1. Ferran Sanz – GRIB (IMIM-UPF) Bioinformatics: How it can support the Family of International Classifications? Ferran Sanz Research Programme on Biomedical Informatics (GRIB) Hospital del Mar Research Institute (IMIM) Universitat Pompeu Fabra

2. Ferran Sanz – GRIB (IMIM-UPF) Bioinformatics constitutes an expanding discipline that deals with the management and analysis of the huge amount of information that is generated in both biomedical research and clinical practice. It contributes to a more accurate and comprehensive understanding of the molecular mechanisms of diseases, thus providing a valuable basis for their more rigorous classification.

3. Ferran Sanz – GRIB (IMIM-UPF) Integration of heterogeneous biomedical information in order to gain a more complete and powerful view on diseases and therapeutics INTEGRATIVE BIOINFORMATICS Clinical Data Biomedical imaging ‘omics & Systems Biology Drugs & other chemicals Biomedical literature

4. Ferran Sanz – GRIB (IMIM-UPF) Information on the genetic basis of human diseases is abundant but scattered among different sources

5. Ferran Sanz – GRIB (IMIM-UPF) A comprehensive resource on gene-disease associations Integrates information from publicly available databases and the literature (text mining) Freely available at: http://ibi.imim.es/DisGeNEThttp://ibi.imim.es/DisGeNET

6. Ferran Sanz – GRIB (IMIM-UPF) source databases CTD human UniProt GAD MGD RDG Mouse and rat genes projected into human orthologs Curated Predicted Literature LHGDN BeFree CTD mouse & rat

7. Ferran Sanz – GRIB (IMIM-UPF) v2.1 (2014 release) Database Statistics

8. Ferran Sanz – GRIB (IMIM-UPF) Knowledge pockets in genetics of diseases

9. Ferran Sanz – GRIB (IMIM-UPF) Simplified data model of DisGeNET RDF representation

10. Ferran Sanz – GRIB (IMIM-UPF) The DisGeNET association type ontology

11. Ferran Sanz – GRIB (IMIM-UPF) Examples of the questions that can be answered using DisGeNET

12. Ferran Sanz – GRIB (IMIM-UPF) DisGeNET web interface: the Search view and the Browser view

13. Ferran Sanz – GRIB (IMIM-UPF) disease centric view gene centric view network clustering Analysis of gene-disease networks Groups of diseases based on shared genetic background Disease classification Disease comorbidities Groups of genes based on shared diseases Might reveal common functional processes underlying diseases

14. Ferran Sanz – GRIB (IMIM-UPF)

15. Identification of shared mechanisms for comorbid diseases: COPD comorbidities Application

16. Ferran Sanz – GRIB (IMIM-UPF) COPD comorbidome Proportion of shared proteins targeted by chemical compounds present in tobacco smoke

17. Ferran Sanz – GRIB (IMIM-UPF) Connexion between COPD and Anemia at the molecular level

18. Ferran Sanz – GRIB (IMIM-UPF) 18 Database of psychiatric disorders and their genes Set of tools for data exploration and analysis http://www.psygenet.org/

19. Ferran Sanz – GRIB (IMIM-UPF) 19 To develop a resource on psychiatric diseases and their genes Goal Initial focus in three psychiatric disorders: MD, AUD, CUD Close collaboration between psychiatry experts and bioinformaticians Gather and integrate data scattered in publications and other public databases

20. Ferran Sanz – GRIB (IMIM-UPF) 20 Bio-Entity Finder and Relation Extraction Gene-disease associations Retrieval based on terminology selected by experts PsyGeNET database Gene-disease associations Reviewed by experts GAD CTD RGD MGD PsyCUR 900,000 abstracts 800 associations 2,000 assoc

21. Ferran Sanz – GRIB (IMIM-UPF) 21 PsyGeNET database DatasetOriginal data source GenesDisease terms Associations GAD 844201165 MODELS MGD 33639 RGD CURATED CTD 755372061 PsyCUR ALL1317372823

22. Ferran Sanz – GRIB (IMIM-UPF) 22 PsyGeNETPsyCURExclusive to PsyCUR CTD 1 OMIM 2 Depression877546501706 Alcoholism555221198346 Cocaine use disorder 13233181080 1 Comparative Toxicogenomics Database 2 Online Mendelian Inheritance on Man Number of genes associated to each psychiatric disorder in PsyGeNET PsyGeNET contains information on the genetics of psychiatric disorders not available in other resources

23. Ferran Sanz – GRIB (IMIM-UPF)

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25. Ferran Sanz – GRIB (IMIM-UPF) Depression, alcoholism and cocaine use disorders might be linked at the molecular level through shared genes Disease ADisease B genes AGenes BShared genes Jaccard Index DepressionAlcoholism8775551690.13* DepressionCocaine UD877132630.07* AlcoholismCocaine UD555132570.06* *significant by bootstrap testing

26. Ferran Sanz – GRIB (IMIM-UPF) 26 Functional analysis of psychiatric disease genes GO and pathway enrichment of individual diseases and their comorbidities Enrichment analysis of depression genes with cocaine and alcohol chemicals

27. Ferran Sanz – GRIB (IMIM-UPF) 27 Serotonin and dopamine signaling

28. Ferran Sanz – GRIB (IMIM-UPF) 28 Alcohol use disorder 232 genes in PsyGeNET curated 386 genes targeted by alcohol compounds in CTD 51 genes in common Cocaine use disorder 126 genes in PsyGeNET curated 291 genes targeted by cocaine compounds in CTD 59 genes in common

29. Ferran Sanz – GRIB (IMIM-UPF) J. Piñero Integrative Biomedical Informatics Group (GRIB) http://grib.upf.edu M. Cases F. Sanz L.Furlong S.Grosdidier N.Queralt A. Bravo M.A. Mayer A. Gutiérrez A. Bauer-Mehren