CADLIVCADLIVEE

GRAPHICAL NOTATION

http://www.cadlive.jp

Regulator-reaction model and graphical notation

RegulatorReaction

ChemicalReaction

GraphicalNotation

S→ P S→ P

E -o S→ PE: Enzyme

E+S <-> E:S → P

A ->> S→ PA: Activator

I - || S→ PI: Inhibitor

MechanisticModel

SemanticModel

S P

S P

E

S P

A

S P

I

Generality(regulator-reaction equation in SBML extension)

Process diagram (temporal order of reaction)

Compactness (Each molecule appears once in a diagram)

Concept of Graphical NotationConcept of Graphical Notation

A B

P Q

A

B

A B

P Q

CADLIVEOther Notations

Process diagramTemporal order of reactions

Entity relationship

Non-redundant appearance of molecules,Compact drawing

CADLIVE(Kurata)

Kohn

Redundant appearance of molecules

Cell DesignerPatikaEdinburghBioD

Comparison of graphical notations

Homo association or modification

Homo association or modificationwith stoichiometric changes

Binding

Binding with stoichiometric changes

Reversible conversion

Irreversible conversion

Degradation

Translation

Transport

Transition state

Reaction

Set Modified from transition state

Activation

Inhibition

Enzymatic catalysis

Regulatory interaction

Protein synthesis

Transcription

DNAs, gene, enhancer, promoter

Fundamental Notation

Binding with stoichiometric changes

A B

A+B<->A-B+H2O3A+ 2B <-> A3:B2

Binding

The number of molecules

A B23

A

ATP ADP

Reaction with cofactors

A+ATP ->A-P+ADP

Homo association or modificationwith stoichiometric changes

+/-Number

SiteSpecies

A

+2P(Ser141)

A+P->A-2P

Multi-substarate and -product reaction

A

B

C

A

B

C

Set Transition state

Select reaction arrows from the transition state

E -o A+B ->C

E

Enhancer Promoter gene

Transcription

mRNA

proteinActivator

Suppressor

Gene expression

New notation for domain level drawing

Virtual binding

Virtual binding with stoichiometric changes

InnerLink arrow

Virtual homo association or modification

Virtual homo association or modificationwith stoichiometric changes

P D1 D2

Domain expansion

A

B

C

RNA D1 D2

1. Domain expansion

2. Virtual reactions and nodes

3. Link of a real node to virtual nodes (InnerLink)

Pro

A

B

+P(A) +P(B)

3 4 5

2

1A

ATPADP

(A) Phosphorylation reactions at the domain level. The protein of Pro is expanded into the domains of A and B. <1> The virtual node indicates the state that Pro is phosphorylated on the B domain. <2> The virtual node indicates the state that Pro is phosphorylated on the A domain. <3> The real node of phosphorylated Pro (Pro-P) is produced. The InnerLink arrow (green) shows that the A domain is phosphorylated. <4> The real node of Pro-P-P is produced. The InnerLink arrow shows both the A and B domains are phosphorylated. <5> The real node of Pro-P is produced by dephosphorylation of Pro-P-P. The InnerLink arrow indicates the B domain is phosphorylated.

Pro1

Pro2

+P 2

3

+P 1B

(B) A phosphorus exchange reaction (Pro1 + Pro2-P -> Pro1-P + Pro2). <1> The virtual node indicates the state that Pro1 is phosphorylated. <2> The real node of Pro2-P is produced. <3> The InnerLink arrow indicates that the real node is Pro1-P.

Pro1 A B C

Pro2 D E

Pro3 F G H

1

2

3

4

C

(C) Synthesis of the protein complex of Pro1:Pro2:Pro3. <1> The virtual node indicates the state that the B domain of Pro1 is bound to the E domain of Pro2. <2> The virtual node indicates the state that the D domain of Pro2 is bound to the F domain of Pro3. <3> The real node of Pro1:Pro2 is produced. The InnerLink arrow indicates that the B domain of Pro1 is bound to the E domain of Pro2. <4> The real node of Pro1:Pro2:Pro3 is produced. The InnerLinik arrow indicates that the D domain of Pro2 is bound to the F domain of Pro3.

Mammalian translation initiation system

A

B

Separation of real reactions and nodes from a domain-level interaction map(A) A domain- or subunit- based map with virtual reactions and nodes. (B) A real map containing no virtual reaction and node. CADLIVE can switch off the display of subunits, domains, virtual reactions and nodes, and InnerLink.

A B

C D

A B

C D

A hierarchical modular architecture by using WhiteBox One can pack molecular networks or modules into the WhiteBox. (A) The entire network. (B) Six functional modules. (C) Seven functional modules. (D) A biochemical network map at the domain-or subunit- level.

Hiroyuki Kurata, Kentaro Inoue, Kazuhiro Maeda, Koichi Masaki, Yuki Shimokawa, Quanyu Zhao, Extended CADLIVE: a novel graphical notation for designing a biochemical network map that enables computational pathway analysis, Nucleic Acids Res. On the web 2007.

Hiroyuki Kurata, Nana Matoba, Natsumi Shimizu, CADLIVE for constructing a large-scale biochemical network based on a simulation-directed notation and its application to yeast cell cycle. Nucleic Acids Res. 31: 4071-4084, 2003.