def get_sanger_unevaluated(store, institute_id, user_id):
"""Get all variants for an institute having Sanger validations ordered but still not evaluated
Args:
store(scout.adapter.MongoAdapter)
institute_id(str)
Returns:
unevaluated: a list that looks like this: [ {'case1': [varID_1, varID_2, .., varID_n]}, {'case2' : [varID_1, varID_2, .., varID_n]} ],
where the keys are case_ids and the values are lists of variants with Sanger ordered but not yet validated
"""
# Retrieve a list of ids for variants with Sanger ordered grouped by case from the 'event' collection
# This way is much faster than querying over all variants in all cases of an institute
sanger_ordered_by_case = store.sanger_ordered(institute_id, user_id)
unevaluated = []
# for each object where key==case and value==[variant_id with Sanger ordered]
for item in sanger_ordered_by_case:
case_id = item["_id"]
# Get the case to collect display name
case_obj = store.case(case_id=case_id)
if not case_obj: # the case might have been removed
continue
case_display_name = case_obj.get("display_name")
# List of variant document ids
varid_list = item["vars"]
unevaluated_by_case = {}
unevaluated_by_case[case_display_name] = []
for var_id in varid_list:
# For each variant with sanger validation ordered
variant_obj = store.variant(document_id=var_id, case_id=case_id)
# Double check that Sanger was ordered (and not canceled) for the variant
if (
variant_obj is None
or variant_obj.get("sanger_ordered") is None
or variant_obj.get("sanger_ordered") is False
):
continue
validation = variant_obj.get("validation", "not_evaluated")
# Check that the variant is not evaluated
if validation in ["True positive", "False positive"]:
continue
unevaluated_by_case[case_display_name].append(variant_obj["_id"])
# If for a case there is at least one Sanger validation to evaluate add the object to the unevaluated objects list
if len(unevaluated_by_case[case_display_name]) > 0:
unevaluated.append(unevaluated_by_case)
return unevaluated
def mark_causative(institute_id,
case_name,
variant_id,
partial_causative=False):
"""Mark a variant as confirmed causative."""
institute_obj, case_obj = institute_and_case(store, institute_id,
case_name)
variant_obj = store.variant(variant_id)
user_obj = store.user(current_user.email)
link = url_for("variant.variant",
institute_id=institute_id,
case_name=case_name,
variant_id=variant_id)
if request.form["action"] == "ADD":
if "partial_causative" in request.form:
omim_terms = request.form.getlist("omim_select")
hpo_terms = request.form.getlist("hpo_select")
store.mark_partial_causative(institute_obj, case_obj, user_obj,
link, variant_obj, omim_terms,
hpo_terms)
else:
store.mark_causative(institute_obj, case_obj, user_obj, link,
variant_obj)
elif request.form["action"] == "DELETE":
if partial_causative == "True":
store.unmark_partial_causative(institute_obj, case_obj, user_obj,
link, variant_obj)
else:
store.unmark_causative(institute_obj, case_obj, user_obj, link,
variant_obj)
# send the user back to the case that was marked as solved
case_url = url_for(".case", institute_id=institute_id, case_name=case_name)
return redirect(request.referrer)
def verify(institute_id, case_name, variant_id, variant_category, order):
"""Start procedure to validate variant using other techniques."""
institute_obj, case_obj = institute_and_case(store, institute_id,
case_name)
variant_obj = store.variant(variant_id)
user_obj = store.user(current_user.email)
comment = request.form.get('verification_comment')
try:
controllers.variant_verification(
store=store,
mail=mail,
institute_obj=institute_obj,
case_obj=case_obj,
user_obj=user_obj,
comment=comment,
variant_obj=variant_obj,
sender=current_app.config['MAIL_USERNAME'],
variant_url=request.referrer,
order=order,
url_builder=url_for)
except controllers.MissingVerificationRecipientError:
flash('No verification recipients added to institute.', 'danger')
return redirect(request.referrer)
def marrvel_link(build, variant_id):
"""Redirect to MARRVEL when user clicks on the relative button on variant page"""
variant_obj = store.variant(document_id=variant_id)
build = "38" if "38" in str(build) else "37"
url_template = "http://marrvel.org/human/variant/{}:{} {}>{}"
chrom = variant_obj["chromosome"]
start = variant_obj["position"]
ref = variant_obj["reference"]
alt = variant_obj["alternative"]
if build == "38": # liftover is necessary before returning link
client = EnsemblRestApiClient()
mapped_coords = client.liftover(
build,
chrom,
start,
)
if mapped_coords:
chrom = mapped_coords[0]["mapped"].get("seq_region_name")
start = mapped_coords[0]["mapped"].get("start")
else:
flash(
"MARRVEL requires variant coordinates in genome build 37, but variant liftover failed",
"warning",
)
return redirect(request.referrer)
return redirect(url_template.format(chrom, start, ref, alt), code=302)
def variant_update(institute_id, case_name, variant_id):
"""Update user-defined information about a variant: manual rank & ACMG."""
institute_obj, case_obj = institute_and_case(store, institute_id,
case_name)
variant_obj = store.variant(variant_id)
user_obj = store.user(current_user.email)
link = request.referrer
manual_rank = request.form.get('manual_rank')
if manual_rank:
new_manual_rank = int(manual_rank) if manual_rank != '-1' else None
store.update_manual_rank(institute_obj, case_obj, user_obj, link,
variant_obj, new_manual_rank)
if new_manual_rank:
flash("updated variant tag: {}".format(new_manual_rank), 'info')
else:
flash("reset variant tag: {}".format(variant_obj['manual_rank']),
'info')
elif request.form.get('acmg_classification'):
new_acmg = request.form['acmg_classification']
acmg_classification = variant_obj.get('acmg_classification')
if isinstance(acmg_classification,
int) and (new_acmg == ACMG_MAP[acmg_classification]):
new_acmg = None
store.update_acmg(institute_obj, case_obj, user_obj, link, variant_obj,
new_acmg)
flash("updated ACMG classification: {}".format(new_acmg), 'info')
return redirect(request.referrer)
def events(institute_id, case_name, event_id=None):
"""Handle events."""
institute_obj, case_obj = institute_and_case(store, institute_id,
case_name)
link = request.form.get("link")
content = request.form.get("content")
variant_id = request.args.get("variant_id")
user_obj = store.user(current_user.email)
if event_id:
# delete the event
store.delete_event(event_id)
else:
if variant_id:
# create a variant comment
variant_obj = store.variant(variant_id)
level = request.form.get("level", "specific")
store.comment(
institute_obj,
case_obj,
user_obj,
link,
variant=variant_obj,
content=content,
comment_level=level,
)
else:
# create a case comment
store.comment(institute_obj,
case_obj,
user_obj,
link,
content=content)
return redirect(request.referrer)
def test_causatives(app, user_obj, institute_obj, case_obj):
# GIVEN an initialized app
# GIVEN a valid user and institute
# There should be no causative variants for test case:
assert "causatives" not in case_obj
var1_id = "4c7d5c70d955875504db72ef8e1abe77" # in POT1 gene
var2_id = "e24b65bf27feacec6a81c8e9e19bd5f1" # in TBX1 gene
var_ids = [var1_id, var2_id]
# for each variant
for var_id in var_ids:
# update case by marking variant as causative:
variant_obj = store.variant(document_id=var_id)
store.mark_causative(
institute=institute_obj,
case=case_obj,
user=user_obj,
link="causative_var_link/{}".format(variant_obj["_id"]),
variant=variant_obj,
)
updated_case = store.case_collection.find_one({"_id": case_obj["_id"]})
# The above variants should be registered as causatives in case object
assert updated_case["causatives"] == var_ids
# Call scout causatives view and check if the above causatives are displayed
with app.test_client() as client:
# GIVEN that the user could be logged in
resp = client.get(url_for("auto_login"))
assert resp.status_code == 200
# WHEN accessing the case page
resp = client.get(
url_for("overview.causatives",
institute_id=institute_obj["internal_id"]))
# THEN it should return a page
assert resp.status_code == 200
# with variant 1
assert var1_id in str(resp.data)
# and variant 2
assert var2_id in str(resp.data)
# Filter causatives by gene (POT1)
resp = client.get(
url_for(
"overview.causatives",
institute_id=institute_obj["internal_id"],
query="17284 | POT1 (DKFZp586D211, hPot1, POT1)",
))
# THEN it should return a page
assert resp.status_code == 200
# with variant 1
assert var1_id in str(resp.data)
# but NOT variant 2
assert var2_id not in str(resp.data)
def mark_validation(institute_id, case_name, variant_id):
"""Mark a variant as sanger validated."""
institute_obj, case_obj = institute_and_case(store, institute_id, case_name)
variant_obj = store.variant(variant_id)
user_obj = store.user(current_user.email)
validate_type = request.form['type'] or None
link = url_for('variants.variant', institute_id=institute_id, case_name=case_name,
variant_id=variant_id)
store.validate(institute_obj, case_obj, user_obj, link, variant_obj, validate_type)
return redirect(request.referrer or link)
def mark_validation(institute_id, case_name, variant_id):
"""Mark a variant as sanger validated."""
institute_obj, case_obj = institute_and_case(store, institute_id, case_name)
variant_obj = store.variant(variant_id)
user_obj = store.user(current_user.email)
validate_type = request.form['type'] or None
link = url_for('variants.variant', institute_id=institute_id, case_name=case_name,
variant_id=variant_id)
store.validate(institute_obj, case_obj, user_obj, link, variant_obj, validate_type)
return redirect(request.referrer or link)
def manual_rank(institute_id, case_name, variant_id):
"""Update the manual variant rank for a variant."""
institute_obj, case_obj = institute_and_case(store, institute_id,
case_name)
variant_obj = store.variant(variant_id)
user_obj = store.user(current_user.email)
new_manual_rank = int(request.form['manual_rank'])
link = request.referrer
store.update_manual_rank(institute_obj, case_obj, user_obj, link,
variant_obj, new_manual_rank)
return redirect(request.referrer)
def variant_update(institute_id, case_name, variant_id):
"""Update user-defined information about a variant: manual rank & ACMG."""
institute_obj, case_obj = institute_and_case(store, institute_id, case_name)
variant_obj = store.variant(variant_id)
user_obj = store.user(current_user.email)
link = request.referrer
manual_rank = request.form.get('manual_rank')
if manual_rank:
new_manual_rank = int(manual_rank) if manual_rank != '-1' else None
store.update_manual_rank(institute_obj, case_obj, user_obj, link, variant_obj,
new_manual_rank)
if new_manual_rank:
flash("updated variant tag: {}".format(new_manual_rank), 'info')
else:
flash("reset variant tag: {}".format(variant_obj.get('manual_rank', 'NA')), 'info')
elif request.form.get('acmg_classification'):
new_acmg = request.form['acmg_classification']
acmg_classification = variant_obj.get('acmg_classification')
if isinstance(acmg_classification, int) and (new_acmg == ACMG_MAP[acmg_classification]):
new_acmg = None
store.update_acmg(institute_obj, case_obj, user_obj, link, variant_obj, new_acmg)
flash("updated ACMG classification: {}".format(new_acmg), 'info')
new_dismiss = request.form.getlist('dismiss_variant')
if request.form.getlist('dismiss_variant'):
store.update_dismiss_variant(institute_obj, case_obj, user_obj, link, variant_obj,
new_dismiss)
if new_dismiss:
flash("Dismissed variant: {}".format(new_dismiss), 'info')
if variant_obj.get('dismiss_variant') and not new_dismiss:
if 'dismiss' in request.form:
store.update_dismiss_variant(institute_obj, case_obj, user_obj, link, variant_obj,
new_dismiss)
flash("Reset variant dismissal: {}".format(variant_obj.get('dismiss_variant')), 'info')
else:
log.debug("DO NOT reset variant dismissal: {}".format(variant_obj.get('dismiss_variant')), 'info')
mosaic_tags = request.form.getlist('mosaic_tags')
if mosaic_tags:
store.update_mosaic_tags(institute_obj, case_obj, user_obj, link, variant_obj,
mosaic_tags)
if new_dismiss:
flash("Added mosaic tags: {}".format(mosaic_tags), 'info')
if variant_obj.get('mosaic_tags') and not mosaic_tags:
if 'mosaic' in request.form:
store.update_mosaic_tags(institute_obj, case_obj, user_obj, link, variant_obj,
mosaic_tags)
flash("Reset mosaic tags: {}".format(variant_obj.get('mosaic_tags')), 'info')
return redirect(request.referrer)
def pin_variant(institute_id, case_name, variant_id):
"""Pin and unpin variants to/from the list of suspects."""
institute_obj, case_obj = institute_and_case(store, institute_id, case_name)
variant_obj = store.variant(variant_id)
user_obj = store.user(current_user.email)
link = url_for('variants.variant', institute_id=institute_id, case_name=case_name,
variant_id=variant_id)
if request.form['action'] == 'ADD':
store.pin_variant(institute_obj, case_obj, user_obj, link, variant_obj)
elif request.form['action'] == 'DELETE':
store.unpin_variant(institute_obj, case_obj, user_obj, link, variant_obj)
return redirect(request.referrer or link)
def variant_update(institute_id, case_name, variant_id):
"""Update user-defined information about a variant: manual rank & ACMG."""
institute_obj, case_obj = institute_and_case(store, institute_id, case_name)
variant_obj = store.variant(variant_id)
user_obj = store.user(current_user.email)
link = request.referrer
manual_rank = request.form.get('manual_rank')
if manual_rank:
new_manual_rank = int(manual_rank) if manual_rank != '-1' else None
store.update_manual_rank(institute_obj, case_obj, user_obj, link, variant_obj,
new_manual_rank)
if new_manual_rank:
flash("updated variant tag: {}".format(new_manual_rank), 'info')
else:
flash("reset variant tag: {}".format(variant_obj.get('manual_rank', 'NA')), 'info')
elif request.form.get('acmg_classification'):
new_acmg = request.form['acmg_classification']
acmg_classification = variant_obj.get('acmg_classification')
if isinstance(acmg_classification, int) and (new_acmg == ACMG_MAP[acmg_classification]):
new_acmg = None
store.update_acmg(institute_obj, case_obj, user_obj, link, variant_obj, new_acmg)
flash("updated ACMG classification: {}".format(new_acmg), 'info')
new_dismiss = request.form.getlist('dismiss_variant')
if request.form.getlist('dismiss_variant'):
store.update_dismiss_variant(institute_obj, case_obj, user_obj, link, variant_obj,
new_dismiss)
if new_dismiss:
flash("Dismissed variant: {}".format(new_dismiss), 'info')
if variant_obj.get('dismiss_variant') and not new_dismiss:
if 'dismiss' in request.form:
store.update_dismiss_variant(institute_obj, case_obj, user_obj, link, variant_obj,
new_dismiss)
flash("Reset variant dismissal: {}".format(variant_obj.get('dismiss_variant')), 'info')
else:
log.debug("DO NOT reset variant dismissal: {}".format(variant_obj.get('dismiss_variant')), 'info')
mosaic_tags = request.form.getlist('mosaic_tags')
if mosaic_tags:
store.update_mosaic_tags(institute_obj, case_obj, user_obj, link, variant_obj,
mosaic_tags)
if new_dismiss:
flash("Added mosaic tags: {}".format(mosaic_tags), 'info')
if variant_obj.get('mosaic_tags') and not mosaic_tags:
if 'mosaic' in request.form:
store.update_mosaic_tags(institute_obj, case_obj, user_obj, link, variant_obj,
mosaic_tags)
flash("Reset mosaic tags: {}".format(variant_obj.get('mosaic_tags')), 'info')
return redirect(request.referrer)
def pin_variant(institute_id, case_name, variant_id):
"""Pin and unpin variants to/from the list of suspects."""
institute_obj, case_obj = institute_and_case(store, institute_id, case_name)
variant_obj = store.variant(variant_id)
user_obj = store.user(current_user.email)
link = url_for('variants.variant', institute_id=institute_id, case_name=case_name,
variant_id=variant_id)
if request.form['action'] == 'ADD':
store.pin_variant(institute_obj, case_obj, user_obj, link, variant_obj)
elif request.form['action'] == 'DELETE':
store.unpin_variant(institute_obj, case_obj, user_obj, link, variant_obj)
return redirect(request.referrer or link)
def sanger(institute_id, case_name, variant_id):
"""Send Sanger email for confirming a variant."""
institute_obj, case_obj = institute_and_case(store, institute_id,
case_name)
variant_obj = store.variant(variant_id)
user_obj = store.user(current_user.email)
try:
controllers.sanger(store, mail, institute_obj, case_obj, user_obj,
variant_obj, current_app.config['MAIL_USERNAME'])
except controllers.MissingSangerRecipientError:
flash('No sanger recipients added to institute.', 'danger')
return redirect(request.referrer)
def mark_causative(institute_id, case_name, variant_id):
"""Mark a variant as confirmed causative."""
institute_obj, case_obj = institute_and_case(store, institute_id, case_name)
variant_obj = store.variant(variant_id)
user_obj = store.user(current_user.email)
link = url_for('variants.variant', institute_id=institute_id, case_name=case_name,
variant_id=variant_id)
if request.form['action'] == 'ADD':
store.mark_causative(institute_obj, case_obj, user_obj, link, variant_obj)
elif request.form['action'] == 'DELETE':
store.unmark_causative(institute_obj, case_obj, user_obj, link, variant_obj)
# send the user back to the case that was marked as solved
case_url = url_for('.case', institute_id=institute_id, case_name=case_name)
return redirect(case_url)
def mark_causative(institute_id, case_name, variant_id):
"""Mark a variant as confirmed causative."""
institute_obj, case_obj = institute_and_case(store, institute_id, case_name)
variant_obj = store.variant(variant_id)
user_obj = store.user(current_user.email)
link = url_for('variants.variant', institute_id=institute_id, case_name=case_name,
variant_id=variant_id)
if request.form['action'] == 'ADD':
store.mark_causative(institute_obj, case_obj, user_obj, link, variant_obj)
elif request.form['action'] == 'DELETE':
store.unmark_causative(institute_obj, case_obj, user_obj, link, variant_obj)
# send the user back to the case that was marked as solved
case_url = url_for('.case', institute_id=institute_id, case_name=case_name)
return redirect(case_url)
def verify(institute_id, case_name, variant_id, variant_category, order):
"""Start procedure to validate variant using other techniques."""
institute_obj, case_obj = institute_and_case(store, institute_id, case_name)
variant_obj = store.variant(variant_id)
user_obj = store.user(current_user.email)
comment = request.form.get('verification_comment')
try:
controllers.variant_verification(store=store, mail=mail, institute_obj=institute_obj, case_obj=case_obj, user_obj=user_obj, comment=comment,
variant_obj=variant_obj, sender=current_app.config['MAIL_USERNAME'], variant_url=request.referrer, order=order, url_builder=url_for)
except controllers.MissingVerificationRecipientError:
flash('No verification recipients added to institute.', 'danger')
return redirect(request.referrer)
def events(institute_id, case_name, event_id=None):
"""Handle events."""
institute_obj, case_obj = institute_and_case(store, institute_id, case_name)
link = request.form.get('link')
content = request.form.get('content')
variant_id = request.args.get('variant_id')
user_obj = store.user(current_user.email)
if event_id:
# delete the event
store.delete_event(event_id)
else:
if variant_id:
# create a variant comment
variant_obj = store.variant(variant_id)
level = request.form.get('level', 'specific')
store.comment(institute_obj, case_obj, user_obj, link,
variant=variant_obj, content=content, comment_level=level)
else:
# create a case comment
store.comment(institute_obj, case_obj, user_obj, link, content=content)
return redirect(request.referrer)
def variant(institute_id, case_name, variant_id):
"""Display a specific SNV variant."""
institute_obj, case_obj = institute_and_case(store, institute_id, case_name)
variant_obj = store.variant(variant_id)
return Response(json_util.dumps(variant_obj), mimetype='application/json')
def make_sashimi_tracks(case_obj, variant_id):
"""Create a dictionary containing the required tracks for a splice junction plot
Args:
case_obj(scout.models.Case)
variant_id(str) _id of a variant
Returns:
display_obj(dict): A display object containing case name, list of genes, lucus and tracks
"""
build = "38" # This feature is only available for RNA tracks in build 38
variant_obj = store.variant(document_id=variant_id)
# Initialize locus coordinates it with variant coordinates so it won't crash if variant gene(s) no longer exist in database
locus_start_coords = []
locus_end_coords = []
# Check if variant coordinates are in genome build 38
# Otherwise do variant coords liftover
if build not in str(case_obj.get("genome_build")):
client = EnsemblRestApiClient()
mapped_coords = client.liftover(
case_obj.get("genome_build"),
variant_obj.get("chromosome"),
variant_obj.get("position"),
variant_obj.get("end"),
)
if mapped_coords:
mapped_start = mapped_coords[0]["mapped"].get("start")
mapped_end = mapped_coords[0]["mapped"].get("end") or mapped_start
locus_start_coords.append(mapped_start)
locus_end_coords.append(mapped_end)
# Use original coordinates only genome build was already 38 or liftover didn't work
if not locus_start_coords:
locus_start_coords.append(variant_obj.get("position"))
if not locus_end_coords:
locus_end_coords.append(variant_obj.get("end"))
# Collect locus coordinates. Take into account that variant can hit multiple genes
variant_genes_ids = [
gene["hgnc_id"] for gene in variant_obj.get("genes", [])
]
for gene_id in variant_genes_ids:
gene_caption = store.hgnc_gene_caption(hgnc_identifier=gene_id,
build=build)
if gene_caption is None:
continue
locus_start_coords.append(gene_caption["start"])
locus_end_coords.append(gene_caption["end"])
locus_start = min(locus_start_coords)
locus_end = max(locus_end_coords)
locus = f"{variant_obj['chromosome']}:{locus_start}-{locus_end}" # Locus will span all genes the variant falls into
display_obj = {"locus": locus, "tracks": []}
# Add Genes and reference tracks to display object
set_common_tracks(display_obj, build)
# Populate tracks for each individual with splice junction track data
for ind in case_obj.get("individuals", []):
if not all(
[ind.get("splice_junctions_bed"),
ind.get("rna_coverage_bigwig")]):
continue
coverage_wig = ind["rna_coverage_bigwig"]
splicej_bed = ind["splice_junctions_bed"]
splicej_bed_index = f"{splicej_bed}.tbi" if os.path.isfile(
f"{splicej_bed}.tbi") else None
if splicej_bed_index is None:
flash(
f"Missing bed file index for individual {ind['display_name']}")
track = {
"name": ind["display_name"],
"coverage_wig": coverage_wig,
"splicej_bed": splicej_bed,
"splicej_bed_index": splicej_bed_index,
}
display_obj["tracks"].append(track)
display_obj["case"] = case_obj["display_name"]
return display_obj
def variant_update(institute_id, case_name, variant_id):
"""Update user-defined information about a variant: manual rank & ACMG."""
institute_obj, case_obj = institute_and_case(store, institute_id,
case_name)
variant_obj = store.variant(variant_id)
user_obj = store.user(current_user.email)
link = request.referrer
manual_rank = request.form.get("manual_rank")
cancer_tier = request.form.get("cancer_tier")
if manual_rank:
try:
new_manual_rank = int(manual_rank) if manual_rank != "-1" else None
except ValueError:
LOG.warning(
"Attempt to update manual rank with invalid value {}".format(
manual_rank))
manual_rank = "-1"
new_manual_rank = -1
store.update_manual_rank(institute_obj, case_obj, user_obj, link,
variant_obj, new_manual_rank)
if new_manual_rank:
flash("updated variant tag: {}".format(new_manual_rank), "info")
else:
flash(
"reset variant tag: {}".format(
variant_obj.get("manual_rank", "NA")),
"info",
)
elif cancer_tier:
try:
new_cancer_tier = cancer_tier if cancer_tier != "-1" else None
except ValueError:
LOG.warning(
"Attempt to update cancer tier with invalid value {}".format(
cancer_tier))
cancer_tier = "-1"
new_cancer_tier = "-1"
store.update_cancer_tier(institute_obj, case_obj, user_obj, link,
variant_obj, new_cancer_tier)
if new_cancer_tier:
flash("updated variant tag: {}".format(new_cancer_tier), "info")
else:
flash(
"reset variant tag: {}".format(
variant_obj.get("cancer_tier", "NA")),
"info",
)
elif request.form.get("acmg_classification"):
new_acmg = request.form["acmg_classification"]
acmg_classification = variant_obj.get("acmg_classification")
# If there already is a classification and the same one is sent again this means that
# We want to remove the classification
if isinstance(acmg_classification,
int) and (new_acmg == ACMG_MAP[acmg_classification]):
new_acmg = None
store.submit_evaluation(
variant_obj=variant_obj,
user_obj=user_obj,
institute_obj=institute_obj,
case_obj=case_obj,
link=link,
classification=new_acmg,
)
flash("updated ACMG classification: {}".format(new_acmg), "info")
new_dismiss = request.form.getlist("dismiss_variant")
if new_dismiss:
store.update_dismiss_variant(institute_obj, case_obj, user_obj, link,
variant_obj, new_dismiss)
flash("Dismissed variant: {}".format(new_dismiss), "info")
variant_dismiss = variant_obj.get("dismiss_variant")
if variant_dismiss and not new_dismiss:
if "dismiss" in request.form:
store.update_dismiss_variant(institute_obj, case_obj, user_obj,
link, variant_obj, new_dismiss)
flash(
"Reset variant dismissal: {}".format(
variant_obj.get("dismiss_variant")),
"info",
)
else:
LOG.debug("DO NOT reset variant dismissal: {}".format(
",".join(variant_dismiss), "info"))
mosaic_tags = request.form.getlist("mosaic_tags")
if mosaic_tags:
store.update_mosaic_tags(institute_obj, case_obj, user_obj, link,
variant_obj, mosaic_tags)
flash("Added mosaic tags: {}".format(mosaic_tags), "info")
variant_mosaic = variant_obj.get("mosaic_tags")
if variant_mosaic and not mosaic_tags:
if "mosaic" in request.form:
store.update_mosaic_tags(institute_obj, case_obj, user_obj, link,
variant_obj, mosaic_tags)
flash("Reset mosaic tags: {}".format(",".join(variant_mosaic),
"info"))
return redirect(request.referrer)
def variant(institute_id, case_name, variant_id):
"""Display a specific SNV variant."""
institute_obj, case_obj = institute_and_case(store, institute_id,
case_name)
variant_obj = store.variant(variant_id)
return Response(json_util.dumps(variant_obj), mimetype='application/json')
def make_igv_tracks(case_obj, variant_id, chrom=None, start=None, stop=None):
"""Create a dictionary containing the required tracks for displaying IGV tracks for case or a group of cases
Args:
institute_id(str): institute _id
case_obj(scout.models.Case)
variant_id(str): _id of a variant
chrom(str/None): requested chromosome [1-22], X, Y, [M-MT]
start(int/None): start of the genomic interval to be displayed
stop(int/None): stop of the genomic interval to be displayed
Returns:
display_obj(dict): A display object containing case name, list of genes, lucus and tracks
"""
display_obj = {}
variant_obj = store.variant(document_id=variant_id)
if variant_obj:
# Set display locus
start = start or variant_obj["position"]
stop = stop or variant_obj["end"]
chromosome = chrom or variant_obj.get("chromosome")
chromosome = chromosome.replace("MT", "M")
display_obj["locus"] = "chr{0}:{1}-{2}".format(chromosome, start, stop)
else:
chromosome = "All"
# Set genome build for displaying alignments:
if "38" in str(case_obj.get("genome_build", "37")) or chromosome == "M":
build = "38"
else:
build = "37"
# Set general tracks (Genes, Clinvar and ClinVar SNVs are shown according to user preferences)
set_common_tracks(display_obj, build)
# Build tracks for main case and all connected cases (cases grouped with main case)
grouped_cases = []
for group in case_obj.get("group", []):
group_cases = list(store.cases(group=group))
for case in group_cases:
case_append_alignments(
case) # Add track data to connected case dictionary
grouped_cases.append(case)
if not grouped_cases: # Display case individuals tracks only
case_append_alignments(
case_obj) # Add track data to main case dictionary
grouped_cases.append(case_obj)
# Set up bam/cram alignments for case group samples:
set_sample_tracks(display_obj, grouped_cases, chromosome)
# When chrom != MT, set up case-specific tracks (might be present according to the pipeline)
if chrom != "M":
set_case_specific_tracks(display_obj, case_obj)
# Set up custom cloud public tracks, if available
set_cloud_public_tracks(display_obj, build)
display_obj["display_center_guide"] = True
return display_obj
def case_report_variants(store, case_obj, institute_obj, data):
"""Gather evaluated variants info to include in case report
Args:
store(adapter.MongoAdapter)
case_obj(dict): case dictionary
data(dict): data dictionary containing case report information
"""
evaluated_variants = {vt: [] for vt in CASE_REPORT_VARIANT_TYPES}
# We collect all causatives (including the partial ones) and suspected variants
# These are handeled in separate since they are on case level
for var_type in ["causatives", "suspects", "partial_causatives"]:
# These include references to variants
vt = "_".join([var_type, "detailed"])
for var_id in case_obj.get(var_type, []):
variant_obj = store.variant(var_id)
if not variant_obj:
continue
if var_type == "partial_causatives": # Collect associated phenotypes
variant_obj["phenotypes"] = [
value for key, value in case_obj["partial_causatives"].items() if key == var_id
][0]
evaluated_variants[vt].append(variant_obj)
## get variants for this case that are either classified, commented, tagged or dismissed.
for var_obj in store.evaluated_variants(
case_id=case_obj["_id"], institute_id=institute_obj["_id"]
):
# Check which category it belongs to
for vt in CASE_REPORT_VARIANT_TYPES:
keyword = CASE_REPORT_VARIANT_TYPES[vt]
# When found we add it to the category
# Each variant can belong to multiple categories
if keyword not in var_obj:
continue
evaluated_variants[vt].append(var_obj)
data["variants"] = {}
for var_type in evaluated_variants:
decorated_variants = []
for var_obj in evaluated_variants[var_type]:
# We decorate the variant with some extra information
filtered_var_obj = {}
for feat in VARIANT_REPORT_VARIANT_FEATURES:
filtered_var_obj[feat] = var_obj.get(feat)
variant_category = var_obj["category"]
populate_individual_callers(filtered_var_obj, var_obj)
decorated_info = variant_decorator(
store=store,
institute_id=institute_obj["_id"],
case_name=case_obj["display_name"],
variant_id=None,
variant_obj=filtered_var_obj,
add_case=False,
add_other=False,
get_overlapping=False,
variant_type=variant_category,
institute_obj=institute_obj,
case_obj=case_obj,
)
decorated_variants.append(decorated_info["variant"])
# Add the decorated variants to the case
data["variants"][var_type] = decorated_variants
def case(store, institute_obj, case_obj):
"""Preprocess a single case.
Prepare the case to be displayed in the case view.
Args:
store(adapter.MongoAdapter)
institute_obj(models.Institute)
case_obj(models.Case)
Returns:
data(dict): includes the cases, how many there are and the limit.
"""
# Convert individual information to more readable format
case_obj["individual_ids"] = []
for individual in case_obj["individuals"]:
try:
sex = int(individual.get("sex", 0))
except ValueError as err:
sex = 0
individual["sex_human"] = SEX_MAP[sex]
pheno_map = PHENOTYPE_MAP
if case_obj.get("track", "rare") == "cancer":
pheno_map = CANCER_PHENOTYPE_MAP
individual["phenotype_human"] = pheno_map.get(individual["phenotype"])
case_obj["individual_ids"].append(individual["individual_id"])
case_obj["assignees"] = [store.user(user_email) for user_email in case_obj.get("assignees", [])]
# Provide basic info on alignment files availability for this case
case_has_alignments(case_obj)
case_has_mt_alignments(case_obj)
case_groups = {}
case_group_label = {}
_populate_case_groups(store, case_obj, case_groups, case_group_label)
# Fetch the variant objects for suspects and causatives
suspects = [
store.variant(variant_id) or variant_id for variant_id in case_obj.get("suspects", [])
]
_populate_assessments(suspects)
causatives = [
store.variant(variant_id) or variant_id for variant_id in case_obj.get("causatives", [])
]
_populate_assessments(causatives)
# get evaluated variants
evaluated_variants = store.evaluated_variants(case_obj["_id"], case_obj["owner"])
_populate_assessments(evaluated_variants)
# check for partial causatives and associated phenotypes
partial_causatives = []
if case_obj.get("partial_causatives"):
for var_id, values in case_obj["partial_causatives"].items():
causative_obj = {
"variant": store.variant(var_id) or var_id,
"omim_terms": values.get("diagnosis_phenotypes"),
"hpo_terms": values.get("phenotype_terms"),
}
partial_causatives.append(causative_obj)
_populate_assessments(partial_causatives)
# Set of all unique genes in the default gene panels
distinct_genes = set()
case_obj["panel_names"] = []
case_obj["outdated_panels"] = {}
for panel_info in case_obj.get("panels", []):
if not panel_info.get("is_default"):
continue
panel_name = panel_info["panel_name"]
panel_version = panel_info.get("version")
panel_obj = store.gene_panel(panel_name, version=panel_version)
latest_panel = store.gene_panel(panel_name)
panel_info["removed"] = False if latest_panel is None else latest_panel.get("hidden", False)
if not panel_obj:
panel_obj = latest_panel
if not panel_obj:
flash(f"Case default panel '{panel_name}' could not be found.", "warning")
continue
flash(
f"Case default panel '{panel_name}' version {panel_version} could not be found, using latest existing version",
"warning",
)
# Check if case-specific panel is up-to-date with latest version of the panel
if panel_obj["version"] < latest_panel["version"]:
extra_genes, missing_genes = _check_outdated_gene_panel(panel_obj, latest_panel)
if extra_genes or missing_genes:
case_obj["outdated_panels"][panel_name] = {
"missing_genes": missing_genes,
"extra_genes": extra_genes,
}
distinct_genes.update([gene["hgnc_id"] for gene in panel_obj.get("genes", [])])
full_name = "{} ({})".format(panel_obj["display_name"], panel_obj["version"])
case_obj["panel_names"].append(full_name)
case_obj["default_genes"] = list(distinct_genes)
for hpo_term in itertools.chain(
case_obj.get("phenotype_groups", []), case_obj.get("phenotype_terms", [])
):
hpo_term["hpo_link"] = "http://hpo.jax.org/app/browse/term/{}".format(
hpo_term["phenotype_id"]
)
if case_obj.get("rank_model_version"):
rank_model_link = "".join(
[
current_app.config.get("RANK_MODEL_LINK_PREFIX", ""),
str(case_obj["rank_model_version"]),
current_app.config.get("RANK_MODEL_LINK_POSTFIX", ""),
]
)
case_obj["rank_model_link"] = rank_model_link
if case_obj.get("sv_rank_model_version"):
case_obj["sv_rank_model_link"] = "".join(
[
current_app.config.get("SV_RANK_MODEL_LINK_PREFIX", ""),
str(case_obj["sv_rank_model_version"]),
current_app.config.get("SV_RANK_MODEL_LINK_POSTFIX", ""),
]
)
# other collaborators than the owner of the case
o_collaborators = []
for collab_id in case_obj.get("collaborators", []):
if collab_id != case_obj["owner"] and store.institute(collab_id):
o_collaborators.append(store.institute(collab_id))
case_obj["o_collaborators"] = [
(collab_obj["_id"], collab_obj["display_name"]) for collab_obj in o_collaborators
]
collab_ids = None
if institute_obj.get("collaborators"):
collab_ids = [
(collab["_id"], collab["display_name"])
for collab in store.institutes()
if institute_obj.get("collaborators")
and collab["_id"] in institute_obj.get("collaborators")
]
events = list(store.events(institute_obj, case=case_obj))
