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

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

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

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

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

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

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

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

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

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

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

14. Liver functional unit

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

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

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

19. LIO@Duke

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

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

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

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

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

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