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WP 6.3: Pilot on genomics and chronic inflammation

WP 6.3: Pilot on genomics and chronic inflammation. ACTA Bruno Loos, activity leader. ISCIII UPM KI/Leicester AV EI RO Custodix. 1st Annual Technical Review, Brussels, 16 March 2005. WP 6.3: Pilot on genomics and chronic inflammation. WP 6.3 Genomics and chronic inflammation.

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WP 6.3: Pilot on genomics and chronic inflammation

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  1. WP 6.3: Pilot on genomics and chronic inflammation ACTA Bruno Loos, activity leader ISCIII UPM KI/Leicester AVEIRO Custodix 1st Annual Technical Review, Brussels, 16 March 2005

  2. WP 6.3: Pilot on genomics and chronic inflammation WP 6.3 Genomics and chronic inflammation use PERIODONTITIS as model for complex chronic inflammatory diseases Periodontitis is an inflammatory, destructive disease of the supporting tissues of the teeth 1st Annual Technical Review, Brussels, 16 March 2005

  3. normal situation periodontitis

  4. WP 6.3: Pilot on genomics and chronic inflammation PERIODONTITIS is an excellent model: complex disease that is multifactorial • Genetic susceptibility – polygenic (modifying genes) • Infectious component – at least 5 periodontopathogens • Environmental influences – smoking, stress, diet • Relative high prevalence – 15% in general population • Easy access to samples – non-invasive sampling • Patient cooperation – no life threatening disease • Existence of network: – within universities • universities to specialists 1st Annual Technical Review, Brussels, 16 March 2005

  5. WP 6.3: Pilot on genomics and chronic inflammation Most complex inflammatory diseases suffer from lack of: • Insight in the complex pathophysiology • Clear disease classification schemes • Risk profiling and possibilities for screening Goal of WP 6.3 – with integrated efforts of the INFOBIOMED network to explore periodontitis - pathophysiology classification risk assesment Then with new knowledge and tools expand horizon 1st Annual Technical Review, Brussels, 16 March 2005

  6. WP 6.3: Pilot on genomics and chronic inflammation challenge to structure and integrate data streams and use data analysis tools Data streams originate from: raw clinical data bio-informatics medical informatics 1st Annual Technical Review, Brussels, 16 March 2005

  7. WP 6.3: Pilot on genomics and chronic inflammation links External sources Interm Interm SNPs (SPSS) format format dbSNP Microbiology (paper, excel) Genet { lab ….. Locus Micro … Limk arrays Direct Interm Pat Pat Env Env Gene Gene Clinic Micro Micro x x ENSEMBL pheno pheno taxon 1 1 Images (X - ray) paper micro 2 2 Life habits data (EMR) paper biol { NCBI clinic Smoking data 3 3 ….. 4 4 ICD - io clinic LOINC UMLS n n Environ Data mining ontology smoking lifestyle Query Clinic 1st Annual Technical Review, Brussels, 16 March 2005

  8. Environmental Data Genomic data Phenomic data Microbiology data Life habits data Assesment / Annotation External DBs Programs (PRDW) Periodontitis Research Data Warehouse

  9. WP 6.3: Pilot on genomics and chronic inflammation 2004 2005 2006 SPSS, Excel, Hard copy, DMA, ……. Periodontitis Research Data Warehouse (PRDW) Data mining (results) Visualization ACTA, KI, UAVR and ISCIII ACTA, Custodix, ISCIII and UPM 1st Annual Technical Review, Brussels, 16 March 2005

  10. WP 6.3: Pilot on genomics and chronic inflammation Actions WP 6.3 in 2004 • Define external sources, analyze needs, possibilities, costs, how to feed/download. • SOA and DOW (ACTA, ISCIII, KI, CUSTODIX, UAVR, UPM) • Dental Image Tool (DIA) (ACTA, UAVR) • Start building data warehouse (PRDW) • Convert the SOA report to manuscript for an European Dental Journal 1st Annual Technical Review, Brussels, 16 March 2005

  11. WP 6.3: Pilot on genomics and chronic inflammation Demonstrate DIA tool (dental X-ray analyses) 1st Annual Technical Review, Brussels, 16 March 2005

  12. WP 6.3: Pilot on genomics and chronic inflammation 2004 2005 2006 • Insight in the complex pathophysiology • Clear disease classification schemes • Risk profiling and possibilities for screening 1st Annual Technical Review, Brussels, 16 March 2005

  13. WP 6.3: Pilot on genomics and chronic inflammation 1st Annual Technical Review, Brussels, 16 March 2005

  14. Environmental factors Life habits Mutagens Genes inherited Mutations and Polymorphisms Intermediate phenotypes Disease Phenotype Infectious agent

  15. Disease phenotypes • AGGRESSIVE PERIODONTITIS • CHRONIC PERIODONTITIS • PERIODONTITIS ASSOCIATED WITH SYSTEMIC DISEASES: DIABETES SYNDROME PAPILLON-LEFEVRE EHLERS-DANLOS SYNDROME CHRONIC/CYCLIC NEUTROPENIA LEUKOCYTE ADHESION DEFICIENCY HIV/AIDS

  16. Genes • INTERLEUKIN 1-ALPHA; IL1A • INTERLEUKIN 18; IL18 • INTERLEUKIN 10 • VIT D • TOLL-LIKE RECEPTORS (TLR) • LEUCINE RICH REPEATS (LRR) • CATHEPSIN C; CTSC • HISTATIN 1; HTN1 • PRTN3 • LPS • IFNG • STR • INTEGRIN, BETA-2; ITGB2

  17. WP 6.3: Pilot on genomics and chronic inflammation General overview of contents of data warehouse (DWH) Periodontitis intermediate phenotype disease phenotype genetics infection environment 1st Annual Technical Review, Brussels, 16 March 2005

  18. Infectious agents • Endogenous bacteria • Porphyromonas gingivalis, • Prevotella intermedia, • Tannerella forsythensis, • Fusobacterium nucleatum, • Actinobacillus actinomycetemcomitans • Several spirochaetal species • Exogenous • A. actinomycetemcomitans • P .gingivalis

  19. Environmental factors and life habits • Smoking • Diet (Vitamins) • Stress • Hygiene • Drugs prescription (antidepressants, cold remedies and antihistamines, anti-seizure medications, calcium channel blockers and drugs that suppress your immune system)

  20. Intermediate phenotypes • Age, Gender • Weight, Height, Body Mass Index • Blood presure • Biochemical parameters (triglycerides, sugar).

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