如何将通量比设置为约束条件？

Question

在某些数据集中，我有时会观察到固定的通量比，我想将其纳入我的模拟中。我如何在 CBMPy 中执行此操作？

例如，我有来自 here 的模型，现在想将琥珀酸流出和丙酮酸流出的比率限制为 2.0。我知道如何对个人反应设置约束：

import cbmpy

# downloaded from http://bigg.ucsd.edu/models/e_coli_core
ecoli = cbmpy.CBRead.readSBML3FBC('e_coli_core.xml')

ecoli.setReactionBounds('R_EX_pyr_e', 1.0, 1000.0)
ecoli.setReactionBounds('R_EX_succ_e', 2.0, 1000.0)

# solve the model
cbmpy.doFBA(ecoli)

# get all reaction values
solution = ecoli.getReactionValues()
print(solution['R_EX_pyr_e'])
print(solution['R_EX_succ_e'])

对于这种情况，比率是正确的，但我如何将其添加为在所有条件下都满足的约束条件？

Answer 1

这确实是通量平衡分析 (FBA) 中的常用方法，您可以使用函数 addUserConstraint 来完成此操作。

整个代码示例可能如下所示（解释如下）：

import cbmpy as cbm

# downloaded from http://bigg.ucsd.edu/models/e_coli_core
ecoli = cbm.CBRead.readSBML3FBC('e_coli_core.xml')

# make a clone of the original model
ecoli_ratio = ecoli.clone()

# add the desired user constraint; explanation follows below
ecoli_ratio.addUserConstraint("pyr_succ_ratio", fluxes=[(1.0, 'R_EX_pyr_e' ),(-0.5, 'R_EX_succ_e')], operator='=', rhs=0.0)

# now we have to set only one flux bound; if you think it is naturally excreted, this step is not needed
ecoli_ratio.setReactionBounds('R_EX_succ_e', 4.0, cbm.INF)

cbm.doFBA(ecoli_ratio)
solution = ecoli_ratio.getReactionValues()
print("{}: {}".format("succinate excretion rate", solution['R_EX_succ_e']))
print("{}: {}".format("pyruvate excretion rate", solution['R_EX_pyr_e']))

这将打印

succinate excretion rate: 4.0
pyruvate excretion rate: 2.0

如您所见，比率是 2.0，符合要求。

更多解释：

约束是

J_succ / J_pyr = 2.0

可以重写为

J_succ = 2.0 J_pyr

最后

J_pyr - 0.5 J_succ = 0

这正是我们在 addUserConstraint 中传递给 fluxes 的内容：

fluxes=[(1.0, 'R_EX_pyr_e' ),(-0.5, 'R_EX_succ_e')], operator='=', rhs=0.0)

您可以通过打印来检查用户定义的约束：

print(ecoli_ratio.user_constraints)
{'pyr_succ_ratio': {'operator': 'E', 'rhs': 0.0, 'fluxes': [(1.0, 'R_EX_pyr_e'), (-0.5, 'R_EX_succ_e')]}}

由于这是一本字典，您只需执行以下操作即可删除约束：

del ecoli_ratio.user_constraints['pyr_succ_ratio']
print(ecoli_ratio.user_constraints)
{}

但我强烈建议您每次对模型进行重大更改时都创建一个克隆。

如何将通量比设置为约束条件？

How to set a flux ratio as a constraint?

python

cbmpy