Cell%20Signaling%20Ontology

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Cell Signaling Ontology

• Takako Takai-Igarashi and Toshihisa Takagi
• Human Genome Center, Institute of Medical
  Science, University of Tokyo

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Bioinformatics in the post-genome sequencing era
We have to learn more from the biological system
investigate the biological system thoroughly, and
find underlying algorithms of information
processing in common to all the species.
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Cell signaling is an algorithm of information
processing
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SIGNAL-ONTOLOGY - ontology for cell signaling -
Abstract the common features from the cell
signaling systems of model species of eukaryotes
(yeast, fruit fly, nematode, rat, mouse, and
human) and reconstruct them in computers.
Based on the knowledge accumulated in the Cell
Signaling Networks Database (CSNDB)
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Cell Signaling in Biology
Many signaling processes were shown to be
conserved throughout the eukaryotic kingdom, from
yeast to vertebrates.
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SIGNAL-ONTOLOGY

• Conceptual classes of SIGNAL-ONTOLOGY
• Signal Module an unit of signal processing in
  common to the model species.
• Molecular Functionbiochemical properties of a
  molecule.
• Cellular Functiona biological response performed
  by a series of Molecular Functions.
• Gene and Proteingenes and gene products which
  link to entries of GeneOntology and NCBI UniGene.

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SIGNAL-ONTOLOGY

• Signal Module
• Minimum units of signal processing in common to
  the model species.
• Every signaling cascade can be reconstructed by a
  set of Signal Modules.

Signal Module Input Signal (property,
location) Output Signal (property,
location) Pointer to Molecular Function
Concept Pointer to Cellular Function Concept
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Signal Module
ligand -gt transmembrane signaling -gt
phosphorylation -gt clustering
ligand -gt G protein-coupled receptor -gt G-protein
switching
phospholipid -gt second messenger
second messenger -gt kinase
G-protein switching -gt kinase
kinase cascade
conformation change and release of signal peptide
-gt nuclear localization
target gene expression
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SIGNAL-ONTOLOGY
Signal Modules in eukaryotes
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SIGNAL-ONTOLOGY

• Molecular Function
• Biochemical property of molecules
• Refer to the GeneOntology

Molecular Function Higher Concept Lower
Concept Pointer to Signal Module
Concept Pointer to Gene and Protein Concept
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SIGNAL-ONTOLOGY
ligand -gt G protein-coupled receptor -gt G-protein
switching
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SIGNAL-ONTOLOGY

• Cellular Function
• Biological response performed by a series of
  Molecular Functions.
• Similar classification of biological processes in
  the metabolic system, such as TCA cycle,
  chlorophyll synthesis, and fatty acid
  desaturation.

Cellular Function Higher Concept Lower
Concept Pointer to Signal Module
Concept Pointer to Gene and Protein Concept
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Cellular Function
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Cellular Function
Data are collected from original articles by
hand. We refer review articles of Cell.
Another group of signaling molecules likely to
mediate axon guidance signals is the Rho family
of small GTPases. Activation of the Rho GTPases
Rac and Cdc42 promotes the formation of
lamellipodia and filopodia, respectively, and
induces the formation of adhesive complexes that
stabilize these structures. In contrast,
activation of the Rho family member RhoA leads
increased actinomyosin contractility and growth
cone collapse. (Cell, 101, 239-242, 2000)
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System design

• SIGNAL-ONTOLOGY is implemented on an
  object-oriented system. All the components of
  Signal Module, Molecular Function and Cellular
  Function concepts are implemented as objects in
  the system.

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System design

• Input and output signals that represent
  connections between objects of the Signal Module
  concept are implemented as methods that can pass
  the messages between objects. Methods are
  implemented as table lookup or by logic
  programming.

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System design

• The system will have external linkages to
  dictionaries, text books, and the Internet
  resources.
• Graphical user interface, with which we propose a
  standard representation of the cell signaling,
  will be implemented.

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SIGNAL-ONTOLOGY

• Applications
• Comparative genome analysis
• Genome annotation
• Knowledge extraction from texts
• Information retrieval (query relaxation)
• Knowledge-based integration of existing databases
  in the Internet
• Gene expression profile analysis
• Cell signaling simulation

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SIGNAL-ONTOLOGY
SIGNAL-ONTOLOGY
ApplicationGenome annotation It will be a
reference of functional roles of individual
molecules in the cell signaling system and
provide a list of molecules belong to the same
functional role in the cell signaling.
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Every gene will be mapped to a node in the
signaling ontology.
ligand -gt transmembrane signaling -gt
phosphorylation -gt clustering
ligand -gt G protein-coupled receptor -gt G-protein
switching
phospholipid -gt second messenger
second messenger -gt kinase
G-protein switching -gt kinase
kinase cascade
conformation change and release of signal peptide
-gt nuclear localization
target gene expression
In our final goal, signaling networks will be
deducted from the genome information