def gene_edit(panel_id, hgnc_id):
"""Edit additional information about a panel gene."""
panel_obj = store.panel(panel_id)
hgnc_gene = store.hgnc_gene(hgnc_id)
panel_gene = controllers.existing_gene(store, panel_obj, hgnc_id)
form = PanelGeneForm()
transcript_choices = []
for transcript in hgnc_gene['transcripts']:
if transcript.get('refseq_id'):
refseq_id = transcript.get('refseq_id')
transcript_choices.append((refseq_id, refseq_id))
form.disease_associated_transcripts.choices = transcript_choices
if form.validate_on_submit():
action = 'edit' if panel_gene else 'add'
info_data = form.data.copy()
if 'csrf_token' in info_data:
del info_data['csrf_token']
store.add_pending(panel_obj, hgnc_gene, action=action, info=info_data)
return redirect(url_for('.panel', panel_id=panel_id))
if panel_gene:
for field_key in ['disease_associated_transcripts', 'reduced_penetrance',
'mosaicism', 'inheritance_models', 'database_entry_version', 'comment']:
form_field = getattr(form, field_key)
if not form_field.data:
panel_value = panel_gene.get(field_key)
if panel_value is not None:
form_field.process_data(panel_value)
return dict(panel=panel_obj, form=form, gene=hgnc_gene, panel_gene=panel_gene)
def panel(panel_id):
"""Display (and add pending updates to) a specific gene panel."""
panel_obj = store.gene_panel(panel_id) or store.panel(panel_id)
if request.method == 'POST':
raw_hgnc_id = request.form['hgnc_id']
if '|' in raw_hgnc_id:
raw_hgnc_id = raw_hgnc_id.split(' | ', 1)[0]
hgnc_id = int(raw_hgnc_id)
action = request.form['action']
gene_obj = store.hgnc_gene(hgnc_id)
if gene_obj is None:
flash("HGNC id not found: {}".format(hgnc_id))
return redirect(request.referer)
if action == 'add':
panel_gene = controllers.existing_gene(store, panel_obj, hgnc_id)
if panel_gene:
flash("gene already in panel: {}".format(panel_gene['symbol']),
'warning')
else:
# ask user to fill-in more information about the gene
return redirect(
url_for('.gene_edit', panel_id=panel_id, hgnc_id=hgnc_id))
elif action == 'delete':
log.debug("marking gene to be deleted: %s", hgnc_id)
store.add_pending(panel_obj, gene_obj, action='delete')
data = controllers.panel(store, panel_obj)
if request.args.get('case_id'):
data['case'] = store.case(request.args['case_id'])
if request.args.get('institute_id'):
data['institute'] = store.institute(request.args['institute_id'])
return data
def gene_variants(institute_id):
"""Display a list of SNV variants."""
page = int(request.form.get('page', 1))
institute_obj = institute_and_case(store, institute_id)
# populate form, conditional on request method
if (request.method == "POST"):
form = GeneVariantFiltersForm(request.form)
else:
form = GeneVariantFiltersForm(request.args)
variant_type = form.data.get('variant_type', 'clinical')
# check if supplied gene symbols exist
hgnc_symbols = []
non_clinical_symbols = []
not_found_symbols = []
not_found_ids = []
data = {}
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
log.debug("query {}".format(form.data))
variants_query = store.gene_variants(query=form.data,
category='snv',
variant_type=variant_type)
data = controllers.gene_variants(store, variants_query, page)
return dict(institute=institute_obj, form=form, page=page, **data)
def gene_edit(panel_id, hgnc_id):
"""Edit additional information about a panel gene."""
panel_obj = store.panel(panel_id)
hgnc_gene = store.hgnc_gene(hgnc_id)
panel_gene = controllers.existing_gene(store, panel_obj, hgnc_id)
form = PanelGeneForm()
transcript_choices = []
for transcript in hgnc_gene['transcripts']:
if transcript.get('refseq_id'):
refseq_id = transcript.get('refseq_id')
transcript_choices.append((refseq_id, refseq_id))
form.disease_associated_transcripts.choices = transcript_choices
if form.validate_on_submit():
action = 'edit' if panel_gene else 'add'
info_data = form.data.copy()
if 'csrf_token' in info_data:
del info_data['csrf_token']
store.add_pending(panel_obj, hgnc_gene, action=action, info=info_data)
return redirect(url_for('.panel', panel_id=panel_id))
if panel_gene:
for field_key in ['disease_associated_transcripts', 'reduced_penetrance',
'mosaicism', 'inheritance_models', 'database_entry_version', 'comment']:
form_field = getattr(form, field_key)
if not form_field.data:
panel_value = panel_gene.get(field_key)
if panel_value is not None:
form_field.process_data(panel_value)
return dict(panel=panel_obj, form=form, gene=hgnc_gene, panel_gene=panel_gene)
def gene_edit(panel_id, hgnc_id):
"""Edit additional information about a panel gene."""
panel_obj = store.panel(panel_id)
hgnc_gene = store.hgnc_gene(hgnc_id)
panel_gene = controllers.existing_gene(store, panel_obj, hgnc_id)
form = PanelGeneForm()
transcript_choices = []
for transcript in hgnc_gene["transcripts"]:
if transcript.get("refseq_id"):
refseq_id = transcript.get("refseq_id")
transcript_choices.append((refseq_id, refseq_id))
# collect even refseq version provided by user for this transcript (might have a version)
if panel_obj.get("genes"):
genes_dict = {gene_obj["symbol"]: gene_obj for gene_obj in panel_obj["genes"]}
gene_obj = genes_dict.get(hgnc_gene["hgnc_symbol"])
if gene_obj:
for transcript in gene_obj.get("disease_associated_transcripts", []):
if (transcript, transcript) not in transcript_choices:
transcript_choices.append((transcript, transcript))
form.disease_associated_transcripts.choices = transcript_choices
if form.validate_on_submit():
action = "edit" if panel_gene else "add"
info_data = form.data.copy()
if "csrf_token" in info_data:
del info_data["csrf_token"]
if info_data["custom_inheritance_models"] != "":
info_data["custom_inheritance_models"] = info_data[
"custom_inheritance_models"
].split(",")
store.add_pending(panel_obj, hgnc_gene, action=action, info=info_data)
return redirect(url_for(".panel", panel_id=panel_id))
if panel_gene:
form.custom_inheritance_models.data = ", ".join(
panel_gene.get("custom_inheritance_models", [])
)
for field_key in [
"disease_associated_transcripts",
"reduced_penetrance",
"mosaicism",
"inheritance_models",
"custom_inheritance_models",
"database_entry_version",
"comment",
]:
form_field = getattr(form, field_key)
if not form_field.data:
panel_value = panel_gene.get(field_key)
if panel_value is not None:
form_field.process_data(panel_value)
return dict(panel=panel_obj, form=form, gene=hgnc_gene, panel_gene=panel_gene)
def gene_variants(institute_id):
"""Display a list of SNV variants."""
page = int(request.form.get('page', 1))
institute_obj = institute_and_case(store, institute_id)
# populate form, conditional on request method
if(request.method == "POST"):
form = GeneVariantFiltersForm(request.form)
else:
form = GeneVariantFiltersForm(request.args)
variant_type = form.data.get('variant_type', 'clinical')
# check if supplied gene symbols exist
hgnc_symbols = []
non_clinical_symbols = []
not_found_symbols = []
not_found_ids = []
data = {}
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
log.debug("query {}".format(form.data))
variants_query = store.gene_variants(query=form.data, category='snv',
variant_type=variant_type)
data = controllers.gene_variants(store, variants_query, page)
return dict(institute=institute_obj, form=form, page=page, **data)
def panel(panel_id):
"""Display (and add pending updates to) a specific gene panel."""
panel_obj = store.gene_panel(panel_id) or store.panel(panel_id)
if request.method == "POST":
if request.form.get("update_description"):
panel_obj["description"] = request.form["panel_description"]
if panel_write_granted(panel_obj, current_user):
store.update_panel(panel_obj=panel_obj)
else:
flash(
"Permission denied: please ask a panel maintainer or admin for help.",
"danger",
)
return redirect(url_for("panels.panel", panel_id=panel_obj["_id"]))
raw_hgnc_id = request.form["hgnc_id"]
if "|" in raw_hgnc_id:
raw_hgnc_id = raw_hgnc_id.split(" | ", 1)[0]
hgnc_id = 0
try:
hgnc_id = int(raw_hgnc_id)
except ValueError:
flash("Provided HGNC is not valid : '{}'".format(raw_hgnc_id), "danger")
return redirect(request.referrer)
action = request.form["action"]
gene_obj = store.hgnc_gene(hgnc_id)
if gene_obj is None:
flash("HGNC id not found: {}".format(hgnc_id), "warning")
return redirect(request.referrer)
if action == "add":
panel_gene = controllers.existing_gene(store, panel_obj, hgnc_id)
if panel_gene:
flash(
"gene already in panel: {}".format(panel_gene["symbol"]), "warning"
)
else:
# ask user to fill-in more information about the gene
return redirect(
url_for(".gene_edit", panel_id=panel_id, hgnc_id=hgnc_id)
)
elif action == "delete":
LOG.debug("marking gene to be deleted: %s", hgnc_id)
panel_obj = store.add_pending(panel_obj, gene_obj, action="delete")
data = controllers.panel(store, panel_obj)
if request.args.get("case_id"):
data["case"] = store.case(request.args["case_id"])
if request.args.get("institute_id"):
data["institute"] = store.institute(request.args["institute_id"])
return data
def gene(hgnc_id=None, hgnc_symbol=None):
"""Render information about a gene."""
if hgnc_symbol:
query = store.hgnc_genes(hgnc_symbol)
if query.count() < 2:
gene_obj = query.first()
else:
return redirect(url_for('.genes', query=hgnc_symbol))
else:
gene_obj = store.hgnc_gene(hgnc_id)
if gene_obj is None:
return abort(404)
controllers.gene(gene_obj)
return dict(gene=gene_obj)
def update_HGNC_symbols(store, variant_genes, genome_build):
"""Update the HGNC symbols if they are not set
Returns:
gene_object()"""
if variant_genes is not None:
for gene_obj in variant_genes:
# If there is no hgnc id there is nothin we can do
if not gene_obj["hgnc_id"]:
continue
# Else we collect the gene object and check the id
if gene_obj.get("hgnc_symbol") is None or gene_obj.get("description") is None:
hgnc_gene = store.hgnc_gene(gene_obj["hgnc_id"], build=genome_build)
if not hgnc_gene:
continue
gene_obj["hgnc_symbol"] = hgnc_gene["hgnc_symbol"]
gene_obj["description"] = hgnc_gene["description"]
def tx_choices(hgnc_id, panel_obj):
"""Collect transcripts from a gene both in build 37 and 38
Args:
hgnc_id(int): a gene HGNC ID
panel_obj(dict): a gene panel dictionary representation
Returns:
transcript_choices(list) a list with the options for a form select field
"""
transcript_choices = []
hgnc_gene = None
for build in ["37", "38"]:
build_specific_hgnc_gene = store.hgnc_gene(hgnc_identifier=hgnc_id,
build=build)
if build_specific_hgnc_gene is None:
continue
hgnc_gene = build_specific_hgnc_gene
for transcript in build_specific_hgnc_gene["transcripts"]:
if transcript.get("refseq_id"):
refseq_id = transcript.get("refseq_id")
transcript_choices.append(
(refseq_id, f"{refseq_id} (build {build})"))
# collect even refseq version provided by user for this transcript (might have a version)
if panel_obj.get("genes"):
genes_dict = {
gene_obj["symbol"]: gene_obj
for gene_obj in panel_obj["genes"]
}
gene_obj = genes_dict.get(hgnc_gene["hgnc_symbol"])
if gene_obj:
for transcript in gene_obj.get("disease_associated_transcripts",
[]):
if (transcript, transcript) not in transcript_choices:
transcript_choices.append(
(transcript, f"{transcript} (previous choice)"))
return transcript_choices
def panel(panel_id):
"""Display (and add pending updates to) a specific gene panel."""
panel_obj = store.gene_panel(panel_id) or store.panel(panel_id)
if request.method == 'POST':
raw_hgnc_id = request.form['hgnc_id']
if '|' in raw_hgnc_id:
raw_hgnc_id = raw_hgnc_id.split(' | ', 1)[0]
hgnc_id = 0
try:
hgnc_id = int(raw_hgnc_id)
except:
flash("Provided HGNC is not valid : '{}'". format(raw_hgnc_id), 'danger')
return redirect(request.referrer)
action = request.form['action']
gene_obj = store.hgnc_gene(hgnc_id)
if gene_obj is None:
flash("HGNC id not found: {}".format(hgnc_id), 'warning')
return redirect(request.referrer)
if action == 'add':
panel_gene = controllers.existing_gene(store, panel_obj, hgnc_id)
if panel_gene:
flash("gene already in panel: {}".format(panel_gene['symbol']),
'warning')
else:
# ask user to fill-in more information about the gene
return redirect(url_for('.gene_edit', panel_id=panel_id,
hgnc_id=hgnc_id))
elif action == 'delete':
log.debug("marking gene to be deleted: %s", hgnc_id)
panel_obj = store.add_pending(panel_obj, gene_obj, action='delete')
data = controllers.panel(store, panel_obj)
if request.args.get('case_id'):
data['case'] = store.case(request.args['case_id'])
if request.args.get('institute_id'):
data['institute'] = store.institute(request.args['institute_id'])
return 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 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 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.get('is_default') and panel['is_default'] is True) or ('default_panels' in case_obj and panel['panel_id'] in case_obj['default_panels']):
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
# 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)
# 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 gene_variants(institute_id):
"""Display a list of SNV variants."""
page = int(request.form.get("page", 1))
institute_obj = institute_and_case(store, institute_id)
# populate form, conditional on request method
if request.method == "POST":
form = GeneVariantFiltersForm(request.form)
else:
form = GeneVariantFiltersForm(request.args)
if form.variant_type.data == []:
form.variant_type.data = ["clinical"]
variant_type = form.data.get("variant_type")
# check if supplied gene symbols exist
hgnc_symbols = []
non_clinical_symbols = []
not_found_symbols = []
not_found_ids = []
data = {}
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_find_one(hgnc_symbol) is None:
not_found_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",
)
if hgnc_symbols == []:
# If there are not genes to search, return to previous page with a warning
flash("No valid gene provided for variant search.", "warning")
return redirect(request.referrer)
form.hgnc_symbols.data = hgnc_symbols
variants_query = store.gene_variants(query=form.data,
institute_id=institute_id,
category="snv",
variant_type=variant_type)
result_size = store.count_gene_variants(query=form.data,
institute_id=institute_id,
category="snv",
variant_type=variant_type)
data = controllers.gene_variants(store, variants_query, result_size,
institute_id, page)
return dict(institute=institute_obj, form=form, page=page, **data)
def gene_variants(institute_id):
"""Display a list of SNV variants."""
page = int(request.form.get("page", 1))
institute_obj = institute_and_case(store, institute_id)
# populate form, conditional on request method
if request.method == "POST":
form = GeneVariantFiltersForm(request.form)
else:
form = GeneVariantFiltersForm(request.args)
if form.variant_type.data == []:
form.variant_type.data = ["clinical"]
variant_type = form.data.get("variant_type")
# check if supplied gene symbols exist
hgnc_symbols = []
non_clinical_symbols = []
not_found_symbols = []
not_found_ids = []
data = {}
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
LOG.debug("query {}".format(form.data))
variants_query = store.gene_variants(
query=form.data,
institute_id=institute_id,
category="snv",
variant_type=variant_type,
)
data = controllers.gene_variants(store, variants_query, institute_id,
page)
return dict(institute=institute_obj, form=form, 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 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 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)
