cz5225 methods in computational biology lecture 9: biological pathways and pathway simulation prof....
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CZ5225 Methods in Computational BiologyCZ5225 Methods in Computational Biology
Lecture 9: Biological pathways and Lecture 9: Biological pathways and pathway simulationpathway simulation
Prof. Chen Yu ZongProf. Chen Yu Zong
Tel: 6874-6877Tel: 6874-6877Email: Email: [email protected]@nus.edu.sghttp://xin.cz3.nus.edu.sghttp://xin.cz3.nus.edu.sg
Room 07-24, level 7, SOC1, NUSRoom 07-24, level 7, SOC1, NUSAugust 2004August 2004
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Biological pathways • Describe series of molecular events in living systems. • Important in understanding living systems, disease processes,
effect of drugs or mutations on living systems.
Annu. Rev. Biophys. Biomol. Struct. 27, 199-224 (1998)
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Biological pathwaysBiological pathways
Map of pathways:
Pathway database: KEGG http://www.genome.ad.jp/kegg/kegg2.html
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Multiple biological pathways:Multiple biological pathways: Viral infection as an exampleViral infection as an example
How SARS coronavirus enters a cell and reproduce
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Multiple biological pathways: Multiple biological pathways: Viral infection as an exampleViral infection as an example
Viral induced immune response: cytosine productionTherapeutically relevant multiple pathways database http://xin.cz3.nus.edu.sg/group/trmp/trmp.asp
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Multiple biological pathways: Multiple biological pathways: Viral infection as an exampleViral infection as an example
Viral induced immune response: cytosine productionTherapeutically relevant multiple pathways database http://xin.cz3.nus.edu.sg/group/trmp/trmp.asp
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Biological pathway databases
Biological pathway databases:
• KEGG: Kyoto Encyclopedia of Genes and Genomes. • SPAD: Signaling Pathway Database. • CSNDB: Cell Signaling Networks Database. • PFBP: Protein Function and Biochemical Pathways.
Multiple pathway databases:
• Therapeutically relevant multiple pathways database http://xin.cz3.nus.edu.sg/group/trmp/trmp.asp
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Simulation of a biological pathway
Computer method appears to be the only practical approach (mainly involving no more than a few dozen proteins)
Nature Biotech. 18, 768-774 (2000)
dx1/dt = k1- X2 - k1+ L x1 + w1
dx2/dt = k1+ L X1 - (k1- + k2 )x2
dx3/dt = k2 X2 + k3- X5
L = Fas ligand, x1=ligand-free Fas surface receptor, x2=ligand-bound Fas surface receptor, x3=clustered ligand-bound Fas surface receptor, x4=FADD protein, x5=complex of FADD-Fas receptor
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Simulation of a biological pathway
Quantitative description of a pathway
Nature Biotech. 18, 768-774 (2000)
Protein concentration and variation
dx1/dt = k1- X2 - k1+ L x1 + w1
dx2/dt = k1+ L X1 - (k1- + k2 )x2
dx3/dt = k2 X2 + k3- X5
L = Fas ligand, x1=ligand-free Fas surface receptor, x2=ligand-bound Fas surface receptor, x3=clustered ligand-bound Fas surface receptor, x4=FADD protein, x5=complex of FADD-Fas receptor
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Simulation of a biological pathway
Construction of reaction/binding equations
Nature Biotech. 18,768-774 (2000)
L = Fas ligand
R=ligand-free Fas surface receptor~RL=ligand-bound Fas surface receptor
RL=clustered ligand-bound Fas surface receptor
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Simulation of a biological pathway
Construction of reaction/binding kinetic equations
Nature Biotech. 18,768-774 (2000)
L = Fas ligand
R=ligand-free Fas surface receptor~RL=ligand-bound Fas surface receptor
RL=clustered ligand-bound Fas surface receptor