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