Refactor RawScoreGeneScorer to require AcmgAssignmentCalculator

Merge changes from PvalueGeneScorer into RawScoreGeneScorer
Delete PvalueGeneScorer.java
Update VariantDataService to extend ClinVarDao (a bit ikky, but there you go)

exomiser-core/src/main/java/org/monarchinitiative/exomiser/core/analysis/AbstractAnalysisRunner.java

@@ -23,6 +23,7 @@
 import org.monarchinitiative.exomiser.core.analysis.sample.PedigreeSampleValidator;
 import org.monarchinitiative.exomiser.core.analysis.sample.Sample;
 import org.monarchinitiative.exomiser.core.analysis.util.*;
+import org.monarchinitiative.exomiser.core.analysis.util.acmg.*;
 import org.monarchinitiative.exomiser.core.filters.*;
 import org.monarchinitiative.exomiser.core.genome.*;
 import org.monarchinitiative.exomiser.core.model.*;
@@ -40,7 +41,6 @@
 import java.util.function.Function;
 import java.util.function.Predicate;
 import java.util.function.UnaryOperator;
-import java.util.stream.Collectors;
 import java.util.stream.Stream;
 
 import static java.util.stream.Collectors.toConcurrentMap;
@@ -129,9 +129,7 @@ public AnalysisResults run(Sample sample, Analysis analysis) {
 
         // If no variant steps have been run and there is a VCF present, don't load it here - See issues #129, #478
         List<Gene> genesToScore = variantsLoaded ? getGenesWithVariants(allGenes) : allGenes.values().stream().filter(genesToScore()).toList();
-        // Temporarily add a new PValueGeneScorer so as not to break semver will revert to RawScoreGeneScorer in 14.0.0
-        CombinedScorePvalueCalculator combinedScorePvalueCalculator = buildCombinedScorePvalueCalculator(sample, analysis, genesToScore.size());
-        GeneScorer geneScorer = new PvalueGeneScorer(probandIdentifier, sample.getSex(), inheritanceModeAnnotator, combinedScorePvalueCalculator);
+        GeneScorer geneScorer = buildGeneScorer(sample, analysis, genesToScore, probandIdentifier, inheritanceModeAnnotator);
 
         logger.info("Scoring genes");
         List<Gene> genes = geneScorer.scoreGenes(genesToScore);
@@ -154,6 +152,15 @@ public AnalysisResults run(Sample sample, Analysis analysis) {
         return analysisResults;
     }
 
+    private GeneScorer buildGeneScorer(Sample sample, Analysis analysis, List<Gene> genesToScore, String probandIdentifier, InheritanceModeAnnotator inheritanceModeAnnotator) {
+        CombinedScorePvalueCalculator combinedScorePvalueCalculator = buildCombinedScorePvalueCalculator(sample, analysis, genesToScore.size());
+
+        AcmgEvidenceAssigner acmgEvidenceAssigner = new Acmg2015EvidenceAssigner(probandIdentifier, inheritanceModeAnnotator.getPedigree(), genomeAnalysisService);
+        AcmgAssignmentCalculator acmgAssignmentCalculator = new AcmgAssignmentCalculator(acmgEvidenceAssigner, new Acmg2020PointsBasedClassifier());
+
+        return new RawScoreGeneScorer(probandIdentifier, sample.getSex(), inheritanceModeAnnotator, combinedScorePvalueCalculator, acmgAssignmentCalculator);
+    }
+
     private List<FilterResultCount> collectFilterCounts(List<AnalysisStep> analysisSteps) {
         // build filter counts
         List<FilterType> filterStepTypes = analysisSteps.stream()

exomiser-core/src/main/java/org/monarchinitiative/exomiser/core/analysis/util/ContributingAlleleCalculator.java

@@ -70,21 +70,18 @@ protected List<VariantEvaluation> findContributingVariantsForInheritanceMode(Mod
                 //It is critical only the PASS variants are used in the scoring
                 .filter(VariantEvaluation::passedFilters)
                 .filter(variantEvaluation -> variantEvaluation.isCompatibleWith(modeOfInheritance))
-                .collect(toUnmodifiableList());
+                .toList();
         //note these need to be filtered for the relevant ModeOfInheritance before being checked for the contributing variants
         if (variantsCompatibleWithMode.isEmpty()) {
             return variantsCompatibleWithMode;
         }
-        switch (modeOfInheritance) {
-            case AUTOSOMAL_RECESSIVE:
-                return findAutosomalRecessiveContributingVariants(modeOfInheritance, variantsCompatibleWithMode);
-            case X_RECESSIVE:
-                return findXRecessiveContributingVariants(modeOfInheritance, variantsCompatibleWithMode);
-            case ANY:
-                return findIncompletePenetranceContributingVariants(modeOfInheritance, variantsCompatibleWithMode);
-            default:
-                return findNonAutosomalRecessiveContributingVariants(modeOfInheritance, variantsCompatibleWithMode);
-        }
+        return switch (modeOfInheritance) {
+            case AUTOSOMAL_RECESSIVE ->
+                    findAutosomalRecessiveContributingVariants(modeOfInheritance, variantsCompatibleWithMode);
+            case X_RECESSIVE -> findXRecessiveContributingVariants(modeOfInheritance, variantsCompatibleWithMode);
+            case ANY -> findIncompletePenetranceContributingVariants(modeOfInheritance, variantsCompatibleWithMode);
+            default -> findNonAutosomalRecessiveContributingVariants(modeOfInheritance, variantsCompatibleWithMode);
+        };
 
     }
 

exomiser-core/src/main/java/org/monarchinitiative/exomiser/core/analysis/util/RawScoreGeneScorer.java

@@ -55,6 +55,7 @@ public class RawScoreGeneScorer implements GeneScorer {
     private final ContributingAlleleCalculator contributingAlleleCalculator;
     private final GenePriorityScoreCalculator genePriorityScoreCalculator;
 
+    private final CombinedScorePvalueCalculator pValueCalculator;
     private final AcmgAssignmentCalculator acmgAssignmentCalculator;
 
     /**
@@ -63,25 +64,27 @@ public class RawScoreGeneScorer implements GeneScorer {
      * @throws NullPointerException if any input arguments are null.
      * @since 10.0.0
      */
-    public RawScoreGeneScorer(String probandId, Sex probandSex, InheritanceModeAnnotator inheritanceModeAnnotator) {
+    public RawScoreGeneScorer(String probandId, Sex probandSex, InheritanceModeAnnotator inheritanceModeAnnotator, CombinedScorePvalueCalculator pValueCalculator, AcmgAssignmentCalculator acmgAssignmentCalculator) {
         Objects.requireNonNull(probandId);
         Objects.requireNonNull(inheritanceModeAnnotator);
         this.inheritanceModes = inheritanceModeAnnotator.getDefinedModes();
         this.contributingAlleleCalculator = new ContributingAlleleCalculator(probandId, probandSex, inheritanceModeAnnotator);
         this.genePriorityScoreCalculator = new GenePriorityScoreCalculator();
-        AcmgEvidenceAssigner acmgEvidenceAssigner = new Acmg2015EvidenceAssigner(probandId, inheritanceModeAnnotator.getPedigree());
-        AcmgEvidenceClassifier acmgEvidenceClassifier = new Acmg2020PointsBasedClassifier();
-        this.acmgAssignmentCalculator = new AcmgAssignmentCalculator(acmgEvidenceAssigner, acmgEvidenceClassifier);
+        this.pValueCalculator = Objects.requireNonNull(pValueCalculator);
+        this.acmgAssignmentCalculator = Objects.requireNonNull(acmgAssignmentCalculator);
     }
 
     @Override
     public List<Gene> scoreGenes(List<Gene> genes) {
-        for (Gene gene : genes) {
-            List<GeneScore> geneScores = scoreGene().apply(gene);
-            gene.addGeneScores(geneScores);
-        }
-        Collections.sort(genes);
-        return genes;
+        return genes.stream()
+                .parallel()
+                .map(gene -> {
+                    List<GeneScore> geneScores = scoreGene().apply(gene);
+                    gene.addGeneScores(geneScores);
+                    return gene;
+                })
+                .sorted()
+                .toList();
     }
 
     /**
@@ -122,23 +125,31 @@ private GeneScore calculateGeneScore(Gene gene, ModeOfInheritance modeOfInherita
 
         GenePriorityScoreCalculator.GenePriorityScore priorityScore = genePriorityScoreCalculator.calculateGenePriorityScore(gene, modeOfInheritance);
 
+        List<ModelPhenotypeMatch<Disease>> compatibleDiseaseMatches = priorityScore.getCompatibleDiseaseMatches();
+
+        List<AcmgAssignment> acmgAssignments = acmgAssignmentCalculator.calculateAcmgAssignments(modeOfInheritance, gene, contributingVariants, compatibleDiseaseMatches);
+
+//        double variantScore = acmgAssignments.stream()
+//                .mapToDouble(acmgAssignment -> acmgAssignment.acmgEvidence().postProbPath())
+//                .average()
+//                .orElse(0.1); // 0.1 is the equivalent of a 0-point VUS
+
         double variantScore = contributingVariants.stream()
                 .mapToDouble(VariantEvaluation::getVariantScore)
                 .average()
                 .orElse(0);
 
         double combinedScore = GeneScorer.calculateCombinedScore(variantScore, priorityScore.getScore(), gene.getPriorityResults().keySet());
 
-        List<ModelPhenotypeMatch<Disease>> compatibleDiseaseMatches = priorityScore.getCompatibleDiseaseMatches();
-
-        List<AcmgAssignment> acmgAssignments = acmgAssignmentCalculator.calculateAcmgAssignments(modeOfInheritance, gene, contributingVariants, compatibleDiseaseMatches);
+        double pValue = pValueCalculator.calculatePvalueFromCombinedScore(combinedScore);
 
         return GeneScore.builder()
                 .geneIdentifier(gene.getGeneIdentifier())
                 .modeOfInheritance(modeOfInheritance)
                 .variantScore(variantScore)
                 .phenotypeScore(priorityScore.getScore())
                 .combinedScore(combinedScore)
+                .pValue(pValue)
                 .contributingVariants(contributingVariants)
                 // TODO this would be a good place to put a contributingModel
                 //  i.e. from HiPhivePrioritiserResult see issue #363