10. Gapfillling

GrowMatch and SMILEY are gap-filling algorithms, which try to to make the minimal number of changes to a model and allow it to simulate growth. For more information, see Kumar et al.. Please note that these algorithms are Mixed-Integer Linear Programs, which need solvers such as gurobi or cplex to function correctly.

In [1]:

import cobra.test

model = cobra.test.create_test_model("salmonella")

In this model D-Fructose-6-phosphate is an essential metabolite. We will remove all the reactions using it, and at them to a separate model.

In [2]:

# remove some reactions and add them to the universal reactions
Universal = cobra.Model("Universal_Reactions")
for i in [i.id for i in model.metabolites.f6p_c.reactions]:
    reaction = model.reactions.get_by_id(i)
    Universal.add_reaction(reaction.copy())
    reaction.remove_from_model()

Now, because of these gaps, the model won’t grow.

In [3]:

model.optimize().f

The history saving thread hit an unexpected error (OperationalError('database is locked',)).History will not be written to the database.

Out[3]:

2.821531499799383e-12

10.1. GrowMatch

We will use GrowMatch to add back the minimal number of reactions from this set of “universal” reactions (in this case just the ones we removed) to allow it to grow.

In [4]:

cobra.flux_analysis.growMatch(model, Universal)

Out[4]:

[[<Reaction GF6PTA at 0x7f762587d0f0>,
  <Reaction F6PP at 0x7f762587d320>,
  <Reaction TKT2_reverse at 0x7f762587d390>,
  <Reaction F6PA_reverse at 0x7f762587d3c8>,
  <Reaction MAN6PI_reverse at 0x7f762587d4e0>]]

We can obtain multiple possible reaction sets by having the algorithm go through multiple iterations.

In [5]:

result = cobra.flux_analysis.growMatch(model, Universal,
                                       iterations=4)
for i, entries in enumerate(result):
    print("---- Run %d ----" % (i + 1))
    for e in entries:
        print(e.id)

---- Run 1 ----
GF6PTA
TKT2_reverse
F6PA_reverse
PGI_reverse
MAN6PI_reverse
---- Run 2 ----
GF6PTA
FBP
TALA
F6PP
MAN6PI_reverse
---- Run 3 ----
GF6PTA
TKT2_reverse
F6PA_reverse
PGI_reverse
MAN6PI_reverse
---- Run 4 ----
GF6PTA
FBP
TALA
F6PP
MAN6PI_reverse

10.2. SMILEY

SMILEY is very similar to growMatch, only instead of setting growth as the objective, it sets production of a specific metabolite

In [6]:

cobra.flux_analysis.gapfilling.SMILEY(model, "ac_e", Universal)

Out[6]:

[[<Reaction GF6PTA at 0x7f764d98aeb8>,
  <Reaction TKT2_reverse at 0x7f764d98a2e8>,
  <Reaction F6PA_reverse at 0x7f764d98a978>,
  <Reaction PGI_reverse at 0x7f764d98a780>,
  <Reaction MAN6PI_reverse at 0x7f764d98ae10>]]