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
LIO@Duke
LIVER
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
1971 1981 1991 2001 2011-100
-50
0
50
100
150
200
250
300Changes in mortality
LiverHearthRespiratoryDiabetes
Year
% C
hang
es v
s 19
71
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?
LIO@Duke
CONTEXT
IMMUNE RESPONSE IS HIGHLY CONTEXT DEPENDENT
LIO@Duke
LIO@Duke
Immune response is context dependent
Tumor Necrosis Factor (TNF)
GO:0043066
negative regulation of apoptosis
induction of apoptosis
GO:0006917
positive regulation of apoptosis
GO:0043065
IsA
Where is the truth?
induction of apoptosis
negative regulation of apoptosis
LIO@Duke
Liver immune response• Objects involved (cell and molecules)
• The environment (liver anatomy)
Relations
LIO@Duke
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
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
Selection
Expansion
Combination
LIO developmental approach
LIO@Duke
LIVER IMMUNOLOGY ONTOLOGY
Liver tissue Liver cell type Macromolecule
Liver Biological Process
occurs_in ha
s_pa
rtic
ipan
thas_p
articipant
part_ofpart_of
LIO@Duke
LIVER IMMUNOLOGY ONTOLOGY
Liver tissue Liver cell type Macromolecule
Liver Biological Process
occurs_in ha
s_pa
rtic
ipan
thas_p
articipant
part_ofpart_of
FMA CL PRO, SO, CheBi
GOLIO@Duke
Liver functional unit
Central veinPortal vein
HepatocyteInterlobular Bile duct
Hepatic arteriole
Portal triade
Disse space
Sinusoid
Disse space
Hepatocyte
Kupffer cell
KC
KC
HSC
HSC Hepatic Stellate cell LIO@Duke
SPACE OF DISSE ADJACENT_TO HEPATIC LAMINA
SPACE OF DISSE ADJACENT_TO ENDOTHELIUM OF HEPATIC SINUSOIDS
Expansion
LIO@Duke
LIO needs more than anatomy
Combination
LIO@Duke
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
isAoccursIn
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
FMA:63137
LIO
LIO@Duke
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
LIO@Duke
LIO has the ability to capture differences between physiological and pathological responses
Bridging biological ontologies
Cellular componentGO CC
Molecular functionGO MF
MacromoleculePRO, SO, CheBi
Biological processGO BP
Anatomical entityFMAOther
ontologies
Cell typeCL
LIO
LIO@Duke
CONS
Loss of the capacity to connect with other domains
Loss of interoperability within other ontologies
PROS
Specific representation of Liver immune response
Maintain a formal structure
Create a complex network of knowledge by bridging multiple ontologies
LIO@Duke
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
Aknowledgements and ongoing collaborations
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 BonoPierre Grenon
Lindsay Cowell
Anna Mae Diehl