Adding distinct de novo genotype setting (#562)

Closes: #562
Related-Issue: #562
Projected-Results-Impact: require-revalidation

HISTORY.rst

@@ -44,6 +44,7 @@ End-User Summary
   Alternatively, you can use ``python manage.py svs_sv_fill_nulls`` to update the records on the fly.
 - Implement new in-house background database for structural variants (#32).
 - Allow to exclude cases from in-house database through project settings (#579).
+- Adding distinct de novo genotype setting (#562).
 
 Full Change List
 ================
@@ -83,6 +84,7 @@ Full Change List
 - Making ``keyvalue`` more robust to failure (#613).
 - Implement new in-house background database for structural variants (#32).
 - Allow to exclude cases from in-house database through project settings (#579).
+- Adding distinct de novo genotype setting (#562).
 
 ------
 v1.2.0

varfish/static/js/filter_form.js

@@ -501,8 +501,11 @@ const presets = {
   },
   "inheritance-dominant": {
       "ids": {},
-      // dom-denovo doesn't exist in the select. this triggers a function
-      "classes": {"genotype-field-gt": "dom-denovo"},
+      "classes": {"genotype-field-gt": "dominant"},
+  },
+  "inheritance-de-novo": {
+      "ids": {},
+      "classes": {"genotype-field-gt": "de-novo"},
   },
   "inheritance-hom-recessive": {
       "ids": {},
@@ -1469,7 +1472,21 @@ function enableHomRecessiveMode(target) {
 }
 
 
-function enableDomDenovoMode() {
+function enableDeNovoMode() {
+    // Index will be set to variant, all others to ref
+    $("[id^=id_][id$=_gt]").each(
+        function () {
+            console.log($(this), $(this).data("default-index"))
+            if ($(this).data("default-index") === 1) {
+                $(this).val("variant")
+            } else {
+                $(this).val("ref")
+            }
+        }
+    )
+}
+
+function enableDominantMode() {
     // All affected will be set to het
     $("[id^=id_][id$=_gt].affected").val("het");
     // All unaffected will be set to ref
@@ -1637,18 +1654,13 @@ function applyPresetsToSettings(presets, name) {
             (
                 val == "index"
                 || val == "recessive-index"
-                || val == "dom-denovo"
                 || val == "hom-recessive"
                 || val == "mitochondrial"
                 || val == "x-recessive"
             ) && tag.data("default-index") != "1"
         ) {
             continue;
         }
-        // Dominant denovo is not an option in the genotype select, so let a function do the change.
-        if (val == "dom-denovo") {
-            enableDomDenovoMode();
-        }
         // Homozygous recessive is not an option in the genotype select, so let a function do the change.
         else if (val == "hom-recessive") {
             enableHomRecessiveMode(tag);
@@ -1661,6 +1673,14 @@ function applyPresetsToSettings(presets, name) {
         else if (val == "x-recessive") {
             enableXRecessiveMode(tag);
         }
+        // X recessive is not an option in the genotype select, so let a function do the change.
+        else if (val == "de-novo") {
+            enableDeNovoMode();
+        }
+        // X recessive is not an option in the genotype select, so let a function do the change.
+        else if (val == "dominant") {
+            enableDominantMode();
+        }
         // Default change behaviour for all others
         else {
             tag.val(val);
@@ -1698,7 +1718,7 @@ function updateQuickPresets(settings) {
   }
   const quickPresetCategories = ["inheritance", "frequency", "impact", "quality", "region", "flags"];
   const quickPresetCandidates = {
-    "inheritance": ["any", "dominant", "hom-recessive", "comp-het", "recessive", "mitochondrial", "x-recessive"],
+    "inheritance": ["any", "dominant", "de-novo", "hom-recessive", "comp-het", "recessive", "mitochondrial", "x-recessive"],
     "frequency": ["super-strict", "strict", "relaxed", "recessive-strict", "recessive-relaxed", "all"],
     "impact": ["null-variant", "aa-change", "all-coding-deep-intronic", "whole-transcript", "any"],
     "quality": ["super-strict", "strict", "relaxed", "ignore"],
@@ -1852,7 +1872,7 @@ function loadPresets(element) {
     $("#input-presets-region").val("region-whole-genome")
     $("#input-presets-flags").val("flags-default")
   } else if (presetsName == "de-novo") {
-    $("#input-presets-inheritance").val("inheritance-dominant")
+    $("#input-presets-inheritance").val("inheritance-de-novo")
     $("#input-presets-frequency").val("frequency-strict")
     $("#input-presets-impact").val("impact-aa-change")
     $("#input-presets-quality").val("quality-relaxed")

variants/forms.py

@@ -442,10 +442,7 @@ def clean(self):
                     result["compound_recessive_indices"][family] = name
                 elif result[self.get_genotype_field_names()[name]["gt"]] == "recessive-index":
                     result["recessive_indices"][family] = name
-                elif result[self.get_genotype_field_names()[name]["gt"]] in (
-                    "hom-recessive-index",
-                    "dom-denovo-index",
-                ):
+                elif result[self.get_genotype_field_names()[name]["gt"]] == "hom-recessive-index":
                     self.add_error(
                         self.get_genotype_field_names()[name]["gt"],
                         "This option value shouldn't be passed. Selecting it should trigger JS code which changes the value.",

variants/query_presets.py

@@ -77,6 +77,7 @@ class GenotypeChoice(Enum):
 class Inheritance(Enum):
     """Preset options for category inheritance"""
 
+    DE_NOVO = "de_novo"
     DOMINANT = "dominant"
     HOMOZYGOUS_RECESSIVE = "homozygous_recessive"
     COMPOUND_HETEROZYGOUS = "compound_heterozygous"
@@ -204,6 +205,17 @@ def to_settings(
                     for s in samples
                 },
             }
+        elif self == Inheritance.DE_NOVO:
+            return {
+                "recessive_index": None,
+                "recessive_mode": None,
+                "genotype": {
+                    s.name: GenotypeChoice.VARIANT.value
+                    if s.name == index_candidates[0].name
+                    else GenotypeChoice.REF.value
+                    for s in samples
+                },
+            }
         elif self == Inheritance.DOMINANT:
             return {
                 "recessive_index": None,
@@ -998,7 +1010,7 @@ class _QuickPresetList:
     )
     #: *de novo* presets
     de_novo: QuickPresets = QuickPresets(
-        inheritance=Inheritance.DOMINANT,
+        inheritance=Inheritance.DE_NOVO,
         frequency=Frequency.DOMINANT_STRICT,
         impact=Impact.AA_CHANGE_SPLICING,
         quality=Quality.RELAXED,

variants/query_schemas.py

@@ -243,7 +243,6 @@ class CaseQueryV1:
 
     recessive_mode: typing.Optional[RecessiveModeV1] = None
     recessive_index: typing.Optional[str] = None
-    denovo_index: typing.Optional[str] = None
 
     exac_frequency: typing.Optional[float] = None
     exac_heterozygous: typing.Optional[int] = None
@@ -406,8 +405,6 @@ def convert(self, case: Case, query: CaseQueryV1) -> typing.Dict[str, typing.Any
                 result["%s_gt" % sample] = "recessive-index"
             elif sample in result["compound_recessive_indices"].values():
                 result["%s_gt" % sample] = "index"
-            elif sample == query.denovo_index:
-                result["%s_gt" % sample] = "dom-denovo-index"
             else:
                 gt = query.genotype.get(sample, GenotypeChoiceV1.ANY)
                 if gt:

variants/schemas/case-query-v1.json

@@ -1293,22 +1293,6 @@
         }
       ]
     },
-    "denovo_index": {
-      "anyOf": [
-        {
-          "type": "null"
-        },
-        {
-          "$id": "#/properties/denovo_index",
-          "type": "string",
-          "title": "Select the denovo index",
-          "description": "Set to the identifier of the de novo index",
-          "examples": [
-            "CHILD-NAME"
-          ]
-        }
-      ]
-    },
     "quality": {
       "$id": "#/properties/quality",
       "type": "object",

variants/templates/variants/filter_form/presets.html

@@ -28,7 +28,8 @@
     <label for="input-presets-inheritance" class="font-weight-bold small">Inheritance</label>
     <select id="input-presets-inheritance" class="form-control form-control-sm">
       <option value="inheritance-any" selected="selected">any (default)</option>
-      <option value="inheritance-dominant" >dominant / de novo</option>
+      <option value="inheritance-de-novo" >de novo</option>
+      <option value="inheritance-dominant" >dominant</option>
       <option value="inheritance-hom-recessive" >hom. recessive</option>
       <option value="inheritance-comp-het" >comp. heterozygous</option>
       <option value="inheritance-recessive" >recessive</option>

variants/tests/test_query_presets.py

@@ -230,6 +230,7 @@ def setUp(self):
 
 class TestEnumInheritance(PedigreesMixin, TestCase):
     def testValues(self):
+        self.assertEqual(query_presets.Inheritance.DE_NOVO.value, "de_novo")
         self.assertEqual(query_presets.Inheritance.DOMINANT.value, "dominant")
         self.assertEqual(
             query_presets.Inheritance.HOMOZYGOUS_RECESSIVE.value, "homozygous_recessive"
@@ -243,6 +244,78 @@ def testValues(self):
         self.assertEqual(query_presets.Inheritance.CUSTOM.value, "custom")
         self.assertEqual(query_presets.Inheritance.ANY.value, "any")
 
+    def testToSettingsDeNovo(self):
+        # singleton
+        actual = query_presets.Inheritance.DE_NOVO.to_settings(self.singleton, self.singleton[0])
+        self.assertEqual(
+            actual,
+            {
+                "genotype": {"index": query_presets.GenotypeChoice.VARIANT.value},
+                "recessive_index": None,
+                "recessive_mode": None,
+            },
+        )
+        # child with father
+        actual = query_presets.Inheritance.DE_NOVO.to_settings(
+            self.child_father, self.child_father[0].name
+        )
+        self.assertEqual(
+            actual,
+            {
+                "recessive_index": None,
+                "recessive_mode": None,
+                "genotype": {
+                    "index": query_presets.GenotypeChoice.VARIANT.value,
+                    "father": query_presets.GenotypeChoice.REF.value,
+                },
+            },
+        )
+        # child with mother
+        actual = query_presets.Inheritance.DE_NOVO.to_settings(
+            self.child_mother, self.child_mother[0].name
+        )
+        self.assertEqual(
+            actual,
+            {
+                "recessive_index": None,
+                "recessive_mode": None,
+                "genotype": {
+                    "index": query_presets.GenotypeChoice.VARIANT.value,
+                    "mother": query_presets.GenotypeChoice.REF.value,
+                },
+            },
+        )
+        # trio denovo
+        actual = query_presets.Inheritance.DE_NOVO.to_settings(self.trio_denovo, self.singleton[0])
+        self.assertEqual(
+            actual,
+            {
+                "recessive_index": None,
+                "recessive_mode": None,
+                "genotype": {
+                    "index": query_presets.GenotypeChoice.VARIANT.value,
+                    "father": query_presets.GenotypeChoice.REF.value,
+                    "mother": query_presets.GenotypeChoice.REF.value,
+                },
+            },
+        )
+        # trio dominant inherited
+        actual = query_presets.Inheritance.DE_NOVO.to_settings(
+            self.trio_dominant, self.trio_dominant[0].name
+        )
+        self.assertEqual(
+            actual,
+            {
+                "recessive_index": None,
+                "recessive_mode": None,
+                "genotype": {
+                    "index": query_presets.GenotypeChoice.VARIANT.value,
+                    "father": query_presets.GenotypeChoice.REF.value,
+                    "mother": query_presets.GenotypeChoice.REF.value,
+                },
+            },
+        )
+
     def testToSettingsDominant(self):
         # singleton
         actual = query_presets.Inheritance.DOMINANT.to_settings(self.singleton, self.singleton[0])
@@ -1469,7 +1542,7 @@ def testValueDefaults(self):
     def testValueDeNovo(self):
         self.assertEqual(
             str(query_presets.QUICK_PRESETS.de_novo),
-            "QuickPresets(inheritance=<Inheritance.DOMINANT: 'dominant'>, "
+            "QuickPresets(inheritance=<Inheritance.DE_NOVO: 'de_novo'>, "
             "frequency=<Frequency.DOMINANT_STRICT: 'dominant_strict'>, "
             "impact=<Impact.AA_CHANGE_SPLICING: 'aa_change_splicing'>, "
             "quality=<Quality.RELAXED: 'relaxed'>, chromosomes=<Chromosomes.WHOLE_GENOME: 'whole_genome'>, "