def test_no_shared_objects():
"""Make sure shared objects are not being created between statements"""
verbs = ('phosphorylates', 'binds', 'activates',
' causes activation of ', 'increases', 'degrades', 'synthesizes',
'transcribes', 'ubiquitinates')
for verb in verbs:
text = 'HEDGEHOG %s SMURF1 and SMURF2' % verb
tp = trips.process_text(text)
stmts = tp.statements
assert len(stmts) == 2
stmt1, stmt2 = stmts
# assert stmt1.evidence[0] is not stmt2.evidence[0]
hedgehog1 = stmt1.agent_list()[0]
hedgehog2 = stmt2.agent_list()[0]
assert hedgehog1 is not hedgehog2
# autophosphorylation
text = 'HEDGEHOG phosphorylates itself at Ser1337 and Tyr99'
tp = trips.process_text(text)
stmts = tp.statements
assert len(stmts) == 2
stmt1, stmt2 = stmts
assert stmt1.evidence[0] is not stmt2.evidence[0]
hedgehog1 = stmt1.agent_list()[0]
hedgehog2 = stmt2.agent_list()[0]
assert hedgehog1 is not hedgehog2
def test_ubiquitination():
tp = trips.process_text('MDM2 ubiquitinates TP53.')
assert len(tp.statements) == 1
st = tp.statements[0]
assert isinstance(st, ist.Ubiquitination)
assert unicode_strs((tp, st))
assert_grounding_value_or_none(st)
assert_if_hgnc_then_up(st)
assert st.evidence
def trips_process_text():
"""Process text with TRIPS and return INDRA Statements."""
if request.method == 'OPTIONS':
return {}
response = request.body.read().decode('utf-8')
body = json.loads(response)
text = body.get('text')
tp = trips.process_text(text)
return _stmts_from_proc(tp)
def test_synthesis():
tp = trips.process_text('NFKB transcribes IKB.')
assert len(tp.statements) == 1
st = tp.statements[0]
assert isinstance(st, ist.IncreaseAmount)
assert st.subj is not None
assert st.obj is not None
assert unicode_strs((tp, st))
assert_if_hgnc_then_up(st)
assert_grounding_value_or_none(st)
assert st.evidence
def test_degradation():
tp = trips.process_text('MDM2 degrades TP53.')
assert len(tp.statements) == 1
st = tp.statements[0]
assert isinstance(st, ist.DecreaseAmount)
assert st.subj is not None
assert st.obj is not None
assert unicode_strs((tp, st))
assert_if_hgnc_then_up(st)
assert_grounding_value_or_none(st)
assert st.evidence
def test_phosphorylation_nosite():
tp = trips.process_text('BRAF phosphorylates MEK1 at Serine.')
assert len(tp.statements) == 1
st = tp.statements[0]
assert isinstance(st, ist.Phosphorylation)
assert st.residue == 'S'
assert st.position is None
assert unicode_strs((tp, st))
assert_if_hgnc_then_up(st)
assert_grounding_value_or_none(st)
assert st.evidence
def test_actform_bound():
tp = trips.process_text('HRAS bound to GTP is activated.')
assert len(tp.statements) == 1
st = tp.statements[0]
assert isinstance(st, ist.ActiveForm)
assert isinstance(st.agent.bound_conditions[0], ist.BoundCondition)
assert st.agent.bound_conditions[0].agent.name == 'GTP'
assert st.agent.bound_conditions[0].is_bound == True
assert unicode_strs((tp, st))
assert_if_hgnc_then_up(st)
assert_grounding_value_or_none(st)
assert st.evidence
def test_phosphorylation():
tp = trips.process_text('BRAF phosphorylates MEK1 at Ser222.')
assert len(tp.statements) == 1
st = tp.statements[0]
assert isinstance(st, ist.Phosphorylation)
assert st.residue == 'S'
assert st.position == '222'
assert st.evidence
assert_if_hgnc_then_up(st)
assert_grounding_value_or_none(st)
assert st.sub.db_refs['TEXT'] == 'MEK1'
assert unicode_strs((tp, st))
def test_actform_muts():
tp = trips.process_text('BRAF V600E is activated.')
assert len(tp.statements) == 1
st = tp.statements[0]
assert isinstance(st, ist.ActiveForm)
assert isinstance(st.agent.mutations[0], ist.MutCondition)
assert st.agent.mutations[0].residue_from == 'V'
assert st.agent.mutations[0].residue_to == 'E'
assert st.agent.mutations[0].position == '600'
assert unicode_strs((tp, st))
assert_if_hgnc_then_up(st)
assert_grounding_value_or_none(st)
assert st.evidence
def test_actmods2():
tp = trips.process_text('BRAF phosphorylated at Ser536 binds MEK1.')
assert len(tp.statements) == 1
st = tp.statements[0]
assert isinstance(st, ist.Complex)
braf = st.members[0]
assert braf.mods[0].mod_type == 'phosphorylation'
assert braf.mods[0].residue == 'S'
assert braf.mods[0].position == '536'
assert unicode_strs((tp, st, braf))
assert_if_hgnc_then_up(st)
assert_grounding_value_or_none(st)
assert st.evidence
def test_simple_decrease():
tp = trips.process_text('Selumetinib decreases FOS.')
assert len(tp.statements) == 1
st = tp.statements[0]
assert isinstance(st, ist.DecreaseAmount)
assert st.subj is not None
assert st.obj is not None
assert st.subj.name.upper() == 'SELUMETINIB'
assert st.obj.name.upper() == 'FOS'
assert unicode_strs((tp, st))
assert_if_hgnc_then_up(st)
assert_grounding_value_or_none(st)
assert st.evidence
def test_simple_decrease():
tp = trips.process_text('Selumetinib decreases FOS.')
assert len(tp.statements) == 1
st = tp.statements[0]
assert isinstance(st, ist.DecreaseAmount)
assert st.subj is not None
assert st.obj is not None
assert st.subj.name.upper() == 'SELUMETINIB'
assert st.obj.name.upper() == 'FOS'
assert unicode_strs((tp, st))
assert_if_hgnc_then_up(st)
assert_grounding_value_or_none(st)
assert st.evidence
def test_actmods2():
tp = trips.process_text('BRAF phosphorylated at Ser536 binds MEK1.')
assert len(tp.statements) == 1
st = tp.statements[0]
assert isinstance(st, ist.Complex)
braf = st.members[0]
assert braf.mods[0].mod_type == 'phosphorylation'
assert braf.mods[0].residue == 'S'
assert braf.mods[0].position == '536'
assert unicode_strs((tp, st, braf))
assert_if_hgnc_then_up(st)
assert_grounding_value_or_none(st)
assert st.evidence
def test_not_bound_to4():
fname = sys._getframe().f_code.co_name + '.xml'
txt = 'BRAF that is not bound to NRAS and Vemurafenib binds BRAF ' +\
'that is not bound to Vemurafenib.'
tp = trips.process_text(txt, fname, False)
assert (len(tp.statements) == 1)
st = tp.statements[0]
assert (is_complex(st))
assert (st.members[0].name == 'BRAF')
assert (st.members[1].name == 'BRAF')
assert (len(st.members[0].bound_conditions) == 2)
assert (len(st.members[1].bound_conditions) == 1)
os.remove(fname)
def test_actform_muts():
tp = trips.process_text('BRAF V600E is activated.')
assert len(tp.statements) == 1
st = tp.statements[0]
assert isinstance(st, ist.ActiveForm)
assert isinstance(st.agent.mutations[0], ist.MutCondition)
assert st.agent.mutations[0].residue_from == 'V'
assert st.agent.mutations[0].residue_to == 'E'
assert st.agent.mutations[0].position == '600'
assert unicode_strs((tp, st))
assert_if_hgnc_then_up(st)
assert_grounding_value_or_none(st)
assert st.evidence
def test_actmod():
tp = trips.process_text('MEK1 phosphorylated at Ser222 is activated.')
assert len(tp.statements) == 1
st = tp.statements[0]
assert isinstance(st, ist.ActiveForm)
assert isinstance(st.agent.mods[0], ist.ModCondition)
assert st.agent.mods[0].mod_type == 'phosphorylation'
assert st.agent.mods[0].residue == 'S'
assert st.agent.mods[0].position == '222'
assert unicode_strs((tp, st))
assert_if_hgnc_then_up(st)
assert_grounding_value_or_none(st)
assert st.evidence
def test_actmod():
tp = trips.process_text('MEK1 phosphorylated at Ser222 is activated.')
assert len(tp.statements) == 1
st = tp.statements[0]
assert isinstance(st, ist.ActiveForm)
assert isinstance(st.agent.mods[0], ist.ModCondition)
assert st.agent.mods[0].mod_type == 'phosphorylation'
assert st.agent.mods[0].residue == 'S'
assert st.agent.mods[0].position == '222'
assert unicode_strs((tp, st))
assert_if_hgnc_then_up(st)
assert_grounding_value_or_none(st)
assert st.evidence
def test_mod_cond():
tp = trips.process_text('Phosphorylated BRAF binds ubiquitinated MAP2K1.')
assert len(tp.statements) == 1
st = tp.statements[0]
assert isinstance(st, ist.Complex)
braf = st.members[0]
mek = st.members[1]
assert len(braf.mods) == 1
assert braf.mods[0].mod_type == 'phosphorylation'
assert len(mek.mods) == 1
assert mek.mods[0].mod_type == 'ubiquitination'
assert unicode_strs((tp, st))
assert_if_hgnc_then_up(st)
assert_grounding_value_or_none(st)
assert st.evidence
def read_model(model_name, reread=False):
xml_fname = model_name + '.xml'
if not reread:
print('Processing %s' % xml_fname)
if os.path.exists(xml_fname):
with open(xml_fname, 'rb') as fh:
tp = trips.process_xml(fh.read())
else:
reread = True
if reread:
fname = model_name + '.txt'
print('Reading %s' % fname)
with open(fname, 'rb') as fh:
ts = time.time()
tp = trips.process_text(fh.read(), xml_fname)
te = time.time()
print('Reading took %.2fs' % (te-ts))
print('Assembling statements:')
for i, st in enumerate(tp.statements):
print('%d: %s' % (i, st))
print('----------------------')
return tp.statements
def assemble_model(model_id, reread=False):
model_name = 'model%d' % model_id
# If model has already been read, just process the EKB XML
if os.path.exists(model_name + '.xml') and not reread:
tp = trips.process_xml(open(model_name + '.xml').read())
else:
# Start with the basic model
model_txt = open('model1.txt').read()
# Apply patches one by one to get to the current model text
for j in range(1, model_id):
patch_txt = open('model%d_from%d.txt' % (j+1, j)).read()
model_txt = apply_patch(model_txt, patch_txt)
print('Reading model %d text:' % model_id)
print(model_txt)
# Process model text and save result EKB XML
tp = trips.process_text(model_txt, model_name + '.xml')
print('Assembling statements:')
for i, st in enumerate(tp.statements):
print('%d: %s' % (i, st))
# Assemble the PySB model
pa = PysbAssembler()
pa.add_statements(tp.statements)
model = pa.make_model(policies='two_step')
# Set initial conditions
erk = model.monomers['ERK']
obs = Observable('ERK_p', erk(phospho='p'))
model.add_component(obs)
vem = model.monomers['VEMURAFENIB']
obs = Observable('Vem_free', vem(map3k=None))
model.add_component(obs)
ras = model.monomers['RAS']
obs = Observable('RAS_active', ras(gtp=ANY))
model.add_component(obs)
braf = model.monomers['BRAF']
obs = Observable('BRAF_active', braf(vemurafenib=None))
model.add_component(obs)
model.parameters['BRAF_0'].value = 0
egf = model.monomers['EGF']
obs = Observable('EGF_free', egf(erbb=None))
model.add_component(obs)
# Add mutated form of BRAF as initial condition
sites_dict = {}
for site in braf.sites:
if site in braf.site_states:
sites_dict[site] = braf.site_states[site][0]
else:
sites_dict[site] = None
sites_dict['V600'] = 'E'
model.add_component(Parameter('BRAF_mut_0', 1e5))
model.initial(braf(**sites_dict), model.parameters['BRAF_mut_0'])
# Set up model parameters
model.parameters['kf_ee_bind_1'].value = 1
model.parameters['kr_ee_bind_1'].value = 0.1
model.parameters['kf_ee_bind_2'].value = 1
model.parameters['kr_ee_bind_2'].value = 0.1
model.parameters['kf_eg_bind_1'].value = 1
model.parameters['kr_eg_bind_1'].value = 0.1
model.parameters['kf_gs_bind_1'].value = 1
model.parameters['kr_gs_bind_1'].value = 0.1
model.parameters['kf_sr_bind_1'].value = 1
model.parameters['kr_sr_bind_1'].value = 50
model.parameters['kf_rg_bind_1'].value = 50
model.parameters['kr_rg_bind_1'].value = 0.5
model.parameters['kf_rb_bind_1'].value = 1
model.parameters['kr_rb_bind_1'].value = 0.5
model.parameters['kf_vb_bind_1'].value = 10
model.parameters['kr_vb_bind_1'].value = 1
model.parameters['kf_bm_bind_1'].value = 1
model.parameters['kr_bm_bind_1'].value = 0.1
model.parameters['kc_bm_phosphorylation_1'].value = 3
model.parameters['kf_pm_bind_1'].value = 1
model.parameters['kr_pm_bind_1'].value = 0.001
model.parameters['kc_pm_dephosphorylation_1'].value = 10
model.parameters['kf_me_bind_1'].value = 1
model.parameters['kr_me_bind_1'].value = 0.1
model.parameters['kc_me_phosphorylation_1'].value = 10
model.parameters['kf_de_bind_1'].value = 1
model.parameters['kr_de_bind_1'].value = 0.001
model.parameters['kc_de_dephosphorylation_1'].value = 10
model.parameters['VEMURAFENIB_0'].value = 0
model.parameters['EGF_0'].value = 1e3
model.parameters['EGFR_0'].value = 1e5
model.parameters['SOS_0'].value = 1e3
model.parameters['GRB2_0'].value = 1e5
model.parameters['RAS_0'].value = 2e5
model.parameters['GTP_0'].value = 1e7
model.parameters['MEK_0'].value = 1e5
model.parameters['ERK_0'].value = 1e5
model.parameters['DUSP6_0'].value = 1e3
model.parameters['PPP2CA_0'].value = 1e5
if model_id >= 2:
model.parameters['Phosphatase_0'].value = 1e2
model.parameters['kf_es_bind_1'].value = 1e-05
model.parameters['kr_es_bind_1'].value = 1e-04
model.parameters['kc_es_phosphorylation_1'].value = 1
model.parameters['kf_ps_bind_1'].value = 1
model.parameters['kr_ps_bind_1'].value = 0.1
model.parameters['kc_ps_dephosphorylation_1'].value = 1e-04
if model_id >= 3:
model.parameters['kf_bb_bind_1'].value = 10
model.parameters['kr_bb_bind_1'].value = 1
model.parameters['kf_vb_bind_2'].value = 1e-04
pa.model = model
pa.save_model('model%d.py' % model_id)
return model
def export_hello(model, formats):
for f in formats:
model_export = export(model, f)
extension = (f if f != 'pysb_flat' else 'py')
fname = 'hello_indra_model.%s' % extension
with open(fname, 'wb') as fh:
fh.write(model_export.encode('utf-8'))
# User defines text
text = 'MEK1 phosphorylates ERK2 on threonine 185 and tyrosine 187.'
# Process text using TRIPS processor
tp = trips.process_text(text)
# Get the list of extracted Statements
stmts = tp.statements
# Assemble a PySB model
pa = PysbAssembler()
pa.add_statements(stmts)
pa.make_model()
# Run simulation
t = np.linspace(0, 300)
sol = Solver(pa.model, t)
sol.run()
# Plot the result
