fix: properly representing recessive for genotypes (#1808)

varfish-org · Jul 19, 2024 · 8dbb5fb · 8dbb5fb
1 parent aced8af
commit 8dbb5fb
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Showing 10 changed files with 139 additions and 12 deletions.
diff --git a/backend/seqvars/migrations/0005_seqvarsquerysettingsgenotype_recessive_mode.py b/backend/seqvars/migrations/0005_seqvarsquerysettingsgenotype_recessive_mode.py
@@ -0,0 +1,27 @@
+# Generated by Django 3.2.25 on 2024-07-17 10:30
+
+from django.db import migrations, models
+
+
+class Migration(migrations.Migration):
+
+    dependencies = [
+        ("seqvars", "0004_auto_20240712_1236"),
+    ]
+
+    operations = [
+        migrations.AddField(
+            model_name="seqvarsquerysettingsgenotype",
+            name="recessive_mode",
+            field=models.CharField(
+                choices=[
+                    ("disabled", "disabled"),
+                    ("comphet_recessive", "comphet_recessive"),
+                    ("homozygous_recessive", "homozygous_recessive"),
+                    ("recessive", "recessive"),
+                ],
+                default="disabled",
+                max_length=128,
+            ),
+        ),
+    ]
diff --git a/backend/seqvars/models.py b/backend/seqvars/models.py
@@ -2,7 +2,6 @@
 import typing
 import uuid as uuid_object
 
-import django
 from django.contrib.auth import get_user_model
 from django.db import models, transaction
 from django_pydantic_field.v2.fields import PydanticSchemaField as SchemaField
@@ -796,12 +795,12 @@ class SeqvarsGenotypeChoice(str, Enum):
     HET = "het"
     #: Homozygous alternative genotype (or hemizygous alt for chrX / male).
     HOM = "hom"
+    #: Non-heterozygous.
+    NON_HET = "non_het"
     #: Non-homozygous.
-    NON_HOM = "non-hom"
+    NON_HOM = "non_hom"
     #: Variant.
     VARIANT = "variant"
-    #: Compound heterozygous index.
-    COMPHET_INDEX = "comphet_index"
     #: Recessive index.
     RECESSIVE_INDEX = "recessive_index"
     #: Recessive parent.
@@ -819,6 +818,8 @@ class SeqvarsSampleGenotypeChoice(pydantic.BaseModel):
     sample: str
     #: The genotype.
     genotype: SeqvarsGenotypeChoice
+    #: Include no-call genotype, will disable quality filter.
+    include_no_call: bool = False
 
 
 class SeqvarsQuerySettingsGenotype(SeqvarsQuerySettingsCategoryBase):
@@ -829,6 +830,27 @@ class SeqvarsQuerySettingsGenotype(SeqvarsQuerySettingsCategoryBase):
         SeqvarsQuerySettings, on_delete=models.CASCADE, related_name="genotype"
     )
 
+    RECESSIVE_MODE_DISABLED = "disabled"
+    RECESSIVE_MODE_COMPHET_RECESSIVE = "comphet_recessive"
+    RECESSIVE_MODE_HOMOZYGOUS_RECESSIVE = "homozygous_recessive"
+    RECESSIVE_MODE_RECESSIVE = "recessive"
+
+    RECESSIVE_MODE_CHOICES = (
+        (RECESSIVE_MODE_DISABLED, RECESSIVE_MODE_DISABLED),
+        (RECESSIVE_MODE_COMPHET_RECESSIVE, RECESSIVE_MODE_COMPHET_RECESSIVE),
+        (RECESSIVE_MODE_HOMOZYGOUS_RECESSIVE, RECESSIVE_MODE_HOMOZYGOUS_RECESSIVE),
+        (RECESSIVE_MODE_RECESSIVE, RECESSIVE_MODE_RECESSIVE),
+    )
+
+    #: The recessive mode.
+    recessive_mode = models.CharField(
+        max_length=128,
+        choices=RECESSIVE_MODE_CHOICES,
+        default=RECESSIVE_MODE_DISABLED,
+        null=False,
+        blank=False,
+    )
+
     #: Per-sample genotype choice.
     sample_genotype_choices = SchemaField(schema=list[SeqvarsSampleGenotypeChoice], default=list)
 

diff --git a/backend/seqvars/serializers.py b/backend/seqvars/serializers.py
@@ -663,11 +663,20 @@ class Meta:
 class SeqvarsQuerySettingsGenotypeSerializer(SeqvarsQuerySettingsBaseSerializer):
     """Serializer for ``QuerySettingsGenotype``."""
 
+    recessive_mode = serializers.ChoiceField(
+        choices=SeqvarsQuerySettingsGenotype.RECESSIVE_MODE_CHOICES,
+        default=SeqvarsQuerySettingsGenotype.RECESSIVE_MODE_DISABLED,
+        required=False,
+    )
+
     sample_genotype_choices = SchemaField(schema=list[SeqvarsSampleGenotypeChoice], default=list)
 
     class Meta:
         model = SeqvarsQuerySettingsGenotype
-        fields = SeqvarsQuerySettingsBaseSerializer.Meta.fields + ["sample_genotype_choices"]
+        fields = SeqvarsQuerySettingsBaseSerializer.Meta.fields + [
+            "recessive_mode",
+            "sample_genotype_choices",
+        ]
         read_only_fields = fields
 
 

diff --git a/backend/seqvars/tests/factories.py b/backend/seqvars/tests/factories.py
@@ -396,6 +396,8 @@ class SeqvarsQuerySettingsGenotypeFactory(BaseModelFactory):
     # ``QuerySettingsGenotype``.
     querysettings = factory.SubFactory(SeqvarsQuerySettingsFactory, genotype=None)
 
+    recessive_mode = SeqvarsQuerySettingsGenotype.RECESSIVE_MODE_DISABLED
+
     sample_genotype_choices = [SampleGenotypeChoiceFactory()]
 
     class Meta:

diff --git a/backend/seqvars/tests/test_models.py b/backend/seqvars/tests/test_models.py
@@ -31,6 +31,7 @@
     SeqvarsQuerySettingsVariantPrio,
     SeqvarsResultRow,
     SeqvarsResultSet,
+    SeqvarsSampleGenotypeChoice,
 )
 from seqvars.tests.factories import (
     SampleGenotypeChoiceFactory,
@@ -71,16 +72,30 @@ def test_values(self):
                 "ref",
                 "het",
                 "hom",
-                "non-hom",
+                "non_het",
+                "non_hom",
                 "variant",
-                "comphet_index",
                 "recessive_index",
                 "recessive_parent",
             ],
             SeqvarsGenotypeChoice.values(),
         )
 
 
+class TestSeqvarsSampleGenotypeChoice(TestCase):
+
+    def test_values(self):
+        self.assertEqual(
+            [
+                "disabled",
+                "comphet_recessive",
+                "homozygous_recessive",
+                "recessive",
+            ],
+            SeqvarsSampleGenotypeChoice.values(),
+        )
+
+
 class TestSeqvarsSampleGenotypeChoice(TestCase):
 
     def test_values(self):

diff --git a/backend/seqvars/tests/test_serializers.py b/backend/seqvars/tests/test_serializers.py
@@ -837,6 +837,7 @@ def test_serialize_existing(self):
             # QuerySettingsBase
             "querysettings",
             # GenotypeSettingsBase
+            "recessive_mode",
             "sample_genotype_choices",
         ]
         expected = model_to_dict(

diff --git a/backend/varfish/tests/drf_openapi_schema/varfish_api_schema.yaml b/backend/varfish/tests/drf_openapi_schema/varfish_api_schema.yaml
@@ -7684,6 +7684,18 @@ components:
 
             * `grch37` - GRCh37
             * `grch38` - GRCh38
+    RecessiveModeEnum:
+      enum:
+      - disabled
+      - comphet_recessive
+      - homozygous_recessive
+      - recessive
+      type: string
+      description: |-
+        * `disabled` - disabled
+        * `comphet_recessive` - comphet_recessive
+        * `homozygous_recessive` - homozygous_recessive
+        * `recessive` - recessive
     RegionCoverageStats:
       description: Per-region QC stats for alignment.
       properties:
@@ -8506,9 +8518,8 @@ components:
       - ref
       - het
       - hom
-      - non-hom
+      - non_hom
       - variant
-      - comphet_index
       - recessive_index
       - recessive_parent
       title: SeqvarsGenotypeChoice
@@ -10109,6 +10120,10 @@ components:
           type: string
           format: uuid
           readOnly: true
+        recessive_mode:
+          allOf:
+          - $ref: '#/components/schemas/RecessiveModeEnum'
+          default: disabled
         sample_genotype_choices:
           $ref: '#/components/schemas/SeqvarsSampleGenotypeChoiceList'
       required:
@@ -10340,6 +10355,10 @@ components:
             type: string
           genotype:
             $ref: '#/components/schemas/SeqvarsGenotypeChoice'
+          include_no_call:
+            default: false
+            title: Include No Call
+            type: boolean
         required:
         - sample
         - genotype

diff --git a/frontend/ext/reev-frontend-lib b/frontend/ext/reev-frontend-lib
diff --git a/frontend/ext/varfish-api/src/lib/schemas.gen.ts b/frontend/ext/varfish-api/src/lib/schemas.gen.ts
@@ -4141,6 +4141,15 @@ export const $PatchedTargetBedFile = {
     }
 } as const;
 
+export const $RecessiveModeEnum = {
+    enum: ['disabled', 'comphet_recessive', 'homozygous_recessive', 'recessive'],
+    type: 'string',
+    description: `* \`disabled\` - disabled
+* \`comphet_recessive\` - comphet_recessive
+* \`homozygous_recessive\` - homozygous_recessive
+* \`recessive\` - recessive`
+} as const;
+
 export const $RegionCoverageStats = {
     description: 'Per-region QC stats for alignment.',
     properties: {
@@ -5119,7 +5128,7 @@ export const $SeqvarsColumnConfigList = {
 
 export const $SeqvarsGenotypeChoice = {
     description: 'Store genotype choice of a ``SampleGenotype``.',
-    enum: ['any', 'ref', 'het', 'hom', 'non-hom', 'variant', 'comphet_index', 'recessive_index', 'recessive_parent'],
+    enum: ['any', 'ref', 'het', 'hom', 'non_hom', 'variant', 'recessive_index', 'recessive_parent'],
     title: 'SeqvarsGenotypeChoice',
     type: 'string'
 } as const;
@@ -7212,6 +7221,14 @@ export const $SeqvarsQuerySettingsGenotype = {
             format: 'uuid',
             readOnly: true
         },
+        recessive_mode: {
+            allOf: [
+                {
+                    '$ref': '#/components/schemas/RecessiveModeEnum'
+                }
+            ],
+            default: 'disabled'
+        },
         sample_genotype_choices: {
             '$ref': '#/components/schemas/SeqvarsSampleGenotypeChoiceList'
         }
@@ -7474,6 +7491,11 @@ export const $SeqvarsSampleGenotypeChoiceList = {
             },
             genotype: {
                 '$ref': '#/components/schemas/SeqvarsGenotypeChoice'
+            },
+            include_no_call: {
+                default: false,
+                title: 'Include No Call',
+                type: 'boolean'
             }
         },
         required: ['sample', 'genotype'],

diff --git a/frontend/ext/varfish-api/src/lib/types.gen.ts b/frontend/ext/varfish-api/src/lib/types.gen.ts
@@ -1333,6 +1333,14 @@ export type PatchedTargetBedFile = {
     genome_release?: GenomeReleaseEnum;
 };
 
+/**
+ * * `disabled` - disabled
+ * * `comphet_recessive` - comphet_recessive
+ * * `homozygous_recessive` - homozygous_recessive
+ * * `recessive` - recessive
+ */
+export type RecessiveModeEnum = 'disabled' | 'comphet_recessive' | 'homozygous_recessive' | 'recessive';
+
 /**
  * Per-region QC stats for alignment.
  */
@@ -1592,7 +1600,7 @@ export type SeqvarsColumnConfigList = Array<{
 /**
  * Store genotype choice of a ``SampleGenotype``.
  */
-export type SeqvarsGenotypeChoice = 'any' | 'ref' | 'het' | 'hom' | 'non-hom' | 'variant' | 'comphet_index' | 'recessive_index' | 'recessive_parent';
+export type SeqvarsGenotypeChoice = 'any' | 'ref' | 'het' | 'hom' | 'non_hom' | 'variant' | 'recessive_index' | 'recessive_parent';
 
 /**
  * Presets value for the chosen genotype.
@@ -2102,6 +2110,7 @@ export type SeqvarsQuerySettingsGenotype = {
     readonly date_created: string;
     readonly date_modified: string;
     readonly querysettings: string;
+    recessive_mode?: RecessiveModeEnum;
     sample_genotype_choices?: SeqvarsSampleGenotypeChoiceList;
 };
 
@@ -2194,6 +2203,7 @@ export type SeqvarsResultSet = {
 export type SeqvarsSampleGenotypeChoiceList = Array<{
     sample: string;
     genotype: SeqvarsGenotypeChoice;
+    include_no_call?: boolean;
 }>;
 
 export type SeqvarsSampleQualityFilterList = Array<{