Fernando Martín Sánchez, PhD. Head, Medical Bioinformatics Dept. Institute of Health Carlos III

1. Fernando Martín Sánchez, PhD. Head, Medical Bioinformatics Dept. Institute of Health Carlos III Madrid, SPAIN Results of the EC IST BIOINFOMED study: A Research Agenda in Biomedical Informatics Workshop on Biomedical Informatics Brussels March 18, 2004

2. Outline • Genomic medicine • The BIOINFOMED Study • A research agenda • References • Update

3. Genotyping Haplotyping Genomic Medicine Human Genetic Variation Technologies Data Genomic medicine Applications Information Diagnosis Pharmaco-genetics Individual genomics (SNPs and mutations) Individualised healthcare Genomic BIOMEDICAL INFORMATICS Disease reclassification Pharmaco-genomics Functional genomics Proteomics Gene Expression DNA arrays MS, 2D ef Clinical Molecular medicine Technologies Data Applications Preventive medicine Molecular causes of diseases

4. Synergy between Research inMedical Informatics, Bio-Informatics and Neuro-Informatics Knowledge empoweringIndividualised Healthcare and Well-Being 14 December 2001Pyramids, Place Rogier, Brussels European Commission: DG-Information Society, DG Research www.ramit.be

5. BIOINFOMED • Prospective Analysis on the Relationships and Synergy between Medical Informatics and Bioinformatics • URL:http://bioinfomed.isciii.es • Institute of Health “Carlos III” – Madrid –SPAIN • Polytechnical University of Madrid (Prof. Victor Maojo) - SPAIN • Linkoping University (Prof. Ankica Babic) - SWEDEN

6. The BIOINFOMED Study • 30 experts were invited to collaborate with the group carrying out the project in the elaboration of a White Paper. • Questionnaire • Working meetings were held in FORTH (Crete, Greece) in June and Valencia, Spain, in November 2002 • BIOINFOMED web page - (agenda, links to research groups, relevant publications). • Papers to disseminate the work done under this project (MIM, JBI, JAMIA).

8. Structure for the White Paper • Rationale • Background • History of MI and BI • Current situation • Scope and vision • Expected impacts • Gaps and Bridging Solutions • Priorities in R&D http://bioinfomed.isciii.es

10. Translational Research Informatics Clinical Trials, EHRs Genetic factors Basic Research Clinical Research Biomedical Informatics Epidemiological Research Environmental factors

11. Populations Genome epidemiology Public Health Informatics Molecules, cells Diseases BIOMEDICAL INFORMATICS Clinical Informatics Bioinformatics Tissues, organs Patients Medical Imaging

12. Biomedical Informatics • Biomedical Informatics (BMI) is the discipline that aims to create a common conceptual information space to further the discovery of novel diagnostic and therapeutic methods in the rapidly evolving arena of genomic medicine. • The BIOINFOMED White Paper

13. Human Phenome Project? Biomedical Informatics Human Genome Project

18. BI in support of Personalized Medicine Patient Genetic Data and EHRs • New models of EHRs that include structured patient genetic data.

19. BI in support of Personalized Medicine Guidelines and decision making support systems • Clinical guidelines are standard means for dissemination of clinical knowledge and the support of physicians in the course of decision-making. • Using genetic knowledge can further improve decision-making quality.

20. MI in support of Genomic ResearchHuman phenotype databases • Providing research-quality clinical samples and associated information in highly optimized formats to functional genomics researchers • Representing phenotype information in a structured, computable manner • The Human Phenome Project

21. BMI in support of Genomic MedicineAcquiring patient data (clinical and genetic) at the point of care. • New analytical devices (biochips or lab-on-a-chip). • Offer the possibility of accessing patients’ genetic profiles within reasonable time and expenses • General practitioners will need to access other complementary data and place them in context

22. BMI in support of Genomic MedicineSupporting PGx research • Stratified clinical trials • New targets • There exists excellent opportunity to merge fields such as bioinformatics/ cheminformatics, protein and DNA microarray technology with medical informatics in preclinical and clinical toxicity, patient typing and stratification.

23. BMI in support of Genomic MedicineMolecular and functional imaging • Developing novel tools, reagents and methods to image specific molecular pathways in humans, particularly those that are key targets in disease processes”. • Visualisization of gene expression “in vivo”

24. BMI in support of Genomic Medicine Modeling and simulation • Integrated 3-D models of the body, including mapping from genes to clinical findings. • Combining two approaches: • bottom-up, from molecules to clinical manifestations, or • top-down, from clinical manifestations to inner mechanisms. • Realistic, predictive models of disease under different genetic and environmental conditions.

25. BMI in support of Genomic Medicine Genome Epidemiology: biobanks • Large-scale epidemiological studies linking genetic information to information on environment, lifestyles and disease outcomes • Tissue and samples databases

26. References

30. INDIVIDUAL BIOMEDICAL INFORMATICS FELLOWSHIPS RELEASE DATE: February 12, 2003 PA NUMBER: PAR-03-070 EXPIRATION DATE: March 01, 2006, unless reissued. National Library of Medicine (NLM) (http://www.nlm.nih.gov/) This program announcement supersedes PA-92-90.

31. Recent outstanding developments in BMI

32. Genotype (HL7 CG SIG) Bioinformatics Medical Informatics Biomedical Informatics (P3G) Phenotype - PhenoFocus - MIAME-TOX

33. Genetic data in EMR • US Patent Application 20030104470 • June 5, 2003 • EMR, library of EMRs having polymorphism data, and computer systems and methods for use thereof • Claims: prescription, drug reaction, diagnostic data, different pathologies, different detection assays, different physical locations for the EHR

34. HL7 Clinical Genomics SIG • Use of genomic data in health care in support of personalized medicine • Integration of healthcare standards along with bioinformatics emerging formats such as MAGE-ML for gene expression or BSML for sequencing data. • Submission to EHR functional model? • Cystic-Fibrosis testing • Tissue-Typing for Bone-Marrow Transplantation • BRCA 1, 2

35. PhenoFocushttp://www.phenofocus.net/ • Open collection of researchers interested in developing optimal public-domain solutions for computational handling of phenotype data. • Representing Phenotypes: The Challenges • Current Projects Needing Better Solutions • Data Models Being Explored • Flybase, HGVbase, E-A-Value triplets, MetaDataModel Organism Database Network • Ontologies: • GO, UMLS, SNoMed, eVOC, LOINC • Data Exchange Formats • Standardization (OMG) • (Semi) Automated Text Mining • Data Sharing Issues / Intellectual Property • Related Projects and Societies

36. MGED-TOX WG • EMBL-EBI, NIEHS and ILSI HESI • MIAME-Tox • Tox-MIAMEXPRESS • A database for toxicogenomic gene expression data • Including clinical observations, histopathology evaluation and clinical pathology

38. Integrating biomedical terminology Bodenreider O, Nucleic Acids Research, 2004, Vol. 32, Database issue D267-D270

39. Thank you all! - experts - EC staff - ISCIII team - Audience fmartin@isciii.es