})<-[r*]-(types:Class)
RETURN n, r, types

14. What parts of the eye are related to
diseases?MATCH
(eye:Class {obo_id: 'UBERON:0000970'})<-[r:Related
{label : "part_of"}]-(eye_part:Class)<-[r1:Related
{label : "has_disease_location"}]-(disease:Class)
RETURN eye, r,r1, eye_part, disease

15. Finding common ancestors via shortest path
Match p=shortestPath( (a:Class)-[r:SUBCLASSOF*]-(b:Class) )
Return nodes(p)
What is the common taxonomic
superfamily of Gibbons and Chimpanzees?
(or Hylobatidae and Pan troglodytes!)
https://commons.wikimedia.org/wiki/File:Hylobates_lar_pair_of_white_and_black_01.jpg

16. OLS visualisations
• Partonomy for heart from the UBERON anatomy ontology
MATCH path = (n:Class)-[r:SUBCLASSOF|PartOf*]->(ancestor)

17. REST API (Spring Data REST + Neo4j)
• Crawlable API - Hypermedia drivel (HAL)
• Get ontology and term meta data
• /ontologies
• /ontologies/{name}
• /ontologies/{name}/terms
• /ontologies/{name}/terms/{termid}
• Get related terms and navigate ontology structure
• /ontologies/{name}/terms/{termid}/parent
• /ontologies/{name}/terms/{termid}/children
• /ontologies/{name}/terms/{termid}/descendants
• /ontologies/{name}/terms/{termid}/ancestors
• /ontologies/{name}/terms/{termid}/{relation} e.g. part_of
http://www.ebi.ac.uk/ols/beta/api

18. Building the index
• We check all 140 external ontology files nightly for
changes
• We have a master build index
• When ontology updates we remove the old version and
reload using the Neo4j BatchInserter (Potentially fragile)
• We push master index to various production data centers
• Provides load balancing
Nightly crawl of all
>140 registered
ontologies

19. Conclusion
• We’ve built a scalable repository of biomedical ontologies
with Neo4j
• Generic OWL indexer (simplified OWL)
• Powerful REST API built with Spring
• Acts as standalone OWL ontology server
• Now being deployed externally
• Beta ~2000 users / 10 Million requests per month
• Would like to discuss
• Batch Inserter
• Migrating to Spring Data Neo4j 4

20. Acknowledgements
• Sample Phenotypes and Ontologies Team - Tony
Burdett, James Malone, Dani Welter, Catherine Leroy,
Sira Sarntivijai, Ilinca Tudose, Helen Parkinson
• Matt Pearce – Flax (BioSOLR project)
• Michal Bachman and GraphAware team (Neo4j training)
• Funding
• European Molecular Biology Laboratory (EMBL)
• European Union projects: DIACHRON, BioMedBridges and
CORBEL