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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”
MadridJune 3, 2002
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
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
– Sequences (genome projects), SNPs (variability)– Gene expression data (DNA arrays), Proteomics
• Interest of new users– Pharma and Biotech– Biomedical research centers– IT firms– Clinical (not yet?)
• New tools– Internet– Data mining
• New discipline– 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
ATCGCGCTA
Sequencing
Genome databases
Gene prediction
Annotation
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
The Post-Genomics Era
Genome Project(DNA
Consensussequence)
FunctionalGenomics(mRNAs)
Individual Genomics
(mutations, SNPs)
Comparative Genomics
(homology, evolution)
Proteomics(proteins)
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
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
MetabolicPathways
GeneticNetworks
Signaling pathways
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
Genome
Information
Individualisedhealthcare
Genotyping
Haplotyping
Functionalgenomics
proteomics
Individualgenomics (SNPs and mutations)
Gene Expression DNA arraysMS, 2D ef
Disease classificationPharmaco-genomics
Diagnosis
Pharmaco-genetics
Molecular medicine
HumanGenetic
Variation
Molecular causes of diseases
Technologies Data Applications
BIOINFORMATICS & MEDICAL INFORMATICSBIOINFORMATICS & MEDICAL INFORMATICS
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
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
Art by Doug Struthers
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
The convergence between MI and BI
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
A model for studying
interactions
To apply IT to facilitate molecular medicine
To adapt medical informatics systems to the genetics paradigm
To foster the application of bioinformatics in health
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
?
Molecular Medicine
Informatics
Medical Informatics
Medicine
Bioinformatics
Genomics
The application of informatics in Molecular Medicine
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
Chris Sander, Bioinformatics (Editorial). Vol 17. Nº1. 2001, p1-2
Bioinformatics in Health
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
Bioinformatics
Medical Imaging
MedicalInformatics
Public HealthInformatics
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
• Technology assessment, outcomes research
Genome epidemiology
• Genetic Screening
Genome epidemiology databases and networks (CDC-HuGeNet)
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
• 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
• 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 – 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
• ICD• SNOMED• UMLS• MeSH• LOINC• GALEN
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
Knowledge representationin Biology
• The MGED ontology - ontologies for describing gene 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
• Prospective Analysis on the Relationships and Synergy between Medical Informatics and Bioinformatics
• URL: http://bioinfomed.isciii.es (starting from January 2002)
• Institute of Health “Carlos III” – Madrid – SPAIN
• Polytechnical University of Madrid (Prof. Victor Maojo) - SPAIN
• Linkoping University (Prof. Ankica Babic) - SWEDEN
• 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)
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
Methods and tools
Medical Inform.
Bioinform.
Application
Individualised Healthcare
MolecularMedicine
BIOINFOMED
Synergy
Synergy
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
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
• 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)
• 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• 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
AnatomyPhysiologyMetabolismMolecular
Today Tomorrow
CTUS
MRINuclearOpticalNano
Dr. Fernando Martin-Sanchez - ISCIII – Jun. 2002 - Madrid
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
• Collaboration is better – integrated approach to disease
• Synergy – will it be possible?– New developments from scratch
• ¿Birth of a new discipline?– BIOMEDICAL INFORMATICS
MI BI
MI BI
MI BI