ontologies neo4j-graph-workshop-berlin

Building a repository of biomedical

ontologies with Neo4j

Simon Jupp

Samples, Phenotypes and Ontologies Team

European Bioinformatics Institute

Cambridge, UK.

The challenge - thousands of data

attributes

European Archive for molecular data

ENA, EVA, EGA, BioSample, ArrayExpress

How do we make sense of the data?

SPOT team builds tools to support the mapping of this data to ontologies and other standards

Why we need terminology standards (or

ontologies)

Dyschromatopsia

Search PubMed for color blindness

Search PubMed for Dyschromatopsia

Search PubMed for "abnormality of the eye"

The ontology of color blindness

HP:0011518 (Dichromacy )HP:0011518 (Eye)

HP:0000551 (Abnormality of color vision )

HP:0007641 (Dyschromatopsia)

Is-a

Is-aDisease-location

Ontology powered applications

Query expansion in the Gene Expression Atlas searching eye disease finds

genes expressed in Turner syndrome

https://www.ebi.ac.uk/gxa/home

https://www.ebi.ac.uk/gxa/home

Ontology powered applications

Visualising Gene-Disease associations in Open Targets

https://www.opentargets.org

https://www.opentargets.org/

Ontology powered applications

SNP trait

associations in the

GWAS catalog

All traits mapped to

disease, phenotype

and measurements

in EFO

https://www.ebi.ac.uk/gwas/

Cardiovascular disease traits

https://www.ebi.ac.uk/gwas/

11

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

Ontology Lookup Service

Ontology search engine

Ontology term history tracking

Ontology visualisation

Powerful RESTful API

Repository of over 160 pre-selected biomedical ontologies (4.5 million terms, 11

million relationships)

http://www.ebi.ac.uk/ols

Provides unified mechanism to access multiple ontologies

Large community of users (~5000 p/m, 100s of millions of hits p/m)

Open source and dockerised

http://www.ebi.ac.uk/ols

Ontology visualisation tools

Build process

Nightly crawl of

all registered

ontologies

Multiple indexes created

with standalone Spring Boot

applications

API and website

run with Spring data

https://ebispot.github.io

Open Source Software

https://ebispot.github.io

Loading ontologies into Neo4j

Ontologies usually published in W3C OWL format

RDF based (so already a graph)

but not a very friendly graph for our

use-cases (more on this this afternoon)

Primary OLS use-cases for a graph

Term hierarchy (parent/child)

Simple view over other relationships

Part of, develops from

Extracting subgraphs/subsets

e.g. taxon specific subsets

OWL to Neo4j schema

Every term is a node with an label for each ontology

Each relationship and subset relation is labeled (is-a, part-of, develops-from etc..)

Powerful yet simple queries

Get the transitive closure for heart following parent and partonomy relations from the UBERON anatomy ontology

MATCH path = (n:Class)-[r:SUBCLASSOF|RelatedTree*]

->(parent)

Ontology Mappings

We now have too many ontologies!! with overlapping scope

Millions of mappings exists to interlink the ontologies

Datasource 1 Datasource 2

Human

Phenotype

Ontology

SNOMED-CTMappings

Xref

Ontology Mapping Service (OxO)

New database of mappings built with Neo4j

Crawls OLS ontologies and UMLS for mappings and provides UI and API to access all known mappings

* Went live March 2017

http://www.ebi.ac.uk/spot/oxo *

http://www.ebi.ac.uk/spot/oxo

Exploring the Xref graph

We build a graph in Neo4j of known xrefs

Direct mappings to NCIt Retoinoblastoma from Disease ontology (DO) and EFO

Discover new mappings

If we traverse 1 hop in the graph we can infer more mappings

1 hop

Problems with mappings

But exposes inconsistencies in public mapping

Use this as basis for fixing and confirming mappings

Conclusion

Neo4j being adopted in multiple projects across this institute

Liked as provides simple and effective solution to some of our data modelling challenges

Neo4j is a good fit for working with ontologies and taxonomic data

Excellent developer integration for building applications e.g. Spring-data-neo4j

Ontology team

Helen ParkinsonTony Burdett

Sira SarntivijaiOlga Vrousgou Thomas Liener

Funding

EMBL

CORBEL This project receives funding from the

European Unions Horizon 2020 research and

innovation programme under grant agreement No

654248.

EXCELERATE ELIXIR-EXCELERATE is funded by

the European Commission within the Research

Infrastructures programme of Horizon 2020, grant

agreement number 676559.

Predicting annotation

We do a lot of data curation with ontologies

Need better support for mapping prediction

E.g. Sample likes these are usually annotated with these

terms

Need species specificity e.g. only mapping plant samples

with plant ontology terms

Input from submission Ontology class

2-deoxy-5-azacytidine 5-aza-2-deoxycytidine

Ovarian Cancer ovarian carcinoma

Anterior tibialis tibialis anterios

Endothelium, Vascula cardiovascular system endothelium

Tagging with ontologies

We have built a large corpus of known mappings between data values and ontology terms

Piloting building a recommendation engine for our curation tools with Neo4j