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Metabolic Model SKRC
Metabolic Model SKRC
Metabolic Model SKRC
• High mortality
Image: http://emedicine.medscape.com/article/1612043-overview
VHL gene
image: http://www.usmleforum.com/files/forum/2014
Flux Balance Analysis
• Analyze flux through metabolic network
• Constraint-based approach
Mathematical representation of GSMM
S = Stoichiometric matrix
v = flux vector
𝑑𝑥
= concentration change over time
𝑑𝑡
Flux Balance Analysis
SKRC-7
ccRCC cancer cell with mutation in VHL
VHL-7
rescued cell, isogenic pair of SKRC-7
Metabolic model used
http://www.metabolicatlas.org/
Model set up
Cell medium
(metabolite constraint)
E-Flux
Normalization:
Mij = normalized value for metabolite i in reaction j
ci c = vector of metabolite concentration
𝑀𝑖𝑗 = ∗ 𝑘 ∗ 𝑔𝑒𝑛𝑒𝑗 genej = gene expression for reaction j
|c| k = constant ; k = 1000
Fetal Bovine Serum (FBS) constraint
iRenalCancer Human Serum Normalization:
1410 Database
𝑘 ∗ 0.1
𝐹𝑖𝑗 = ∗ 𝑔𝑒𝑛𝑒𝑗
string 𝑛
Exchange matching Human serum
metabolites metabolites
(with all synonyms) Fij = normalized value for metabolite i in
reaction j
k = constant ; k = 1000
190 FBS
metabolites
Analysis Gene
exp
media serum
INIT
model
in silico mechanism which cannot described without full picture of metabolic network
Recommendations
Experimental validation