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Ferran Sanz – GRIB (IMIM-UPF)Ferran Sanz – GRIB (IMIM-UPF)
Bioinformatics: How it can supportthe Family of International Classifications?
Ferran SanzResearch Programme on Biomedical Informatics (GRIB)
Hospital del Mar Research Institute (IMIM)Universitat Pompeu Fabra
Ferran Sanz – GRIB (IMIM-UPF)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.
Ferran Sanz – GRIB (IMIM-UPF)Ferran Sanz – GRIB (IMIM-UPF)
Integration of heterogeneous biomedical information in orderto 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
Ferran Sanz – GRIB (IMIM-UPF)Ferran Sanz – GRIB (IMIM-UPF)
Information on the genetic basis of human diseases is abundant but scattered among different sources
Ferran Sanz – GRIB (IMIM-UPF)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/DisGeNET
Ferran Sanz – GRIB (IMIM-UPF)
source databases
CTDhuman
UniProt GADMGD
RDG
Mouse and rat genes projected into human
orthologs
Curated Predicted Literature
LHGDN
BeFreeCTD
mouse & rat
Ferran Sanz – GRIB (IMIM-UPF)
v2.1 (2014 release)
Database Statistics
Ferran Sanz – GRIB (IMIM-UPF)Ferran Sanz – GRIB (IMIM-UPF)
Knowledge pockets in genetics of diseases
Ferran Sanz – GRIB (IMIM-UPF)Ferran Sanz – GRIB (IMIM-UPF)
Simplified data model of DisGeNET RDF representation
Ferran Sanz – GRIB (IMIM-UPF)Ferran Sanz – GRIB (IMIM-UPF)
The DisGeNET association type ontology
Ferran Sanz – GRIB (IMIM-UPF)Ferran Sanz – GRIB (IMIM-UPF)
Examples of the questions that can be answered using DisGeNET
Ferran Sanz – GRIB (IMIM-UPF)Ferran Sanz – GRIB (IMIM-UPF)
DisGeNET web interface: the Search view and the Browser view
Ferran Sanz – GRIB (IMIM-UPF)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
Ferran Sanz – GRIB (IMIM-UPF)Ferran Sanz – GRIB (IMIM-UPF)
Ferran Sanz – GRIB (IMIM-UPF)Ferran Sanz – GRIB (IMIM-UPF)
Identification of shared mechanisms for comorbid diseases:
COPD comorbidities
Application
Ferran Sanz – GRIB (IMIM-UPF)Ferran Sanz – GRIB (IMIM-UPF)
COPD comorbidome
Mol
ecul
ar C
omor
bidi
ty In
dex
(MCI
)
Proportion of shared proteins targeted by chemical compounds present in tobacco smoke
Ferran Sanz – GRIB (IMIM-UPF)Ferran Sanz – GRIB (IMIM-UPF)
Connexion between COPD and Anemia at the molecular level
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/
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
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 expertsGAD
CTDRGD
MGDPsyCUR
900,000 abstracts
800 associations
2,000 assoc
Ferran Sanz – GRIB (IMIM-UPF)21
PsyGeNET database
Dataset Original data source
Genes Disease terms
Associations
GAD GAD 844 20 1165
MODELSMGD
33 6 39RGD
CURATEDCTD
755 37 2061PsyCUR
ALL 1317 37 2823
Ferran Sanz – GRIB (IMIM-UPF)22
PsyGeNET PsyCUR Exclusive to PsyCUR
CTD1 OMIM2
Depression 877 546 501 70 6Alcoholism 555 221 198 34 6Cocaine use disorder
132 33 18 108 0
1Comparative Toxicogenomics Database2Online 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
Ferran Sanz – GRIB (IMIM-UPF)
Ferran Sanz – GRIB (IMIM-UPF)24
Ferran Sanz – GRIB (IMIM-UPF)
Depression, alcoholism and cocaine use disorders might be linked at the molecular level through shared genes
Disease A Disease B genes A Genes B Shared genes
Jaccard Index
Depression Alcoholism 877 555 169 0.13*
Depression Cocaine UD 877 132 63 0.07*
Alcoholism Cocaine UD 555 132 57 0.06*
*significant by bootstrap testing
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
Ferran Sanz – GRIB (IMIM-UPF)27
Serotonin and dopamine signaling
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
Ferran Sanz – GRIB (IMIM-UPF)Ferran Sanz – GRIB (IMIM-UPF)
J. Piñero
Integrative Biomedical Informatics Group (GRIB)http://grib.upf.edu
M. CasesF. Sanz L.Furlong
S.GrosdidierN.Queralt
A. Bravo
M.A. Mayer A. Gutiérrez
A. Bauer-Mehren