Merge pull request #1125 from griffithlab/fusion_bugfixes

Various fusion bugfixes and improvements

client/src/app/components/molecular-profiles/molecular-profile-fusion-variant-card/molecular-profile-fusion-variant-card.component.html

@@ -14,19 +14,25 @@
     <nz-row [nzGutter]="[8, 16]">
       <nz-col [nzSpan]="24">
         <nz-row [nzGutter]="[8, 8]">
-          <!-- gene attributes block -->
+          <!-- fusion variant attributes block -->
           <nz-col nzSpan="24">
             <nz-descriptions
               nzLayout="horizontal"
               nzSize="small"
               [nzColumn]="4"
               nzBordered="true">
               <nz-descriptions-item
-                [nzSpan]="4"
+                [nzSpan]="2"
                 nzTitle="Fusion Variant">
                 <cvc-feature-variant-tag
                   [variant]="variant"></cvc-feature-variant-tag>
               </nz-descriptions-item>
+              <!-- VICC compliant name -->
+              <nz-descriptions-item
+                [nzSpan]="2"
+                nzTitle="VICC Compliant Name">
+                {{ variant.viccCompliantName }}
+              </nz-descriptions-item>
               <!-- aliases -->
               <nz-descriptions-item
                 [nzSpan]="2"

client/src/app/components/variants/factor-variant-summary/factor-variant-summary.page.html

@@ -71,7 +71,8 @@
             nzLayout="vertical"
             nzSize="small"
             [nzColumn]="{ xxl: 2, xl: 2, lg: 1, md: 1, sm: 1, xs: 1 }"
-            nzBordered="true">
+            nzBordered="true"
+            *ngIf="variant.creationActivity || variant.deprecationActivity">
             <!-- creation/deprecation curation events -->
             <ng-container *ngIf="variant.creationActivity">
               <nz-descriptions-item [nzTitle]="createdTitle">

client/src/app/components/variants/fusion-variant-summary/fusion-variant-summary.page.html

@@ -71,7 +71,8 @@
             nzLayout="vertical"
             nzSize="small"
             [nzColumn]="{ xxl: 2, xl: 2, lg: 1, md: 1, sm: 1, xs: 1 }"
-            nzBordered="true">
+            nzBordered="true"
+            *ngIf="variant.creationActivity || variant.deprecationActivity">
             <!-- creation/deprecation curation events -->
             <ng-container *ngIf="variant.creationActivity">
               <nz-descriptions-item [nzTitle]="createdTitle">

client/src/app/components/variants/gene-variant-summary/gene-variant-summary.page.html

@@ -119,7 +119,8 @@
             nzLayout="vertical"
             nzSize="small"
             [nzColumn]="{ xxl: 2, xl: 2, lg: 1, md: 1, sm: 1, xs: 1 }"
-            nzBordered="true">
+            nzBordered="true"
+            *ngIf="variant.creationActivity || variant.deprecationActivity">
             <!-- creation/deprecation curation events -->
             <ng-container *ngIf="variant.creationActivity">
               <nz-descriptions-item [nzTitle]="createdTitle">

client/src/app/components/variants/variant-popover/variant-popover.component.html

@@ -23,6 +23,13 @@
         nzSize="small"
         [nzColumn]="2"
         nzBordered="true">
+        <!-- VICC compliant name -->
+        <nz-descriptions-item
+          nzTitle="VICC compliant name"
+          nzSpan="2"
+          *ngIf="variant.__typename == 'FusionVariant'">
+          {{ variant.viccCompliantName }}
+        </nz-descriptions-item>
         <!-- aliases -->
         <nz-descriptions-item
           nzTitle="Aliases"

client/src/app/components/variants/variant-popover/variant-popover.query.gql

@@ -11,6 +11,9 @@ fragment variantPopoverFields on VariantInterface {
   ... on GeneVariant {
     alleleRegistryId
   }
+  ... on FusionVariant {
+    viccCompliantName
+  }
   feature {
     id
     name

client/src/app/generated/civic.apollo.ts

@@ -8433,11 +8433,11 @@ export type VariantPopoverQueryVariables = Exact<{
 }>;
 
 
-export type VariantPopoverQuery = { __typename: 'Query', variant?: { __typename: 'FactorVariant', id: number, name: string, variantAliases: Array<string>, feature: { __typename: 'Feature', id: number, name: string, link: string, deprecated: boolean, flagged: boolean }, molecularProfiles: { __typename: 'MolecularProfileConnection', totalCount: number }, revisions: { __typename: 'RevisionConnection', totalCount: number }, comments: { __typename: 'CommentConnection', totalCount: number }, flags: { __typename: 'FlagConnection', totalCount: number } } | { __typename: 'FusionVariant', id: number, name: string, variantAliases: Array<string>, feature: { __typename: 'Feature', id: number, name: string, link: string, deprecated: boolean, flagged: boolean }, molecularProfiles: { __typename: 'MolecularProfileConnection', totalCount: number }, revisions: { __typename: 'RevisionConnection', totalCount: number }, comments: { __typename: 'CommentConnection', totalCount: number }, flags: { __typename: 'FlagConnection', totalCount: number } } | { __typename: 'GeneVariant', alleleRegistryId?: string | undefined, id: number, name: string, variantAliases: Array<string>, feature: { __typename: 'Feature', id: number, name: string, link: string, deprecated: boolean, flagged: boolean }, molecularProfiles: { __typename: 'MolecularProfileConnection', totalCount: number }, revisions: { __typename: 'RevisionConnection', totalCount: number }, comments: { __typename: 'CommentConnection', totalCount: number }, flags: { __typename: 'FlagConnection', totalCount: number } } | { __typename: 'Variant', id: number, name: string, variantAliases: Array<string>, feature: { __typename: 'Feature', id: number, name: string, link: string, deprecated: boolean, flagged: boolean }, molecularProfiles: { __typename: 'MolecularProfileConnection', totalCount: number }, revisions: { __typename: 'RevisionConnection', totalCount: number }, comments: { __typename: 'CommentConnection', totalCount: number }, flags: { __typename: 'FlagConnection', totalCount: number } } | undefined };
+export type VariantPopoverQuery = { __typename: 'Query', variant?: { __typename: 'FactorVariant', id: number, name: string, variantAliases: Array<string>, feature: { __typename: 'Feature', id: number, name: string, link: string, deprecated: boolean, flagged: boolean }, molecularProfiles: { __typename: 'MolecularProfileConnection', totalCount: number }, revisions: { __typename: 'RevisionConnection', totalCount: number }, comments: { __typename: 'CommentConnection', totalCount: number }, flags: { __typename: 'FlagConnection', totalCount: number } } | { __typename: 'FusionVariant', viccCompliantName: string, id: number, name: string, variantAliases: Array<string>, feature: { __typename: 'Feature', id: number, name: string, link: string, deprecated: boolean, flagged: boolean }, molecularProfiles: { __typename: 'MolecularProfileConnection', totalCount: number }, revisions: { __typename: 'RevisionConnection', totalCount: number }, comments: { __typename: 'CommentConnection', totalCount: number }, flags: { __typename: 'FlagConnection', totalCount: number } } | { __typename: 'GeneVariant', alleleRegistryId?: string | undefined, id: number, name: string, variantAliases: Array<string>, feature: { __typename: 'Feature', id: number, name: string, link: string, deprecated: boolean, flagged: boolean }, molecularProfiles: { __typename: 'MolecularProfileConnection', totalCount: number }, revisions: { __typename: 'RevisionConnection', totalCount: number }, comments: { __typename: 'CommentConnection', totalCount: number }, flags: { __typename: 'FlagConnection', totalCount: number } } | { __typename: 'Variant', id: number, name: string, variantAliases: Array<string>, feature: { __typename: 'Feature', id: number, name: string, link: string, deprecated: boolean, flagged: boolean }, molecularProfiles: { __typename: 'MolecularProfileConnection', totalCount: number }, revisions: { __typename: 'RevisionConnection', totalCount: number }, comments: { __typename: 'CommentConnection', totalCount: number }, flags: { __typename: 'FlagConnection', totalCount: number } } | undefined };
 
 type VariantPopoverFields_FactorVariant_Fragment = { __typename: 'FactorVariant', id: number, name: string, variantAliases: Array<string>, feature: { __typename: 'Feature', id: number, name: string, link: string, deprecated: boolean, flagged: boolean }, molecularProfiles: { __typename: 'MolecularProfileConnection', totalCount: number }, revisions: { __typename: 'RevisionConnection', totalCount: number }, comments: { __typename: 'CommentConnection', totalCount: number }, flags: { __typename: 'FlagConnection', totalCount: number } };
 
-type VariantPopoverFields_FusionVariant_Fragment = { __typename: 'FusionVariant', id: number, name: string, variantAliases: Array<string>, feature: { __typename: 'Feature', id: number, name: string, link: string, deprecated: boolean, flagged: boolean }, molecularProfiles: { __typename: 'MolecularProfileConnection', totalCount: number }, revisions: { __typename: 'RevisionConnection', totalCount: number }, comments: { __typename: 'CommentConnection', totalCount: number }, flags: { __typename: 'FlagConnection', totalCount: number } };
+type VariantPopoverFields_FusionVariant_Fragment = { __typename: 'FusionVariant', viccCompliantName: string, id: number, name: string, variantAliases: Array<string>, feature: { __typename: 'Feature', id: number, name: string, link: string, deprecated: boolean, flagged: boolean }, molecularProfiles: { __typename: 'MolecularProfileConnection', totalCount: number }, revisions: { __typename: 'RevisionConnection', totalCount: number }, comments: { __typename: 'CommentConnection', totalCount: number }, flags: { __typename: 'FlagConnection', totalCount: number } };
 
 type VariantPopoverFields_GeneVariant_Fragment = { __typename: 'GeneVariant', alleleRegistryId?: string | undefined, id: number, name: string, variantAliases: Array<string>, feature: { __typename: 'Feature', id: number, name: string, link: string, deprecated: boolean, flagged: boolean }, molecularProfiles: { __typename: 'MolecularProfileConnection', totalCount: number }, revisions: { __typename: 'RevisionConnection', totalCount: number }, comments: { __typename: 'CommentConnection', totalCount: number }, flags: { __typename: 'FlagConnection', totalCount: number } };
 
@@ -11034,6 +11034,9 @@ export const VariantPopoverFieldsFragmentDoc = gql`
   ... on GeneVariant {
     alleleRegistryId
   }
+  ... on FusionVariant {
+    viccCompliantName
+  }
   feature {
     id
     name

server/app/jobs/populate_fusion_coordinates.rb

@@ -18,16 +18,23 @@ def perform(variant)
   end
 
   def populate_coords(coords, secondary_coordinates)
+    #For representative fusions, these fields are empty when the representative exons coords are first curated/revisions accepted
+    #For all fusions, these require updating when a revision on the primary set of coords edits these fields
+    secondary_coordinates.representative_transcript = coords.representative_transcript
+    secondary_coordinates.reference_build = coords.reference_build
+    secondary_coordinates.ensembl_version = coords.ensembl_version
+    secondary_coordinates.save!
+
     if coords.present? && coords.representative_transcript.present?
       (exon, highest_exon) = get_exon_for_transcript(coords.representative_transcript, coords.exon)
-      populate_exon_coordinates(coords, exon)
+      populate_exon_coordinates(coords, exon, coords.exon)
 
       if coords.coordinate_type =~ /Five Prime/
         (secondary_exon, _) = get_exon_for_transcript(secondary_coordinates.representative_transcript, 1)
-        populate_exon_coordinates(secondary_coordinates, secondary_exon)
+        populate_exon_coordinates(secondary_coordinates, secondary_exon, 1)
       else
         (secondary_exon, _) = get_exon_for_transcript(secondary_coordinates.representative_transcript, highest_exon)
-        populate_exon_coordinates(secondary_coordinates, secondary_exon)
+        populate_exon_coordinates(secondary_coordinates, secondary_exon, highest_exon)
       end
     end
   end
@@ -58,7 +65,9 @@ def get_exon_for_transcript(transcript, exon_number)
     [exon.first, max_exon_on_transcript]
   end
 
-  def populate_exon_coordinates(coordinates, exon)
+  def populate_exon_coordinates(coordinates, exon, exon_number)
+    coordinates.exon = exon_number
+
     strand = if exon['strand'] == -1
                'negative'
              else

server/app/lib/scrapers/ensembl_api_helpers.rb

@@ -26,9 +26,12 @@ def self.get_exons_for_ensembl_id(ensembl_id, warning = nil)
           elsif error_message == "ID '#{ensembl_id}' not found"
             return EnsemblResult.new(nil, "Transcript doesn't exist in GRCh37 at any version: #{ensembl_id}", warning)
           else
-            return EnsemblResult.new(nil, nil, warning)
+            return EnsemblResult.new(nil, error_message, warning)
           end
         end
+      if data.nil?
+        return EnsemblResult.new(nil, "No data returned for transcript: #{ensembl_id}", warning)
+      end
       EnsemblResult.new(data.sort_by { |exon| exon['start'] }, nil, warning)
     end
 

server/app/models/activities/create_fusion_variant.rb

@@ -47,11 +47,21 @@ def call_actions
 
     def stub_remaining_coordinates
       if variant.fusion.five_prime_partner_status == 'known'
-        variant.five_prime_start_exon_coordinates = ExonCoordinate.generate_stub(variant, 'Five Prime Start Exon Coordinate')
+        e = ExonCoordinate.generate_stub(variant, 'Five Prime Start Exon Coordinate')
+        e.representative_transcript = five_prime_end_exon_coords.representative_transcript
+        e.reference_build = five_prime_end_exon_coords.reference_build
+        e.ensembl_version = five_prime_end_exon_coords.ensembl_version
+        e.save!
+        variant.five_prime_start_exon_coordinates = e
         variant.five_prime_coordinates = VariantCoordinate.generate_stub(variant, 'Five Prime Fusion Coordinate')
       end
       if variant.fusion.three_prime_partner_status == 'known'
-        variant.three_prime_end_exon_coordinates = ExonCoordinate.generate_stub(variant, 'Three Prime End Exon Coordinate')
+        e = ExonCoordinate.generate_stub(variant, 'Three Prime End Exon Coordinate')
+        e.representative_transcript = three_prime_start_exon_coords.representative_transcript
+        e.reference_build = three_prime_start_exon_coords.reference_build
+        e.ensembl_version = three_prime_start_exon_coords.ensembl_version
+        e.save!
+        variant.three_prime_end_exon_coordinates = e
         variant.three_prime_coordinates = VariantCoordinate.generate_stub(variant, 'Three Prime Fusion Coordinate')
       end
     end

server/app/models/features/fusion.rb

@@ -27,11 +27,6 @@ class Fusion < ActiveRecord::Base
     validate :partner_status_valid_for_gene_ids
     validate :at_least_one_gene_id
 
-    #When displayed as part of an MP, the Variant Name specifies the feature
-    def mp_name
-      nil
-    end
-
     def partner_status_valid_for_gene_ids
       if !self.in_revision_validation_context
         [self.five_prime_gene, self.three_prime_gene].zip([self.five_prime_partner_status, self.three_prime_partner_status], [:five_prime_gene, :three_prime_gene]).each do |gene, status, fk|

server/app/models/variants/fusion_variant.rb

@@ -2,10 +2,6 @@ module Variants
   class FusionVariant < Variant
     has_one :fusion, through: :feature, source: :feature_instance, source_type: 'Features::Fusion'
 
-    #TODO - make this
-    #validates_with FusionVariantValidator
-    #check feature partner status and corresponding stubbed coords
-
     has_one :five_prime_coordinates,
       ->() { where(coordinate_type: 'Five Prime Fusion Coordinate') },
       foreign_key: 'variant_id',
@@ -67,18 +63,6 @@ def required_fields
       ]
     end
 
-    def mp_name
-      if name == Constants::REPRESENTATIVE_FUSION_VARIANT_NAME
-        "#{feature.name} #{Constants::REPRESENTATIVE_FUSION_VARIANT_NAME}"
-      else
-        [
-          construct_five_prime_name(name_type: :molecular_profile),
-          construct_three_prime_name(name_type: :molecular_profile)
-        ].join("::")
-      end
-
-    end
-
     def generate_vicc_name
       if name == Constants::REPRESENTATIVE_FUSION_VARIANT_NAME
         "#{construct_five_prime_name(name_type: :representative)}::#{construct_three_prime_name(name_type: :representative)}"
@@ -100,10 +84,10 @@ def generate_name
 
     def forbidden_fields
       [
-        # :ncit_id,
-        # :hgvs_description_ids,
-        # :clinvar_entry_ids,
-        # :allele_registry_id,
+        :ncit_id,
+        :hgvs_description_ids,
+        :clinvar_entry_ids,
+        :allele_registry_id,
       ]
     end
 
@@ -132,11 +116,9 @@ def construct_partner_name(name_type:, partner_status:, gene:, exon_coords:)
         when :representative
           "#{gene.name}(entrez:#{gene.entrez_id})"
         when :civic
-          "e.#{exon_coords.exon}#{exon_coords.formatted_offset}#{exon_coords.exon_offset}"
+          "e#{exon_coords.exon}#{exon_coords.formatted_offset}#{exon_coords.exon_offset}"
         when :vicc
           "#{exon_coords.representative_transcript}(#{gene.name}):e.#{exon_coords.exon}#{exon_coords.formatted_offset}#{exon_coords.exon_offset}"
-        when :molecular_profile
-          "#{gene.name}:e.#{exon_coords.exon}#{exon_coords.formatted_offset}#{exon_coords.exon_offset}"
         end
       elsif partner_status == 'unknown'
         '?'