def test_genomic_features(real_variant_database, case_obj):
"""Test function that parses pinned variants from a case and returns them as MatchMaker genomic features"""
# GIVEN a case with a pinned variant that is in the database
adapter = real_variant_database
test_variant = adapter.variant_collection.find_one(
{"hgnc_symbols": ["POT1"]})
case_obj["suspects"] = [test_variant["_id"]]
sample_name = "NA12882"
# WHEN the parse genomic_features is used to parse genotype features of this case
g_features = genomic_features(
store=adapter,
case_obj=case_obj,
sample_name=sample_name,
candidate_vars=case_obj["suspects"],
genes_only=False,
)
# THEN it should return the expected data
assert isinstance(g_features, list)
assert g_features[0]["gene"] == {"id": "POT1"}
assert isinstance(g_features[0]["variant"], dict)
def mme_add(
store,
user_obj,
case_obj,
add_gender,
add_features,
add_disorders,
genes_only,
mme_base_url,
mme_accepts,
mme_token,
):
"""Add a patient to MatchMaker server
Args:
store(adapter.MongoAdapter)
user_obj(dict) a scout user object (to be added as matchmaker contact)
case_obj(dict) a scout case object
add_gender(bool) if True case gender will be included in matchmaker
add_features(bool) if True HPO features will be included in matchmaker
add_disorders(bool) if True OMIM diagnoses will be included in matchmaker
genes_only(bool) if True only genes and not variants will be shared
mme_base_url(str) base url of the MME server
mme_accepts(str) request content accepted by MME server
mme_token(str) auth token of the MME server
Returns:
submitted_info(dict) info submitted to MatchMaker and its responses
"""
if not mme_base_url or not mme_accepts or not mme_token:
return "Please check that Matchmaker connection parameters are valid"
url = "".join([mme_base_url, "/patient/add"])
features = [] # this is the list of HPO terms
disorders = [] # this is the list of OMIM diagnoses
g_features = []
# create contact dictionary
contact_info = {
"name": user_obj["name"],
"href": "".join(["mailto:", user_obj["email"]]),
"institution": "Scout software user, Science For Life Laboratory, Stockholm, Sweden",
}
if add_features: # create features dictionaries
features = hpo_terms(case_obj)
if add_disorders: # create OMIM disorders dictionaries
disorders = omim_terms(case_obj)
# send a POST request and collect response for each affected individual in case
server_responses = []
submitted_info = {
"contact": contact_info,
"sex": add_gender,
"features": features,
"disorders": disorders,
"genes_only": genes_only,
"patient_id": [],
}
for individual in case_obj.get("individuals"):
if not individual["phenotype"] in [
2,
"affected",
]: # include only affected individuals
continue
patient = {
"contact": contact_info,
"id": ".".join(
[case_obj["_id"], individual.get("individual_id")]
), # This is a required field form MME
"label": ".".join([case_obj["display_name"], individual.get("display_name")]),
"features": features,
"disorders": disorders,
}
if add_gender:
if individual["sex"] == "1":
patient["sex"] = "MALE"
else:
patient["sex"] = "FEMALE"
if case_obj.get("suspects"):
g_features = genomic_features(
store, case_obj, individual.get("display_name"), genes_only
)
patient["genomicFeatures"] = g_features
# send add request to server and capture response
resp = matchmaker_request(
url=url,
token=mme_token,
method="POST",
content_type=mme_accepts,
accept="application/json",
data={"patient": patient},
)
server_responses.append(
{
"patient": patient,
"message": resp.get("message"),
"status_code": resp.get("status_code"),
}
)
submitted_info["server_responses"] = server_responses
return submitted_info
def test_mme_add(self, populated_database, user_obj, case_obj,
parsed_variant):
"""test calling the controller that submits new patients to Matchmaker"""
session = requests.Session()
adapter = populated_database
# Add an HPO term to this scout case
assert case_obj.get('phenotype_terms') == None
phenotype_term = {
'phenotype_id': 'HP:0011031',
'feature': 'Abnormality of iron homeostasis'
}
updated_case = adapter.case_collection.find_one_and_update(
{'_id': case_obj['_id']},
{'$set': {
'phenotype_terms': [phenotype_term]
}},
return_document=pymongo.ReturnDocument.AFTER)
assert updated_case['phenotype_terms'][0] == phenotype_term
# Check that features (HPO) terms are obtained by MME parser
features = hpo_terms(updated_case)
assert features
# Add a couple of OMIM diagnoses to this case
assert case_obj.get('diagnosis_phenotypes') == None
updated_case = adapter.case_collection.find_one_and_update(
{'_id': case_obj['_id']},
{'$set': {
'diagnosis_phenotypes': [615349, 616833]
}},
return_document=pymongo.ReturnDocument.AFTER)
assert updated_case['diagnosis_phenotypes']
# Check that OMIM terms are obtained by MME parser
diagnoses = omim_terms(updated_case)
assert diagnoses
# Add variant containing a gene to database and pin it for this case
a_gene = adapter.hgnc_collection.find_one()
assert a_gene['hgnc_id']
assert adapter.variant_collection.find_one() is None
parsed_variant['hgnc_ids'] = [a_gene['hgnc_id']]
parsed_variant['samples'] = [
{ # pretend the affected subject has the allele
'sample_id': 'ADM1059A2',
'display_name': 'NA12882',
'genotype_call': '0/1'
}
]
adapter.variant_collection.insert_one(parsed_variant)
assert adapter.variant_collection.find_one()
# pin it
updated_case = adapter.case_collection.find_one_and_update(
{'_id': case_obj['_id']},
{'$set': {
'suspects': [parsed_variant['_id']]
}},
return_document=pymongo.ReturnDocument.AFTER)
assert updated_case['suspects'] == [parsed_variant['_id']]
# Check that genomic features are created correcly by MME parser
g_feat = genomic_features(adapter, updated_case, 'NA12882', 'False')
assert g_feat
# use controller to send request and collect response
mme_base_url = 'http://localhost:{port}'.format(
port=self.mock_server_port)
submitted_info = controllers.mme_add(store=adapter,
user_obj=user_obj,
case_obj=updated_case,
add_gender=True,
add_features=True,
add_disorders=True,
genes_only=False,
mme_base_url=mme_base_url,
mme_accepts=MME_ACCEPTS,
mme_token=MME_TOKEN)
assert submitted_info['server_responses'][0]['patient']
def matchmaker_add(request, institute_id, case_name):
"""Add all affected individuals from a case to a MatchMaker server
Args:
request(werkzeug.local.LocalProxy)
institute_id(str): _id of an institute
case_name(str): display name of a case
"""
# Check that general MME request requirements are fulfilled
matchmaker_check_requirements(request)
_, case_obj = institute_and_case(store, institute_id, case_name)
candidate_vars = request.form.getlist("selected_var")
if len(candidate_vars) > 3:
flash(
"At the moment it is not possible to save to MatchMaker more than 3 candidate variants / genes",
"warning",
)
return redirect(request.referrer)
save_gender = "sex" in request.form
features = (
hpo_terms(case_obj)
if "features" in request.form and case_obj.get("phenotype_terms")
else []
)
disorders = omim_terms(store, case_obj) if "disorders" in request.form else []
genes_only = request.form.get("genomicfeatures") == "genes"
if not features and not candidate_vars:
flash(
"In order to upload a case to MatchMaker you need to pin a variant or at least assign a phenotype (HPO term)",
"danger",
)
return redirect(request.referrer)
# create contact dictionary
user_obj = store.user(current_user.email)
contact_info = {
"name": user_obj["name"],
"href": "".join(["mailto:", user_obj["email"]]),
"institution": "Scout software user, Science For Life Laboratory, Stockholm, Sweden",
}
submitted_info = {
"contact": contact_info,
"sex": save_gender,
"features": features,
"disorders": disorders,
"genes_only": genes_only,
"patient_id": [],
"server_responses": [],
}
server_responses = []
n_updated = 0
for individual in case_obj.get("individuals"):
if not individual["phenotype"] in [
2,
"affected",
]: # include only affected individuals
continue
patient = {
"contact": contact_info,
"id": ".".join(
[case_obj["_id"], individual.get("individual_id")]
), # This is a required field form MME
"label": ".".join([case_obj["display_name"], individual.get("display_name")]),
"features": features,
"disorders": disorders,
}
if save_gender:
if individual["sex"] == "1":
patient["sex"] = "MALE"
else:
patient["sex"] = "FEMALE"
if candidate_vars:
g_features = genomic_features(
store, case_obj, individual.get("display_name"), candidate_vars, genes_only
)
patient["genomicFeatures"] = g_features
resp = matchmaker.patient_submit(patient)
submitted_info["server_responses"].append(
{
"patient": patient,
"message": resp.get("message"),
"status_code": resp.get("status_code"),
}
)
if resp.get("status_code") != 200:
flash(
"an error occurred while adding patient to matchmaker: {}".format(resp),
"warning",
)
continue
flash(f"Patient {individual.get('display_name')} saved to MatchMaker", "success")
n_updated += 1
if n_updated > 0:
store.case_mme_update(case_obj=case_obj, user_obj=user_obj, mme_subm_obj=submitted_info)
return n_updated
def mme_add(store, user_obj, case_obj, add_gender, add_features, add_disorders,
genes_only, mme_base_url, mme_accepts, mme_token):
"""Add a patient to MatchMaker server
Args:
store(adapter.MongoAdapter)
user_obj(dict) a scout user object (to be added as matchmaker contact)
case_obj(dict) a scout case object
add_gender(bool) if True case gender will be included in matchmaker
add_features(bool) if True HPO features will be included in matchmaker
add_disorders(bool) if True OMIM diagnoses will be included in matchmaker
genes_only(bool) if True only genes and not variants will be shared
mme_base_url(str) base url of the MME server
mme_accepts(str) request content accepted by MME server
mme_token(str) auth token of the MME server
Returns:
submitted_info(dict) info submitted to MatchMaker and its responses
"""
if not mme_base_url or not mme_accepts or not mme_token:
return 'Please check that Matchmaker connection parameters are valid'
url = ''.join([mme_base_url, '/patient/add'])
features = [] # this is the list of HPO terms
disorders = [] # this is the list of OMIM diagnoses
g_features = []
# create contact dictionary
contact_info = {
'name':
user_obj['name'],
'href':
''.join(['mailto:', user_obj['email']]),
'institution':
'Scout software user, Science For Life Laboratory, Stockholm, Sweden'
}
if add_features: # create features dictionaries
features = hpo_terms(case_obj)
if add_disorders: # create OMIM disorders dictionaries
disorders = omim_terms(case_obj)
# send a POST request and collect response for each affected individual in case
server_responses = []
submitted_info = {
'contact': contact_info,
'sex': add_gender,
'features': features,
'disorders': disorders,
'genes_only': genes_only,
'patient_id': []
}
for individual in case_obj.get('individuals'):
if not individual['phenotype'] in [
2, 'affected'
]: # include only affected individuals
continue
patient = {
'contact':
contact_info,
'id':
'.'.join([case_obj['_id'],
individual.get('individual_id')
]), # This is a required field form MME
'label':
'.'.join(
[case_obj['display_name'],
individual.get('display_name')]),
'features':
features,
'disorders':
disorders
}
if add_gender:
if individual['sex'] == '1':
patient['sex'] = 'MALE'
else:
patient['sex'] = 'FEMALE'
if case_obj.get('suspects'):
g_features = genomic_features(store, case_obj,
individual.get('display_name'),
genes_only)
patient['genomicFeatures'] = g_features
# send add request to server and capture response
resp = matchmaker_request(url=url,
token=mme_token,
method='POST',
content_type=mme_accepts,
accept='application/json',
data={'patient': patient})
server_responses.append({
'patient': patient,
'message': resp.get('message'),
'status_code': resp.get('status_code')
})
submitted_info['server_responses'] = server_responses
return submitted_info
def mme_add(store, user_obj, case_obj, add_gender, add_features, add_disorders, genes_only,
mme_base_url, mme_accepts, mme_token):
"""Add a patient to MatchMaker server
Args:
store(adapter.MongoAdapter)
user_obj(dict) a scout user object (to be added as matchmaker contact)
case_obj(dict) a scout case object
add_gender(bool) if True case gender will be included in matchmaker
add_features(bool) if True HPO features will be included in matchmaker
add_disorders(bool) if True OMIM diagnoses will be included in matchmaker
genes_only(bool) if True only genes and not variants will be shared
mme_base_url(str) base url of the MME server
mme_accepts(str) request content accepted by MME server
mme_token(str) auth token of the MME server
Returns:
submitted_info(dict) info submitted to MatchMaker and its responses
"""
if not mme_base_url or not mme_accepts or not mme_token:
return 'Please check that Matchmaker connection parameters are valid'
url = ''.join([mme_base_url, '/patient/add'])
features = [] # this is the list of HPO terms
disorders = [] # this is the list of OMIM diagnoses
g_features = []
# create contact dictionary
contact_info = {
'name' : user_obj['name'],
'href' : ''.join( ['mailto:',user_obj['email']] ),
'institution' : 'Scout software user, Science For Life Laboratory, Stockholm, Sweden'
}
if add_features: # create features dictionaries
features = hpo_terms(case_obj)
if add_disorders: # create OMIM disorders dictionaries
disorders = omim_terms(case_obj)
# send a POST request and collect response for each affected individual in case
server_responses = []
submitted_info = {
'contact' : contact_info,
'sex' : add_gender,
'features' : features,
'disorders' : disorders,
'genes_only' : genes_only,
'patient_id' : []
}
for individual in case_obj.get('individuals'):
if not individual['phenotype'] in [2, 'affected']: # include only affected individuals
continue
patient = {
'contact' : contact_info,
'id' : '.'.join([case_obj['_id'], individual.get('individual_id')]), # This is a required field form MME
'label' : '.'.join([case_obj['display_name'], individual.get('display_name')]),
'features' : features,
'disorders' : disorders
}
if add_gender:
if individual['sex'] == '1':
patient['sex'] = 'MALE'
else:
patient['sex'] = 'FEMALE'
if case_obj.get('suspects'):
g_features = genomic_features(store, case_obj, individual.get('display_name'), genes_only)
patient['genomicFeatures'] = g_features
# send add request to server and capture response
resp = matchmaker_request(url=url, token=mme_token, method='POST', content_type=mme_accepts,
accept='application/json', data={'patient':patient})
server_responses.append({
'patient': patient,
'message': resp.get('message'),
'status_code' : resp.get('status_code')
})
submitted_info['server_responses'] = server_responses
return submitted_info
def test_mme_add(self, populated_database, user_obj, case_obj,
parsed_variant):
"""test calling the controller that submits new patients to Matchmaker"""
session = requests.Session()
adapter = populated_database
# Add an HPO term to this scout case
assert len(case_obj.get("phenotype_terms")) == 0
phenotype_term = {
"phenotype_id": "HP:0011031",
"feature": "Abnormality of iron homeostasis",
}
updated_case = adapter.case_collection.find_one_and_update(
{"_id": case_obj["_id"]},
{"$set": {
"phenotype_terms": [phenotype_term]
}},
return_document=pymongo.ReturnDocument.AFTER,
)
assert updated_case["phenotype_terms"][0] == phenotype_term
# Check that features (HPO) terms are obtained by MME parser
features = hpo_terms(updated_case)
assert features
# Add a couple of OMIM diagnoses to this case
assert case_obj.get("diagnosis_phenotypes") is None
updated_case = adapter.case_collection.find_one_and_update(
{"_id": case_obj["_id"]},
{"$set": {
"diagnosis_phenotypes": [615349, 616833]
}},
return_document=pymongo.ReturnDocument.AFTER,
)
assert updated_case["diagnosis_phenotypes"]
# Check that OMIM terms are obtained by MME parser
diagnoses = omim_terms(updated_case)
assert diagnoses
# Add variant containing a gene to database and pin it for this case
a_gene = adapter.hgnc_collection.find_one()
assert a_gene["hgnc_id"]
assert adapter.variant_collection.find_one() is None
parsed_variant["hgnc_ids"] = [a_gene["hgnc_id"]]
parsed_variant["samples"] = [
{ # pretend the affected subject has the allele
"sample_id": "ADM1059A2",
"display_name": "NA12882",
"genotype_call": "0/1",
}
]
adapter.variant_collection.insert_one(parsed_variant)
assert adapter.variant_collection.find_one()
# pin it
updated_case = adapter.case_collection.find_one_and_update(
{"_id": case_obj["_id"]},
{"$set": {
"suspects": [parsed_variant["_id"]]
}},
return_document=pymongo.ReturnDocument.AFTER,
)
assert updated_case["suspects"] == [parsed_variant["_id"]]
# Check that genomic features are created correcly by MME parser
g_feat = genomic_features(adapter, updated_case, "NA12882", "False")
assert g_feat
# use controller to send request and collect response
mme_base_url = "http://localhost:{port}".format(
port=self.mock_server_port)
submitted_info = controllers.mme_add(
store=adapter,
user_obj=user_obj,
case_obj=updated_case,
add_gender=True,
add_features=True,
add_disorders=True,
genes_only=False,
mme_base_url=mme_base_url,
mme_accepts=MME_ACCEPTS,
mme_token=MME_TOKEN,
)
assert submitted_info["server_responses"][0]["patient"]
