View
213
Download
0
Category
Tags:
Preview:
Citation preview
XML Documentation of Biopathways XML Documentation of Biopathways and Their Simulations in Genomic Object Netand Their Simulations in Genomic Object Net
Speaker : Hungwei chen
A Software A Software TowardToward
Biopathway Biopathway Modeling & SimulationModeling & Simulation
Genomic Object NetGenomic Object Net
What is Genomic Object NetWhat is Genomic Object Net• Genomic Object Net is a software tools for Modeling and Simulation Biopathways
• Employing the notion of HFPN as its basic Architecture
• Using XML Documents for representation simulations and visualization for Biopathway
About Genomic Object NetAbout Genomic Object Net
• Genomic Object Net Assembler
• Genomic Object Net Describing tool.
• Genomic Object Net Visualizer
• Biopathway Describing Tool– helps to describe a biopathway according to the traditi
onal description methods in biology
– releasing users from the mathematical knowledge
• Genomic Object Net Assembler1. Designs HFPN which represents and simulates a syste
m of genomic objects.
2. Produces Biopathway Representation Source File as an XML document.
3. Produces Simulation Results Files (CSV format) each of which contains a time-series of the numerical values representing the behavior of places in HFPN.
In order for biosimulation tools to be accepted by users in
(1)Remove issues which are irrelevant to biological importance,
(2)Allow users to represent biopathways intuitively and understand/manage easily the details of representation and simulation mechanism
From these criteria, software tools currently developed might not be enough satisfactory.
Apoptosis induced by Fas
Cytoplasm
cascade
caspase
Signal
Fas ligand
Fas receptor
complex
Signaling Pathway
What is the Petri Net ??What is the Petri Net ??• A Petri Net is a collection of directed arcs
connecting places and transitions .
• Arcs have capacity 1 by default .
• Places may hold tokens
• transitions have no capacity, and cannot store tokens .
How to enable token through transition
• A transition is enabled when the number of tokens in each of its input places is at least equal to the arc weight going from the place to the transition.
• An enabled transition may fire at any time. When fired, the tokens in the input places are moved to output place
The inhibitor arcThe inhibitor arc
• This transition cannot fire, because the token in P2 inhibits it.
Hybrid Petri Net
•Easy to describe biological facts and biological phenomenon on computers and •Acceptable technical expression of the tool to biologists.
Extension to Hybrid Dynamic Net
© Copyright 2002 Satoru Miyano, Human Genome Center, University of Tokyo
Elements
Michaelis
- Menten
Equation
Hybrid Dynamic Net
© Copyright 2002 Satoru Miyano, Human Genome Center, University of Tokyo
Hybrid functional Petri net
)(2
1 , , 313322211 mmfmmfmmf
323213
1 , log2
2
1 1 megmmg m
• Assign any function to each arc
• Transition T fires as long as mi > 0 for all 1 < i < p
© Copyright 2002 Satoru Miyano, Human Genome Center, University of Tokyo
dimer monomers 1 2
discrete Petri net
1 1
1 1
hybrid dynamic net
1 2
hybrid functional Petri net
describe naturally
explosion of tokens
Not intuitive nor natural© Copyright 2002 Satoru Miyano, Human Genome Center, University of Tokyo
1. Identify main events in the biopathway of concern.2. placesplaces :• Continuous places (doubled circles) : contain real numbers which represent concentrations of mRNA and Proteins.
• Discrete places (single circles) : are corresponded to the promoter or operator sites for expressing the binding situation of transcription factor
Design of hybrid functional Petri net
• 3. transitionstransitions: interactions between objects – hidden interaction should also be identified
• 4. functionsfunctions assigned to transitions : – based on the logical structure in events and biol
ogical/biochemical knowledge about objects
• 5. Simulate, evaluate, and tune up the designed HFPN
3. transitiontransition :• Continuous transitions (white rectangles) : are used for expressing the production/degradation speed of mRNAs or proteins.
Discrete transitions (black rectangles) : are used for expressing the required time for RNA polymerase which moves between two genes.
Design of hybrid functional Petri net
XML Integration of Biopathway XML Integration of Biopathway in Genomic Object Netin Genomic Object Net
<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE hybridFunctionalPetriNet SYSTEM "SampleHFPNet.dtd"><HFPN> <place id="P1" type="continuos" variableName="m1"/> <place id="P2" type="continuos" variableName="m2"/> <transition id="T1" speedFunction="m1/2.5" type="continuos"/> <arc from="P1" to="T1" type="normal" weight="1"/> <arc from="T1" to="P2" type="normal" weight="m1/2"/></HFPN>
m1 m2
T1
1 m1/2
P1 P2
m1/2.5
XML representation of HFPN
XML Biopathway Visualization
(Upper left) Lambda phage chromosome – brightness or color of gene is changed according to t
he protein concentration level
(upper right) Concentrations of proteins N and CI– Direct display of csv file in Simulation Result Files
(bottom) CI and Cro binding to OR1, OR2, OR3
ConclusionConclusion• The HFPN model for representing and simulating
biopathways.
• XML documents for description and visualization of HFPN together with simulation results.
• The future plan of Genomic Object Net is to construct a knowledge database of biopathways which allow computer simulation and visualization.
Recommended