1. Ferran Sanz – GRIB (IMIM-UPF)Ferran Sanz – GRIB (IMIM-UPF)
PERSONALIZED RESPIRATORY MEDICINE
Integrative Bioinformatics
Ferran Sanz, Laura Furlong
Research Programme on Biomedical Informatics (GRIB)
Hospital del Mar Research Institute (IMIM)
Universitat Pompeu Fabra
2. Ferran Sanz – GRIB (IMIM-UPF)
“Big Data” in Biomedicine: Clinical data
Health care generates one (or several) clinical
records per citizen, each one containing thousands
of data in electronic format (anamnesis, lab tests,
images, diagnosis, treatments, etc.)
3. Ferran Sanz – GRIB (IMIM-UPF)
Genome sequence of a human being: 3.000.000.000 bases !
( 1 million of pages like this! )
It costs < 1000 $ !
....ACTCAGCCCCAGCGGAGGTGAAGGACGTCCTTCCCCAGGAGCCGGTGAGAAGCGCAGTCGGGGGCACGGGGATGAGCTCAGGGGCCTCTAGAAAGA
TGTAGCTGGGACCTCGGGAAGCCCTGGCCTCCAGGTAGTCTCAGGAGAGCTACTCAGGGTCGGGCTTGGGGAGAGGAGGAGCGGGGGTGAGGCCAGCAGC
AGGGGACTGGACCTGGGAAGGGCTGGGCAGCAGAGACGACCCGACCCGCTAGAAGGTGGGGTGGGGAGAGCATGTGGACTAGGAGCTAAGCCACAGCAGG
ACCCCCACGAGTTGTCACTGTCATTTATCGAGCACCTACTGGGTGTCCCCAGTGTCCTCAGATCTCCATAACTGGGAAGCCAGGGGCAGCGACACGGTAG
CTAGCCGTCGATTGGAGAACTTTAAAATGAGGACTGAATTAGCTCATAAATGGAAAACGGCGCTTAAATGTGAGGTTAGAGCTTAGAATGTGAAGGGAGA
ATGAGGAATGCGAGACTGGGACTGAGATGGAACCGGCGGTGGGGAGGGGGAGGGGGTGTGGAATTTGAACCCCGGGAGAGAAAGATGGAATTTTGGCTAT
GGAGGCCGACCTGGGGATGGGGAAATAAGAGAAGACCAGGAGGGAGTTAAATAGGGAATGGGTTGGGGGCGGCTTGGTAACTGTTTGTGCTGGGATTAGG
CTGTTGCAGATAATGGAGCAAGGCTTGGAAGGCTAACCTGGGGTGGGGCCGGGTTGGGGTCGGGCTGGGGGCGGGAGGAGTCCTCACTGGCGGTTGATTG
ACAGTTTCTCCTTCCCCAGACTGGCCAATCACAGGCAGGAAGATGAAGGTTCTGTGGGCTGCGTTGCTGGTCACATTCCTGGCAGGTATGGGGCGGGGCT
TGCTCGGTTTTCCCCGCTTCTCCCCCTCTCATCCTCACCTCAACCTCCTGGCCCCATTCAAGCACACCCTGGGCCCCCTCTTCTTCTGCTGGTCTGTCCC
CTGAGGGGAAAGCCCAGGTCTGAGGCTTCTATGCTGCTTTCTGGCTCAGAACAGCGATTTGACGCTCTGTGAGCCTCGGTTCCTCCCCCGCTTTTTTTTT
TTCAGCCAGAGTCTCACTCTGTCGCCCAGGCTGGAGTGCAGTGGCGCAATCTCAGCTCACTGCAAGCTCCGCCTCCCGGGTTCACGCTATTCTCCCGCCT
CAGCCTCCCGAGTAGCTGGGACTACAGGCGCCCGCCACCATGCCCGGCTAATTTTTTGTACTTTGAGTAGGGAAGGGGTTTCACTGTATTATCCAGGATG
GTCTCTATCTCCTGACCTCGTGATCTGCCCGCCTGGCCTCCCAAAGTGCTGGAATTACAGGCGTGAGCCTCCGCGCCCGGCCTCCCCATCCTTAATATAG
GAGTTAGAAGTTTTTGTTTGTTTGTTTTGTTTTGTTTTTGTTTTGTTTTGAGATGAAGTCCCTCTGTCGCCCAGGCTGGAGTGCAGTGGCTCCCAGGCTG
GAGTTCAGTGGCTGGATCTCGGCTCACTGCAAGCTCCGCCTCCCAGGTTCACGCCATTCTCCTGCCTCAGCCTCCGGAGTAGCTGGGACTACAGGAACAT
GCCACCACACCCGACTAACTTTTTTTGTATTTTTAGTAGAGACGGGGTTTCACCATGTTGGCCAGGCTGGTCTGGAACTCCTGACCTCAGGTGATCTGCC
TGCTTCAACCTCCCAAAGTGCTGGGATTACAGACGTGGGCCACCGCGCCCGGCTGGGAGTTAAGAGGTTTCTAATGCATTGCATTAGAATACCAGACACG
GGACAGCTGTGATCTTTATTCTCCATCACCCCACACAGCCCTGCCTGGGGCACACAAGGACACTCAATACACGCTTTTCGGGCGCGGTGGCTCAAGCTGT
AATCCCAGCACTTTGGGAGGCTGAGGCGGGTGGTACATGAGGTCAGGAGATCGAGACCATCCTGGCTAACATGGTGAAACCCCGTCTCTACTAAAAATAC
AAAAAACTAGCCCGGGCGTGGTGGCGGGCGCCTGTAGTCCCAGCTACTCGGAGGCTGAGGCAGGAGAATGGCGTGAACCTGGGAGGCGGAGCTTGCAGTG
AGCCGAGATCGCGCCACTGCACTCCAGCCTGGGTGACACAGCGCGAGACTCCGTCTCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAATACACGCTTTTCC
GCTAGGCACGGTGGCTCACCCCTGTAATCCCAGCATTTTGGGAGGCCAAGGTGGGAGGATCACTTGAGCCCAGGAGTTCAACACCAGACTCAGCAACATA
GTGAGACTCTCTCTACTAAAAATACAAAAATTAGCCAGGCCTGGTGCCACACACCTGTGGTCCCAGCTACTCAGAAGGCTAAGGCAGGAGGATCGCTTAA
GCCCAGAAGGTCAAGGTTGCAGTGAACCACGTTCAGGCCACTGCAGTCCAGCCTGGGTGACAGAGCAAGACCCTGTCTGTAAATAAATAACGCTTTTCAA
GTGATTAAACAGACTCCCCCCTCACCCTGCCCACCATGGCTCCAAAGCAGCATTTGTGGAGCACCTTCTGTGTGCCCCTAGGTACTAGCTGCCTGGACGG
GGTCAGAAGGAACCTGAACCACCTTCAACTTGTTCCACACAGGATGCCAGGCCAAGGTGGAGCAACCGGTGGAGCCAGAGACAGAACCCGACGTTCGCCA
GCAGGCTGAGTGGCAGAGCGGCCAGCCCTGGGAGCTGGCACTGGGTCGCTTTTGGGATTACCTGCGCTGGGTGCAGACACTGTCTGAGCAGGTGCAGGAG
GAGCTGCTCAGCCCCCAGGTCACCCAGGAACTGACGTGAGTGTCCCCATCCCGGCCCTTGACCCTCCTGGTGGGCGGCTATACCTCCCCAGGTCCAGGTT
TCATTCTGCCCCTGCCACTAAGTCTTGGGGGCCTGGGTCTCTGCTGGTTCTAGCTTCCTCTTCCCATTTCTGACTCCTGGCTTTAGCTCTCTGGAATTCT
CTCTCTCAGTTCTGTTTCTCCCTCTTCCCTTCTGACTCAGCCTGTCACACTCGTCCTGGCGCTGTCTCTGTCCTTCACTAGCTCTTTTATATAGAGACAG
AGAGATGGGGTCTCACTGTGTTGCCCAGGCTGGTCTTGAACTTCTGGGCTCAAGCGATCCTCCCACCTCGCCTCCCAAAGTGCTGGGAATAGAGACATGA
GCCACCTTGCTCGGCCTCCTAGCTCTTTCTTCGTCTCTGCCTCTGCTCTCTGCGTCTGTCTTTGTCTCCTCTCTGCCTCTGTCCCGTTCCTTCTCTCTTG
GTTCACTGCCCTTCTGTCTCTCCCTGTTCTCCTTAGGAGACTCTCCTCTCTTCCTTCTCGAGTCTCTCTGGCTGATCCCCATCTCACCCACACCTA....
“Big Data” in Biomedicine: ‘omics data
4. Ferran Sanz – GRIB (IMIM-UPF)
“Big Data” in Biomedicine: Biomedical literature
• Biomedical research generates huge amounts
of scientific articles, the abstracts of the most
important are stored in PubMed (open access
public library):
http://www.ncbi.nlm.nih.gov/pubmed
• 23,000,000 articles
• 500,000 new articles per year
5. Ferran Sanz – GRIB (IMIM-UPF)Ferran Sanz – GRIB (IMIM-UPF)
Integration of heterogeneous biomedical information in order
to gain a more complete and powerful view on diseases and therapeutics
Clinical Data
Biomedical
imaging
‘omics &
Systems
Biology
Drugs & other
chemicals
Biomedical
literature
6. Ferran Sanz – GRIB (IMIM-UPF)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
7. Ferran Sanz – GRIB (IMIM-UPF)Ferran Sanz – GRIB (IMIM-UPF)
Interdiscipline and intradiscipline knowledge ‘silos’ to be overcome:
Bridging gaps between Bioinformatics and Medical informatics
Bridging gaps between Bioinformatics and MI
Bioinformatics
Computational approaches
in biological research
(molecular, “omics”,
systems biology)
Medical Informatics
Information technologies
in health care and clinical
research
Translational
Bioinformatics
Reuse of clinical
information in
biomedical research
Adapted from Cases M et al. J Intern Med. 2013; 274: 321–8
8. Ferran Sanz – GRIB (IMIM-UPF)
Required operations in Integrative Bioinformatics
• Mining (e.g., text mining from biomedical
literature)
• Integration (standards and ontologies
required)
• Filtering and priorisation
• Annotation and curation
• Analysis
• Visualisation
10. Ferran Sanz – GRIB (IMIM-UPF)Ferran Sanz – GRIB (IMIM-UPF)
From Bauer-Mehren A, Bundschus M, Rautschka M, Mayer MA, Sanz F, Furlong LI. PLoS One 2011; 6(6): e20284
Side-effect substantiation by information linkage
11. 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
12. Ferran Sanz – GRIB (IMIM-UPF)Ferran Sanz – GRIB (IMIM-UPF)
Anna Bauer-Mehren, Markus Bundschus, Michael Rautschka, Miguel A. Mayer, Ferran Sanz, Laura I. Furlong. Gene-disease network analysis
reveals functional modules in mendelian, complex and environmental diseases. PLoS ONE 2011 6(6): e20284.
Knowledge pockets in genetics of diseases
13. 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://www.disgenet.org/
14. Ferran Sanz – GRIB (IMIM-UPF)
source databases
CTD
human
UniProt GADMGD
RDG
Mouse and rat genes
projected into human
orthologs
Curated Predicted Literature
LHGDN
BeFree
CTD
mouse & rat
19. Ferran Sanz – GRIB (IMIM-UPF)Ferran Sanz – GRIB (IMIM-UPF)
• Provides a score to each gene-disease association
• Based on the supporting evidence (number and
type of source, number of publications that report
the association)
• Allows prioritization of gene-disease associations
based on evidence available
score
26. Ferran Sanz – GRIB (IMIM-UPF)Ferran Sanz – GRIB (IMIM-UPF)
COPD comorbidome
Proportion of shared proteins targeted by
chemical compounds present in tobacco smoke
Grosdidier et al. Submitted.
27. Ferran Sanz – GRIB (IMIM-UPF)Ferran Sanz – GRIB (IMIM-UPF)
Connexion between COPD and Anemia at the molecular level
Grosdidier et al. Submitted.
28. Ferran Sanz – GRIB (IMIM-UPF)Ferran Sanz – GRIB (IMIM-UPF)
Similarities between COPD comorbidities
Grosdidier et al.
Submitted.
29. Ferran Sanz – GRIB (IMIM-UPF)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
CIBERES:
Alvar Agustí,
Joaquim Gea
Antoni Ferrer
Rosa Faner
Josep Roca
Borja Cosío
