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

Metabolic functions Synthesis and secretion of protein Storage Purification transformation and clearance of toxins

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

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?

CONTEXT IMMUNE RESPONSE IS HIGHLY CONTEXT DEPENDENT

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

induction of apoptosis negative regulation of apoptosis

Liver immune response Objects involved (cell and molecules) The environment (liver anatomy) Relations

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

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

LIVER IMMUNOLOGY ONTOLOGY Liver tissue Liver cell type Macromolecule Liver Biological Process occurs_in has_participant part_of

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

Liver functional unit

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

SPACE OF DISSE ADJACENT_TO HEPATIC LAMINA SPACE OF DISSE ADJACENT_TO ENDOTHELIUM OF HEPATIC SINUSOIDS

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: partOf PATO: FMA:9672 GO: GO: PR: PR: PR: FMA:63137 LIO

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

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

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

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

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

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