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_multiple_bnd_templates(self):
dummy_partner = SiteActor(
protoform=Protoform("C"),
region=Region(name="C_RegionActor"),
site=Site(name="C_SiteActor"))
enzyme = SiteActor(
protoform=Protoform("A", bound_to=[dummy_partner]),
region=Region(name="A_RegionActor", bound_to=[dummy_partner]),
site=Site(name="A_SiteActor", bound_to=[dummy_partner]))
substrate = SiteActor(
protoform=Protoform("B", bound_to=[dummy_partner]),
region=Region(name="B_RegionActor", bound_to=[dummy_partner]),
site=Site(name="B_SiteActor", bound_to=[dummy_partner]))
mod = Modification(
enzyme,
substrate,
target=Residue("Y", 100, State("phosphorylation", False)),
value=True)
corpus = KamiCorpus("test")
identifier = EntityIdentifier(
corpus.action_graph,
corpus.get_action_graph_typing())
generator = ModGenerator(identifier)
n, _, _, _ = generator.generate(mod)
def test_mod_generator(self):
"""Test generation of a modification nugget graph."""
enzyme_gene = Protoform("A")
enzyme_region_actor = RegionActor(
protoform=enzyme_gene,
region=Region("Pkinase"))
enzyme_site_actor = SiteActor(
protoform=enzyme_gene,
region=Region("Pkinase"),
site=Site("tail"))
substrate_gene = Protoform("B")
substrate_region_actor = RegionActor(
protoform=substrate_gene,
region=Region("SH2"))
substrate_site_actor = SiteActor(
protoform=substrate_gene,
region=Region("SH2"),
site=Site("finger"))
residue_mod_target = Residue("Y", 100, State("activity", False))
state_mod_target = State("activity", False)
mod1 = Modification(
enzyme=enzyme_gene,
substrate=substrate_gene,
target=state_mod_target
)
mod2 = Modification(
enzyme=enzyme_region_actor,
substrate=substrate_gene,
target=state_mod_target
)
mod3 = Modification(
enzyme=enzyme_site_actor,
substrate=substrate_gene,
target=state_mod_target
)
mod4 = Modification(
enzyme=enzyme_site_actor,
substrate=substrate_region_actor,
target=state_mod_target
)
mod5 = Modification(
enzyme=enzyme_site_actor,
substrate=substrate_site_actor,
target=residue_mod_target
)
corpus = KamiCorpus("test")
identifier = EntityIdentifier(
corpus.action_graph,
corpus.get_action_graph_typing())
generator = ModGenerator(identifier)
n, _, _, _ = generator.generate(mod5)
print_graph(n.graph)
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_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 __init__(self):
uniprotid = "P00533"
simple_region = Region("SH2")
regions = [simple_region]
sites = [Site("pY")]
residues = [
Residue("Y", 100),
Residue("S", 155, State("phosphorylation", True))
]
states = [State("activity", True), State("phosphorylation", True)]
bounds = [
SiteActor(protoform=Protoform("Q07890"),
site=Site("binding_site")),
Protoform("P00519")
]
self.protoform = Protoform(
uniprotid,
regions=regions,
residues=residues,
sites=sites,
states=states,
bound_to=bounds,
hgnc_symbol="EGFR",
synonyms=["EGFR", "Epidermal growth factor receptor"])
self.enzyme_gene = Protoform("Q07890")
self.enzyme_site_actor = SiteActor(protoform=self.enzyme_gene,
region=Region("Pkinase"),
site=Site("tail"))
self.substrate_gene = Protoform("P00519")
self.substrate_region_actor = RegionActor(
protoform=self.substrate_gene, region=Region("SH2"))
self.residue_mod_target = Residue("Y", 100, State("activity", False))
def test_bnd_generation(self):
"""Test generation of a binding nugget graph."""
left = SiteActor(Protoform("A"), Site("pY"), Region("Reg"))
right = Protoform("B")
bnd = Binding(left, right)
corpus = KamiCorpus("test")
identifier = EntityIdentifier(
corpus.action_graph,
corpus.get_action_graph_typing())
generator = BndGenerator(identifier)
n, _, _, _ = generator.generate(bnd)
print_graph(n.graph)
def test_site_actor_generator(self):
"""Test generation of graph components for a SiteActor object."""
# no region
site_actor = SiteActor(
protoform=Protoform("B"), site=Site("pY"))
nugget = KamiGraph()
nugget.reference_typing[self.default_ag_gene] = self.default_ag_gene
(gene_id, site_id, region_id, _) =\
self.generator.generate_site_actor(nugget, site_actor)
assert((site_id, gene_id) in nugget.edges())
# with a region in the middle
site_actor_with_region = SiteActor(
protoform=Protoform("B"), site=Site("pY"), region=Region("kinase"))
(gene_id, site_id, region_id, _) =\
self.generator.generate_site_actor(nugget, site_actor_with_region)
assert((site_id, region_id) in nugget.edges())
assert((region_id, gene_id) in nugget.edges())
def test_ligandmod_generation(self):
"""Test generation of a transmodification nugget graph."""
enzyme_gene = Protoform("A")
enzyme_region_actor = RegionActor(
protoform=enzyme_gene,
region=Region("Pkinase"))
substrate = Protoform("B")
automod = LigandModification(
enzyme_region_actor,
substrate,
Residue("Y", 100, State("phosphorylation", True)),
value=True,
enzyme_bnd_region=Region("EbndRegion"),
substrate_bnd_region=Region("SbndRegion"),
substrate_bnd_site=Site("SbndSite"))
corpus = KamiCorpus("test")
identifier = EntityIdentifier(
corpus.action_graph,
corpus.get_action_graph_typing())
generator = LigandModGenerator(identifier)
n, _, _, _ = generator.generate(automod)
print_graph(n.graph)
inter = LigandModification(
enzyme=RegionActor(protoform=Protoform(uniprotid="P30530",
hgnc_symbol="AXL"),
region=Region(name="Tyr_kinase",
interproid="IPR020635",
start=536, end=807)),
substrate=SiteActor(protoform=Protoform(uniprotid="P06239",
hgnc_symbol="LCK"),
site=Site(name="pY394",
start=391, end=397)),
target=Residue(aa="Y", loc=394,
state=State("phosphorylation", False)),
value=True,
rate=10,
enzyme_bnd_region=Region(name="Tyr_kinase",
interproid="IPR020635",
start=536, end=807),
substrate_bnd_site=Site(name='pY394',
start=391, end=397)
)
corpus = KamiCorpus("test")
corpus.add_interaction(inter, anatomize=False)
print_graph(corpus.get_nugget('test_nugget_1'))
def test_site_residue_reconnect(self):
sh2 = Region(name="SH2")
b = Binding(
SiteActor(protoform=Protoform(uniprotid="P00533",
hgnc_symbol="EGFR",
residues=[
Residue("Y",
1092,
state=State(
"phosphorylation",
True))
]),
site=Site(name="motif1092", start=1088, end=1096)),
RegionActor(protoform=Protoform("P62993", hgnc_symbol="GRB2"),
region=sh2))
corpus = KamiCorpus("test")
corpus.add_interaction(b)
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 __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_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_is_bnd_generator(self):
"""Test generation of graph components for a bound condition."""
protoform = Protoform("A")
site_actor = SiteActor(protoform=Protoform("A"), site=Site("pY"))
region_actor = RegionActor(
protoform=Protoform("A"), region=Region("Pkinase"))
nugget = KamiGraph()
nugget.reference_typing[self.default_ag_gene] = self.default_ag_gene
site = Site(
"lala",
bound_to=[protoform, protoform]
)
site_id, _ =\
self.generator.generate_site(
nugget, site,
self.default_ag_gene, self.default_ag_gene)
nugget = KamiGraph()
nugget.reference_typing[self.default_ag_gene] = self.default_ag_gene
site = Site(
"lala",
bound_to=[site_actor]
)
site_id, _ =\
self.generator.generate_site(
nugget, site, self.default_ag_gene,
self.default_ag_gene)
nugget = KamiGraph()
nugget.reference_typing[self.default_ag_gene] = self.default_ag_gene
site = Site(
"lala",
bound_to=[region_actor]
)
self.generator.generate_site(
nugget, site, self.default_ag_gene, self.default_ag_gene)
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_advanced_ligand_mod_generator(self):
"""Test generation with advanced usage of LigandModification."""
corpus = KamiCorpus("test")
identifier = EntityIdentifier(
corpus.action_graph,
corpus.get_action_graph_typing())
generator = LigandModGenerator(identifier)
enzyme = SiteActor(
protoform=Protoform("A"),
region=Region(name="RegionActor"),
site=Site(name="SiteActor"))
substrate = SiteActor(
protoform=Protoform("B"),
region=Region(name="RegionActor"),
site=Site(name="SiteActor"))
# simple subactors switching
subactors = ["protoform", "region", "site"]
for ea in subactors:
for sa in subactors:
mod = LigandModification(
enzyme=enzyme,
substrate=substrate,
target=Residue("Y", 100, State("phosphorylation", True)),
value=False,
enzyme_bnd_subactor=ea,
substrate_bnd_subactor=sa)
n, _, _, _ = generator.generate(mod)
mod = LigandModification(
enzyme=enzyme,
substrate=substrate,
target=Residue("Y", 100, State("phosphorylation", True)),
value=False,
enzyme_bnd_region=Region(name="SpecialBindingRegion"),
substrate_bnd_region=Region(name="SpecialBindingRegion"))
n, _, _, _ = generator.generate(mod)
mod = LigandModification(
enzyme=enzyme,
substrate=substrate,
target=Residue("Y", 100, State("phosphorylation", True)),
value=False,
enzyme_bnd_subactor="region",
substrate_bnd_subactor="region",
enzyme_bnd_site=Site(name="SpecialBindingSite"),
substrate_bnd_site=Site(name="SpecialBindingSite"))
n, _, _, _ = generator.generate(mod)
mod = LigandModification(
enzyme=enzyme,
substrate=substrate,
target=Residue("Y", 100, State("phosphorylation", True)),
value=False,
enzyme_bnd_region=Region(name="SpecialBindingRegion"),
substrate_bnd_region=Region(name="SpecialBindingRegion"),
enzyme_bnd_site=Site(name="SpecialBindingSite"),
substrate_bnd_site=Site(name="SpecialBindingSite"))
n, _, _, _ = generator.generate(mod)
print_graph(n.graph)
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)