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Fernando J. Martin-Sanchez, Ph. D.
Head, Health Bioinformatics Dept.
National Institute of Health “Carlos III”
Ministry of Health and Consumer Affairs
Madrid, SPAIN
EC IST BIOINFOMED Study
Coordinator
Health Information Systems
in the age of Post-Genomic
Research
CEN/TC251
“Joint Working Group Meeting”
Madrid
June 3, 2002
Agenda
 Presentation
 Overview of Bioinformatics
 Molecular Medicine and Individualised
Healthcare
 The convergence between Medical
Informatics and Bioinformatics
 Issues on integrating genetic data into health
information systems
 EC IST BIOINFOMED Study
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
Institute of Health “Carlos III”
Ministry of Health and Consumer
Affairs
• Public Research Institute
• Scientific and technological support to the
National Health System
• Competences in:
– Epidemiology, Public health laboratories (Food,
Microbiology, Environmental Health)
– Health Technology Assesment
– Biomedical research funding and coordination
– School of Public Health, Health Sciences Library
– New technologies - Telemedicine, Bioinformatics and
genomics, Health information systems
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
Forces driving the bioinformatics revolution
• The promise of health applications of the human genome information
• Proof of concept with the human genome sequencing
• Availability of new raw information
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Sequences (genome projects), SNPs (variability)
Gene expression data (DNA arrays), Proteomics
• Interest of new users
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Pharma and Biotech
Biomedical research centers
IT firms
Clinical (not yet?)
• New tools
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Internet
Data mining
• New discipline
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Innovation brand
Search for funding
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
Overview of Bioinformatics
• Bioinformatics, Biocomputing,
Computational Biology
• Interface between biotechnology and
computer science
• “Flavours”
– Integration of relevant biomedical
information
– Platform for “in silico” biology
– Focus on Health Applications
– From Genetics to Genomics to
Postgenomics to Molecular Medicine
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
The role of bioinformatics
supporting genetics
Sequences
Phylogenetic trees
Alignments
Structures
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
The role of Bioinformatics in
support of genomics
Sequencing
Gene prediction
ATCGCGCTA
Annotation
Genome
databases
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
The Post-Genomics Era
Comparative
Genomics
(homology,
evolution)
Genome Project
(DNA
Consensus
sequence)
Individual
Genomics
(mutations, SNPs)
Functional
Genomics
(mRNAs)
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
Proteomics
(proteins)
Bioinformatics in support of
Post-Genomic Research
Genomes
SNPs
Proteomics
DNA microarrays
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
Bioinformatics in support of
Systems Biology
Metabolic
Pathways
Signaling
pathways
Genetic
Networks
Interactions
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
New opportunities for
health informatics
• Genome Project
– Interest for
biologists
– One gene at a
time
– Monogenic
diseases
– Tedious
genotyping
– DNA level
– Bioinformatics
explosion
• Post-Genomics
– Clinical interest
– Hundreds or
thousands of genes
simultaneously
– Complex diseases
– High throughput
genotyping
– DNA, RNA, Proteins
– Integration of clinical
and genetic
information
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
Overview
Human
Genetic
Variation
Technologies
Genotyping
Genome
Haplotyping
Data
Applications
Diagnosis
Individual
genomics
(SNPs and
mutations)
Pharmacogenetics
Individualised
healthcare
BIOINFORMATICS & MEDICAL INFORMATICS
Information
Gene
Expression
DNA arrays
MS, 2D ef
Functional
genomics
proteomics
Disease
classification
Pharmacogenomics
Molecular causes of
diseases
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
Molecular
medicine
Molecular Medicine and
Individualised Healthcare
New approaches: Pharmacogenetics, DNA arrays,
proteomics, SNPs, genetic diag.
• Molecular Medicine - Effort in explaining life
and disease in terms of the presence and
regulation of molecular entities
• Individualised Healthcare – Application of
genomics to identify individual predispositions to
disease and to design therapies adapted to the
genetic profiles of patients and that could be
prescribed with guarantee of security and
efficiency
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
Art by Doug Struthers
The convergence between
MI and BI
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
A model for studying interactions
To foster the application of
bioinformatics in health
To adapt medical
informatics systems to the
genetics paradigm
To apply IT to facilitate molecular medicine
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
The application of informatics in
Molecular Medicine
Informatics
Medical
Informatics
Bioinformatics
?
Medicine
Genomics
Molecular
Medicine
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
Bioinformatics in Health
Chris Sander, Bioinformatics (Editorial). Vol 17. Nº1. 2001, p1-2
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
Karolinska Institute,
Sweden
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
Bioinformatics and medical
information
• EBI - SOFG - Standards and Ontologies for
Functional Genomics, November, 2002, Hinxton,
Cambridge, UK
• Topics include vocabularies such as chemical and
biochemical nomenclature and the molecular
biology vocabularies developed by the Gene
Ontology Consortium
• But also: vocabularies for phenotypes, anatomies
and developmental stages; and other areas such
as diseases, pathology and toxicology
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
Health Information levels
Public Health
Informatics
Medical
Informatics
Medical Imaging
Bioinformatics
Martin-Sanchez et al, Methods. Inf. Med. 2002, 41:25-30
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
Health
information level
Classical health informatics
applications
New genomic data and
information
New health informatics
applications
Population
• Public Health & epidemiology
databases and surveillance
networks

Genome epidemiology
•
Genetic Screening
 Genome epidemiology
databases and networks
(CDC-HuGeNet)
• Technology assessment,
outcomes research
Disease

Computerized clinical practice
guidelines (CCPGs)
 Information systems in clinical
trials
 New classification of disease
based on its molecular causes
 Clinical trials in
pharmacogenetics
• CCPGs including genetic
tests and therapy follow-up
based on genetic data
• Decision-making support
tools
• Pharmacogenetics
databases
Patient
 Computerized patient health
record (CPHR)

Genetic individual profiles
(SNPs, mutations)
 Genetic data in the CPHR
Tissue, organ
 Pathology lab systems,
medical image processing
 Physiological genomics
 Genetic networks
 Disease models
 Tumour databanks
(Integration of clinical markers
and genomic analysis)
Cell
 Imaging in Cytogenetics,
histology
 Microbiology lab information
systems

Gene expression profiling
 Proteomics
 Molecular classification of
disease
 Information systems in
pharmacogenomics (drug
R&D)
• Molecular imaging
Molecule
 Biochemistry and genetic
tests and laboratory information
management systems
 DNA and protein sequences
 Macromolecular structures
 Facilitating integrated and
guided access to relevant
databases to health
professionals
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
Types of medical data
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lab results
administrative orders, appointments
images
signals, EKG
microbiology results
demographic
familiar
history of prescriptions
GENETIC
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
Genetic data special features
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multiple sources
large amounts
More static
probabilistic
Multilevel (DNA, RNA, Prot)
Accumulative (SNPs,
multifactorial diseases)
• Context-dependent
• Needs comparison with
public databases
• Not quantitative
• Complex
• Informs about relatives,
not only about patients
• Predictive power, even in
the absence of clinical
signs or symptoms;
• Has the potential to
generate a unique
identifier profile for
individuals.
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
Sources of Genetic Data
• Genome and sequence databases
– EMBL
• Protein sequence and structures
– PDB, SwissProt
• Genetic diseases
– OMIM, GeneCards, GeneReviews
• Genetic tests
– Geneclinics, EddNal
• Mutations
– Central variation databases – HGMD
– Single Locus Databases
• SNPs
– (dbSNP)
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
Examples
• Gene - RPS6KA4
• Mutations
– [76A>C; 83G>C]
– 112_117delAGGTCAinsTG
– K29_M29insQSK
• SNP: rs1472728
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Submitter Handle: TSC-CSHL
Submitter Method ID: TSC-WUGSC-1-2
GenBanK Accession: AC011382.2
Length: 673
Flanking Sequence Information: GATGGGACCA
CTGGTAGGAG...
– Observed: C/T
– No. of Chromosomes Sampled: 16
– Allele: C = 0.437 / T = 0.563
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
Genetic data in medical
coding systems
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ICD
SNOMED
UMLS
MeSH
LOINC
GALEN
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
Knowledge representation
in Biology
• The MGED ontology - ontologies for describing gene
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expression experiments and data.
TAMBIS ontology (TaO) an ontology of bioinformatics
and molecular biology.
RiboWeb an ontology describing ribosomal components,
associated data and computations for processing those
data.
EcoCyc an ontology describing the genes, gene product
function, metabolism and regulation within E. coli.
Gene Ontology (GO) an ontology describing the
function, the process and cellular location of gene
products from eukaryotes.
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
Related scientific activities
• Dec, 2001. Brussels – EC – Synergy between
Research in Medical Informatics, Bioinformatics
and Neuroinformatics
• Manchester March 2002 meeting:
– “Genotype To Phenotype: Linking Bioinformatics and
Medical Informatics Ontologies”
• Nov 2002. AMIA Conference:
– “Bio-medical informatics: one discipline”
• EC IST BIOINFOMED
• ACMI - NLM
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
BIOINFOMED
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Prospective Analysis on the Relationships and
Synergy between Medical Informatics and
Bioinformatics
URL: http://bioinfomed.isciii.es (starting from January
2002)
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Institute of Health “Carlos III” – Madrid – SPAIN
Polytechnical University of Madrid (Prof. Victor Maojo) - SPAIN
Linkoping University (Prof. Ankica Babic) - SWEDEN
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State of the Art and Inventory of resources of interest
and standardisation initiatives
Identification of key groups and priority research lines
Collaboration between experts and groups
Final report and Workshop (Nov 2002)
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Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
Modelling
• MI – Top-down approach from clinical
manifestations to the underlying
pathophysiological processes
• BI - Bottom-up approach, from genomic
information to physiological function
• An integrated approach could provide a
unified vision
Maojo, Martin-Sanchez et al, Journal of Biomedical Informatics. In press
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
BIOINFOMED
Methods and tools
Medical
Inform.
Individualised
Healthcare
Application
Synergy
Molecular
Medicine
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
Synergy
Bioinform.
Integrating genetic data
into health information
systems
• Telemedicine – genetic diagnosis networks -- telegenetics
• Accessing genetic databases using clinical inputs
• Integrating genetic data into clinical trials infrastructures and
methods
• Genetic data in clinical records
• Genetics in Clinical practice guidelines
• Adapting terminologies, vocabularies, ontologies
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
Bioinformatics. Health
applications
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SNP & haplotype information management and analysis
Disease reclassification based on gene expression data
Clinical proteomics
Systems Biology
Pharmacogenomics
Clinical-genetic databases
Genomics of pathogenic micro-organisms
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
Synergy
(integrated use of genetic and clinical information
with an application in individualised healthcare
and/or molecular medicine)
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Virtual Tumor databases (clinical-genetic analysis)
Decision-making support tools
Integrated clinical-genetic workstations
Interoperability between genetic lab and health information systems
Linking phenotype to genotype in patients and populations
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Pharmacogenetics Databases
Genome epidemiology
Molecular imaging
Computer models of disease
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
Molecular imaging
• Medical imaging + genomics
• Imaging molecular alterations that
are the basis of disease rather than
their effects
• Weissleder, R. Radiology 2001;
219:316-333
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
Levels and tech´s
Tomorrow
Today
CT
US
Anatomy
Physiology
Metabolism
Molecular
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
MRI
Nuclear
Optical
Nano
Molecular imaging
• New markers for early disease
detection
• Specific markers for therapy
assesment
• Drug screening
• Imaging of gene expression
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
Conclusions
• Interaction between MI and BI is needed:
– Not reinventing the wheel
– Not making the same mistakes
MI
BI
MI
BI
• Collaboration is better
– integrated approach to disease
• Synergy – will it be possible?
– New developments from scratch
• ¿Birth of a new discipline?
– BIOMEDICAL INFORMATICS
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
MI
BI