Merge pull request #573 from hpi-dhc/issue/443-include-drug-drug-and-…

…drug-drug-gene-interaction-checking Include drug-drug and drug-drug-gene interaction checking
hpi-dhc · Feb 18, 2023 · db57fdc · db57fdc
2 parents b0bf4c0 + 001922a
commit db57fdc
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Showing 18 changed files with 123 additions and 91 deletions.
diff --git a/app/integration_test/drugs_test.dart b/app/integration_test/drugs_test.dart
@@ -50,7 +50,7 @@ void main() {
         geneSymbol: 'CYP2C9',
         phenotype: 'Normal Metabolizer',
         genotype: '*1/*1',
-        lookupkey: 'Normal Metabolizer')
+        lookupkey: '2')
   };
   UserData.instance.diplotypes = {
     'CYP2C9': Diplotype(
@@ -71,7 +71,7 @@ void main() {
         brandNames: ['brand name', 'another brand name']),
     guidelines: [],
   );
-  UserData.instance.starredDrugIds = ['1'];
+  UserData.instance.activeDrugNames = ['Ibuprofen'];
 
   group('integration test for the drugs page', () {
     testWidgets('test loading', (tester) async {
@@ -124,7 +124,7 @@ void main() {
 
     testWidgets('test loaded page', (tester) async {
       when(() => mockDrugsCubit.state)
-          .thenReturn(DrugState.loaded(testDrug, isStarred: false));
+          .thenReturn(DrugState.loaded(testDrug, isActive: false));
 
       late BuildContext context;
 
@@ -188,7 +188,7 @@ void main() {
 
     testWidgets('test loaded page without guidelines', (tester) async {
       when(() => mockDrugsCubit.state).thenReturn(
-          DrugState.loaded(testDrugWithoutGuidelines, isStarred: true));
+          DrugState.loaded(testDrugWithoutGuidelines, isActive: true));
 
       await tester.pumpWidget(
         MaterialApp(

diff --git a/app/integration_test/search_test.dart b/app/integration_test/search_test.dart
@@ -8,7 +8,7 @@ import 'package:mocktail/mocktail.dart';
 
 class MockSearchCubit extends MockCubit<SearchState> implements SearchCubit {
   @override
-  bool get filterStarred => false;
+  bool get filterActive => false;
 }
 
 void main() {

diff --git a/app/lib/common/models/drug/drug.dart b/app/lib/common/models/drug/drug.dart
@@ -66,9 +66,9 @@ class DrugAnnotations {
   List<String> brandNames;
 }
 
-extension DrugIsStarred on Drug {
-  bool isStarred() {
-    return UserData.instance.starredDrugIds?.contains(id) ?? false;
+extension DrugIsActive on Drug {
+  bool isActive() {
+    return UserData.instance.activeDrugNames?.contains(name) ?? false;
   }
 }
 
@@ -80,52 +80,20 @@ extension DrugMatchesQuery on Drug {
   }
 }
 
-/// Removes the guidelines that are not relevant to the user
-extension DrugWithUserGuidelines on Drug {
-  Drug filterUserGuidelines() {
-    final matchingGuidelines = guidelines.where((guideline) {
-      // Guideline matches if all user has any of the gene results for all gene
-      // symbols
-      return guideline.lookupkey.all((geneSymbol, geneResults) =>
-          (UserData.instance.lookups?.containsKey(geneSymbol) ?? false) &&
-          geneResults
-              .contains(UserData.instance.lookups?[geneSymbol]?.lookupkey));
-    });
-
-    return Drug(
-      id: id,
-      version: version,
-      name: name,
-      rxNorm: rxNorm,
-      annotations: annotations,
-      guidelines: matchingGuidelines.toList(),
-    );
-  }
-}
-
-/// Removes the guidelines that are not relevant to the user
-extension DrugsWithUserGuidelines on List<Drug> {
-  List<Drug> filterUserGuidelines() {
-    return map((drug) => drug.filterUserGuidelines()).toList();
-  }
+/// Gets the User's matching guideline
+extension DrugWithUserGuideline on Drug {
+  Guideline? userGuideline() => guidelines.firstOrNullWhere(
+        (guideline) => guideline.lookupkey.all((geneSymbol, geneResults) =>
+            geneResults.contains(UserData.lookupFor(geneSymbol))),
+      );
 }
 
 /// Filters for drugs with non-OK warning level
 extension CriticalDrugs on List<Drug> {
   List<Drug> filterCritical() {
     return filter((drug) {
-      final warningLevel = drug.highestWarningLevel();
+      final warningLevel = drug.userGuideline()?.annotations.warningLevel;
       return warningLevel != null && warningLevel != WarningLevel.green;
     }).toList();
   }
 }
-
-/// Gets most severe warning level
-extension DrugWarningLevel on Drug {
-  WarningLevel? highestWarningLevel() {
-    final filtered = filterUserGuidelines();
-    return filtered.guidelines
-        .map((guideline) => guideline.annotations.warningLevel)
-        .maxBy((level) => level.severity);
-  }
-}
diff --git a/app/lib/common/models/drug/drug_inhibitors.dart b/app/lib/common/models/drug/drug_inhibitors.dart
@@ -0,0 +1,24 @@
+// Everything has to match literally. The final value is not a phenotype but
+// the CPIC lookupkey value. If a user has multiple of the given drugs active,
+// the topmost one will be used, i.e. the inhibitors should go from most to
+// least severe.
+
+// structure: gene symbol -> drug name -> overwriting lookupkey
+
+const Map<String, Map<String, String>> drugInhibitors = {
+  'CYP2D6': {
+    // 0.0 is a lookupkey for a type of poor metabolizer
+    'bupropion': '0.0',
+    'fluoxetine': '0.0',
+    'paroxetine': '0.0',
+    'quinidine': '0.0',
+    'terbinafine': '0.0',
+    // 1.0 is a lookupkey for a type of poor (but less poor than 0.0)
+    // metabolizer
+    'abiraterone': '1.0',
+    'cinacalcet': '1.0',
+    'duloxetine': '1.0',
+    'lorcaserin': '1.0',
+    'mirabegron': '1.0',
+  }
+};
diff --git a/app/lib/common/models/module.dart b/app/lib/common/models/module.dart
@@ -1,5 +1,6 @@
 export 'anni_response.dart';
 export 'drug/drug.dart';
+export 'drug/drug_inhibitors.dart';
 export 'drug/guideline.dart';
 export 'drug/warning_level.dart';
 export 'metadata.dart';

diff --git a/app/lib/common/models/userdata/userdata.dart b/app/lib/common/models/userdata/userdata.dart
@@ -1,3 +1,4 @@
+import 'package:collection/collection.dart';
 import 'package:hive/hive.dart';
 
 import '../../../search/module.dart';
@@ -31,12 +32,31 @@ class UserData {
 
   @HiveField(0)
   Map<String, Diplotype>? diplotypes;
+  static String? phenotypeFor(String gene) =>
+      UserData.instance.diplotypes?[gene]?.phenotype;
 
   @HiveField(1)
   Map<String, CpicPhenotype>? lookups;
 
+  static MapEntry<String, String>? overwrittenLookup(String gene) {
+    final inhibitors = drugInhibitors[gene];
+    if (inhibitors == null) return null;
+    final lookup = inhibitors.entries.firstWhereOrNull((entry) =>
+        UserData.instance.activeDrugNames?.contains(entry.key) ?? false);
+    if (lookup == null) return null;
+    return lookup;
+  }
+
+  static String? lookupFor(String gene) {
+    final overwrittenLookup = UserData.overwrittenLookup(gene);
+    if (overwrittenLookup != null) {
+      return overwrittenLookup.value;
+    }
+    return UserData.instance.lookups?[gene]?.lookupkey;
+  }
+
   @HiveField(2)
-  List<String>? starredDrugIds;
+  List<String>? activeDrugNames;
 }
 
 /// Initializes the user's data by registering all necessary adapters and

diff --git a/app/lib/common/pages/drug/cubit.dart b/app/lib/common/pages/drug/cubit.dart
@@ -6,32 +6,32 @@ part 'cubit.freezed.dart';
 
 class DrugCubit extends Cubit<DrugState> {
   DrugCubit(this._drug) : super(DrugState.initial()) {
-    emit(DrugState.loaded(_drug, isStarred: _drug.isStarred()));
+    emit(DrugState.loaded(_drug, isActive: _drug.isActive()));
   }
 
   final Drug _drug;
 
-  Future<void> toggleStarred() async {
+  Future<void> toggleActive() async {
     final drug = state.whenOrNull(loaded: (drug, _) => drug);
     if (drug == null) return;
 
-    final stars = UserData.instance.starredDrugIds ?? [];
-    if (drug.isStarred()) {
-      UserData.instance.starredDrugIds =
-          stars.filter((element) => element != _drug.id).toList();
+    final active = UserData.instance.activeDrugNames ?? [];
+    if (drug.isActive()) {
+      UserData.instance.activeDrugNames =
+          active.filter((element) => element != _drug.name).toList();
     } else {
-      UserData.instance.starredDrugIds = stars + [_drug.id];
+      UserData.instance.activeDrugNames = active + [_drug.name];
     }
     await UserData.save();
-    emit(DrugState.loaded(drug, isStarred: drug.isStarred()));
+    emit(DrugState.loaded(drug, isActive: drug.isActive()));
   }
 }
 
 @freezed
 class DrugState with _$DrugState {
   const factory DrugState.initial() = _InitialState;
   const factory DrugState.loading() = _LoadingState;
-  const factory DrugState.loaded(Drug drug, {required bool isStarred}) =
+  const factory DrugState.loaded(Drug drug, {required bool isActive}) =
       _LoadedState;
   const factory DrugState.error() = _ErrorState;
 }
diff --git a/app/lib/common/pages/drug/drug.dart b/app/lib/common/pages/drug/drug.dart
@@ -28,12 +28,12 @@ class DrugPage extends StatelessWidget {
                 body: [errorIndicator(context.l10n.err_generic)]),
             loading: () =>
                 pageScaffold(title: drugName, body: [loadingIndicator()]),
-            loaded: (drug, isStarred) => pageScaffold(
+            loaded: (drug, isActive) => pageScaffold(
               title: drugName,
               actions: [
                 IconButton(
-                  onPressed: () => context.read<DrugCubit>().toggleStarred(),
-                  icon: PharMeTheme.starIcon(isStarred: isStarred),
+                  onPressed: () => context.read<DrugCubit>().toggleActive(),
+                  icon: PharMeTheme.activeDrugIcon(isActive: isActive),
                 ),
                 IconButton(
                   onPressed: () => sharePdf(drug),
@@ -44,7 +44,7 @@ class DrugPage extends StatelessWidget {
                 )
               ],
               body: [
-                _buildDrugsPage(drug, isStarred: isStarred, context: context)
+                _buildDrugsPage(drug, isActive: isActive, context: context)
               ],
             ),
           );
@@ -55,9 +55,10 @@ class DrugPage extends StatelessWidget {
 
   Widget _buildDrugsPage(
     Drug drug, {
-    required bool isStarred,
+    required bool isActive,
     required BuildContext context,
   }) {
+    final userGuideline = drug.userGuideline();
     return Padding(
         padding: const EdgeInsets.symmetric(horizontal: 12, vertical: 16),
         child: Column(
@@ -72,11 +73,11 @@ class DrugPage extends StatelessWidget {
               tooltip: context.l10n.drugs_page_tooltip_guideline,
             ),
             SizedBox(height: 12),
-            ...(drug.guidelines.isNotEmpty)
+            ...(userGuideline != null)
                 ? [
                     Disclaimer(),
                     SizedBox(height: 12),
-                    GuidelineAnnotationCard(drug.guidelines[0])
+                    GuidelineAnnotationCard(userGuideline)
                   ]
                 : [Text(context.l10n.drugs_page_no_guidelines_for_phenotype)]
           ],

diff --git a/app/lib/common/pages/drug/widgets/annotation_cards/guideline.dart b/app/lib/common/pages/drug/widgets/annotation_cards/guideline.dart
@@ -34,7 +34,8 @@ class GuidelineAnnotationCard extends StatelessWidget {
         color: guideline.annotations.warningLevel.color,
         child: Padding(
             padding: EdgeInsets.all(12),
-            child: Column(children: [
+            child:
+                Column(crossAxisAlignment: CrossAxisAlignment.start, children: [
               Row(children: [
                 Icon(guideline.annotations.warningLevel.icon,
                     color: PharMeTheme.onSurfaceText),
@@ -55,15 +56,22 @@ class GuidelineAnnotationCard extends StatelessWidget {
   }
 
   Widget _buildHeader(BuildContext context) {
-    final geneDescriptions = guideline.lookupkey.keys.map((geneSymbol) =>
-        '$geneSymbol (${UserData.instance.diplotypes![geneSymbol]!.phenotype})');
+    final geneDescriptions = guideline.lookupkey.keys.map((geneSymbol) {
+      final overwritingDrug = UserData.overwrittenLookup(geneSymbol)?.key;
+      final hint = overwritingDrug.isNotNullOrEmpty
+          ? '(${context.l10n.drugs_page_overwritten_phenotype(overwritingDrug!)})'
+          : '';
+      final genePhenotype =
+          '$geneSymbol: ${UserData.phenotypeFor(geneSymbol)!}';
+      return [genePhenotype, hint].join(' ');
+    });
     return Column(crossAxisAlignment: CrossAxisAlignment.start, children: [
       SubHeader(context.l10n.drugs_page_your_genome),
       SizedBox(height: 12),
       Text(
         geneDescriptions.join(', '),
         style: PharMeTheme.textTheme.bodyLarge!,
-      )
+      ),
     ]);
   }
 

diff --git a/app/lib/common/pages/drug/widgets/disclaimer.dart b/app/lib/common/pages/drug/widgets/disclaimer.dart
@@ -4,7 +4,9 @@ import '../../../l10n.dart';
 import '../../../theme.dart';
 
 class Disclaimer extends StatelessWidget {
-  const Disclaimer();
+  const Disclaimer({this.text});
+
+  final String? text;
 
   @override
   Widget build(BuildContext context) {
@@ -24,7 +26,7 @@ class Disclaimer extends StatelessWidget {
         SizedBox(width: 8),
         Flexible(
           child: Text(
-            context.l10n.drugs_page_disclaimer,
+            text ?? context.l10n.drugs_page_disclaimer,
             style: PharMeTheme.textTheme.labelMedium!.copyWith(
               fontWeight: FontWeight.w100,
             ),

diff --git a/app/lib/common/theme.dart b/app/lib/common/theme.dart
@@ -71,8 +71,8 @@ class PharMeTheme {
   static const errorColor = Color(0xccf52a2a);
   static final borderColor = Colors.black.withOpacity(.2);
 
-  static Icon starIcon({required bool isStarred, double? size}) {
-    return Icon(isStarred ? Icons.star_rounded : Icons.star_border_rounded,
+  static Icon activeDrugIcon({required bool isActive, double? size}) {
+    return Icon(isActive ? Icons.star_rounded : Icons.star_border_rounded,
         size: size, color: primaryColor);
   }
 }

diff --git a/app/lib/common/utilities/drug_utils.dart b/app/lib/common/utilities/drug_utils.dart
@@ -20,8 +20,6 @@ Future<void> updateCachedDrugs() async {
 
   final dataResponse = await get(anniUrl('data'));
   if (dataResponse.statusCode != 200) throw Exception();
-  final drugs =
-      AnniDataResponse.fromJson(jsonDecode(dataResponse.body)).data.drugs;
-  CachedDrugs.instance.drugs = drugs.filterUserGuidelines();
+  CachedDrugs.instance.drugs = AnniDataResponse.fromJson(jsonDecode(dataResponse.body)).data.drugs;
   await CachedDrugs.save();
 }
diff --git a/app/lib/common/utilities/pdf_utils.dart b/app/lib/common/utilities/pdf_utils.dart
@@ -75,7 +75,7 @@ List<pw.Widget> _buildGuidelinePart(Guideline guideline) {
           title: 'Relevant gene phenotypes: ',
           text: guideline.lookupkey.keys
               .map((geneSymbol) =>
-                  '$geneSymbol: ${UserData.instance.lookups![geneSymbol]!}')
+                  '$geneSymbol: ${UserData.phenotypeFor(geneSymbol)!}')
               .join(', ')),
     ),
     pw.SizedBox(height: 8, width: double.infinity),

diff --git a/app/lib/l10n/app_en.arb b/app/lib/l10n/app_en.arb
@@ -6,7 +6,7 @@
   "err_could_not_retrieve_access_token": "An unexpected error occurred while retrieving the access token",
   "err_fetch_user_data_failed": "An unexpected error occurred while fetching your genomic data",
   "err_generic": "Error!",
-  "err_no_starred_drugs": "You have no starred drugs! Try disabling the filter by tapping the star icon above.",
+  "err_no_active_drugs": "You have no active drugs! Try disabling the filter next to the search bar above.",
 
   "faq_page_description": "Here you can find answers to common questions about PGx",
   "faq_pharmacogenomics": "Pharmacogenomics",
@@ -19,6 +19,16 @@
   "search_page_tooltip_search": "Search for drugs by their name, brand name or class.",
 
   "drugs_page_disclaimer": "This assessment is ONLY based on your genetics. Important factors like weight, age and pre-existing conditions are not considered.",
+  "drugs_page_overwritten_phenotype": "adjusted based on you taking {drugName}",
+  "@drugs_page_overwritten_phenotype": {
+      "description": "Disclaimer for when the phenotype has been adjusted based on an active drug",
+      "placeholders": {
+          "drugName": {
+              "type": "String",
+              "example": "bupropion"
+          }
+      }
+  },
   "drugs_page_your_genome": "Your genome",
   "drugs_page_header_further_info": "Further Information",
   "drugs_page_header_synonyms": "Synonyms",