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Bridging Multiple Ontologies: Route to Representation of the Liver Immune Response

Bridging Multiple Ontologies: Route to Representation of the Liver Immune Response Anna Maria Masci , Jeffrey Roach, Bernard de Bono, Pierre Grenon , Lindsay Cowell. WOMBO, ICBO, 2011. Purification transformation and clearance of toxins. Metabolic functions . LIO@Duke. LIVER.

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Bridging Multiple Ontologies: Route to Representation of the Liver Immune Response

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  1. Bridging Multiple Ontologies: Route to Representation of the Liver Immune Response Anna Maria Masci, Jeffrey Roach, Bernard de Bono, Pierre Grenon, Lindsay Cowell WOMBO, ICBO, 2011

  2. Purification transformation and clearance of toxins Metabolic functions LIO@Duke LIVER Synthesis and secretion of protein Storage

  3. Why the Liver Immunology is important? Office for National Statistics: Health Service Quarterly, Winter 2008, No. 40 p59-60 Local immune response play a key role in the pathogenesis of the majority of liver diseases

  4. Why do we need an ontology for a liver immunology? LIO@Duke • Normal liver anatomy (FMA, CARO, UBERON) • Normal liver Cell type (CL) • Developmental and metabolic liver processes (GO BP) • Liver diseases (DO, HP, MP) WHAT IS STILL MISSING?

  5. LIO@Duke CONTEXT IMMUNE RESPONSE IS HIGHLY CONTEXT DEPENDENT

  6. Immune response is context dependent LIO@Duke Tumor Necrosis Factor (TNF) negative regulation of apoptosis induction of apoptosis GO:0043066 GO:0006917 IsA Where is the truth? positive regulation of apoptosis GO:0043065

  7. LIO@Duke negative regulation of apoptosis induction of apoptosis

  8. Liver immune response LIO@Duke • Objects involved (cell and molecules) • The environment (liver anatomy) Relations

  9. LIVER IMMUNOLOGY ONTOLOGY(LIO) LIO@Duke • Scales: molecules, cells, tissue, organ • Organisms: human, mouse • Domains: biological, clinical care, public health • Diseases: pathogenesis of liver disorders

  10. Purpose of Liver Immunology Ontology LIO@Duke • Integration and retrieval of cellular and molecular data for liver immune response • Liver injury • Infectious agents • Genetic disorders • Alcohol abuse • Obesity • Drug toxicity

  11. LIO developmental approach LIO@Duke Selection Expansion Combination

  12. LIVER IMMUNOLOGY ONTOLOGY LIO@Duke part_of part_of Liver cell type Liver tissue Macromolecule has_participant occurs_in has_participant Liver Biological Process

  13. LIVER IMMUNOLOGY ONTOLOGY PRO, SO, CheBi FMA CL LIO@Duke part_of part_of Liver cell type Liver tissue Macromolecule has_participant occurs_in has_participant Liver Biological Process GO

  14. Liver functional unit

  15. Portal triade Hepatocyte LIO@Duke Interlobular Bile duct HSC Disse space Portal vein Central vein KC Sinusoid Disse space Hepatocyte Hepatic arteriole KC Kupffer cell Hepatic Stellate cell HSC

  16. Expansion LIO@Duke SPACE OF DISSE ADJACENT_TO HEPATIC LAMINA SPACE OF DISSE ADJACENT_TO ENDOTHELIUM OF HEPATIC SINUSOIDS

  17. LIO@Duke LIO needs more than anatomy Combination

  18. Platelet aggregation GO:0070527 isA Injured liver platelet aggregation LIO occursIn hasQuality damaged Endothelium of hepatic sinusoid PATO:0001167 FMA:63137 hasParticipant PR:000009128 Collagen type I, collagen type IV VLA-3, vWF, VLA-2 PR:000017364 GO:0005587 PR:000001008 GO:0005584 partOf partOf Portion of extracellular matrix FMA:9672 platelet Surronds Endothelium of hepatic sinusoid FMA:63137

  19. LIO@Duke

  20. Liver Vascular Injury Liver Inflammation Liver Acute Tissue Injury Liver Fibrogenesis Liver Tissue Remodeling Liver Chronic Tissue Damage Liver Vascular Remodeling

  21. VLA-3, vWF, VLA2 part of platelet , collagen I and collagen IV part of extracellular matrix Injured liver platelet aggregation LIO@Duke Injured liver platelet degranulation Injured liver blood clotting Liver Vascular Injury Injured liver cytokine secretion Injured liver positive regulation of vascular permeability Injured liver neutrophil cellular extravasation Injured liver neutrophil cell degranulation

  22. LIO has the ability to capture differences between physiological and pathological responses

  23. Bridging biological ontologies Anatomical entity FMA LIO@Duke Biological process GO BP Other ontologies LIO Macromolecule PRO, SO, CheBi Cellular component GO CC Molecularfunction GO MF Cell type CL

  24. PROS CONS LIO@Duke Loss of the capacity to connect with other domains Specific representation of Liver immune response Loss of interoperability within other ontologies Maintain a formal structure Create a complex network of knowledge by bridging multiple ontologies

  25. Long term goals of LIO LIO@Duke • Support and enhance analysis of high- throughput data • Allow annotation for biological events relevant for development of mathematical models and computer simulations

  26. Aknowledgementsand ongoing collaborations LIO@Duke Research Computing Center, University of North Carolina, Jeffrey Roach Bernard de Bono European Molecular Biology Laboratory, European Bioinformatics Institute, UK Pierre Grenon Department of Gastroenterology, Duke University Anna Mae Diehl Lindsay Cowell UT Southwestern Medical Center

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