diff --git a/modelpruner/graph/linear_pathway.py b/modelpruner/graph/linear_pathway.py
index 5bba14acc3455194a2971d8c0298c44e2b78661e..fbf2b9522183783a66c471603e7d3aca6e89590a 100644
--- a/modelpruner/graph/linear_pathway.py
+++ b/modelpruner/graph/linear_pathway.py
@@ -1,12 +1,13 @@
-"""
+"""Implementation of LinearPathway Class.
-Peter Schubert, October 2022
+Peter Schubert, HHU Duesseldorf, October 2022
"""
import numpy as np
from modelpruner.graph.pathway_segment import PathwaySegment
+from modelpruner.graph.pathway_segment import ReactionLeg
class LinearPathway:
@@ -21,11 +22,48 @@ class LinearPathway:
self.init_sid = init_sid
self.balance_c2_sids = set(balance_c2_sids)
self.ng = network_graph
+ self.net_reactants = {}
+ self.net_products = {}
+ # construct the linear pathway
self.segments = [self.get_initial_segment()]
self.add_downstream_segments()
self.add_upstream_segments()
+ # collect pathway data
+ self.sids = []
+ self.rids = [self.segments[0].producing.rid]
+ self.reversible = self.segments[0].reversible
+ scale = 1.0
+ direction = 1.0 if self.segments[0].producing.forward is True else -1.0
+ self.rids_scale = {self.segments[0].producing.rid: scale * direction}
+ for pwy_seg in self.segments:
+ self.sids.append(pwy_seg.sid)
+ self.rids.append(pwy_seg.consuming.rid)
+ scale *= pwy_seg.producing.stoic / pwy_seg.consuming.stoic
+ direction = 1.0 if pwy_seg.consuming.forward is True else -1.0
+ self.rids_scale[pwy_seg.consuming.rid] = scale * direction
+
+ net_stoic = self.get_net_stoichiometry()
+ self.net_reactants = {sid: -stoic for sid, stoic in net_stoic.items() if stoic < 0.0}
+ self.net_products = {sid: stoic for sid, stoic in net_stoic.items() if stoic > 0.0}
+
+ def get_net_stoichiometry(self):
+
+ substrates = set()
+ for rid in self.rids_scale:
+ substrates |= set(self.ng.edges[rid].reactants)
+ substrates |= set(self.ng.edges[rid].products)
+ net_stoic = {substrate: 0.0 for substrate in substrates}
+
+ for rid, scale in self.rids_scale.items():
+ for sid, stoic in self.ng.edges[rid].reactants.items():
+ net_stoic[sid] -= stoic * scale
+ for sid, stoic in self.ng.edges[rid].products.items():
+ net_stoic[sid] += stoic * scale
+
+ return net_stoic
+
def get_initial_segment(self):
"""get initial pathway segment for inital node.
@@ -37,64 +75,56 @@ class LinearPathway:
:rtype: PathwaySegment
"""
self.balance_c2_sids.remove(self.init_sid)
-
connectivity = self.get_us_ds_neighbors(self.init_sid)
- pwy_seg = PathwaySegment(connectivity['sid'])
- pwy_seg.set_upstream(connectivity['p_rid'], connectivity['nb_us'])
- pwy_seg.set_downstream(connectivity['c_rid'], connectivity['nb_ds'])
- pwy_seg.set_reversible(connectivity['reversible'])
- return pwy_seg
+ return PathwaySegment(connectivity)
def add_downstream_segments(self):
"""add downstream segments """
lcount = 1
upstream_seg = self.segments[-1]
- while upstream_seg.nb_ds is not None and lcount < 50:
+ while ((upstream_seg.consuming is not None) and
+ (upstream_seg.consuming.nb is not None) and
+ (lcount < 50)):
lcount += 1
pwy_rev = upstream_seg.reversible
- self.balance_c2_sids.remove(upstream_seg.nb_ds)
+ self.balance_c2_sids.remove(upstream_seg.consuming.nb)
connectivity = self.get_ds_neighbor(upstream_seg)
+ pwy_seg = PathwaySegment(connectivity)
+ pwy_seg.set_reversible(pwy_rev and connectivity['reversible'])
+ self.segments.append(pwy_seg)
- if 'c_rid' in connectivity:
- pwy_seg = PathwaySegment(connectivity['sid'])
- pwy_seg.set_upstream(upstream_seg.c_rid, upstream_seg.sid)
- pwy_seg.set_downstream(connectivity['c_rid'], connectivity['nb_ds'])
- pwy_seg.set_reversible(pwy_rev and connectivity['reversible'])
- self.segments.append(pwy_seg)
+ if connectivity['consuming'] is None:
+ # termination of the pathway at a c1 metabolite (blocked node)
+ break
- if connectivity['nb_ds'] is not None:
- # treat a reversible pathway that becomes directional (i.e. continue ds)
- if (pwy_rev is True) and (connectivity['reversible'] is False):
+ if connectivity['consuming'].nb is None:
+ # termination of the pathway with connectivity towards the network
+ if pwy_rev is True:
+ if connectivity['reversible'] is False:
+ # irreversible termination in a reversible pathway
for pwy_seg in self.segments:
pwy_seg.set_reversible(False)
- # in other cases, just continue ds
- # cases of path termination
- else:
- # pathway termination of a reversible pathway (reverse pwy_segs and continue ds)
- if (pwy_rev is True) and (connectivity['reversible'] is True):
+ else:
+ # reversible termination in a reversible pathway
for pwy_seg in self.segments:
- pwy_seg.set_reversible(False)
pwy_seg.reverse_direction()
self.segments.reverse()
- # in other cases, the path termination terminates the while loop
- # i.e. no consuming node, but only one producing node
- # we reverse tha pwy_segments and their direction and continue ds
+ if connectivity['consuming'].nb is not upstream_seg.sid:
+ # downstream connectivity to a c2 node
+ if (pwy_rev is True) and (connectivity['reversible'] is False):
+ for pwy_seg in self.segments:
+ pwy_seg.set_reversible(False)
elif pwy_rev is True:
- assert 'p_rid' in connectivity
+ # pathway reversal situation
assert connectivity['reversible'] is False
- pwy_seg = PathwaySegment(connectivity['sid'])
- pwy_seg.set_upstream(upstream_seg.c_rid, upstream_seg.sid)
- pwy_seg.set_downstream(connectivity['p_rid'], connectivity['nb_us'])
- self.segments.append(pwy_seg)
- for pwy_seg in self.segments:
+ for pwy_seg in self.segments[:-1]:
pwy_seg.set_reversible(False)
pwy_seg.reverse_direction()
self.segments.reverse()
else:
- # conditions when directional pathway has producing reaction
- print(f'inconsistent configuration, starting at {self.init_sid}')
+ print(f'inconsistent configuration at {pwy_seg.sid}, starting from {self.init_sid}')
break
upstream_seg = self.segments[-1]
@@ -102,37 +132,46 @@ class LinearPathway:
lcount = 1
downstream_seg = self.segments[0]
- while downstream_seg.nb_us in self.balance_c2_sids and lcount < 50:
+ while ((downstream_seg.producing is not None) and
+ (downstream_seg.producing.nb in self.balance_c2_sids) and
+ (lcount < 50)):
lcount += 1
pwy_rev = downstream_seg.reversible
- self.balance_c2_sids.remove(downstream_seg.nb_us)
+ self.balance_c2_sids.remove(downstream_seg.producing.nb)
connectivity = self.get_us_neighbor(downstream_seg)
+ pwy_seg = PathwaySegment(connectivity)
+ pwy_seg.set_reversible(pwy_rev and connectivity['reversible'])
+ self.segments.insert(0, pwy_seg)
- if 'p_rid' in connectivity:
- pwy_seg = PathwaySegment(connectivity['sid'])
- pwy_seg.set_downstream(downstream_seg.p_rid, downstream_seg.sid)
- pwy_seg.set_upstream(connectivity['p_rid'], connectivity['nb_us'])
- pwy_seg.set_reversible(pwy_rev and connectivity['reversible'])
- self.segments.insert(0, pwy_seg)
- if (connectivity['reversible'] is False) and (pwy_rev is True):
+ if connectivity['producing'] is None:
+ # termination of the pathway at a c1 metabolite (blocked node)
+ break
+
+ if connectivity['producing'].nb is None:
+ # termination of the pathway with connectivity towards the network
+ if (pwy_rev is True) and (connectivity['reversible'] is False):
+ for pwy_seg in self.segments:
+ pwy_seg.set_reversible(False)
+ break
+
+ if connectivity['producing'].nb is not downstream_seg.sid:
+ # upstream connectivity to a c2 node
+ if (pwy_rev is True) and (connectivity['reversible'] is False):
for pwy_seg in self.segments:
pwy_seg.set_reversible(False)
elif pwy_rev is True:
- assert 'c_rid' in connectivity
+ # pathway reversal situation
assert connectivity['reversible'] is False
- pwy_seg = PathwaySegment(connectivity['sid'])
- pwy_seg.set_downstream(downstream_seg.c_rid, downstream_seg.sid)
- pwy_seg.set_upstream(connectivity['c_rid'], connectivity['nb_ds'])
- self.segments.insert(0, pwy_seg)
- for pwy_seg in self.segments:
+ for pwy_seg in self.segments[:-1]:
+ pwy_seg.set_reversible(False)
pwy_seg.reverse_direction()
self.segments.reverse()
else:
- print(f'inconsistent configuration, starting at {self.init_sid}')
+ print(f'inconsistent configuration at {pwy_seg.sid}, starting from {self.init_sid}')
break
downstream_seg = self.segments[0]
- def get_neighbor_node(self, substrate_sids):
+ def get_neighbor_node(self, substrates):
"""Get a c2 node from reactants/product sids
If none of the reactant/products is a c2 node,
@@ -141,12 +180,12 @@ class LinearPathway:
In case of several c2 nodes, return the first node
after sorting.
- :param substrate_sids: metabolite ids (reactants or products)
- :type substrate_sids: list-like of str
+ :param substrates: substrates with stoichiometry
+ :type substrates: dict (key: sid - str, val: stoichiometry - float)
:return: metabolite id (sid) for neighbor node
:rtype: str or None
"""
- nbs = substrate_sids.intersection(self.balance_c2_sids)
+ nbs = set(substrates.keys()).intersection(self.balance_c2_sids)
if len(nbs) == 0:
nb = None
else:
@@ -164,49 +203,57 @@ class LinearPathway:
cur_node = self.ng.nodes[init_sid]
rids = [rid for rid in (cur_node.consuming_rids | cur_node.producing_rids)]
- revs = [rev for rev in (cur_node.consuming_rids | cur_node.producing_rids).values()]
+ revs = [val['rev'] for val in (cur_node.consuming_rids | cur_node.producing_rids).values()]
rev = bool(np.all(np.array(revs)))
- p_rid = None
- c_rid = None
- nb_us = None
- nb_ds = None
+ producing_leg = None
+ consuming_leg = None
if cur_node.connectivity == 1:
# c1 nodes are actually blocked nodes where a pathway ends
rid = rids[0]
if rid in cur_node.consuming_rids:
- c_rid = rid
- nb_ds = self.get_neighbor_node(self.ng.edges[c_rid].products)
+ stoic = cur_node.consuming_rids[rid]['stoic']
+ nb = self.get_neighbor_node(self.ng.edges[rid].products)
+ consuming_leg = ReactionLeg(rid, stoic, nb, True)
else:
- p_rid = rid
- nb_us = self.get_neighbor_node(self.ng.edges[p_rid].reactants)
-
- # in case of a reversible reaction, configure consuming path
- if (rev is True) and (c_rid is None):
- c_rid = p_rid
- nb_ds = nb_us
- p_rid = None
- nb_us = None
+ stoic = cur_node.producing_rids[rid]['stoic']
+ nb = self.get_neighbor_node(self.ng.edges[rid].reactants)
+ if rev is False:
+ producing_leg = ReactionLeg(rid, stoic, nb, True)
+ else:
+ # in case of a reversible producing reaction, configure consuming path
+ consuming_leg = ReactionLeg(rid, stoic, nb, False)
if cur_node.connectivity == 2:
if rev is True:
# process a node with reversible fluxes on both sides
# one being considered as producing, one as consuming reaction
- nb_sids = [None, None]
- for idx, rid in enumerate(rids):
- if rid in cur_node.consuming_rids:
- nb_sids[idx] = self.get_neighbor_node(self.ng.edges[rid].products)
+ nbs = [None, None]
+ stoics = [0.0, 0.0]
+ fwds = [True, True]
+
+ # arbitrarily select first reaction as producing and second as consuming
+ if rids[0] in cur_node.consuming_rids:
+ fwds[0] = False
+ if rids[1] in cur_node.producing_rids:
+ fwds[1] = False
+
+ for idx in range(2):
+ if rids[idx] in cur_node.consuming_rids:
+ stoics[idx] = cur_node.consuming_rids[rids[idx]]['stoic']
+ nbs[idx] = self.get_neighbor_node(self.ng.edges[rids[idx]].products)
else:
- nb_sids[idx] = self.get_neighbor_node(self.ng.edges[rid].reactants)
+ stoics[idx] = cur_node.producing_rids[rids[idx]]['stoic']
+ nbs[idx] = self.get_neighbor_node(self.ng.edges[rids[idx]].reactants)
- # if one of the reversible reactions connects to network, let it be the producing side
- if nb_sids[0] is None:
- p_rid, c_rid = rids
- nb_us, nb_ds = nb_sids
+ # preferably the producing leg connects to the network (nb = None)
+ if nbs[0] is None:
+ producing_leg = ReactionLeg(rids[0], stoics[0], nbs[0], fwds[0])
+ consuming_leg = ReactionLeg(rids[1], stoics[1], nbs[1], fwds[1])
else:
- c_rid, p_rid = rids
- nb_ds, nb_us = nb_sids
+ producing_leg = ReactionLeg(rids[1], stoics[1], nbs[1], not fwds[1])
+ consuming_leg = ReactionLeg(rids[0], stoics[0], nbs[0], not fwds[0])
# get neighbors of a node in a directional pathway segment
else:
@@ -221,29 +268,44 @@ class LinearPathway:
if drid in cur_node.consuming_rids:
c_rid = drid
p_rid = orid
+ c_stoic = cur_node.consuming_rids[c_rid]['stoic']
nb_ds = self.get_neighbor_node(self.ng.edges[c_rid].products)
+ c_fwd = True
+ # the 'producing' reaction can be a producing or a reversible consuming reaction
if p_rid in cur_node.producing_rids:
+ p_stoic = cur_node.producing_rids[p_rid]['stoic']
nb_us = self.get_neighbor_node(self.ng.edges[p_rid].reactants)
- # in case the 2nd reaction is also a consuming reaction, it must be reversible
+ p_fwd = True
else:
- assert cur_node.consuming_rids[p_rid] is True
+ # case of a consuming reaction run in reverse
+ assert cur_node.consuming_rids[p_rid]['rev'] is True
+ p_stoic = cur_node.consuming_rids[p_rid]['stoic']
nb_us = self.get_neighbor_node(self.ng.edges[p_rid].products)
+ p_fwd = False
# case, where the selected directional reaction is a producing reaction
else:
p_rid = drid
c_rid = orid
+ p_stoic = cur_node.producing_rids[p_rid]['stoic']
nb_us = self.get_neighbor_node(self.ng.edges[p_rid].reactants)
+ p_fwd = True
if c_rid in cur_node.consuming_rids:
+ c_stoic = cur_node.consuming_rids[c_rid]['stoic']
nb_ds = self.get_neighbor_node(self.ng.edges[c_rid].products)
+ c_fwd = True
else:
- assert cur_node.producing_rids[c_rid] is True
+ assert cur_node.producing_rids[c_rid]['rev'] is True
+ c_stoic = cur_node.producing_rids[c_rid]['stoic']
nb_ds = self.get_neighbor_node(self.ng.edges[c_rid].reactants)
+ c_fwd = False
- return {'sid': init_sid, 'p_rid': p_rid, 'nb_us': nb_us,
- 'c_rid': c_rid, 'nb_ds': nb_ds, 'reversible': rev}
+ producing_leg = ReactionLeg(p_rid, p_stoic, nb_us, p_fwd)
+ consuming_leg = ReactionLeg(c_rid, c_stoic, nb_ds, c_fwd)
+
+ return {'sid': init_sid, 'producing': producing_leg, 'consuming': consuming_leg, 'reversible': rev}
def get_ds_neighbor(self, us_pwy_seg):
"""get downstream neighbor at us_sid coming from p_rid.
@@ -263,51 +325,92 @@ class LinearPathway:
the upstream pathway is reversible (leading to a directional pathway
in opposite direction)
"""
- sid = us_pwy_seg.nb_ds
+ sid = us_pwy_seg.consuming.nb
cur_node = self.ng.nodes[sid]
- revs = [rev for rev in (cur_node.consuming_rids | cur_node.producing_rids).values()]
+ revs = [val['rev'] for val in (cur_node.consuming_rids | cur_node.producing_rids).values()]
rev = bool(np.all(np.array(revs)))
- c_rid = None
- nb_ds = None
+ producing_leg = None
+ consuming_leg = None
+
+ # collect information for upstream leg
+ p_rid = us_pwy_seg.consuming.rid
+ us_nb = us_pwy_seg.sid
+ if p_rid in cur_node.producing_rids:
+ p_stoic = cur_node.producing_rids[p_rid]['stoic']
+ p_fwd = True
+ else:
+ assert cur_node.consuming_rids[p_rid]['rev'] is True
+ p_stoic = cur_node.consuming_rids[p_rid]['stoic']
+ p_fwd = False
- if cur_node.connectivity == 2:
+ if cur_node.connectivity == 1:
+ producing_leg = ReactionLeg(p_rid, p_stoic, us_nb, p_fwd)
- p_rid = us_pwy_seg.c_rid
+ if cur_node.connectivity == 2:
c_rid = [rid for rid in (cur_node.consuming_rids | cur_node.producing_rids) if rid != p_rid][0]
-
if c_rid in cur_node.consuming_rids:
- nb_ds = self.get_neighbor_node(self.ng.edges[c_rid].products)
+ c_stoic = cur_node.consuming_rids[c_rid]['stoic']
+ ds_nb = self.get_neighbor_node(self.ng.edges[c_rid].products)
+ c_fwd = True
+ else:
+ # a 'producing' reaction consuming the metabolite
+ c_stoic = cur_node.producing_rids[c_rid]['stoic']
+ ds_nb = self.get_neighbor_node(self.ng.edges[c_rid].reactants)
+ c_fwd = False
+
+ # check for reversal in case the producing reaction is directional
+ if (c_rid in cur_node.consuming_rids) or (cur_node.producing_rids[c_rid]['rev'] is True):
+ producing_leg = ReactionLeg(p_rid, p_stoic, us_nb, p_fwd)
+ consuming_leg = ReactionLeg(c_rid, c_stoic, ds_nb, c_fwd)
else:
- nb_ds = self.get_neighbor_node(self.ng.edges[c_rid].reactants)
- if cur_node.producing_rids[c_rid] is False:
- # flow reversal in case the producing reaction is directional
- return {'sid': sid, 'p_rid': c_rid, 'nb_us': nb_ds, 'reversible': rev}
+ producing_leg = ReactionLeg(c_rid, c_stoic, ds_nb, not c_fwd)
+ consuming_leg = ReactionLeg(p_rid, p_stoic, us_nb, not p_fwd)
- return {'sid': sid, 'c_rid': c_rid, 'nb_ds': nb_ds, 'reversible': rev}
+ return {'sid': sid, 'producing': producing_leg, 'consuming': consuming_leg, 'reversible': rev}
def get_us_neighbor(self, ds_pwy_seg):
- sid = ds_pwy_seg.nb_us
+ sid = ds_pwy_seg.producing.nb
cur_node = self.ng.nodes[sid]
- revs = [rev for rev in (cur_node.consuming_rids | cur_node.producing_rids).values()]
+ revs = [val['rev'] for val in (cur_node.consuming_rids | cur_node.producing_rids).values()]
rev = bool(np.all(np.array(revs)))
- p_rid = None
- nb_us = None
+ producing_leg = None
+ consuming_leg = None
+
+ # collect information for downstream leg
+ c_rid = ds_pwy_seg.producing.rid
+ ds_nb = ds_pwy_seg.sid
+ if c_rid in cur_node.consuming_rids:
+ c_stoic = cur_node.consuming_rids[c_rid]['stoic']
+ c_fwd = True
+ else:
+ assert cur_node.producing_rids[c_rid]['rev'] is True, f'{sid},{c_rid}'
+ c_stoic = cur_node.producing_rids[c_rid]['stoic']
+ c_fwd = False
- if cur_node.connectivity == 2:
+ if cur_node.connectivity == 1:
+ consuming_leg = ReactionLeg(c_rid, c_stoic, ds_nb, c_fwd)
- c_rid = ds_pwy_seg.p_rid
+ if cur_node.connectivity == 2:
p_rid = [rid for rid in (cur_node.consuming_rids | cur_node.producing_rids) if rid != c_rid][0]
-
if p_rid in cur_node.producing_rids:
- nb_us = self.get_neighbor_node(self.ng.edges[p_rid].reactants)
+ p_stoic = cur_node.producing_rids[p_rid]['stoic']
+ us_nb = self.get_neighbor_node(self.ng.edges[p_rid].reactants)
+ p_fwd = True
+ else:
+ p_stoic = cur_node.consuming_rids[p_rid]['stoic']
+ us_nb = self.get_neighbor_node(self.ng.edges[p_rid].products)
+ p_fwd = False
+
+ # check for reversal in case the producing reaction is directional
+ if (p_rid in cur_node.producing_rids) or (cur_node.consuming_rids[p_rid]['rev'] is True):
+ producing_leg = ReactionLeg(p_rid, p_stoic, us_nb, p_fwd)
+ consuming_leg = ReactionLeg(c_rid, c_stoic, ds_nb, c_fwd)
else:
- nb_us = self.get_neighbor_node(self.ng.edges[p_rid].products)
- if cur_node.consuming_rids[p_rid] is False:
- # flow reversal in case the consuming reaction is directional
- return {'sid': sid, 'c_rid': p_rid, 'nb_ds': nb_us, 'reversible': rev}
+ producing_leg = ReactionLeg(c_rid, c_stoic, ds_nb, not c_fwd)
+ consuming_leg = ReactionLeg(p_rid, p_stoic, us_nb, not p_fwd)
- return {'sid': sid, 'p_rid': p_rid, 'nb_us': nb_us, 'reversible': rev}
+ return {'sid': sid, 'producing': producing_leg, 'consuming': consuming_leg, 'reversible': rev}
def get_reactions(self):
diff --git a/modelpruner/graph/linear_pathways.py b/modelpruner/graph/linear_pathways.py
index 66eb7b84c65b4e22e952bd0f8198dcec7ca673ec..d488269cf36ebc8573c8501f2141dbc35dc32ddd 100644
--- a/modelpruner/graph/linear_pathways.py
+++ b/modelpruner/graph/linear_pathways.py
@@ -1,6 +1,6 @@
-"""
+"""Implementation of LinearPathways Class.
-Peter Schubert, October 2022
+Peter Schubert, HHU Duesseldorf, October 2022
"""
from modelpruner.graph.linear_pathway import LinearPathway
@@ -8,7 +8,14 @@ from modelpruner.graph.linear_pathway import LinearPathway
class LinearPathways:
- def __init__(self, network_graph, biomass_rid=None):
+ # TODO: rework again to first get lin_pathways from each of the nodes (excluding biomass precursors)
+ # idea to get as long pathways as possible
+ # sort for longest pathways
+ # remove duplicated pathways
+ # accept longest pathways first and drop pathways that contain already consumed reactions
+ # check if c2_nodes remain, and for these request again pathways
+
+ def __init__(self, network_graph, protected_rids=None):
"""
Construct linear pathways from metabolites with a connectivity of 2
@@ -19,12 +26,17 @@ class LinearPathways:
self.ng = network_graph
- if biomass_rid in self.ng.edges:
- biomass_sids = self.ng.edges[biomass_rid].reactants | self.ng.edges[biomass_rid].products
- else:
- biomass_sids = set()
- self.c2_sids = {node.id: None for node in self.ng.nodes.values()
- if node.id not in biomass_sids and node.is_c2_node()}
+ # TODO: biomass protected, external metabolites protected
+ # metabolites connected to protected reactions get protected
+ protected_sids = set()
+ if protected_rids is not None:
+ for rid in protected_rids:
+ if rid in self.ng.edges:
+ protected_sids |= set(self.ng.edges[rid].reactants.keys())
+ protected_sids |= set(self.ng.edges[rid].products.keys())
+
+ self.c2_sids = {node.sid: None for node in self.ng.nodes.values()
+ if node.sid not in protected_sids and node.is_c2_node()}
self.pwy_rids = {}
self.pathways = []
@@ -45,8 +57,8 @@ class LinearPathways:
def pwy_substrates(self, lin_pwy):
sids = set()
for pwy_seg in lin_pwy.segments:
- sids |= set(self.ng.edges[pwy_seg.p_rid].reactants)
- sids |= set(self.ng.edges[pwy_seg.p_rid].products)
- sids |= set(self.ng.edges[pwy_seg.c_rid].reactants)
- sids |= set(self.ng.edges[pwy_seg.c_rid].products)
+ sids |= set(self.ng.edges[pwy_seg.producing.rid].reactants.keys())
+ sids |= set(self.ng.edges[pwy_seg.producing.rid].products.keys())
+ sids |= set(self.ng.edges[pwy_seg.consuming.rid].reactants.keys())
+ sids |= set(self.ng.edges[pwy_seg.consuming.rid].products.keys())
return sids
diff --git a/modelpruner/graph/metabolite_node.py b/modelpruner/graph/metabolite_node.py
index 31db57394c1b6dfe09f133c5bec81e81a72fcb0d..df0e70427cd008ff8e062087a8d97ede9bab04fe 100644
--- a/modelpruner/graph/metabolite_node.py
+++ b/modelpruner/graph/metabolite_node.py
@@ -1,3 +1,7 @@
+"""Implementation of MetaboliteNode Class.
+
+Peter Schubert, HHU Duesseldorf, October 2022
+"""
import numpy as np
@@ -5,17 +9,17 @@ import numpy as np
class MetaboliteNode:
def __init__(self, sid):
- self.id = sid
+ self.sid = sid
self.producing_rids = {}
self.consuming_rids = {}
self.connectivity = 0
- def add_producing_rid(self, rid, reversible):
- self.producing_rids[rid] = reversible
+ def add_producing_rid(self, rid, stoic, reversible):
+ self.producing_rids[rid] = {'stoic': stoic, 'rev': reversible}
self.connectivity = len(self.producing_rids) + len(self.consuming_rids)
- def add_consuming_rid(self, rid, reversible):
- self.consuming_rids[rid] = reversible
+ def add_consuming_rid(self, rid, stoic, reversible):
+ self.consuming_rids[rid] = {'stoic': stoic, 'rev': reversible}
self.connectivity = len(self.producing_rids) + len(self.consuming_rids)
def is_c2_node(self):
@@ -23,10 +27,10 @@ class MetaboliteNode:
if len(self.producing_rids) == 1 and len(self.consuming_rids) == 1:
return True
if len(self.producing_rids) == 2:
- if bool(np.any(np.array([val for val in self.producing_rids.values()]))) is True:
+ if bool(np.any(np.array([val['rev'] for val in self.producing_rids.values()]))) is True:
return True
if len(self.consuming_rids) == 2:
- if bool(np.any(np.array([val for val in self.consuming_rids.values()]))) is True:
+ if bool(np.any(np.array([val['rev'] for val in self.consuming_rids.values()]))) is True:
return True
elif self.connectivity == 1: # blocked metabolite
return True
diff --git a/modelpruner/graph/network_graph.py b/modelpruner/graph/network_graph.py
index 5e2e0ba10491179f5ce5b577abd565080c95e9a7..323805e3adb49e526d5539d92695d7184706cbbf 100644
--- a/modelpruner/graph/network_graph.py
+++ b/modelpruner/graph/network_graph.py
@@ -1,6 +1,6 @@
-"""
+"""Implementation of NetworkGraph Class.
-Peter Schubert, October 2022
+Peter Schubert, HHU Duesseldorf, October 2022
"""
from modelpruner.graph.metabolite_node import MetaboliteNode
@@ -25,8 +25,8 @@ class NetworkGraph:
rid = fba_model.rids[col]
reversible = bool(fba_model.reversible[col])
if stoic > 0:
- self.edges[rid].add_product(sid)
- self.nodes[sid].add_producing_rid(rid, reversible)
+ self.edges[rid].add_product(sid, stoic)
+ self.nodes[sid].add_producing_rid(rid, stoic, reversible)
else:
- self.edges[rid].add_reactant(sid)
- self.nodes[sid].add_consuming_rid(rid, reversible)
+ self.edges[rid].add_reactant(sid, -stoic)
+ self.nodes[sid].add_consuming_rid(rid, -stoic, reversible)
diff --git a/modelpruner/graph/pathway_segment.py b/modelpruner/graph/pathway_segment.py
index 34217f1ec17c003ec7eccb1b11f517ee89a47cf4..d5a1414ad53642c97fe2d03b2ba94ec423c16dad 100644
--- a/modelpruner/graph/pathway_segment.py
+++ b/modelpruner/graph/pathway_segment.py
@@ -1,27 +1,38 @@
+"""Implementation of PathwaySegment Class.
+
+Peter Schubert, HHU Duesseldorf, October 2022
"""
-Peter Schubert, October 2022
-"""
+class ReactionLeg:
+
+ def __init__(self, rid, stoic, nb, forward):
+ self.rid = rid
+ self.stoic = stoic
+ self.nb = nb
+ self.forward = forward
class PathwaySegment:
- def __init__(self, sid):
- self.sid = sid
- self.reversible = False
- self.p_rid = None
- self.nb_us = None
- self.c_rid = None
- self.nb_ds = None
+ def __init__(self, connectivity):
+ self.sid = connectivity['sid']
+ self.reversible = connectivity.get('reversible', False)
+ self.producing = connectivity.get('producing')
+ self.consuming = connectivity.get('consuming')
- def set_upstream(self, rid, sid):
- self.p_rid = rid
- self.nb_us = sid
+ def set_producing(self, reaction_leg):
+ """Set the producing reaction leg.
- def set_downstream(self, rid, sid):
- self.c_rid = rid
- self.nb_ds = sid
+ A reversible 'consuming' reaction can be a producing reaction
+
+ :param reaction_leg: producing reaction leg with stoic,
+ :type reaction_leg: ReactionLeg
+ """
+ self.producing = reaction_leg
+
+ def set_consuming(self, reaction_leg):
+ self.consuming = reaction_leg
def set_reversible(self, reversible):
"""Set reversible flag of pathway segment.
@@ -37,12 +48,12 @@ class PathwaySegment:
self.reversible = reversible
def reverse_direction(self):
- temp_rid = self.p_rid
- temp_sid = self.nb_us
- self.p_rid = self.c_rid
- self.nb_us = self.nb_ds
- self.c_rid = temp_rid
- self.nb_ds = temp_sid
+
+ tmp_leg = self.producing
+ self.producing = self.consuming
+ self.consuming = tmp_leg
+ self.producing.forward = not self.producing.forward
+ self.consuming.forward = not self.consuming.forward
def get_reactions(self):
"""Get the reactions connecting the pathway segments
@@ -51,8 +62,8 @@ class PathwaySegment:
:rtype: set of str
"""
rids = set()
- if self.p_rid is not None:
- rids.add(self.p_rid)
- if self.c_rid is not None:
- rids.add(self.c_rid)
+ if type(self.producing) is ReactionLeg:
+ rids.add(self.producing.rid)
+ if type(self.consuming) is ReactionLeg:
+ rids.add(self.consuming.rid)
return rids
diff --git a/modelpruner/graph/reaction_edge.py b/modelpruner/graph/reaction_edge.py
index eb235725a46c8fc3b4139c1ebeacdb5f9ce50de8..7a1ca92e0f00e393e29eb18d73acc116a25be8ce 100644
--- a/modelpruner/graph/reaction_edge.py
+++ b/modelpruner/graph/reaction_edge.py
@@ -1,15 +1,20 @@
+"""Implementation of ReactionEdge Class.
+
+Peter Schubert, HHU Duesseldorf, October 2022
+"""
+
class ReactionEdge:
def __init__(self, rid, reversible):
- self.id = rid
+ self.rid = rid
self.reversible = reversible
- self.reactants = set()
- self.products = set()
+ self.reactants = {}
+ self.products = {}
- def add_product(self, sid):
- self.products.add(sid)
+ def add_product(self, sid, stoic):
+ self.products[sid] = stoic
- def add_reactant(self, sid):
- self.reactants.add(sid)
+ def add_reactant(self, sid, stoic):
+ self.reactants[sid] = stoic
diff --git a/sample_data/SBML_models/Deniz_model_fba_reduced.xml b/sample_data/SBML_models/Deniz_model_fba_reduced.xml
new file mode 100644
index 0000000000000000000000000000000000000000..726739323635c88cbf3db6172abc69b34d94eeee
--- /dev/null
+++ b/sample_data/SBML_models/Deniz_model_fba_reduced.xml
@@ -0,0 +1,564 @@
+<?xml version="1.0" encoding="UTF-8"?>
+<!-- Created by sbmlxdf version 0.2.7 on 2022-07-25 13:58 with libSBML version 5.19.5. -->
+<sbml xmlns="http://www.sbml.org/sbml/level3/version2/core" xmlns:fbc="http://www.sbml.org/sbml/level3/version1/fbc/version2" xmlns:groups="http://www.sbml.org/sbml/level3/version1/groups/version1" level="3" version="2" fbc:required="false" groups:required="false">
+ <model metaid="Deniz_model_fba_pruned" id="Deniz_model_fba_pruned" name="Deniz_model_fba_pruned" substanceUnits="substance" timeUnits="time" extentUnits="substance" fbc:strict="true">
+ <notes>
+ <body xmlns="http://www.w3.org/1999/xhtml">
+ <h2>FBA model based on Deinz's model 11_12, presented Nov. 2020. </h2>
+ <p> including biomass reaction, external metabolites, ATPM maintenance reaction, oxidative and fermenative phenotypes</p>
+ <p>Based on Deniz Sezer </p>
+ </body>
+ </notes>
+ <annotation>
+ <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:vCard4="http://www.w3.org/2006/vcard/ns#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
+ <rdf:Description rdf:about="#Deniz_model_fba_pruned">
+ <dcterms:creator>
+ <rdf:Bag>
+ <rdf:li rdf:parseType="Resource">
+ <vCard4:hasName rdf:parseType="Resource">
+ <vCard4:family-name>Schubert</vCard4:family-name>
+ <vCard4:given-name>Peter</vCard4:given-name>
+ </vCard4:hasName>
+ <vCard4:hasEmail>Peter.Schubert@hhu.de</vCard4:hasEmail>
+ <vCard4:organization-name>HHU-CCB</vCard4:organization-name>
+ </rdf:li>
+ </rdf:Bag>
+ </dcterms:creator>
+ <dcterms:created rdf:parseType="Resource">
+ <dcterms:W3CDTF>2022-07-18T14:55:18+02:00</dcterms:W3CDTF>
+ </dcterms:created>
+ <dcterms:modified rdf:parseType="Resource">
+ <dcterms:W3CDTF>2022-07-18T14:55:18+02:00</dcterms:W3CDTF>
+ </dcterms:modified>
+ <dcterms:modified rdf:parseType="Resource">
+ <dcterms:W3CDTF>2022-07-25T13:58:14+02:00</dcterms:W3CDTF>
+ </dcterms:modified>
+ </rdf:Description>
+ </rdf:RDF>
+ </annotation>
+ <listOfUnitDefinitions>
+ <unitDefinition id="mmol_per_gDW_per_hr" name="Millimoles per gram (dry weight) per hour">
+ <listOfUnits>
+ <unit kind="mole" exponent="1" scale="-3" multiplier="1"/>
+ <unit kind="gram" exponent="-1" scale="0" multiplier="1"/>
+ <unit kind="second" exponent="-1" scale="0" multiplier="3600"/>
+ </listOfUnits>
+ </unitDefinition>
+ <unitDefinition id="substance" name="Millimoles per gram (dry weight)">
+ <listOfUnits>
+ <unit kind="mole" exponent="1" scale="-3" multiplier="1"/>
+ <unit kind="gram" exponent="-1" scale="0" multiplier="1"/>
+ </listOfUnits>
+ </unitDefinition>
+ <unitDefinition id="time" name="Hour">
+ <listOfUnits>
+ <unit kind="second" exponent="1" scale="0" multiplier="3600"/>
+ </listOfUnits>
+ </unitDefinition>
+ </listOfUnitDefinitions>
+ <listOfCompartments>
+ <compartment id="c" name="cytosol" spatialDimensions="3" size="1e-06" units="litre" constant="true"/>
+ <compartment id="e" name="extracellular space" spatialDimensions="3" size="1" units="litre" constant="true"/>
+ </listOfCompartments>
+ <listOfSpecies>
+ <species id="M_aa_c" name="M_aa_c" compartment="c" hasOnlySubstanceUnits="false" boundaryCondition="false" constant="false"/>
+ <species id="M_accoa_c" name="M_accoa_c" compartment="c" hasOnlySubstanceUnits="false" boundaryCondition="false" constant="false"/>
+ <species id="M_adp_c" name="M_adp_c" compartment="c" hasOnlySubstanceUnits="false" boundaryCondition="false" constant="false"/>
+ <species id="M_atp_c" name="M_atp_c" compartment="c" hasOnlySubstanceUnits="false" boundaryCondition="false" constant="false"/>
+ <species id="M_co2_c" name="M_co2_c" compartment="c" hasOnlySubstanceUnits="false" boundaryCondition="false" constant="false"/>
+ <species id="M_for_c" name="M_for_c" compartment="c" hasOnlySubstanceUnits="false" boundaryCondition="false" constant="false"/>
+ <species id="M_glc__D_c" name="M_glc__D_c" compartment="c" hasOnlySubstanceUnits="false" boundaryCondition="false" constant="false"/>
+ <species id="M_lac_c" name="M_lac_c" compartment="c" hasOnlySubstanceUnits="false" boundaryCondition="false" constant="false"/>
+ <species id="M_nh4_c" name="M_nh4_c" compartment="c" hasOnlySubstanceUnits="false" boundaryCondition="false" constant="false"/>
+ <species id="M_o2_c" name="M_o2_c" compartment="c" hasOnlySubstanceUnits="false" boundaryCondition="false" constant="false"/>
+ <species id="M_co2_e" name="M_co2_e" compartment="e" hasOnlySubstanceUnits="false" boundaryCondition="false" constant="false"/>
+ <species id="M_for_e" name="M_for_e" compartment="e" hasOnlySubstanceUnits="false" boundaryCondition="false" constant="false"/>
+ <species id="M_glc__D_e" name="M_glc__D_e" compartment="e" hasOnlySubstanceUnits="false" boundaryCondition="false" constant="false">
+ <notes>
+ <body xmlns="http://www.w3.org/1999/xhtml"> main carbon source </body>
+ </notes>
+ </species>
+ <species id="M_lac_e" name="M_lac_e" compartment="e" hasOnlySubstanceUnits="false" boundaryCondition="false" constant="false"/>
+ <species id="M_nh4_e" name="M_nh4_e" compartment="e" hasOnlySubstanceUnits="false" boundaryCondition="false" constant="false"/>
+ <species id="M_o2_e" name="M_o2_e" compartment="e" hasOnlySubstanceUnits="false" boundaryCondition="false" constant="false"/>
+ <species id="M_rib_c" name="M_rib_c" compartment="c" hasOnlySubstanceUnits="false" boundaryCondition="false" constant="false"/>
+ <species id="Biomass" name="Biomass" compartment="c" hasOnlySubstanceUnits="false" boundaryCondition="false" constant="false">
+ <notes>
+ <body xmlns="http://www.w3.org/1999/xhtml"> this is a note </body>
+ </notes>
+ </species>
+ </listOfSpecies>
+ <listOfParameters>
+ <parameter id="default_lb" name="default_lb" value="-1000" units="mmol_per_gDW_per_hr" constant="true"/>
+ <parameter id="default_ub" name="default_ub" value="1000" units="mmol_per_gDW_per_hr" constant="true"/>
+ <parameter id="zero_bound" name="zero_bound" value="0" units="mmol_per_gDW_per_hr" constant="true"/>
+ <parameter id="R_EX_glc__D_e_lb" name="R_EX_glc__D_e_lb" value="-10" units="mmol_per_gDW_per_hr" constant="true"/>
+ <parameter id="R_ATPM_lb" name="R_ATPM_lb" value="3.15" units="mmol_per_gDW_per_hr" constant="true"/>
+ </listOfParameters>
+ <listOfReactions>
+ <reaction id="R_EX_co2" name="R_EX_co2" reversible="true" fbc:lowerFluxBound="default_lb" fbc:upperFluxBound="default_ub">
+ <listOfReactants>
+ <speciesReference species="M_co2_e" stoichiometry="1" constant="true"/>
+ </listOfReactants>
+ </reaction>
+ <reaction id="R_EX_for" name="R_EX_for" reversible="true" fbc:lowerFluxBound="default_lb" fbc:upperFluxBound="default_ub">
+ <listOfReactants>
+ <speciesReference species="M_for_e" stoichiometry="1" constant="true"/>
+ </listOfReactants>
+ </reaction>
+ <reaction id="R_EX_glc__D" name="R_EX_glc__D" reversible="true" fbc:lowerFluxBound="R_EX_glc__D_e_lb" fbc:upperFluxBound="default_ub">
+ <notes>
+ <body xmlns="http://www.w3.org/1999/xhtml"> carbon source transporter </body>
+ </notes>
+ <listOfReactants>
+ <speciesReference species="M_glc__D_e" stoichiometry="1" constant="true"/>
+ </listOfReactants>
+ </reaction>
+ <reaction id="R_EX_lac" name="R_EX_lac" reversible="true" fbc:lowerFluxBound="zero_bound" fbc:upperFluxBound="default_ub">
+ <listOfReactants>
+ <speciesReference species="M_lac_e" stoichiometry="1" constant="true"/>
+ </listOfReactants>
+ </reaction>
+ <reaction id="R_EX_nh4" name="R_EX_nh4" reversible="true" fbc:lowerFluxBound="default_lb" fbc:upperFluxBound="default_ub">
+ <listOfReactants>
+ <speciesReference species="M_nh4_e" stoichiometry="1" constant="true"/>
+ </listOfReactants>
+ </reaction>
+ <reaction id="R_EX_o2" name="R_EX_o2" reversible="true" fbc:lowerFluxBound="default_lb" fbc:upperFluxBound="default_ub">
+ <listOfReactants>
+ <speciesReference species="M_o2_e" stoichiometry="1" constant="true"/>
+ </listOfReactants>
+ </reaction>
+ <reaction id="R_DM_Biomass" name="R_DM_Biomass" reversible="false" fbc:lowerFluxBound="zero_bound" fbc:upperFluxBound="default_ub">
+ <listOfReactants>
+ <speciesReference species="Biomass" stoichiometry="1" constant="true"/>
+ </listOfReactants>
+ </reaction>
+ <reaction id="R_co2_tex" name="R_co2_tex" reversible="true" fbc:lowerFluxBound="default_lb" fbc:upperFluxBound="default_ub">
+ <listOfReactants>
+ <speciesReference species="M_co2_e" stoichiometry="1" constant="true"/>
+ </listOfReactants>
+ <listOfProducts>
+ <speciesReference species="M_co2_c" stoichiometry="1" constant="true"/>
+ </listOfProducts>
+ </reaction>
+ <reaction id="R_for_tex" name="R_for_tex" reversible="true" fbc:lowerFluxBound="default_lb" fbc:upperFluxBound="default_ub">
+ <listOfReactants>
+ <speciesReference species="M_for_e" stoichiometry="1" constant="true"/>
+ </listOfReactants>
+ <listOfProducts>
+ <speciesReference species="M_for_c" stoichiometry="1" constant="true"/>
+ </listOfProducts>
+ <fbc:geneProductAssociation>
+ <fbc:or>
+ <fbc:geneProductRef fbc:geneProduct="G_b1377"/>
+ <fbc:geneProductRef fbc:geneProduct="G_b0929"/>
+ </fbc:or>
+ </fbc:geneProductAssociation>
+ </reaction>
+ <reaction id="R_glc__D_tex" name="R_glc__D_tex" reversible="true" fbc:lowerFluxBound="default_lb" fbc:upperFluxBound="default_ub">
+ <listOfReactants>
+ <speciesReference species="M_glc__D_e" stoichiometry="1" constant="true"/>
+ </listOfReactants>
+ <listOfProducts>
+ <speciesReference species="M_glc__D_c" stoichiometry="1" constant="true"/>
+ </listOfProducts>
+ <fbc:geneProductAssociation>
+ <fbc:or>
+ <fbc:geneProductRef fbc:geneProduct="G_b1377"/>
+ <fbc:geneProductRef fbc:geneProduct="G_b0929"/>
+ </fbc:or>
+ </fbc:geneProductAssociation>
+ </reaction>
+ <reaction id="R_lac_tex" name="R_lac_tex" reversible="true" fbc:lowerFluxBound="default_lb" fbc:upperFluxBound="default_ub">
+ <listOfReactants>
+ <speciesReference species="M_lac_e" stoichiometry="1" constant="true"/>
+ </listOfReactants>
+ <listOfProducts>
+ <speciesReference species="M_lac_c" stoichiometry="1" constant="true"/>
+ </listOfProducts>
+ <fbc:geneProductAssociation>
+ <fbc:or>
+ <fbc:and>
+ <fbc:geneProductRef fbc:geneProduct="G_b3670"/>
+ <fbc:geneProductRef fbc:geneProduct="G_b3671"/>
+ </fbc:and>
+ <fbc:and>
+ <fbc:geneProductRef fbc:geneProduct="G_b0077"/>
+ <fbc:geneProductRef fbc:geneProduct="G_b0078"/>
+ </fbc:and>
+ </fbc:or>
+ </fbc:geneProductAssociation>
+ </reaction>
+ <reaction id="R_nh4_imp" name="R_nh4_imp" reversible="false" fbc:lowerFluxBound="zero_bound" fbc:upperFluxBound="default_ub">
+ <listOfReactants>
+ <speciesReference species="M_nh4_e" stoichiometry="1" constant="true"/>
+ </listOfReactants>
+ <listOfProducts>
+ <speciesReference species="M_nh4_c" stoichiometry="1" constant="true"/>
+ </listOfProducts>
+ <fbc:geneProductAssociation>
+ <fbc:geneProductRef fbc:geneProduct="G_b1377"/>
+ </fbc:geneProductAssociation>
+ </reaction>
+ <reaction id="R_o2_tex" name="R_o2_tex" reversible="true" fbc:lowerFluxBound="default_lb" fbc:upperFluxBound="default_ub">
+ <listOfReactants>
+ <speciesReference species="M_o2_e" stoichiometry="1" constant="true"/>
+ </listOfReactants>
+ <listOfProducts>
+ <speciesReference species="M_o2_c" stoichiometry="1" constant="true"/>
+ </listOfProducts>
+ <fbc:geneProductAssociation>
+ <fbc:geneProductRef fbc:geneProduct="G_b2215"/>
+ </fbc:geneProductAssociation>
+ </reaction>
+ <reaction id="R_mr2" name="R_mr2" reversible="false" fbc:lowerFluxBound="zero_bound" fbc:upperFluxBound="default_ub">
+ <listOfReactants>
+ <speciesReference species="M_glc__D_c" stoichiometry="1" constant="true"/>
+ </listOfReactants>
+ <listOfProducts>
+ <speciesReference species="M_accoa_c" stoichiometry="3" constant="true"/>
+ </listOfProducts>
+ <fbc:geneProductAssociation>
+ <fbc:geneProductRef fbc:geneProduct="G_b0929"/>
+ </fbc:geneProductAssociation>
+ </reaction>
+ <reaction id="R_ppp1" name="R_ppp1" reversible="false" fbc:lowerFluxBound="zero_bound" fbc:upperFluxBound="default_ub">
+ <listOfReactants>
+ <speciesReference species="M_glc__D_c" stoichiometry="1" constant="true"/>
+ </listOfReactants>
+ <listOfProducts>
+ <speciesReference species="M_rib_c" stoichiometry="1" constant="true"/>
+ </listOfProducts>
+ <fbc:geneProductAssociation>
+ <fbc:geneProductRef fbc:geneProduct="G_b0241"/>
+ </fbc:geneProductAssociation>
+ </reaction>
+ <reaction id="R_mrOx" name="R_mrOx" reversible="false" fbc:lowerFluxBound="zero_bound" fbc:upperFluxBound="default_ub">
+ <listOfReactants>
+ <speciesReference species="M_accoa_c" stoichiometry="1" constant="true"/>
+ <speciesReference species="M_adp_c" stoichiometry="4" constant="true"/>
+ <speciesReference species="M_o2_c" stoichiometry="2" constant="true"/>
+ </listOfReactants>
+ <listOfProducts>
+ <speciesReference species="M_atp_c" stoichiometry="4" constant="true"/>
+ <speciesReference species="M_co2_c" stoichiometry="2" constant="true"/>
+ </listOfProducts>
+ <fbc:geneProductAssociation>
+ <fbc:geneProductRef fbc:geneProduct="G_b4033"/>
+ </fbc:geneProductAssociation>
+ </reaction>
+ <reaction id="R_mrFerm" name="R_mrFerm" reversible="false" fbc:lowerFluxBound="zero_bound" fbc:upperFluxBound="default_ub">
+ <listOfReactants>
+ <speciesReference species="M_accoa_c" stoichiometry="1" constant="true"/>
+ <speciesReference species="M_adp_c" stoichiometry="2" constant="true"/>
+ </listOfReactants>
+ <listOfProducts>
+ <speciesReference species="M_atp_c" stoichiometry="2" constant="true"/>
+ <speciesReference species="M_for_c" stoichiometry="1" constant="true"/>
+ </listOfProducts>
+ <fbc:geneProductAssociation>
+ <fbc:geneProductRef fbc:geneProduct="G_b4032"/>
+ </fbc:geneProductAssociation>
+ </reaction>
+ <reaction id="R_mr9" name="R_mr9" reversible="false" fbc:lowerFluxBound="zero_bound" fbc:upperFluxBound="default_ub">
+ <listOfReactants>
+ <speciesReference species="M_lac_c" stoichiometry="1" constant="true"/>
+ </listOfReactants>
+ <listOfProducts>
+ <speciesReference species="M_glc__D_c" stoichiometry="1" constant="true"/>
+ </listOfProducts>
+ <fbc:geneProductAssociation>
+ <fbc:geneProductRef fbc:geneProduct="G_b4213"/>
+ </fbc:geneProductAssociation>
+ </reaction>
+ <reaction id="R_mr11" name="R_mr11" reversible="true" fbc:lowerFluxBound="default_lb" fbc:upperFluxBound="default_ub">
+ <listOfReactants>
+ <speciesReference species="M_aa_c" stoichiometry="1" constant="true"/>
+ <speciesReference species="M_adp_c" stoichiometry="1" constant="true"/>
+ </listOfReactants>
+ <listOfProducts>
+ <speciesReference species="M_accoa_c" stoichiometry="3" constant="true"/>
+ <speciesReference species="M_nh4_c" stoichiometry="1" constant="true"/>
+ <speciesReference species="M_atp_c" stoichiometry="1" constant="true"/>
+ </listOfProducts>
+ <fbc:geneProductAssociation>
+ <fbc:geneProductRef fbc:geneProduct="G_b2835"/>
+ </fbc:geneProductAssociation>
+ </reaction>
+ <reaction id="R_ATPM" name="R_ATPM" reversible="false" fbc:lowerFluxBound="R_ATPM_lb" fbc:upperFluxBound="default_ub">
+ <listOfReactants>
+ <speciesReference species="M_atp_c" stoichiometry="1" constant="true"/>
+ </listOfReactants>
+ <listOfProducts>
+ <speciesReference species="M_adp_c" stoichiometry="1" constant="true"/>
+ </listOfProducts>
+ <fbc:geneProductAssociation>
+ <fbc:geneProductRef fbc:geneProduct="G_b2836"/>
+ </fbc:geneProductAssociation>
+ </reaction>
+ <reaction id="R_Biomass_core" name="R_Biomass_core" reversible="false" fbc:lowerFluxBound="zero_bound" fbc:upperFluxBound="default_ub">
+ <notes>
+ <body xmlns="http://www.w3.org/1999/xhtml"> biomass reaction </body>
+ </notes>
+ <listOfReactants>
+ <speciesReference species="M_aa_c" stoichiometry="1" constant="true"/>
+ <speciesReference species="M_atp_c" stoichiometry="3" constant="true"/>
+ </listOfReactants>
+ <listOfProducts>
+ <speciesReference species="M_adp_c" stoichiometry="3" constant="true"/>
+ <speciesReference species="Biomass" stoichiometry="1" constant="true"/>
+ </listOfProducts>
+ </reaction>
+ </listOfReactions>
+ <fbc:listOfObjectives fbc:activeObjective="obj">
+ <fbc:objective fbc:id="obj" fbc:type="maximize">
+ <fbc:listOfFluxObjectives>
+ <fbc:fluxObjective fbc:reaction="R_Biomass_core" fbc:coefficient="1"/>
+ </fbc:listOfFluxObjectives>
+ </fbc:objective>
+ </fbc:listOfObjectives>
+ <fbc:listOfGeneProducts>
+ <fbc:geneProduct metaid="G_b4033" fbc:id="G_b4033" fbc:label="b4033">
+ <annotation>
+ <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:vCard4="http://www.w3.org/2006/vcard/ns#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
+ <rdf:Description rdf:about="#G_b4033">
+ <bqbiol:is>
+ <rdf:Bag>
+ <rdf:li rdf:resource="http://identifiers.org/uniprot/P02916"/>
+ </rdf:Bag>
+ </bqbiol:is>
+ <bqbiol:isEncodedBy>
+ <rdf:Bag>
+ <rdf:li rdf:resource="http://identifiers.org/asap/ABE-0013195"/>
+ <rdf:li rdf:resource="http://identifiers.org/ecogene/EG10555"/>
+ <rdf:li rdf:resource="http://identifiers.org/ncbigene/948532"/>
+ <rdf:li rdf:resource="http://identifiers.org/ncbigi/gi:16131859"/>
+ </rdf:Bag>
+ </bqbiol:isEncodedBy>
+ </rdf:Description>
+ </rdf:RDF>
+ </annotation>
+ </fbc:geneProduct>
+ <fbc:geneProduct metaid="G_b0241" fbc:id="G_b0241" fbc:label="b0241">
+ <annotation>
+ <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:vCard4="http://www.w3.org/2006/vcard/ns#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
+ <rdf:Description rdf:about="#G_b0241">
+ <bqbiol:is>
+ <rdf:Bag>
+ <rdf:li rdf:resource="http://identifiers.org/uniprot/P02932"/>
+ </rdf:Bag>
+ </bqbiol:is>
+ <bqbiol:isEncodedBy>
+ <rdf:Bag>
+ <rdf:li rdf:resource="http://identifiers.org/asap/ABE-0000823"/>
+ <rdf:li rdf:resource="http://identifiers.org/ecogene/EG10729"/>
+ <rdf:li rdf:resource="http://identifiers.org/ncbigene/944926"/>
+ <rdf:li rdf:resource="http://identifiers.org/ncbigi/gi:16128227"/>
+ </rdf:Bag>
+ </bqbiol:isEncodedBy>
+ </rdf:Description>
+ </rdf:RDF>
+ </annotation>
+ </fbc:geneProduct>
+ <fbc:geneProduct metaid="G_b2215" fbc:id="G_b2215" fbc:label="b2215">
+ <annotation>
+ <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:vCard4="http://www.w3.org/2006/vcard/ns#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
+ <rdf:Description rdf:about="#G_b2215">
+ <bqbiol:is>
+ <rdf:Bag>
+ <rdf:li rdf:resource="http://identifiers.org/uniprot/P06996"/>
+ </rdf:Bag>
+ </bqbiol:is>
+ <bqbiol:isEncodedBy>
+ <rdf:Bag>
+ <rdf:li rdf:resource="http://identifiers.org/asap/ABE-0007321"/>
+ <rdf:li rdf:resource="http://identifiers.org/ecogene/EG10670"/>
+ <rdf:li rdf:resource="http://identifiers.org/ncbigene/946716"/>
+ <rdf:li rdf:resource="http://identifiers.org/ncbigi/gi:16130152"/>
+ </rdf:Bag>
+ </bqbiol:isEncodedBy>
+ </rdf:Description>
+ </rdf:RDF>
+ </annotation>
+ </fbc:geneProduct>
+ <fbc:geneProduct metaid="G_b2836" fbc:id="G_b2836" fbc:label="b2836">
+ <annotation>
+ <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:vCard4="http://www.w3.org/2006/vcard/ns#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
+ <rdf:Description rdf:about="#G_b2836">
+ <bqbiol:is>
+ <rdf:Bag>
+ <rdf:li rdf:resource="http://identifiers.org/uniprot/P31119"/>
+ </rdf:Bag>
+ </bqbiol:is>
+ <bqbiol:isEncodedBy>
+ <rdf:Bag>
+ <rdf:li rdf:resource="http://identifiers.org/asap/ABE-0009302"/>
+ <rdf:li rdf:resource="http://identifiers.org/ecogene/EG11679"/>
+ <rdf:li rdf:resource="http://identifiers.org/ncbigene/947315"/>
+ <rdf:li rdf:resource="http://identifiers.org/ncbigi/gi:16130740"/>
+ </rdf:Bag>
+ </bqbiol:isEncodedBy>
+ </rdf:Description>
+ </rdf:RDF>
+ </annotation>
+ </fbc:geneProduct>
+ <fbc:geneProduct metaid="G_b0077" fbc:id="G_b0077" fbc:label="b0077"/>
+ <fbc:geneProduct metaid="G_b3671" fbc:id="G_b3671" fbc:label="b3671"/>
+ <fbc:geneProduct metaid="G_b3670" fbc:id="G_b3670" fbc:label="b3670"/>
+ <fbc:geneProduct metaid="G_b0929" fbc:id="G_b0929" fbc:label="b0929">
+ <annotation>
+ <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:vCard4="http://www.w3.org/2006/vcard/ns#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
+ <rdf:Description rdf:about="#G_b0929">
+ <bqbiol:is>
+ <rdf:Bag>
+ <rdf:li rdf:resource="http://identifiers.org/uniprot/P02931"/>
+ </rdf:Bag>
+ </bqbiol:is>
+ <bqbiol:isEncodedBy>
+ <rdf:Bag>
+ <rdf:li rdf:resource="http://identifiers.org/asap/ABE-0003153"/>
+ <rdf:li rdf:resource="http://identifiers.org/ecogene/EG10671"/>
+ <rdf:li rdf:resource="http://identifiers.org/ncbigene/945554"/>
+ <rdf:li rdf:resource="http://identifiers.org/ncbigi/gi:16128896"/>
+ </rdf:Bag>
+ </bqbiol:isEncodedBy>
+ </rdf:Description>
+ </rdf:RDF>
+ </annotation>
+ </fbc:geneProduct>
+ <fbc:geneProduct metaid="G_b4213" fbc:id="G_b4213" fbc:label="b4213">
+ <annotation>
+ <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:vCard4="http://www.w3.org/2006/vcard/ns#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
+ <rdf:Description rdf:about="#G_b4213">
+ <bqbiol:is>
+ <rdf:Bag>
+ <rdf:li rdf:resource="http://identifiers.org/uniprot/P08331"/>
+ </rdf:Bag>
+ </bqbiol:is>
+ <bqbiol:isEncodedBy>
+ <rdf:Bag>
+ <rdf:li rdf:resource="http://identifiers.org/asap/ABE-0013782"/>
+ <rdf:li rdf:resource="http://identifiers.org/ecogene/EG10160"/>
+ <rdf:li rdf:resource="http://identifiers.org/ncbigene/948729"/>
+ <rdf:li rdf:resource="http://identifiers.org/ncbigi/gi:16132035"/>
+ </rdf:Bag>
+ </bqbiol:isEncodedBy>
+ </rdf:Description>
+ </rdf:RDF>
+ </annotation>
+ </fbc:geneProduct>
+ <fbc:geneProduct metaid="G_b1377" fbc:id="G_b1377" fbc:label="b1377">
+ <annotation>
+ <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:vCard4="http://www.w3.org/2006/vcard/ns#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
+ <rdf:Description rdf:about="#G_b1377">
+ <bqbiol:is>
+ <rdf:Bag>
+ <rdf:li rdf:resource="http://identifiers.org/uniprot/P77747"/>
+ </rdf:Bag>
+ </bqbiol:is>
+ <bqbiol:isEncodedBy>
+ <rdf:Bag>
+ <rdf:li rdf:resource="http://identifiers.org/asap/ABE-0004608"/>
+ <rdf:li rdf:resource="http://identifiers.org/ecogene/EG13375"/>
+ <rdf:li rdf:resource="http://identifiers.org/ncbigene/946313"/>
+ <rdf:li rdf:resource="http://identifiers.org/ncbigi/gi:16129338"/>
+ </rdf:Bag>
+ </bqbiol:isEncodedBy>
+ </rdf:Description>
+ </rdf:RDF>
+ </annotation>
+ </fbc:geneProduct>
+ <fbc:geneProduct metaid="G_b0078" fbc:id="G_b0078" fbc:label="b0078"/>
+ <fbc:geneProduct metaid="G_b4032" fbc:id="G_b4032" fbc:label="b4032">
+ <annotation>
+ <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:vCard4="http://www.w3.org/2006/vcard/ns#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
+ <rdf:Description rdf:about="#G_b4032">
+ <bqbiol:is>
+ <rdf:Bag>
+ <rdf:li rdf:resource="http://identifiers.org/uniprot/P68183"/>
+ </rdf:Bag>
+ </bqbiol:is>
+ <bqbiol:isEncodedBy>
+ <rdf:Bag>
+ <rdf:li rdf:resource="http://identifiers.org/asap/ABE-0013193"/>
+ <rdf:li rdf:resource="http://identifiers.org/ecogene/EG10556"/>
+ <rdf:li rdf:resource="http://identifiers.org/ncbigene/948530"/>
+ <rdf:li rdf:resource="http://identifiers.org/ncbigi/gi:16131858"/>
+ </rdf:Bag>
+ </bqbiol:isEncodedBy>
+ </rdf:Description>
+ </rdf:RDF>
+ </annotation>
+ </fbc:geneProduct>
+ <fbc:geneProduct metaid="G_b2835" fbc:id="G_b2835" fbc:label="b2835">
+ <annotation>
+ <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:vCard4="http://www.w3.org/2006/vcard/ns#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
+ <rdf:Description rdf:about="#G_b2835">
+ <bqbiol:is>
+ <rdf:Bag>
+ <rdf:li rdf:resource="http://identifiers.org/uniprot/P39196"/>
+ </rdf:Bag>
+ </bqbiol:is>
+ <bqbiol:isEncodedBy>
+ <rdf:Bag>
+ <rdf:li rdf:resource="http://identifiers.org/asap/ABE-0009300"/>
+ <rdf:li rdf:resource="http://identifiers.org/ecogene/EG12455"/>
+ <rdf:li rdf:resource="http://identifiers.org/ncbigene/947317"/>
+ <rdf:li rdf:resource="http://identifiers.org/ncbigi/gi:16130739"/>
+ </rdf:Bag>
+ </bqbiol:isEncodedBy>
+ </rdf:Description>
+ </rdf:RDF>
+ </annotation>
+ </fbc:geneProduct>
+ </fbc:listOfGeneProducts>
+ <groups:listOfGroups>
+ <groups:group groups:id="g1" groups:name="Carbon metabolism" groups:kind="partonomy">
+ <groups:listOfMembers>
+ <groups:member groups:idRef="R_mr2"/>
+ <groups:member groups:idRef="R_mr9"/>
+ <groups:member groups:idRef="R_mr11"/>
+ </groups:listOfMembers>
+ </groups:group>
+ <groups:group groups:id="g2" groups:name="Fermentation" groups:kind="partonomy">
+ <groups:listOfMembers>
+ <groups:member groups:idRef="R_mrFerm"/>
+ </groups:listOfMembers>
+ </groups:group>
+ <groups:group groups:id="g3" groups:name="Maintenance" groups:kind="partonomy">
+ <groups:listOfMembers>
+ <groups:member groups:idRef="R_ATPM"/>
+ </groups:listOfMembers>
+ </groups:group>
+ <groups:group groups:id="g4" groups:name="Oxidative Phosphorylation" groups:kind="partonomy">
+ <groups:listOfMembers>
+ <groups:member groups:idRef="R_mrOx"/>
+ </groups:listOfMembers>
+ </groups:group>
+ <groups:group groups:id="g5" groups:name="Glucolysis" groups:kind="partonomy">
+ <groups:listOfMembers>
+ <groups:member groups:idRef="R_mr2"/>
+ </groups:listOfMembers>
+ </groups:group>
+ <groups:group groups:id="g6" groups:name="Pentose Phosphate Pathway" groups:kind="partonomy">
+ <groups:listOfMembers>
+ <groups:member groups:idRef="R_ppp1"/>
+ </groups:listOfMembers>
+ </groups:group>
+ <groups:group groups:id="g7" groups:name="Transporter" groups:kind="partonomy">
+ <groups:listOfMembers>
+ <groups:member groups:idRef="R_co2_tex"/>
+ <groups:member groups:idRef="R_glc__D_tex"/>
+ <groups:member groups:idRef="R_lac_tex"/>
+ <groups:member groups:idRef="R_o2_tex"/>
+ </groups:listOfMembers>
+ </groups:group>
+ <groups:group groups:id="g9" groups:name="Transport, Importer" groups:kind="partonomy">
+ <groups:listOfMembers>
+ <groups:member groups:idRef="R_nh4_imp"/>
+ </groups:listOfMembers>
+ </groups:group>
+ </groups:listOfGroups>
+ </model>
+</sbml>