def test_complicated_site_actor(self):
m = Modification(enzyme=SiteActor(protoform=Protoform(
"P00519",
sites=[Site(name="bob", start=120, end=150)],
regions=[Region(name="alice", start=100, end=200)],
residues=[Residue("Y", 122)]),
site=Site(name="jack",
start=550,
end=600,
residues=[Residue("T")]),
region=Region(
name="Pkinase",
start=500,
end=800,
sites=[Site(name="billy")])),
substrate=SiteActor(protoform=Protoform("P00533"),
site=Site(name="target"),
region=Region(name="bla")),
target=Residue("Y", 100,
State("phosphorylation", False)),
value=True)
corpus = KamiCorpus("test")
corpus.add_interactions([m], anatomize=True)
print_graph(corpus.get_nugget("test_nugget_1"))
print(ag_to_edge_list(corpus))
def test_regionactor(self):
# Phosphorylated and unphosphrylated states.
phos = State("phosphorylation", True)
unphos = State("phosphorylation", False)
inters = []
# Phosphorylation with RegionActor as substrate.
m = Modification(enzyme=Protoform("P00519"),
substrate=RegionActor(
Protoform("P00533",
regions=[
Region(name='PVPEyINQS',
start=280,
end=290),
Region(name="L receptor",
start=57,
end=167,
states=[phos])
]), Region(start=1000, end=1500)),
target=Residue(aa="Y", loc=1092, state=unphos),
value=True)
inters.append(m)
corpus = KamiCorpus("test")
corpus.add_interactions(inters, anatomize=True)
print_graph(corpus.get_nugget("test_nugget_1"))
def test_siteactor(self):
"""Generate sh2 pY bnd interactions."""
# General phosphorylation state.
phos = State("phosphorylation", True)
unphos = State("phosphorylation", False)
# General SH2 regions.
sh2 = Region(name="SH2")
sh2n = Region(name="SH2", order=1)
sh2c = Region(name="SH2", order=2)
inters = []
enz_uniprot = 'P00519'
sub_uniprot = 'P00533'
rsd = 'Y1092'
location = int(rsd[1:])
strt = location - 4
stop = location + 4
site_name = 'b%i' % location
m = Modification(enzyme=Protoform(enz_uniprot),
substrate=SiteActor(protoform=Protoform(sub_uniprot),
site=Site(name=site_name,
start=strt,
end=stop)),
target=Residue(aa="Y", loc=location, state=unphos),
value=True)
inters.append(m)
corpus = KamiCorpus("test")
corpus.add_interactions(inters, anatomize=True)
def test_non_empty_hierarchy(self):
"""."""
model = KamiCorpus("test")
plcg1_pY1253 = Protoform("P19174",
synonyms=["PLCG1"],
residues=[
Residue("Y",
1253,
state=State(
"phosphorylation", True))
])
sh2 = Region(name="SH2")
abl1 = Protoform("P00519", synonyms=["ABL1"])
abl1_sh2 = RegionActor(abl1, sh2)
bnd = Binding(plcg1_pY1253, abl1_sh2)
model.add_interactions([bnd], model)
assert (model.empty() is False)
model.export_json("test_non_empty_hierarchy.json")
new_model = KamiCorpus.load_json("test",
"test_non_empty_hierarchy.json")
assert (isinstance(new_model, KamiCorpus))
assert (("test_action_graph", "meta_model")
in new_model._hierarchy.edges())
def test_advanced_site_actor(self):
# General phosphorylation state.
phos = State("phosphorylation", True)
unphos = State("phosphorylation", False)
# General SH2 regions.
sh2 = Region(name="SH2")
sh2n = Region(name="SH2", order=1)
sh2c = Region(name="SH2", order=2)
# Test site.
s1 = Site(name="test_site")
inters = []
# Modification using SiteActor.
m = Modification(enzyme=Protoform("P00519", hgnc_symbol="ABL1"),
substrate=SiteActor(protoform=Protoform(
"P00519", hgnc_symbol="ABL1"),
site=Site(name="site800",
start=796,
end=804)),
target=Residue("Y", 800,
State("phosphorylation", False)),
value=True)
inters.append(m)
m = Modification(enzyme=Protoform("P00519", hgnc_symbol="ABL1"),
substrate=SiteActor(protoform=Protoform(
"P00533", hgnc_symbol="EGFR"),
site=Site(name="site800",
start=796,
end=804)),
target=Residue("Y", 800,
State("phosphorylation", False)),
value=True)
inters.append(m)
# Binding using SiteActor.
b = Binding(
SiteActor(protoform=Protoform("P00533", hgnc_symbol="EGFR"),
site=Site(name="site800", start=796, end=804)),
RegionActor(protoform=Protoform("P62993", hgnc_symbol="GRB2"),
region=sh2))
inters.append(b)
corpus = KamiCorpus("test")
corpus.add_interactions(inters, anatomize=True)
def test_sites(self):
# Create genes.
egfr = Protoform("P00533")
grb2 = Protoform("P62993")
# Create a RegionActor and a SiteActor fo GRB2.
grb2_sh2 = RegionActor(protoform=grb2, region=Region(name="SH2"))
grb2_site = SiteActor(protoform=grb2, site=Site(name="pY"))
inters = []
# This works (RegionActor).
# inters.append(BinaryBinding([egfr], [grb2_sh2]))
# This does not work (SiteActor)
inters.append(Binding(egfr, grb2_site))
corpus = KamiCorpus("test")
corpus.add_interactions(inters, anatomize=True)
print_graph(corpus.get_nugget("test_nugget_1"))
def test_bookkeeping(self):
interactions = []
i1 = LigandModification(
RegionActor(Protoform("P00533"), Region(start=712, end=979)),
Protoform("P00533"),
Residue("Y", 1092, state=State("phosphorylation", False)))
interactions.append(i1)
i2 = Modification(
Protoform("P00519"), Protoform("P00533"),
Residue("S", 800, state=State("phosphorylation", False)))
interactions.append(i2)
i3 = Binding(Protoform("P00424"),
SiteActor(Protoform("P00533"), Site(start=799, end=900)))
interactions.append(i3)
corpus = KamiCorpus("test")
corpus.add_interactions(interactions)
def test_multiple_sh2(self):
"""."""
phos = State("phosphorylation", True)
sh2n = Region(name="SH2", order=1)
sh2c = Region(name="SH2", order=2)
pik3r1 = Protoform("P27986", synonyms=["PIK3R1", "PI3K1"])
pik3r1_sh2n = RegionActor(pik3r1, sh2n)
pik3r1_sh2c = RegionActor(pik3r1, sh2c)
frs2_py196 = Protoform("Q8WU20",
synonyms=["FRS2"],
residues=[Residue("Y", 196, phos)])
frs2_py349 = Protoform("Q8WU20",
synonyms=["FRS2"],
residues=[Residue("Y", 349, phos)])
bnds = []
bnds.append(Binding(frs2_py196, pik3r1_sh2n))
bnds.append(Binding(frs2_py349, pik3r1_sh2c))
corpus = KamiCorpus("test")
corpus.add_interactions(bnds, anatomize=True)
def test_phospho_semantics(self):
"""Test black box processing using phosphorylation semantics."""
mek1 = Protoform("Q02750")
stat3 = Protoform("P40763")
mod_state = Residue("S", 727, State("phosphorylation", False))
value = True
mod1 = Modification(mek1, stat3, mod_state, value)
mod_state_1 = Residue("Y", 705, State("phosphorylation", False))
mod2 = Modification(mek1, stat3, mod_state_1, value)
erk1 = Protoform("P27361")
mod_state_2 = Residue("T", 201, State("phosphorylation", False))
mod3 = Modification(mek1, erk1, mod_state_2, value)
erk2 = Protoform("P28482")
mod_state_3 = Residue("T", 182, State("phosphorylation", False))
mod4 = Modification(mek1, erk2, mod_state_3, value)
interactions = [mod1, mod2, mod3, mod4]
corpus = KamiCorpus("test")
corpus.add_interactions(interactions, add_agents=True, anatomize=True)
print(corpus.action_graph.nodes())
print(
corpus._hierarchy.get_relation("test_action_graph",
"semantic_action_graph"))
print(corpus)
print_graph(corpus.action_graph)
print(
corpus._hierarchy.get_relation("test_action_graph",
"semantic_action_graph"))
class TestKamiQL:
"""Unit tests for KamiQL."""
def __init__(self):
"""Initialize tests."""
# Create an empty KAMI corpus
self.nxcorpus = KamiCorpus("EGFR_signalling")
try:
h = Neo4jHierarchy(uri="bolt://localhost:7687",
user="******",
password="******")
h._clear()
self.neo4jcorpus = KamiCorpus("egfr",
backend="neo4j",
uri="bolt://localhost:7687",
user="******",
password="******")
except:
warnings.warn("Neo4j is down, skipping Neo4j-related tests")
self.neo4jcorpus = None
# Create an interaction object
egfr = Protoform("P00533")
egf = Protoform("P01133")
kinase = Region(name="Protein kinase",
start=712,
end=979,
states=[State("activity", True)])
egfr_kinase = RegionActor(protoform=egfr, region=kinase)
interaction1 = LigandModification(
enzyme=egfr_kinase,
substrate=egfr,
target=Residue("Y", 1092, state=State("phosphorylation", False)),
value=True,
rate=1,
desc="Phosphorylation of EGFR homodimer")
# Aggregate the interaction object to the corpus
self.nxcorpus.add_interaction(interaction1)
self.neo4jcorpus.add_interaction(interaction1)
grb2 = Protoform("P62993", states=[State("activity", True)])
grb2_sh2 = RegionActor(protoform=grb2, region=Region(name="SH2"))
shc1 = Protoform("P29353")
shc1_pY = SiteActor(
protoform=shc1,
site=Site(
name="pY",
residues=[Residue("Y", 317, State("phosphorylation", True))]))
interaction1 = Binding(grb2_sh2, shc1_pY)
grb2_sh2_with_residues = RegionActor(protoform=grb2,
region=Region(
name="SH2",
residues=[
Residue("S",
90,
test=True),
Residue("D",
90,
test=False)
]))
egfr_pY = SiteActor(
protoform=egfr,
site=Site(
name="pY",
residues=[Residue("Y", 1092, State("phosphorylation", True))]))
interaction2 = Binding(grb2_sh2_with_residues, egfr_pY)
axl_PK = RegionActor(protoform=Protoform("P30530", hgnc_symbol="AXL"),
region=Region("Protein kinase",
start=536,
end=807))
interaction3 = SelfModification(axl_PK,
target=Residue(
"Y", 821,
State("phosphorylation", False)),
value=True)
interaction4 = AnonymousModification(RegionActor(protoform=Protoform(
"P30530",
hgnc_symbol="AXL",
residues=[
Residue("Y", 703, state=State("phosphorylation", True)),
Residue("Y", 779, state=State("phosphorylation", True))
]),
region=Region(
"Protein kinase",
start=536,
end=807)),
target=State("activity", False),
value=True)
egf_egfr = Protoform(egfr.uniprotid, bound_to=[egf])
interaction5 = Binding(egf_egfr, egf_egfr)
interaction6 = Unbinding(egf_egfr, egf_egfr)
interaction7 = LigandModification(
egfr_kinase,
shc1,
target=Residue("Y", 317, State("phosphorylation", False)),
value=True,
enzyme_bnd_region=Region("egfr_BND"),
enzyme_bnd_site=Site("egfr_BND"),
substrate_bnd_region=Region("shc1_BND"),
substrate_bnd_site=Site("sch1_BND"))
interactions = [
interaction1, interaction2, interaction3, interaction4,
interaction5, interaction6, interaction7
]
self.nxcorpus.add_interactions(interactions)
self.neo4jcorpus.add_interactions(interactions)
# Create a protein definition for GRB2
# protoform = Protoform(
# "P62993",
# regions=[Region(
# name="SH2",
# residues=[
# Residue("S", 90, test=True),
# Residue("D", 90, test=False)])])
# ashl = Product("Ash-L", residues=[Residue("S", 90)])
# s90d = Product("S90D", residues=[Residue("D", 90)])
# grb3 = Product("Grb3", removed_components={"regions": [Region("SH2")]})
# self.grb2_definition = Definition(protoform, [ashl, s90d, grb3])
# self.model = self.nxcorpus.instantiate(
# "EGFR_signalling_GRB2", [self.grb2_definition],
# default_bnd_rate=0.1,
# default_brk_rate=0.1,
# default_mod_rate=0.1)
self.query1 = ("""
MATCH (:protoform)<--(r1:REGION)-->(i:interaction)-*-(n4:protoform)
RETURN p1, i, p2;
""")
# def test_nx_ag_queries(self):
# """Test queries on the action graph."""
# engine = KamiQLEngine(self.nxcorpus)
# start_time = time.time()
# instances = engine.query_action_graph(self.query1)
# print("NX time: ", time.time() - start_time)
# print(instances)
# print()
def test_neo4j_ag_queries(self):
"""Test queries on the action graph."""
engine = KamiQLEngine(self.neo4jcorpus)
start_time = time.time()
instances = engine.query_action_graph(self.query1)
print("Neo4j time: ", time.time() - start_time)
print(instances)
print()
interaction5 = Binding(egf_egfr, egf_egfr)
interaction6 = Unbinding(egf_egfr, egf_egfr)
interaction7 = LigandModification(egfr_kinase,
shc1,
target=Residue(
"Y", 317, State("phosphorylation",
False)),
value=True,
enzyme_bnd_region=Region("egfr_BND"),
enzyme_bnd_site=Site("egfr_BND"),
substrate_bnd_region=Region("shc1_BND"),
substrate_bnd_site=Site("sch1_BND"))
nuggets = TEST_CORPUS.add_interactions([
interaction1, interaction2, interaction3, interaction4, interaction5,
interaction6, interaction7
])
# Create a protein definition for GRB2
protoform = Protoform("P62993",
regions=[
Region(name="SH2",
residues=[
Residue("S", 90, test=True),
Residue("D", 90, test=False)
])
])
ashl = Product("Ash-L", residues=[Residue("S", 90)])
s90d = Product("S90D", residues=[Residue("D", 90)])
grb3 = Product("Grb3", removed_components={"regions": [Region("SH2")]})
def test_sh2_py_semantics(self):
"""."""
phos = State("phosphorylation", True)
dok1_py398 = Protoform("Q99704",
synonyms=["DOK1", "p62DOK1"],
residues=[Residue("Y", 398, phos)])
abl2 = Protoform("P42684", synonyms=["ABL2"])
sh2 = Region(name="SH2")
abl2_sh2 = RegionActor(abl2, sh2)
bnd = Binding(dok1_py398, abl2_sh2)
corpus = KamiCorpus("test")
nugget_id = corpus.add_interaction(bnd)
semantic_entities = [
"sh2_domain", "sh2_domain_pY_bnd", "pY_site", "pY_residue",
"phosphorylation"
]
print(corpus.get_nugget(nugget_id).nodes())
assert ("pY_site" in corpus.get_nugget(nugget_id).nodes())
assert ("pY_residue" in corpus.get_nugget(nugget_id).nodes())
assert ("pY_residue_phospho" in corpus.get_nugget(nugget_id).nodes())
assert ((nugget_id, "sh2_pY_binding_semantic_nugget")
in corpus.nugget_relations())
for entity in semantic_entities:
assert (entity in corpus._hierarchy.get_relation(
"sh2_pY_binding_semantic_nugget", nugget_id).keys())
site_actor_no_residue = SiteActor(Protoform("A"),
Site("pY-site", start=100, end=150))
bnd = Binding(abl2_sh2, site_actor_no_residue)
nugget_id = corpus.add_interaction(bnd)
assert (len(corpus.get_nugget(nugget_id).nodes()) == 7)
binding_nodes = []
for n in corpus.action_graph.nodes():
if corpus.get_action_graph_typing()[n] == "bnd":
binding_nodes.append(n)
assert (len(binding_nodes) == 1)
assert ((nugget_id, "sh2_pY_binding_semantic_nugget")
in corpus.nugget_relations())
for entity in semantic_entities:
assert (entity in corpus._hierarchy.get_relation(
"sh2_pY_binding_semantic_nugget", nugget_id).keys())
site_actor_no_phospho = SiteActor(
Protoform("A"),
Site("pY-site", start=100, end=150, residues=[Residue("Y")]))
bnd = Binding(abl2_sh2, site_actor_no_phospho)
nugget_id = corpus.add_interaction(bnd)
assert (len(corpus.get_nugget(nugget_id).nodes()) == 8)
binding_nodes = []
for n in corpus.action_graph.nodes():
if corpus.get_action_graph_typing()[n] == "bnd":
binding_nodes.append(n)
assert (len(binding_nodes) == 1)
assert ((nugget_id, "sh2_pY_binding_semantic_nugget")
in corpus.nugget_relations())
for entity in semantic_entities:
assert (entity in corpus._hierarchy.get_relation(
"sh2_pY_binding_semantic_nugget", nugget_id).keys())
site_actor_with_residue = SiteActor(
Protoform("A"),
Site("pY-site",
start=100,
end=150,
residues=[
Residue("Y", loc=145, state=State("phosphorylation"))
]))
bnd = Binding(abl2_sh2, site_actor_with_residue)
nugget_id = corpus.add_interaction(bnd)
assert (len(corpus.get_nugget(nugget_id).nodes()) == 7)
binding_nodes = []
for n in corpus.action_graph.nodes():
if corpus.get_action_graph_typing()[n] == "bnd":
binding_nodes.append(n)
assert (len(binding_nodes) == 1)
assert ((nugget_id, "sh2_pY_binding_semantic_nugget")
in corpus.nugget_relations())
for entity in semantic_entities:
assert (entity in corpus._hierarchy.get_relation(
"sh2_pY_binding_semantic_nugget", nugget_id).keys())
site_actor_with_residue1 = SiteActor(
Protoform("B"),
Site("pY-site",
residues=[
Residue("Y", loc=145, state=State("phosphorylation"))
]))
site_actor_with_residue2 = SiteActor(
Protoform("B"),
Site("some site",
residues=[
Residue("Y", loc=145, state=State("phosphorylation"))
]))
bnd1 = Binding(abl2_sh2, site_actor_with_residue1)
bnd2 = Binding(abl2_sh2, site_actor_with_residue2)
corpus.add_interactions([bnd1, bnd2])
print_graph(corpus.action_graph)
class TestKamiCorpus(object):
"""Class for testing KAMI model."""
def __init__(self):
"""Initialize test class with a model."""
self.model = KamiCorpus("test")
egfr = Protoform("P00533")
fgfr1 = Protoform("P11362")
fgfr1_pysite = SiteActor(
Protoform("P11362"),
Site("pY",
residues=[Residue("Y", 463, State("phosphorylation", True))]))
abl1_sh2 = RegionActor(Protoform("P00519"), Region("SH2"))
target = Residue("Y", 463, State("phosphorylation", False))
modification = Modification(enzyme=egfr,
substrate=fgfr1,
target=target)
binding = Binding(abl1_sh2, fgfr1_pysite)
self.model.add_interactions([modification, binding])
def test_empty_hierarchy(self):
"""Test getters for various model components."""
model = KamiCorpus("test")
assert (model.action_graph is not None)
assert (len(model.nuggets()) == 0)
assert (model.empty())
model.export_json("test_empty_hierarchy.json")
new_model = KamiCorpus.load_json("test", "test_empty_hierarchy.json")
assert (isinstance(new_model, KamiCorpus))
# assert(new_model._hierarchy == model._hierarchy)
assert (model.mod_template is
model._hierarchy.get_graph("mod_template"))
assert (model.bnd_template is
model._hierarchy.get_graph("bnd_template"))
assert (model.semantic_action_graph is
model._hierarchy.get_graph("semantic_action_graph"))
def test_non_empty_hierarchy(self):
"""."""
model = KamiCorpus("test")
plcg1_pY1253 = Protoform("P19174",
synonyms=["PLCG1"],
residues=[
Residue("Y",
1253,
state=State(
"phosphorylation", True))
])
sh2 = Region(name="SH2")
abl1 = Protoform("P00519", synonyms=["ABL1"])
abl1_sh2 = RegionActor(abl1, sh2)
bnd = Binding(plcg1_pY1253, abl1_sh2)
model.add_interactions([bnd], model)
assert (model.empty() is False)
model.export_json("test_non_empty_hierarchy.json")
new_model = KamiCorpus.load_json("test",
"test_non_empty_hierarchy.json")
assert (isinstance(new_model, KamiCorpus))
assert (("test_action_graph", "meta_model")
in new_model._hierarchy.edges())
# print(model._hierarchy.graphs())
# print(new_model._hierarchy.graphs())
# assert(model._hierarchy == new_model._hierarchy)
def test_add_gene_component(self):
identifier = EntityIdentifier(self.model.action_graph,
self.model.get_action_graph_typing())
protoform = identifier.identify_protoform(Protoform("P00533"))
residue = Residue("Y", 200)
residue_id = self.model.add_residue(residue, protoform)
assert ((residue_id, protoform) in self.model.action_graph.edges())
for region in self.model.get_attached_regions(protoform):
edge = get_edge(self.model.action_graph, region, protoform)
if "start" in edge.keys() and\
"end" in edge.keys() and\
min(edge["start"]) < 200 and\
max(edge["end"]) > 200:
assert ((residue_id, region)
in self.model.action_graph.edges())
for site in self.model.get_attached_sites(protoform):
edge = get_edge(self.model.action_graph, site, protoform)
if "start" in edge.keys() and\
"end" in edge.keys() and\
min(edge["start"]) < 200 and\
max(edge["end"]) > 200:
assert ((residue_id, site) in self.model.action_graph.edges())
site = Site("TestSite", start=200, end=250)
site_id = self.model.add_site(site, protoform, semantics="pY_site")
assert ((site_id, protoform) in self.model.action_graph.edges())
for region in self.model.get_attached_regions(protoform):
edge = get_edge(self.model.action_graph, region, protoform)
if "start" in edge.keys() and\
"end" in edge.keys() and\
min(edge["start"]) < 200 and\
max(edge["end"]) > 250:
assert ((site_id, region) in self.model.action_graph.edges())
for residue in self.model.get_attached_residues(protoform):
edge = get_edge(self.model.action_graph, residue, protoform)
if "loc" in edge.keys() and\
list(edge["loc"])[0] > 200 and\
list(edge["loc"])[0] < 250:
assert ((residue, site_id) in self.model.action_graph.edges())
region = Region("TestRegion", start=100, end=500)
region_id = self.model.add_region(region,
protoform,
semantics="protein_kinase")
for residue in self.model.get_attached_residues(protoform):
edge = get_edge(self.model.action_graph, residue, protoform)
if "loc" in edge.keys() and\
list(edge["loc"])[0] > 100 and\
list(edge["loc"])[0] < 500:
assert ((residue, region_id)
in self.model.action_graph.edges())
for site in self.model.get_attached_sites(protoform):
edge = get_edge(self.model.action_graph, site, protoform)
if "start" in edge.keys() and\
"end" in edge.keys() and\
min(edge["start"]) > 100 and\
max(edge["end"]) < 500:
assert ((site, region_id) in self.model.action_graph.edges())