def sv_variants(institute_id, case_name):
"""Display a list of structural variants."""
page = int(request.form.get("page", 1))
variant_type = request.args.get("variant_type", "clinical")
category = "sv"
# Define case and institute objects
institute_obj, case_obj = institute_and_case(store, institute_id,
case_name)
if request.form.get("hpo_clinical_filter"):
case_obj["hpo_clinical_filter"] = True
if request.form.getlist("dismiss"): # dismiss a list of variants
controllers.dismiss_variant_list(
store,
institute_obj,
case_obj,
"variant.sv_variant",
request.form.getlist("dismiss"),
request.form.getlist("dismiss_choices"),
)
# update status of case if visited for the first time
controllers.activate_case(store, institute_obj, case_obj, current_user)
form = controllers.populate_sv_filters_form(store, institute_obj, case_obj,
category, request)
cytobands = store.cytoband_by_chrom(case_obj.get("genome_build"))
variants_query = store.variants(case_obj["_id"],
category=category,
query=form.data)
# Setup variant count session with variant count by category
controllers.variant_count_session(store, institute_id, case_obj["_id"],
variant_type, category)
result_size = store.count_variants(case_obj["_id"], form.data, None,
category)
session["filtered_variants"] = result_size
# if variants should be exported
if request.form.get("export"):
return controllers.download_variants(store, case_obj, variants_query)
data = controllers.sv_variants(store, institute_obj, case_obj,
variants_query, result_size, page)
return dict(
institute=institute_obj,
case=case_obj,
dismiss_variant_options=DISMISS_VARIANT_OPTIONS,
variant_type=variant_type,
form=form,
cytobands=cytobands,
severe_so_terms=SEVERE_SO_TERMS,
manual_rank_options=MANUAL_RANK_OPTIONS,
page=page,
expand_search=str(request.method == "POST"),
**data,
)
def sv_variants(institute_id, case_name):
"""Display a list of structural variants."""
page = int(request.args.get('page', 1))
variant_type = request.args.get('variant_type', 'clinical')
form = SvFiltersForm(request.args)
institute_obj, case_obj = institute_and_case(store, institute_id,
case_name)
panel_choices = [(panel['panel_name'], panel['display_name'])
for panel in case_obj.get('panels', [])]
form.gene_panels.choices = panel_choices
query = form.data
query['variant_type'] = variant_type
variants_query = store.variants(case_obj['_id'],
category='sv',
query=form.data)
data = controllers.sv_variants(store, variants_query, page)
return dict(institute=institute_obj,
case=case_obj,
variant_type=variant_type,
form=form,
severe_so_terms=SEVERE_SO_TERMS,
page=page,
**data)
def str_variants(institute_id, case_name):
"""Display a list of STR variants."""
page = int(request.args.get("page", 1))
variant_type = request.args.get("variant_type", "clinical")
category = "str"
form = StrFiltersForm(request.args)
institute_obj, case_obj = institute_and_case(store, institute_id, case_name)
controllers.activate_case(store, institute_obj, case_obj, current_user)
query = form.data
query["variant_type"] = variant_type
variants_query = store.variants(case_obj["_id"], category=category, query=query).sort(
[
("str_repid", pymongo.ASCENDING),
("chromosome", pymongo.ASCENDING),
("position", pymongo.ASCENDING),
]
)
data = controllers.str_variants(store, institute_obj, case_obj, variants_query, page)
return dict(
institute=institute_obj,
case=case_obj,
dismiss_variant_options=DISMISS_VARIANT_OPTIONS,
variant_type=variant_type,
manual_rank_options=MANUAL_RANK_OPTIONS,
form=form,
page=page,
**data,
)
def str_variants(institute_id, case_name):
"""Display a list of STR variants."""
page = int(request.args.get('page', 1))
variant_type = request.args.get('variant_type', 'clinical')
form = StrFiltersForm(request.args)
institute_obj, case_obj = institute_and_case(store, institute_id, case_name)
query = form.data
query['variant_type'] = variant_type
variants_query = store.variants(case_obj['_id'], category='str',
query=query)
data = controllers.str_variants(store, institute_obj, case_obj,
variants_query, page)
return dict(institute=institute_obj, case=case_obj,
variant_type = variant_type, form=form, page=page, **data)
def str_variants(institute_id, case_name):
"""Display a list of STR variants."""
page = int(request.args.get('page', 1))
variant_type = request.args.get('variant_type', 'clinical')
form = StrFiltersForm(request.args)
institute_obj, case_obj = institute_and_case(store, institute_id, case_name)
query = form.data
query['variant_type'] = variant_type
variants_query = store.variants(case_obj['_id'], category='str',
query=query)
data = controllers.str_variants(store, institute_obj, case_obj,
variants_query, page)
return dict(institute=institute_obj, case=case_obj,
variant_type = variant_type, form=form, page=page, **data)
def cancer_sv_variants(institute_id, case_name):
"""Display a list of cancer structural variants."""
page = int(request.form.get("page", 1))
variant_type = request.args.get("variant_type", "clinical")
category = "cancer_sv"
# Define case and institute objects
institute_obj, case_obj = institute_and_case(store, institute_id,
case_name)
if request.form.get("hpo_clinical_filter"):
case_obj["hpo_clinical_filter"] = True
# update status of case if visited for the first time
controllers.activate_case(store, institute_obj, case_obj, current_user)
form = controllers.populate_sv_filters_form(store, institute_obj, case_obj,
category, request)
variants_query = store.variants(case_obj["_id"],
category=category,
query=form.data)
# if variants should be exported
if request.form.get("export"):
return controllers.download_variants(store, case_obj, variants_query)
data = controllers.sv_variants(store, institute_obj, case_obj,
variants_query, page)
return dict(institute=institute_obj,
case=case_obj,
variant_type=variant_type,
form=form,
severe_so_terms=SEVERE_SO_TERMS,
cancer_tier_options=CANCER_TIER_OPTIONS,
manual_rank_options=MANUAL_RANK_OPTIONS,
page=page,
**data)
def variants(institute_id, case_name):
"""Display a list of SNV variants."""
page = int(request.args.get('page', 1))
institute_obj, case_obj = institute_and_case(store, institute_id,
case_name)
form = FiltersForm(request.args)
panel_choices = [(panel['panel_name'], panel['display_name'])
for panel in case_obj.get('panels', [])]
form.gene_panels.choices = panel_choices
# update status of case if vistited for the first time
if case_obj['status'] == 'inactive' and not current_user.is_admin:
flash('You just activated this case!', 'info')
user_obj = store.user(current_user.email)
case_link = url_for('cases.case',
institute_id=institute_obj['_id'],
case_name=case_obj['display_name'])
store.update_status(institute_obj, case_obj, user_obj, 'active',
case_link)
# handle HPO gene list separately
if form.data['gene_panels'] == ['hpo']:
hpo_symbols = list(
set(term_obj['hgnc_symbol']
for term_obj in case_obj['dynamic_gene_list']))
form.hgnc_symbols.data = hpo_symbols
variants_query = store.variants(case_obj['_id'], query=form.data)
data = controllers.variants(store, variants_query, page)
return dict(institute=institute_obj,
case=case_obj,
form=form,
severe_so_terms=SEVERE_SO_TERMS,
page=page,
**data)
def variants(institute_id, case_name):
"""Display a list of SNV variants."""
page = int(request.form.get('page', 1))
institute_obj, case_obj = institute_and_case(store, institute_id,
case_name)
variant_type = request.args.get('variant_type', 'clinical')
# Update filter settings if Clinical Filter was requested
default_panels = []
for panel in case_obj['panels']:
if panel.get('is_default'):
default_panels.append(panel['panel_name'])
request.form.get('gene_panels')
if bool(request.form.get('clinical_filter')):
clinical_filter = MultiDict({
'variant_type':
'clinical',
'region_annotations': ['exonic', 'splicing'],
'functional_annotations':
SEVERE_SO_TERMS,
'clinsig': [4, 5],
'clinsig_confident_always_returned':
True,
'gnomad_frequency':
str(institute_obj['frequency_cutoff']),
'variant_type':
'clinical',
'gene_panels':
default_panels
})
if (request.method == "POST"):
if bool(request.form.get('clinical_filter')):
form = FiltersForm(clinical_filter)
form.csrf_token = request.args.get('csrf_token')
else:
form = FiltersForm(request.form)
else:
form = FiltersForm(request.args)
# populate available panel choices
available_panels = case_obj.get('panels', []) + [{
'panel_name': 'hpo',
'display_name': 'HPO'
}]
panel_choices = [(panel['panel_name'], panel['display_name'])
for panel in available_panels]
form.gene_panels.choices = panel_choices
# upload gene panel if symbol file exists
if (request.files):
file = request.files[form.symbol_file.name]
if request.files and file and file.filename != '':
log.debug("Upload file request files: {0}".format(
request.files.to_dict()))
try:
stream = io.StringIO(file.stream.read().decode('utf-8'),
newline=None)
except UnicodeDecodeError as error:
flash("Only text files are supported!", 'warning')
return redirect(request.referrer)
hgnc_symbols_set = set(form.hgnc_symbols.data)
log.debug("Symbols prior to upload: {0}".format(hgnc_symbols_set))
new_hgnc_symbols = controllers.upload_panel(store, institute_id,
case_name, stream)
hgnc_symbols_set.update(new_hgnc_symbols)
form.hgnc_symbols.data = hgnc_symbols_set
# reset gene panels
form.gene_panels.data = ''
# update status of case if vistited for the first time
if case_obj['status'] == 'inactive' and not current_user.is_admin:
flash('You just activated this case!', 'info')
user_obj = store.user(current_user.email)
case_link = url_for('cases.case',
institute_id=institute_obj['_id'],
case_name=case_obj['display_name'])
store.update_status(institute_obj, case_obj, user_obj, 'active',
case_link)
# check if supplied gene symbols exist
hgnc_symbols = []
non_clinical_symbols = []
not_found_symbols = []
not_found_ids = []
if (form.hgnc_symbols.data) and len(form.hgnc_symbols.data) > 0:
is_clinical = form.data.get('variant_type', 'clinical') == 'clinical'
clinical_symbols = store.clinical_symbols(
case_obj) if is_clinical else None
for hgnc_symbol in form.hgnc_symbols.data:
if hgnc_symbol.isdigit():
hgnc_gene = store.hgnc_gene(int(hgnc_symbol))
if hgnc_gene is None:
not_found_ids.append(hgnc_symbol)
else:
hgnc_symbols.append(hgnc_gene['hgnc_symbol'])
elif store.hgnc_genes(hgnc_symbol).count() == 0:
not_found_symbols.append(hgnc_symbol)
elif is_clinical and (hgnc_symbol not in clinical_symbols):
non_clinical_symbols.append(hgnc_symbol)
else:
hgnc_symbols.append(hgnc_symbol)
if (not_found_ids):
flash("HGNC id not found: {}".format(", ".join(not_found_ids)),
'warning')
if (not_found_symbols):
flash("HGNC symbol not found: {}".format(", ".join(not_found_symbols)),
'warning')
if (non_clinical_symbols):
flash(
"Gene not included in clinical list: {}".format(
", ".join(non_clinical_symbols)), 'warning')
form.hgnc_symbols.data = hgnc_symbols
# handle HPO gene list separately
if form.data['gene_panels'] == ['hpo']:
hpo_symbols = list(
set(term_obj['hgnc_symbol']
for term_obj in case_obj['dynamic_gene_list']))
form.hgnc_symbols.data = hpo_symbols
variants_query = store.variants(case_obj['_id'], query=form.data)
data = {}
if request.form.get('export'):
document_header = controllers.variants_export_header(case_obj)
export_lines = []
if form.data['chrom'] == 'MT':
# Return all MT variants
export_lines = controllers.variant_export_lines(
store, case_obj, variants_query)
else:
# Return max 500 variants
export_lines = controllers.variant_export_lines(
store, case_obj, variants_query.limit(500))
def generate(header, lines):
yield header + '\n'
for line in lines:
yield line + '\n'
headers = Headers()
headers.add('Content-Disposition',
'attachment',
filename=str(case_obj['display_name']) +
'-filtered_variants.csv')
# return a csv with the exported variants
return Response(generate(",".join(document_header), export_lines),
mimetype='text/csv',
headers=headers)
data = controllers.variants(store, institute_obj, case_obj, variants_query,
page)
return dict(institute=institute_obj,
case=case_obj,
form=form,
severe_so_terms=SEVERE_SO_TERMS,
page=page,
**data)
def sv_variants(institute_id, case_name):
"""Display a list of structural variants."""
page = int(request.form.get('page', 1))
variant_type = request.args.get('variant_type', 'clinical')
institute_obj, case_obj = institute_and_case(store, institute_id,
case_name)
form = SvFiltersForm(request.form)
default_panels = []
for panel in case_obj['panels']:
if panel['is_default']:
default_panels.append(panel['panel_name'])
request.form.get('gene_panels')
if bool(request.form.get('clinical_filter')):
clinical_filter = MultiDict({
'variant_type':
'clinical',
'region_annotations': ['exonic', 'splicing'],
'functional_annotations':
SEVERE_SO_TERMS,
'thousand_genomes_frequency':
str(institute_obj['frequency_cutoff']),
'variant_type':
'clinical',
'clingen_ngi':
10,
'swegen':
10,
'size':
100,
'gene_panels':
default_panels
})
if (request.method == "POST"):
if bool(request.form.get('clinical_filter')):
form = SvFiltersForm(clinical_filter)
form.csrf_token = request.args.get('csrf_token')
else:
form = SvFiltersForm(request.form)
else:
form = SvFiltersForm(request.args)
available_panels = case_obj.get('panels', []) + [{
'panel_name': 'hpo',
'display_name': 'HPO'
}]
panel_choices = [(panel['panel_name'], panel['display_name'])
for panel in available_panels]
form.gene_panels.choices = panel_choices
if form.data['gene_panels'] == ['hpo']:
hpo_symbols = list(
set(term_obj['hgnc_symbol']
for term_obj in case_obj['dynamic_gene_list']))
form.hgnc_symbols.data = hpo_symbols
# update status of case if vistited for the first time
if case_obj['status'] == 'inactive' and not current_user.is_admin:
flash('You just activated this case!', 'info')
user_obj = store.user(current_user.email)
case_link = url_for('cases.case',
institute_id=institute_obj['_id'],
case_name=case_obj['display_name'])
store.update_status(institute_obj, case_obj, user_obj, 'active',
case_link)
variants_query = store.variants(case_obj['_id'],
category='sv',
query=form.data)
data = {}
# if variants should be exported
if request.form.get('export'):
document_header = controllers.variants_export_header(case_obj)
export_lines = []
# Return max 500 variants
export_lines = controllers.variant_export_lines(
store, case_obj, variants_query.limit(500))
def generate(header, lines):
yield header + '\n'
for line in lines:
yield line + '\n'
headers = Headers()
headers.add('Content-Disposition',
'attachment',
filename=str(case_obj['display_name']) +
'-filtered_sv-variants.csv')
return Response(
generate(",".join(document_header), export_lines),
mimetype='text/csv',
headers=headers) # return a csv with the exported variants
else:
data = controllers.sv_variants(store, institute_obj, case_obj,
variants_query, page)
return dict(institute=institute_obj,
case=case_obj,
variant_type=variant_type,
form=form,
severe_so_terms=SEVERE_SO_TERMS,
page=page,
**data)
def variants(institute_id, case_name):
"""Display a list of SNV variants."""
page = int(request.form.get("page", 1))
category = "snv"
institute_obj, case_obj = institute_and_case(store, institute_id, case_name)
variant_type = request.args.get("variant_type", "clinical")
if request.form.get("hpo_clinical_filter"):
case_obj["hpo_clinical_filter"] = True
user_obj = store.user(current_user.email)
if request.method == "POST":
# If special filter buttons were selected:
form = controllers.populate_filters_form(
store, institute_obj, case_obj, user_obj, category, request.form
)
else:
form = FiltersForm(request.args)
# set form variant data type the first time around
form.variant_type.data = variant_type
# populate filters dropdown
available_filters = store.filters(institute_id, category)
form.filters.choices = [
(filter.get("_id"), filter.get("display_name")) for filter in available_filters
]
# populate available panel choices
available_panels = case_obj.get("panels", []) + [
{"panel_name": "hpo", "display_name": "HPO"}
]
panel_choices = [
(panel["panel_name"], panel["display_name"]) for panel in available_panels
]
form.gene_panels.choices = panel_choices
# update status of case if visited for the first time
controllers.activate_case(store, institute_obj, case_obj, current_user)
# upload gene panel if symbol file exists
if request.files:
file = request.files[form.symbol_file.name]
if request.files and file and file.filename != "":
log.debug("Upload file request files: {0}".format(request.files.to_dict()))
try:
stream = io.StringIO(file.stream.read().decode("utf-8"), newline=None)
except UnicodeDecodeError as error:
flash("Only text files are supported!", "warning")
return redirect(request.referrer)
hgnc_symbols_set = set(form.hgnc_symbols.data)
log.debug("Symbols prior to upload: {0}".format(hgnc_symbols_set))
new_hgnc_symbols = controllers.upload_panel(
store, institute_id, case_name, stream
)
hgnc_symbols_set.update(new_hgnc_symbols)
form.hgnc_symbols.data = hgnc_symbols_set
# reset gene panels
form.gene_panels.data = ""
# check if supplied gene symbols exist
hgnc_symbols = []
non_clinical_symbols = []
not_found_symbols = []
not_found_ids = []
if (form.hgnc_symbols.data) and len(form.hgnc_symbols.data) > 0:
is_clinical = form.data.get("variant_type", "clinical") == "clinical"
clinical_symbols = store.clinical_symbols(case_obj) if is_clinical else None
for hgnc_symbol in form.hgnc_symbols.data:
if hgnc_symbol.isdigit():
hgnc_gene = store.hgnc_gene(int(hgnc_symbol))
if hgnc_gene is None:
not_found_ids.append(hgnc_symbol)
else:
hgnc_symbols.append(hgnc_gene["hgnc_symbol"])
elif sum(1 for i in store.hgnc_genes(hgnc_symbol)) == 0:
not_found_symbols.append(hgnc_symbol)
elif is_clinical and (hgnc_symbol not in clinical_symbols):
non_clinical_symbols.append(hgnc_symbol)
else:
hgnc_symbols.append(hgnc_symbol)
if not_found_ids:
flash("HGNC id not found: {}".format(", ".join(not_found_ids)), "warning")
if not_found_symbols:
flash(
"HGNC symbol not found: {}".format(", ".join(not_found_symbols)), "warning"
)
if non_clinical_symbols:
flash(
"Gene not included in clinical list: {}".format(
", ".join(non_clinical_symbols)
),
"warning",
)
form.hgnc_symbols.data = hgnc_symbols
# handle HPO gene list separately
if "hpo" in form.data["gene_panels"]:
hpo_symbols = list(
set(term_obj["hgnc_symbol"] for term_obj in case_obj["dynamic_gene_list"])
)
current_symbols = set(hgnc_symbols)
current_symbols.update(hpo_symbols)
form.hgnc_symbols.data = list(current_symbols)
variants_query = store.variants(case_obj["_id"], query=form.data, category=category)
if request.form.get("export"):
return controllers.download_variants(store, case_obj, variants_query)
data = controllers.variants(store, institute_obj, case_obj, variants_query, page)
return dict(
institute=institute_obj,
case=case_obj,
form=form,
manual_rank_options=MANUAL_RANK_OPTIONS,
cancer_tier_options=CANCER_TIER_OPTIONS,
severe_so_terms=SEVERE_SO_TERMS,
page=page,
**data
)
def cancer_variants(institute_id, case_name):
"""Show cancer variants overview."""
category = "cancer"
institute_obj, case_obj = institute_and_case(store, institute_id,
case_name)
user_obj = store.user(current_user.email)
if request.method == "POST":
form = controllers.populate_filters_form(store, institute_obj,
case_obj, user_obj, category,
request.form)
# if user is not loading an existing filter, check filter form
if request.form.get(
"load_filter") is None and form.validate_on_submit() is False:
# Flash a message with errors
for field, err_list in form.errors.items():
for err in err_list:
flash(f"Content of field '{field}' has not a valid format",
"warning")
# And do not submit the form
return redirect(
url_for(
".cancer_variants",
institute_id=institute_id,
case_name=case_name,
expand_search="True",
), )
page = int(request.form.get("page", 1))
else:
page = int(request.args.get("page", 1))
form = CancerFiltersForm(request.args)
form.chrom.data = request.args.get("chrom", None)
# update status of case if visited for the first time
controllers.activate_case(store, institute_obj, case_obj, current_user)
# populate filters dropdown
available_filters = store.filters(institute_id, category)
form.filters.choices = [(filter.get("_id"), filter.get("display_name"))
for filter in available_filters]
available_panels = case_obj.get("panels", []) + [{
"panel_name": "hpo",
"display_name": "HPO"
}]
panel_choices = [(panel["panel_name"], panel["display_name"])
for panel in available_panels]
form.gene_panels.choices = panel_choices
cytobands = store.cytoband_by_chrom(case_obj.get("genome_build"))
variant_type = request.args.get("variant_type", "clinical")
variants_query = store.variants(case_obj["_id"],
category="cancer",
query=form.data)
if request.form.get("export"):
return controllers.download_variants(store, case_obj, variants_query)
data = controllers.cancer_variants(store,
institute_id,
case_name,
variants_query,
form,
page=page)
return dict(
variant_type=variant_type,
cytobands=cytobands,
dismiss_variant_options={
**DISMISS_VARIANT_OPTIONS,
**CANCER_SPECIFIC_VARIANT_DISMISS_OPTIONS,
},
expand_search=str(request.method == "POST"),
**data,
)
def cancer_variants(institute_id, case_name):
"""Show cancer variants overview."""
category = "cancer"
variant_type = Markup.escape(request.args.get("variant_type", "clinical"))
institute_obj, case_obj = institute_and_case(store, institute_id, case_name)
variants_stats = store.case_variants_count(case_obj["_id"], institute_id, variant_type, False)
user_obj = store.user(current_user.email)
if request.method == "POST":
if "dismiss_submit" in request.form: # dismiss a list of variants
controllers.dismiss_variant_list(
store,
institute_obj,
case_obj,
"variant.variant",
request.form.getlist("dismiss"),
request.form.getlist("dismiss_choices"),
)
form = controllers.populate_filters_form(
store, institute_obj, case_obj, user_obj, category, request.form
)
# if user is not loading an existing filter, check filter form
if (
request.form.get("load_filter") is None
and request.form.get("audit_filter") is None
and form.validate_on_submit() is False
):
# Flash a message with errors
for field, err_list in form.errors.items():
for err in err_list:
flash(f"Content of field '{field}' does not have a valid format", "warning")
# And do not submit the form
return redirect(
url_for(
".cancer_variants",
institute_id=institute_id,
case_name=case_name,
expand_search=True,
)
)
page = int(Markup.escape(request.form.get("page", "1")))
else:
page = int(Markup.escape(request.args.get("page", "1")))
form = CancerFiltersForm(request.args)
# set chromosome to all chromosomes
form.chrom.data = request.args.get("chrom", "")
if form.gene_panels.data == []:
form.gene_panels.data = controllers.case_default_panels(case_obj)
# update status of case if visited for the first time
controllers.activate_case(store, institute_obj, case_obj, current_user)
# populate filters dropdown
available_filters = list(store.filters(institute_id, category))
form.filters.choices = [
(filter.get("_id"), filter.get("display_name")) for filter in available_filters
]
# Populate chromosome select choices
controllers.populate_chrom_choices(form, case_obj)
form.gene_panels.choices = controllers.gene_panel_choices(store, institute_obj, case_obj)
genome_build = "38" if "38" in str(case_obj.get("genome_build")) else "37"
cytobands = store.cytoband_by_chrom(genome_build)
controllers.update_form_hgnc_symbols(store, case_obj, form)
variants_query = store.variants(
case_obj["_id"], category="cancer", query=form.data, build=genome_build
)
result_size = store.count_variants(case_obj["_id"], form.data, None, category)
if request.form.get("export"):
return controllers.download_variants(store, case_obj, variants_query)
data = controllers.cancer_variants(
store,
institute_id,
case_name,
variants_query,
result_size,
form,
page=page,
)
expand_search = request.method == "POST" and request.form.get("expand_search") in [
"True",
"",
]
return dict(
variant_type=variant_type,
cytobands=cytobands,
filters=available_filters,
dismiss_variant_options={
**DISMISS_VARIANT_OPTIONS,
**CANCER_SPECIFIC_VARIANT_DISMISS_OPTIONS,
},
expand_search=expand_search,
result_size=result_size,
total_variants=variants_stats.get(variant_type, {}).get(category, "NA"),
**data,
)
def variants(institute_id, case_name):
"""Display a list of SNV variants."""
page = int(request.args.get('page', 1))
institute_obj, case_obj = institute_and_case(store, institute_id,
case_name)
form = FiltersForm(request.args)
panel_choices = [(panel['panel_name'], panel['display_name'])
for panel in case_obj.get('panels', [])]
form.gene_panels.choices = panel_choices
# update status of case if vistited for the first time
if case_obj['status'] == 'inactive' and not current_user.is_admin:
flash('You just activated this case!', 'info')
user_obj = store.user(current_user.email)
case_link = url_for('cases.case',
institute_id=institute_obj['_id'],
case_name=case_obj['display_name'])
store.update_status(institute_obj, case_obj, user_obj, 'active',
case_link)
# check if supplied gene symbols exist
hgnc_symbols = []
if len(form.hgnc_symbols.data) > 0:
is_clinical = form.data.get('variant_type', 'clinical') == 'clinical'
clinical_symbols = store.clinical_symbols(
case_obj) if is_clinical else None
for hgnc_symbol in form.hgnc_symbols.data:
if hgnc_symbol.isdigit():
hgnc_gene = store.hgnc_gene(int(hgnc_symbol))
if hgnc_gene is None:
flash("HGNC id not found: {}".format(hgnc_symbol),
'warning')
else:
hgnc_symbols.append(hgnc_gene['hgnc_symbol'])
elif store.hgnc_genes(hgnc_symbol).count() == 0:
flash("HGNC symbol not found: {}".format(hgnc_symbol),
'warning')
elif is_clinical and (hgnc_symbol not in clinical_symbols):
flash(
"Gene not included in clinical list: {}".format(
hgnc_symbol), 'warning')
else:
hgnc_symbols.append(hgnc_symbol)
form.hgnc_symbols.data = hgnc_symbols
# handle HPO gene list separately
if form.data['gene_panels'] == ['hpo']:
hpo_symbols = list(
set(term_obj['hgnc_symbol']
for term_obj in case_obj['dynamic_gene_list']))
form.hgnc_symbols.data = hpo_symbols
variants_query = store.variants(case_obj['_id'], query=form.data)
data = {}
if request.args.get('export'):
document_header = controllers.variants_export_header(case_obj)
export_lines = []
if form.data['chrom'] == 'MT':
# Return all MT variants
export_lines = controllers.variant_export_lines(
store, case_obj, variants_query)
else:
# Return max 500 variants
export_lines = controllers.variant_export_lines(
store, case_obj, variants_query.limit(500))
def generate(header, lines):
yield header + '\n'
for line in lines:
yield line + '\n'
headers = Headers()
headers.add('Content-Disposition',
'attachment',
filename=str(case_obj['_id']) + '-filtered_variants.csv')
return Response(
generate(",".join(document_header), export_lines),
mimetype='text/csv',
headers=headers) # return a csv with the exported variants
else:
data = controllers.variants(store, institute_obj, case_obj,
variants_query, page)
return dict(institute=institute_obj,
case=case_obj,
form=form,
severe_so_terms=SEVERE_SO_TERMS,
page=page,
**data)
def mt_excel_files(store, case_obj, temp_excel_dir):
"""Collect MT variants and format line of a MT variant report
to be exported in excel format. Create mt excel files, one for each sample,
in a temporary directory.
Args:
store(adapter.MongoAdapter)
case_obj(models.Case)
temp_excel_dir(os.Path): folder where the temp excel files are written to
Returns:
written_files(int): the number of files written to temp_excel_dir
"""
today = datetime.datetime.now().strftime("%Y-%m-%d")
samples = case_obj.get("individuals")
file_header = MT_EXPORT_HEADER
coverage_stats = None
# if chanjo connection is established, include MT vs AUTOSOME coverage stats
if current_app.config.get("SQLALCHEMY_DATABASE_URI"):
coverage_stats = mt_coverage_stats(samples)
query = {"chrom": "MT"}
mt_variants = list(
store.variants(case_id=case_obj["_id"], query=query, nr_of_variants=-1, sort_key="position")
)
written_files = 0
for sample in samples:
sample_id = sample["individual_id"]
display_name = sample["display_name"]
sample_lines = export_mt_variants(variants=mt_variants, sample_id=sample_id)
# set up document name
document_name = ".".join([case_obj["display_name"], display_name, today]) + ".xlsx"
workbook = Workbook(os.path.join(temp_excel_dir, document_name))
Report_Sheet = workbook.add_worksheet()
# Write the column header
row = 0
for col, field in enumerate(MT_EXPORT_HEADER):
Report_Sheet.write(row, col, field)
# Write variant lines, after header (start at line 1)
for row, line in enumerate(sample_lines, 1): # each line becomes a row in the document
for col, field in enumerate(line): # each field in line becomes a cell
Report_Sheet.write(row, col, field)
if bool(
coverage_stats
): # it's None if app is not connected to Chanjo or {} if samples are not in Chanjo db
# Write coverage stats header after introducing 2 empty lines
for col, field in enumerate(MT_COV_STATS_HEADER):
Report_Sheet.write(row + 3, col, field)
# Write sample MT vs autosome coverage stats to excel sheet
for col, item in enumerate(["mt_coverage", "autosome_cov", "mt_copy_number"]):
Report_Sheet.write(row + 4, col, coverage_stats[sample_id].get(item))
workbook.close()
if os.path.exists(os.path.join(temp_excel_dir, document_name)):
written_files += 1
return written_files
def variants(institute_id, case_name):
"""Display a list of SNV variants."""
page = int(request.args.get('page', 1))
institute_obj, case_obj = institute_and_case(store, institute_id,
case_name)
form = FiltersForm(request.args)
panel_choices = [(panel['panel_name'], panel['display_name'])
for panel in case_obj.get('panels', [])]
form.gene_panels.choices = panel_choices
# update status of case if vistited for the first time
if case_obj['status'] == 'inactive' and not current_user.is_admin:
flash('You just activated this case!', 'info')
user_obj = store.user(current_user.email)
case_link = url_for('cases.case',
institute_id=institute_obj['_id'],
case_name=case_obj['display_name'])
store.update_status(institute_obj, case_obj, user_obj, 'active',
case_link)
# check if supplied gene symbols exist
hgnc_symbols = []
if len(form.hgnc_symbols.data) > 0:
is_clinical = form.data.get('variant_type', 'clinical') == 'clinical'
clinical_symbols = store.clinical_symbols(
case_obj) if is_clinical else None
for hgnc_symbol in form.hgnc_symbols.data:
if hgnc_symbol.isdigit():
hgnc_gene = store.hgnc_gene(int(hgnc_symbol))
if hgnc_gene is None:
flash("HGNC id not found: {}".format(hgnc_symbol),
'warning')
else:
hgnc_symbols.append(hgnc_gene['hgnc_symbol'])
elif store.hgnc_genes(hgnc_symbol).count() == 0:
flash("HGNC symbol not found: {}".format(hgnc_symbol),
'warning')
elif is_clinical and (hgnc_symbol not in clinical_symbols):
flash(
"Gene not included in clinical list: {}".format(
hgnc_symbol), 'warning')
else:
hgnc_symbols.append(hgnc_symbol)
form.hgnc_symbols.data = hgnc_symbols
# handle HPO gene list separately
if form.data['gene_panels'] == ['hpo']:
hpo_symbols = list(
set(term_obj['hgnc_symbol']
for term_obj in case_obj['dynamic_gene_list']))
form.hgnc_symbols.data = hpo_symbols
variants_query = store.variants(case_obj['_id'], query=form.data)
data = controllers.variants(store, institute_obj, case_obj, variants_query,
page)
return dict(institute=institute_obj,
case=case_obj,
form=form,
severe_so_terms=SEVERE_SO_TERMS,
page=page,
**data)
def str_variants(institute_id, case_name):
"""Display a list of STR variants."""
page = int(Markup.escape(request.form.get("page", "1")))
variant_type = Markup.escape(request.args.get("variant_type", "clinical"))
category = "str"
institute_obj, case_obj = institute_and_case(store, institute_id, case_name)
variants_stats = store.case_variants_count(case_obj["_id"], institute_id, variant_type, False)
user_obj = store.user(current_user.email)
if request.method == "POST":
form = controllers.populate_filters_form(
store, institute_obj, case_obj, user_obj, category, request.form
)
else:
form = StrFiltersForm(request.args)
if form.gene_panels.data == [] and variant_type == "clinical":
form.gene_panels.data = controllers.case_default_panels(case_obj)
# set form variant data type the first time around
form.variant_type.data = variant_type
# set chromosome to all chromosomes
form.chrom.data = request.args.get("chrom", "")
# populate filters dropdown
available_filters = list(store.filters(institute_id, category))
form.filters.choices = [
(filter.get("_id"), filter.get("display_name")) for filter in available_filters
]
# Populate chromosome select choices
controllers.populate_chrom_choices(form, case_obj)
# populate available panel choices
form.gene_panels.choices = controllers.gene_panel_choices(store, institute_obj, case_obj)
controllers.activate_case(store, institute_obj, case_obj, current_user)
cytobands = store.cytoband_by_chrom(case_obj.get("genome_build"))
query = form.data
query["variant_type"] = variant_type
variants_query = store.variants(case_obj["_id"], category=category, query=query).sort(
[
("str_repid", pymongo.ASCENDING),
("chromosome", pymongo.ASCENDING),
("position", pymongo.ASCENDING),
]
)
result_size = store.count_variants(case_obj["_id"], query, None, category)
if request.form.get("export"):
return controllers.download_str_variants(case_obj, variants_query)
data = controllers.str_variants(
store, institute_obj, case_obj, variants_query, result_size, page
)
return dict(
institute=institute_obj,
case=case_obj,
dismiss_variant_options=DISMISS_VARIANT_OPTIONS,
variant_type=variant_type,
manual_rank_options=MANUAL_RANK_OPTIONS,
cytobands=cytobands,
form=form,
page=page,
filters=available_filters,
expand_search=str(request.method == "POST"),
result_size=result_size,
total_variants=variants_stats.get(variant_type, {}).get(category, "NA"),
**data,
)
def variants(institute_id, case_name):
"""Display a list of SNV variants."""
page = int(request.form.get('page', 1))
institute_obj, case_obj = institute_and_case(store, institute_id, case_name)
variant_type = request.args.get('variant_type', 'clinical')
# Update filter settings if Clinical Filter was requested
default_panels = []
for panel in case_obj['panels']:
if panel.get('is_default'):
default_panels.append(panel['panel_name'])
request.form.get('gene_panels')
if bool(request.form.get('clinical_filter')):
clinical_filter = MultiDict({
'variant_type': 'clinical',
'region_annotations': ['exonic','splicing'],
'functional_annotations': SEVERE_SO_TERMS,
'clinsig': [4,5],
'clinsig_confident_always_returned': True,
'gnomad_frequency': str(institute_obj['frequency_cutoff']),
'variant_type': 'clinical',
'gene_panels': default_panels
})
if(request.method == "POST"):
if bool(request.form.get('clinical_filter')):
form = FiltersForm(clinical_filter)
form.csrf_token = request.args.get('csrf_token')
else:
form = FiltersForm(request.form)
else:
form = FiltersForm(request.args)
# populate available panel choices
available_panels = case_obj.get('panels', []) + [
{'panel_name': 'hpo', 'display_name': 'HPO'}]
panel_choices = [(panel['panel_name'], panel['display_name'])
for panel in available_panels]
form.gene_panels.choices = panel_choices
# upload gene panel if symbol file exists
if (request.files):
file = request.files[form.symbol_file.name]
if request.files and file and file.filename != '':
log.debug("Upload file request files: {0}".format(request.files.to_dict()))
try:
stream = io.StringIO(file.stream.read().decode('utf-8'), newline=None)
except UnicodeDecodeError as error:
flash("Only text files are supported!", 'warning')
return redirect(request.referrer)
hgnc_symbols_set = set(form.hgnc_symbols.data)
log.debug("Symbols prior to upload: {0}".format(hgnc_symbols_set))
new_hgnc_symbols = controllers.upload_panel(store, institute_id, case_name, stream)
hgnc_symbols_set.update(new_hgnc_symbols)
form.hgnc_symbols.data = hgnc_symbols_set
# reset gene panels
form.gene_panels.data = ''
# update status of case if vistited for the first time
if case_obj['status'] == 'inactive' and not current_user.is_admin:
flash('You just activated this case!', 'info')
user_obj = store.user(current_user.email)
case_link = url_for('cases.case', institute_id=institute_obj['_id'],
case_name=case_obj['display_name'])
store.update_status(institute_obj, case_obj, user_obj, 'active', case_link)
# check if supplied gene symbols exist
hgnc_symbols = []
non_clinical_symbols = []
not_found_symbols = []
not_found_ids = []
if (form.hgnc_symbols.data) and len(form.hgnc_symbols.data) > 0:
is_clinical = form.data.get('variant_type', 'clinical') == 'clinical'
clinical_symbols = store.clinical_symbols(case_obj) if is_clinical else None
for hgnc_symbol in form.hgnc_symbols.data:
if hgnc_symbol.isdigit():
hgnc_gene = store.hgnc_gene(int(hgnc_symbol))
if hgnc_gene is None:
not_found_ids.append(hgnc_symbol)
else:
hgnc_symbols.append(hgnc_gene['hgnc_symbol'])
elif store.hgnc_genes(hgnc_symbol).count() == 0:
not_found_symbols.append(hgnc_symbol)
elif is_clinical and (hgnc_symbol not in clinical_symbols):
non_clinical_symbols.append(hgnc_symbol)
else:
hgnc_symbols.append(hgnc_symbol)
if (not_found_ids):
flash("HGNC id not found: {}".format(", ".join(not_found_ids)), 'warning')
if (not_found_symbols):
flash("HGNC symbol not found: {}".format(", ".join(not_found_symbols)), 'warning')
if (non_clinical_symbols):
flash("Gene not included in clinical list: {}".format(", ".join(non_clinical_symbols)), 'warning')
form.hgnc_symbols.data = hgnc_symbols
# handle HPO gene list separately
if form.data['gene_panels'] == ['hpo']:
hpo_symbols = list(set(term_obj['hgnc_symbol'] for term_obj in
case_obj['dynamic_gene_list']))
form.hgnc_symbols.data = hpo_symbols
variants_query = store.variants(case_obj['_id'], query=form.data)
data = {}
if request.form.get('export'):
document_header = controllers.variants_export_header(case_obj)
export_lines = []
if form.data['chrom'] == 'MT':
# Return all MT variants
export_lines = controllers.variant_export_lines(store, case_obj, variants_query)
else:
# Return max 500 variants
export_lines = controllers.variant_export_lines(store, case_obj, variants_query.limit(500))
def generate(header, lines):
yield header + '\n'
for line in lines:
yield line + '\n'
headers = Headers()
headers.add('Content-Disposition','attachment', filename=str(case_obj['display_name'])+'-filtered_variants.csv')
# return a csv with the exported variants
return Response(generate(",".join(document_header), export_lines), mimetype='text/csv',
headers=headers)
data = controllers.variants(store, institute_obj, case_obj, variants_query, page)
return dict(institute=institute_obj, case=case_obj, form=form,
severe_so_terms=SEVERE_SO_TERMS, page=page, **data)
def sv_variants(institute_id, case_name):
"""Display a list of structural variants."""
page = int(request.form.get('page', 1))
variant_type = request.args.get('variant_type', 'clinical')
institute_obj, case_obj = institute_and_case(store, institute_id, case_name)
form = SvFiltersForm(request.form)
default_panels = []
for panel in case_obj['panels']:
if panel['is_default']:
default_panels.append(panel['panel_name'])
request.form.get('gene_panels')
if bool(request.form.get('clinical_filter')):
clinical_filter = MultiDict({
'variant_type': 'clinical',
'region_annotations': ['exonic','splicing'],
'functional_annotations': SEVERE_SO_TERMS,
'thousand_genomes_frequency': str(institute_obj['frequency_cutoff']),
'variant_type': 'clinical',
'clingen_ngi': 10,
'swegen': 10,
'size': 100,
'gene_panels': default_panels
})
if(request.method == "POST"):
if bool(request.form.get('clinical_filter')):
form = SvFiltersForm(clinical_filter)
form.csrf_token = request.args.get('csrf_token')
else:
form = SvFiltersForm(request.form)
else:
form = SvFiltersForm(request.args)
available_panels = case_obj.get('panels', []) + [
{'panel_name': 'hpo', 'display_name': 'HPO'}]
panel_choices = [(panel['panel_name'], panel['display_name'])
for panel in available_panels]
form.gene_panels.choices = panel_choices
if form.data['gene_panels'] == ['hpo']:
hpo_symbols = list(set(term_obj['hgnc_symbol'] for term_obj in
case_obj['dynamic_gene_list']))
form.hgnc_symbols.data = hpo_symbols
# update status of case if vistited for the first time
if case_obj['status'] == 'inactive' and not current_user.is_admin:
flash('You just activated this case!', 'info')
user_obj = store.user(current_user.email)
case_link = url_for('cases.case', institute_id=institute_obj['_id'],
case_name=case_obj['display_name'])
store.update_status(institute_obj, case_obj, user_obj, 'active', case_link)
variants_query = store.variants(case_obj['_id'], category='sv',
query=form.data)
data = {}
# if variants should be exported
if request.form.get('export'):
document_header = controllers.variants_export_header(case_obj)
export_lines = []
# Return max 500 variants
export_lines = controllers.variant_export_lines(store, case_obj, variants_query.limit(500))
def generate(header, lines):
yield header + '\n'
for line in lines:
yield line + '\n'
headers = Headers()
headers.add('Content-Disposition','attachment', filename=str(case_obj['display_name'])+'-filtered_sv-variants.csv')
return Response(generate(",".join(document_header), export_lines), mimetype='text/csv', headers=headers) # return a csv with the exported variants
else:
data = controllers.sv_variants(store, institute_obj, case_obj,
variants_query, page)
return dict(institute=institute_obj, case=case_obj, variant_type=variant_type,
form=form, severe_so_terms=SEVERE_SO_TERMS, page=page, **data)
def cancer_sv_variants(institute_id, case_name):
"""Display a list of cancer structural variants."""
page = int(Markup.escape(request.form.get("page", "1")))
variant_type = Markup.escape(request.args.get("variant_type", "clinical"))
category = "cancer_sv"
# Define case and institute objects
institute_obj, case_obj = institute_and_case(store, institute_id, case_name)
variants_stats = store.case_variants_count(case_obj["_id"], institute_id, variant_type, False)
if request.form.get("hpo_clinical_filter"):
case_obj["hpo_clinical_filter"] = True
if request.form.getlist("dismiss"): # dismiss a list of variants
controllers.dismiss_variant_list(
store,
institute_obj,
case_obj,
"variant.sv_variant",
request.form.getlist("dismiss"),
request.form.getlist("dismiss_choices"),
)
# update status of case if visited for the first time
controllers.activate_case(store, institute_obj, case_obj, current_user)
form = controllers.populate_sv_filters_form(store, institute_obj, case_obj, category, request)
# populate filters dropdown
available_filters = list(store.filters(institute_obj["_id"], category))
form.filters.choices = [
(filter.get("_id"), filter.get("display_name")) for filter in available_filters
]
# Populate chromosome select choices
controllers.populate_chrom_choices(form, case_obj)
genome_build = "38" if "38" in str(case_obj.get("genome_build")) else "37"
cytobands = store.cytoband_by_chrom(genome_build)
controllers.update_form_hgnc_symbols(store, case_obj, form)
variants_query = store.variants(case_obj["_id"], category=category, query=form.data)
result_size = store.count_variants(case_obj["_id"], form.data, None, category)
# if variants should be exported
if request.form.get("export"):
return controllers.download_variants(store, case_obj, variants_query)
data = controllers.sv_variants(
store, institute_obj, case_obj, variants_query, result_size, page
)
expand_search = request.method == "POST" and request.form.get("expand_search") in [
"True",
"",
]
return dict(
institute=institute_obj,
case=case_obj,
dismiss_variant_options={
**DISMISS_VARIANT_OPTIONS,
**CANCER_SPECIFIC_VARIANT_DISMISS_OPTIONS,
},
variant_type=variant_type,
form=form,
filters=available_filters,
severe_so_terms=SEVERE_SO_TERMS,
cancer_tier_options=CANCER_TIER_OPTIONS,
manual_rank_options=MANUAL_RANK_OPTIONS,
cytobands=cytobands,
page=page,
expand_search=expand_search,
result_size=result_size,
total_variants=variants_stats.get(variant_type, {}).get(category, "NA"),
**data,
)
def variants(institute_id, case_name):
"""Display a list of SNV variants."""
page = int(Markup.escape(request.form.get("page", "1")))
category = "snv"
institute_obj, case_obj = institute_and_case(store, institute_id, case_name)
variant_type = request.args.get("variant_type", "clinical")
variants_stats = store.case_variants_count(case_obj["_id"], institute_id, variant_type, False)
if request.form.get("hpo_clinical_filter"):
case_obj["hpo_clinical_filter"] = True
user_obj = store.user(current_user.email)
if request.method == "POST":
if "dismiss_submit" in request.form: # dismiss a list of variants
controllers.dismiss_variant_list(
store,
institute_obj,
case_obj,
"variant.variant",
request.form.getlist("dismiss"),
request.form.getlist("dismiss_choices"),
)
form = controllers.populate_filters_form(
store, institute_obj, case_obj, user_obj, category, request.form
)
else:
form = FiltersForm(request.args)
# set form variant data type the first time around
form.variant_type.data = variant_type
# set chromosome to all chromosomes
form.chrom.data = request.args.get("chrom", "")
if form.gene_panels.data == [] and variant_type == "clinical":
form.gene_panels.data = controllers.case_default_panels(case_obj)
# populate filters dropdown
available_filters = list(store.filters(institute_id, category))
form.filters.choices = [
(filter.get("_id"), filter.get("display_name")) for filter in available_filters
]
# Populate chromosome select choices
controllers.populate_chrom_choices(form, case_obj)
# populate available panel choices
form.gene_panels.choices = controllers.gene_panel_choices(store, institute_obj, case_obj)
# update status of case if visited for the first time
controllers.activate_case(store, institute_obj, case_obj, current_user)
# upload gene panel if symbol file exists
if request.files:
file = request.files[form.symbol_file.name]
if request.files and file and file.filename != "":
LOG.debug("Upload file request files: {0}".format(request.files.to_dict()))
try:
stream = io.StringIO(file.stream.read().decode("utf-8"), newline=None)
except UnicodeDecodeError as error:
flash("Only text files are supported!", "warning")
return redirect(request.referrer)
hgnc_symbols_set = set(form.hgnc_symbols.data)
LOG.debug("Symbols prior to upload: {0}".format(hgnc_symbols_set))
new_hgnc_symbols = controllers.upload_panel(store, institute_id, case_name, stream)
hgnc_symbols_set.update(new_hgnc_symbols)
form.hgnc_symbols.data = hgnc_symbols_set
# reset gene panels
form.gene_panels.data = ""
controllers.update_form_hgnc_symbols(store, case_obj, form)
cytobands = store.cytoband_by_chrom(case_obj.get("genome_build"))
variants_query = store.variants(case_obj["_id"], query=form.data, category=category)
result_size = store.count_variants(case_obj["_id"], form.data, None, category)
if request.form.get("export"):
return controllers.download_variants(store, case_obj, variants_query)
data = controllers.variants(
store, institute_obj, case_obj, variants_query, result_size, page, query_form=form.data
)
expand_search = request.method == "POST" and request.form.get("expand_search") in [
"True",
"",
]
return dict(
institute=institute_obj,
case=case_obj,
form=form,
filters=available_filters,
manual_rank_options=MANUAL_RANK_OPTIONS,
dismiss_variant_options=DISMISS_VARIANT_OPTIONS,
cancer_tier_options=CANCER_TIER_OPTIONS,
severe_so_terms=SEVERE_SO_TERMS,
cytobands=cytobands,
page=page,
expand_search=expand_search,
result_size=result_size,
total_variants=variants_stats.get(variant_type, {}).get(category, "NA"),
**data,
)
