disgenet2rThe DisGeNET R package

Núria Queralt RosinachIntegrative Biomedical Informatics Group (IBI)

Research Programme on Biomedical Informatics (GRIB)Hospital del Mar Research Institute (IMIM)

Pompeu Fabra University (UPF) Barcelona

DisGeNET

http://www.disgenet.org/

• Piñero et al. DisGeNET: a discovery platform for the dynamical exploration of human diseases and their genes. Database (2015) Vol. 2015: article ID bav028, (2015)

• Knowledge platform on human gene-disease associations (GDAs)

Integrates information from the literature (text mining) and expert-curated

databases

• All disease areas

• Supporting evidence

• Analysis tools

DisGeNET – 2016 release (v4.0)

New sources

Updated ontology

New annotation

New indexes

New mappings

New RDF and nanopublications distributions

New Sources

* diseases, disease groups and phenotypes

New Sources

* diseases, disease groups and phenotypes

BeFree is the major source

All sources updated

Data Model

Gene-DiseaseAssociation

Disease Gene

Gene-DiseaseAssociation

Ontology-based integration ID normalization Use of standards

Data Model

Gene-DiseaseAssociation

Disease Gene

EvidenceScore

Gene-DiseaseAssociation

SourcePubMed Sentence SNP

Ontology-based integration ID normalization Use of standards

DisGeNET ontology

Gene Association Disease

PO SP O

http://semanticscience.org/ontology/sio.owl

DisGeNET Association Type Ontology

rdf:type

DisGeNET ontologyhttp://semanticscience.org/ontology/sio.owl

DisGeNET Association Type Ontology

New Annotation

Gene-DiseaseAssociation

Disease Gene

Gene-DiseaseAssociation

MeSH ClassUMLS STY DO Class HPO Class

Disease Ontology (DO) Human Phenotype Ontology (HPO)

New Indexes

Gene-DiseaseAssociation

Disease Gene

Gene-DiseaseAssociation

Protein PathwayPANTHER

ClassDisease

SpecificityPleiotropy

DisGeNET Disease Specificity DisGeNET Pleiotropy

New Mappings

COVERAGE

Experimental Factor Ontoloty (EFO) <= BioHackathon 2015

Disease

New RDF and Nanopublications datasets• RDF

Metadata description (W3C HCLS) Interlinking

• Trusty Nanopublications

• Access• Download Data Dump • SPARQL Endpoint• Faceted Browser• Open PHACTS

• Nanopublication Network

• FAIR (ELIXIR and NIH)

http://lod-cloud.net/; Aug 2014DisGeNET - Tutorial

Tools for exploration

disgenet2r

disgenet2r

What is it? R package To query and expand DisGeNET data To analyze and visualize the results within the

powerful R framework To engage with the R/Bioconductor community Launched within the release of DisGeNET v4.0

(April, 2016)

disgenet2r

How is it implemented? R programming language S4 Object System Free open source To be added to the Bioconductor software project Data

Query: DisGeNET Expand: DisGeNET-RDF

disgenet2r

Who is developing it? DisGeNET project

The IBI Lab, GRIB-IMIM-UPF; Barcelona http://ibi.imim.es/

Developers Alba Gutierrez-Sacristan, PhD student Janet Pinero, PhD Nuria Queralt-Rosinach, PhD Emilio Centeno, Bioinformatician Laura I. Furlong, PhD (PI)

Maintainer: Alba Gutierrez-Sacristan Contact: Laura Furlong, laura.furlong@upf.edu BioHackathon contact: Nuria Queralt (speaker),

nqueralt.r@gmail.com

disgenet2r

Why is it developed? New tool on Bioconductor to analyze high-

throughput genomics data Interaction with other R/Bioconductor packages

AtlasRDF, RpathVisio, DOSE,... Integration in workflows

KNIME

disgenet2r

Where to find it? https://bitbucket.org/ibi_group/disgenet2r Bitbucket repository used for package distribution

and testing until it is ready to be published in Bioconductor

Please test it! Feedback will be very welcome

disgenet2r - Functions

Query Gene-Disease Associations Query Variant-Disease Associations Query Disease-Phenotype Associations Query Disease-Disease Associations Query DisGeNET in the Linked Open Data

Query federation with WikiPathways and ChEMBL More to be added… + Visualization funcionalities

disgenet2r – Functions and Visualization

Query Gene-Disease Associations By Gene(s) or by Disease(s) Filters: database and score Visualization: network and heatmap

disgenet2r – Functions and Visualization

Query Gene-Disease Associations Visualization: grouping by class

MeSH disease class PANTHER protein class

disgenet2r - Functions and Visualization

Query Variant-Disease Associations

disgenet2r – Functions and Visualization

Query Disease-Disease Associations By disease(s)

Disease-Disease Network Comorbidity Network

disgenet2r – Functions and Visualization

Query Disease-Disease Associations By disease(s)

Disease-Disease Network

disgenet2r – Functions and Visualization

Query Disease-Disease Associations By disease(s)

Comorbidity Network

disgenet2r – Functions and Visualization

Query Disease-Disease Associations By disease(s)

Comorbidity Network

disgenet2r - Functions from RDF

IDs and URIs Query Disease-Phenotype Associations

disease2phenotype or phenotype2disease

Query DisGeNET in the Linked Open Data Query federation with WikiPathways and ChEMBL

disease2pathway or pathway2disase disease2compound or compound2disease

Disease Mappings UMLS to other ontologies and viceversa

Ontologies: MeSH, OMIM, ORPHANET, DO, ICD9, EFO, NCIT, DECIPHER, HPO

ANALYSISANALYSIS

KNOWLEDGE DISCOVERY

ACTIONABLEINFORMATION

Evidence

• Which genes are associated to Marfan syndrome?

• Which disease genes have approved drugs annotated?

• Which disease genes have differential expression?

• Which disease genes share a pathway?

• Is there genetic variation related to the MECP2 and Rett Syndrome association?

• What evidence supports the association between APP gene and Alzheimer Disease?

• Which genes and evidence support the comorbidity between Chronic Kidney disease and Diabetes Mellitus, Type 2?

Research Questions

Availability

● DisGeNET

http://www.disgenet.org

● disgenet2r

https://bitbucket.org/ibi_group/disgenet2r

● Open PHACTS, OpenLifeData, Pubannotation, FAIR data port (ELIXIR)

AcknowledgmentsIBI Group

Alba Gutiérrez-SacristánÀlex BravoAngela LeisEmilio CentenoJanet PiñeroNúria Queralt RosinachSantiago de la PenaAlexia GiannoulaMiguel A. MayerLaura I. FurlongFerran Sanz

Special thanksMichel DumontierSimon JuppNick JutyTobias KuhnandDisGeNET users!!!

Especially

OrganizersToshiaki KatayamaShin KawanoShuichi KawashimaJin-Dong KimYuji KoharaMari MinowaHiroyuki Mishima

Yuki MoriyaToshihisa TakagiToshiaki TokimatsuHongyan WuAtsuko YamaguchiYasunori Yamamoto

Thanks for your attention!Questions are welcome!