Correct gene search warning (#2631)

* fix variants filter warning * a couple of fixes * better code * added a couple of tests * Update CHANGELOG.md Co-authored-by: Daniel Nilsson <[email protected]> * Update scout/server/blueprints/variants/controllers.py Co-authored-by: Daniel Nilsson <[email protected]> * Update scout/server/blueprints/variants/controllers.py Co-authored-by: Daniel Nilsson <[email protected]> * add 2 other genes * fix a comment * added comments * fix how form data is passed to request in test * try removing the last 2 tests * letäs see if I fool you * no need to be in the app context Co-authored-by: Daniel Nilsson <[email protected]>
Clinical-Genomics · May 18, 2021 · 3e13d99 · 3e13d99
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Showing 6 changed files with 166 additions and 38 deletions.
diff --git a/CHANGELOG.md b/CHANGELOG.md
@@ -31,9 +31,10 @@ About changelog [here](https://keepachangelog.com/en/1.0.0/)
 - Causative view sort out of memory error
 - Use hgnc_id for gene filter query
 - Typo in case controllers displaying an error every time a patient is matched against external MatchMaker nodes
-- Do not crash while attemping an update for variant documents that are too big (> 16 MB)
+- Do not crash while attempting an update for variant documents that are too big (> 16 MB)
 - Old STR causatives (and other variants) may not have HGNC symbols - fix sort lambda
 - Check if gene_obj has primary_transcript before trying to access it
+- Warn if a gene manually searched is in a clinical panel with an outdated name when filtering variants
 ### Changed
 - Remove parsing of case `genome_version`, since it's not used anywhere downstream
 - Introduce deprecation warning for Loqus configs that are not dictionaries

diff --git a/scout/adapter/mongo/panel.py b/scout/adapter/mongo/panel.py
@@ -532,3 +532,15 @@ def clinical_symbols(self, case_obj):
             ]
         )
         return set(item["_id"] for item in query)
+
+    def clinical_hgnc_ids(self, case_obj):
+        """Return all the clinical gene hgnc IDs for a case."""
+        panel_ids = [panel["panel_id"] for panel in case_obj["panels"]]
+        query = self.panel_collection.aggregate(
+            [
+                {"$match": {"_id": {"$in": panel_ids}}},
+                {"$unwind": "$genes"},
+                {"$group": {"_id": "$genes.hgnc_id"}},
+            ]
+        )
+        return set(item["_id"] for item in query)
diff --git a/scout/server/blueprints/variants/controllers.py b/scout/server/blueprints/variants/controllers.py
@@ -963,6 +963,67 @@ def populate_sv_filters_form(store, institute_obj, case_obj, category, request_o
     return form
 
 
+def check_form_gene_symbols(
+    store, case_obj, is_clinical, genome_build, hgnc_symbols, not_found_ids
+):
+    """Check that gene symbols provided by user exist and are up to date.
+       Flash a warning if gene is not found, gene symbol present in panel is outdated
+       or is not found in clinical list when search is performed on clinical variants
+
+     Args:
+        store(adapter.MongoAdapter)
+        case_obj(dict)
+        is_clinical(bool): type of variants (clinical, research)
+        genome_build(str): "37" or "38"
+        hgnc_symbols(list): list of gene symbols (strings)
+        not_found_ids(list): list of HGNC IDs not found if user provided numberical HGNC IDs in search form
+
+    Returns:
+        updated_hgnc_symbols(list): List of gene symbols that are found in database and are up to date
+    """
+    non_clinical_symbols = []
+    not_found_symbols = []
+    outdated_symbols = []
+    updated_hgnc_symbols = []
+
+    clinical_hgnc_ids = store.clinical_hgnc_ids(case_obj)
+    clinical_symbols = store.clinical_symbols(case_obj)
+
+    for hgnc_symbol in hgnc_symbols:
+        hgnc_gene = store.hgnc_genes_find_one(hgnc_symbol, genome_build)
+
+        if hgnc_gene is None:
+            not_found_symbols.append(hgnc_symbol)
+        elif is_clinical and hgnc_gene["hgnc_id"] in clinical_hgnc_ids:
+            updated_hgnc_symbols.append(hgnc_symbol)
+            if hgnc_symbol not in clinical_symbols:
+                # clinical symbols from gene panels might not be up to date with latest gene names
+                # but their HGNC id would still match
+                outdated_symbols.append(hgnc_symbol)
+        else:
+            non_clinical_symbols.append(hgnc_symbol)
+
+    errors = {
+        "non_clinical_symbols": {
+            "alert": "Gene not included in clinical list",
+            "gene_list": non_clinical_symbols,
+        },
+        "not_found_symbols": {"alert": "HGNC symbol not found", "gene_list": not_found_symbols},
+        "not_found_ids": {"alert": "HGNC id not found", "gene_list": not_found_ids},
+        "outdated_symbols": {
+            "alert": "Clinical list contains a panel with an outdated symbol for genes",
+            "gene_list": outdated_symbols,
+        },
+    }
+
+    # warn user if gene symbols are corresponding to any current gene,
+    for error, item in errors.items():
+        if item["gene_list"]:
+            flash(f"{item['alert']}: {item['gene_list']}", "warning")
+
+    return updated_hgnc_symbols
+
+
 def update_form_hgnc_symbols(store, case_obj, form):
     """Update variants filter form with HGNC symbols from HPO, and check if any non-clinical genes for the case were
     requested. If so, flash a warning to the user.
@@ -977,17 +1038,15 @@ def update_form_hgnc_symbols(store, case_obj, form):
     """
 
     hgnc_symbols = []
-    non_clinical_symbols = []
-    not_found_symbols = []
     not_found_ids = []
-    updated_hgnc_symbols = []
+    genome_build = "38" if "38" in str(case_obj.get("genome_build")) else "37"
 
     # retrieve current symbols from form
     if form.hgnc_symbols.data:
         # if symbols are numeric HGNC id, translate to current symbols
         for hgnc_symbol in form.hgnc_symbols.data:
             if hgnc_symbol.isdigit():
-                hgnc_gene = store.hgnc_gene(int(hgnc_symbol), case_obj["genome_build"])
+                hgnc_gene = store.hgnc_gene(int(hgnc_symbol), genome_build)
                 if hgnc_gene is None:
                     not_found_ids.append(hgnc_symbol)
                 else:
@@ -1008,31 +1067,10 @@ def update_form_hgnc_symbols(store, case_obj, form):
 
     # check if supplied gene symbols exist and are clinical
     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 hgnc_symbols:
-        if 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:
-            updated_hgnc_symbols.append(hgnc_symbol)
-
-    errors = {
-        "non_clinical_symbols": {
-            "alert": "Gene not included in clinical list",
-            "gene_list": non_clinical_symbols,
-        },
-        "not_found_symbols": {"alert": "HGNC symbol not found", "gene_list": not_found_symbols},
-        "not_found_ids": {"alert": "HGNC id not found", "gene_list": not_found_ids},
-    }
-
-    # warn user
-    for error, item in errors.items():
-        if item["gene_list"]:
-            flash(f"{item['alert']}: {item['gene_list']}", "warning")
-
+    updated_hgnc_symbols = check_form_gene_symbols(
+        store, case_obj, is_clinical, genome_build, hgnc_symbols, not_found_ids
+    )
     form.hgnc_symbols.data = sorted(updated_hgnc_symbols)
-
     return form
 
 

diff --git a/tests/adapter/mongo/test_panel_handler.py b/tests/adapter/mongo/test_panel_handler.py
@@ -337,3 +337,35 @@ def test_apply_pending_edit_gene(adapter, testpanel_obj):
         "model_1",
         "model_2",
     ]
+
+
+def test_clinical_symbols(case_obj, real_panel_database):
+    """test function that returns a set of clinical genes symbols from test case panels"""
+
+    # GIVEN an adapter with genes and a gene panel
+    adapter = real_panel_database
+
+    test_panel = adapter.panel_collection.find_one()
+
+    # GIVEN a case analysed with that panel
+    case_obj["panels"] = [{"panel_id": test_panel["_id"]}]
+
+    # THEN the clinical_symbols function should return a valid set of clinical genes symbols for the case panel
+    clinical_symbols = adapter.clinical_symbols(case_obj)
+    assert len(clinical_symbols) > 0
+
+
+def test_clinical_hgnc_ids(case_obj, real_panel_database):
+    """test function that returns a set of clinical genes HGNC IDs from test case panels"""
+
+    # GIVEN an adapter with genes and a gene panel
+    adapter = real_panel_database
+
+    test_panel = adapter.panel_collection.find_one()
+
+    # GIVEN a case analysed with that panel
+    case_obj["panels"] = [{"panel_id": test_panel["_id"]}]
+
+    # THEN the clinical_hgnc_ids function should return a valid set of hgnc IDs for the case panel
+    clinical_hgnc_ids = adapter.clinical_symbols(case_obj)
+    assert len(clinical_hgnc_ids) > 0
diff --git a/tests/server/blueprints/variants/test_variants_controllers.py b/tests/server/blueprints/variants/test_variants_controllers.py
@@ -3,7 +3,7 @@
 
 from bson.objectid import ObjectId
 from flask_wtf import FlaskForm
-from wtforms import SelectField
+from wtforms import SelectField, StringField
 
 from scout.constants import CHROMOSOMES_38, EXPORT_HEADER
 from scout.server.blueprints.variants.controllers import (
@@ -12,10 +12,12 @@
     match_gene_txs_variant_txs,
     populate_chrom_choices,
     sv_variants,
+    update_form_hgnc_symbols,
     variant_export_lines,
     variants,
     variants_export_header,
 )
+from scout.server.extensions import store
 
 LOG = logging.getLogger(__name__)
 
@@ -363,3 +365,49 @@ def test_variant_csv_export(real_variant_database, case_obj):
     for export_line in export_lines:
         export_cols = export_line.split(",")
         assert len(export_cols) == len(export_header)
+
+
+def test_update_form_hgnc_symbols_valid_gene_symbol(app, case_obj):
+    """Test controller that populates HGNC symbols form filter in variants page. Provide valid gene symbol"""
+
+    # GIVEN a case analysed with a gene panel
+    test_panel = store.panel_collection.find_one()
+    case_obj["panels"] = [{"panel_id": test_panel["_id"]}]
+
+    # GIVEN a variants filter form
+    class TestForm(FlaskForm):
+        hgnc_symbols = StringField()
+        data = StringField()
+
+    form = TestForm()
+
+    # GIVEN a user trying to filter clinical variants using a valid gene symbol
+    form.hgnc_symbols.data = ["POT1"]
+    form.data = {"gene_panels": []}
+    updated_form = update_form_hgnc_symbols(store, case_obj, form)
+
+    # Form should be updated correctly
+    assert form.hgnc_symbols.data == ["POT1"]
+
+
+def test_update_form_hgnc_symbols_valid_gene_id(app, case_obj):
+    """Test controller that populates HGNC symbols form filter in variants page. Provide HGNC ID"""
+
+    # GIVEN a case analysed with a gene panel
+    test_panel = store.panel_collection.find_one()
+    case_obj["panels"] = [{"panel_id": test_panel["_id"]}]
+
+    # GIVEN a variants filter form
+    class TestForm(FlaskForm):
+        hgnc_symbols = StringField()
+        data = StringField()
+
+    form = TestForm()
+
+    # GIVEN a user trying to filter clinical variants using a valid gene ID
+    form.hgnc_symbols.data = ["17284"]
+    form.data = {"gene_panels": []}
+    updated_form = update_form_hgnc_symbols(store, case_obj, form)
+
+    # Form should be updated correctly
+    assert form.hgnc_symbols.data == ["POT1"]
diff --git a/tests/server/blueprints/variants/test_variants_views.py b/tests/server/blueprints/variants/test_variants_views.py
@@ -44,13 +44,11 @@ def test_variants_clinical_filter(app, institute_obj, case_obj, mocker, mock_red
         assert resp.status_code == 200
 
         # WHEN submitting form data to the variants page (POST method) with clinical filter
-        data = urlencode(
-            {
-                "clinical_filter": "Clinical filter",
-                "variant_type": "clinical",
-                "gene_panels": "panel1",
-            }
-        )  # clinical filter
+        data = {
+            "clinical_filter": "Clinical filter",
+            "variant_type": "clinical",
+            "gene_panels": "panel1",
+        }
 
         resp = client.post(
             url_for(
@@ -59,7 +57,6 @@ def test_variants_clinical_filter(app, institute_obj, case_obj, mocker, mock_red
                 case_name=case_obj["display_name"],
             ),
             data=data,
-            content_type="application/x-www-form-urlencoded",
         )
 
         # THEN it should return a page