Alter Frequency to be able to represent both percentage frequency val…

…ues and fractional frequencies i.e. AF = AC/AN with a hom count.

Alter FrequencyData to work with Frequency for representing AF, AC, AN and HOM counts
Alter FrequencyData 'get' prefixed methods to remove the 'get' e.g. getMaxFreqForPopulation() is now maxFreqForPopulation(), getScore() -> frequencyScore(), frequencyData.getKnownFrequencies() -> frequencyData.frequencies()

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

@@ -150,10 +150,10 @@ private List<VariantEvaluation> getCompatibleVariantsUnderFrequencyThreshold(Lis
             // float maxFreq = frequencyData.maxFreqIgnoring(Set.of(LOCAL, ESP))
             // float maxFreq = frequencyData.maxFreqFrom(Set.of(LOCAL, ESP))
             FrequencyData frequencyData = variantEvaluation.getFrequencyData();
-            if (frequencyData.getMaxFreq() <= maxFreqForMode || variantEvaluation.isWhiteListed()) {
+            if (frequencyData.maxFreq() <= maxFreqForMode || variantEvaluation.isWhiteListed()) {
                 compatibleVariants.add(variantEvaluation);
             } else {
-                logger.debug("FAIL variant freq {} >= {} (maxFreq for MOI) {}", frequencyData.getMaxFreq(), maxFreqForMode, variantEvaluation);
+                logger.debug("FAIL variant freq {} >= {} (maxFreq for MOI) {}", frequencyData.maxFreq(), maxFreqForMode, variantEvaluation);
             }
         }
         return compatibleVariants;

exomiser-core/src/main/java/org/monarchinitiative/exomiser/core/analysis/util/acmg/Acmg2015EvidenceAssigner.java

@@ -134,7 +134,7 @@ public AcmgEvidence assignVariantAcmgEvidence(VariantEvaluation variantEvaluatio
 //        AlleleProto.AlleleKey alleleKey = AlleleProtoAdaptor.toAlleleKey(variantEvaluation);
         AlleleProto.AlleleKey alleleKey = variantEvaluation.alleleKey();
         boolean isBa1ExcludedVariant = variantEvaluation.getGenomeAssembly() == GenomeAssembly.HG19 ? HG19_BA1_EXCLUSION_VARIANTS.contains(alleleKey) : HG38_BA1_EXCLUSION_VARIANTS.contains(alleleKey);
-        if (!isBa1ExcludedVariant && frequencyData.getMaxFreqForPopulation(FrequencySource.NON_FOUNDER_POPS) >= 5.0) {
+        if (!isBa1ExcludedVariant && frequencyData.maxFreqForPopulation(FrequencySource.NON_FOUNDER_POPS) >= 5.0) {
             acmgEvidenceBuilder.add(BA1);
             // BA1 is supposed to be used as a filtering criterion where no other evidence need be considered.
             return acmgEvidenceBuilder.build();
@@ -436,7 +436,7 @@ private void assignPM2(AcmgEvidence.Builder acmgEvidenceBuilder, FrequencyData f
         // allow local frequency occurrences as these are unverifiable as to their size or content. Also do not use isRepresentedInDatabase()
         // as this will exclude anything with an rsID which could be a ClinVar variant not seen in any population database.
         boolean absentFromDatabase = frequencyData.isEmpty() || (frequencyData.size() == 1 && frequencyData.containsFrequencySource(FrequencySource.LOCAL));
-        boolean atVeryLowFrequencyIfRecessive = modeOfInheritance.isRecessive() && frequencyData.getMaxFreqForPopulation(FrequencySource.NON_FOUNDER_POPS) < 0.01f;
+        boolean atVeryLowFrequencyIfRecessive = modeOfInheritance.isRecessive() && frequencyData.maxFreqForPopulation(FrequencySource.NON_FOUNDER_POPS) < 0.01f;
         if (absentFromDatabase || atVeryLowFrequencyIfRecessive) {
             acmgEvidenceBuilder.add(PM2, Evidence.SUPPORTING);
         }

exomiser-core/src/main/java/org/monarchinitiative/exomiser/core/genome/dao/SvFrequencyDao.java

@@ -96,7 +96,7 @@ private FrequencyData mapToFrequencyData(List<SvResult> topMatches) {
         }
         SvResult first = topMatches.get(0);
         Frequency frequency = toFrequency(first);
-        if (first.an < 10 || frequency.getFrequency() == 0) {
+        if (first.an < 10 || frequency.frequency() == 0) {
             // Don't report poorly defined frequencies
             return FrequencyData.of(first.id());
         }

exomiser-core/src/main/java/org/monarchinitiative/exomiser/core/model/AlleleProtoAdaptor.java

@@ -130,9 +130,15 @@ private static void parseFrequencyData(FrequencyData.Builder frequencyDataBuilde
         for (int i = 0; i < freqsCount; i++) {
             AlleleProto.Frequency frequency = alleleProperties.getFrequencies(i);
             var freqSource = toFreqSource(frequency.getFrequencySource());
-            var freq = Frequency.percentageFrequency(frequency.getAc(), frequency.getAn());
-            var hom = frequency.getHom();
-            frequencyDataBuilder.addFrequency(freqSource, freq, hom);
+            int an = frequency.getAn();
+            if (an == 0) {
+                float af = frequency.getFrequency();
+                frequencyDataBuilder.addFrequency(freqSource, af);
+            } else {
+                int ac = frequency.getAc();
+                int hom = frequency.getHom();
+                frequencyDataBuilder.addFrequency(freqSource, ac, an, hom);
+            }
         }
     }
 

exomiser-core/src/main/java/org/monarchinitiative/exomiser/core/model/VariantEvaluation.java

@@ -356,7 +356,7 @@ public float getVariantScore() {
      * @return a score between 0 and 1
      */
     public float getFrequencyScore() {
-        return whiteListed ? 1f : frequencyData.getScore();
+        return whiteListed ? 1f : frequencyData.frequencyScore();
     }
 
     /**

exomiser-core/src/main/java/org/monarchinitiative/exomiser/core/model/frequency/Frequency.java

@@ -36,62 +36,93 @@ public class Frequency {
 
     private final FrequencySource source;
     private final float value;
+    private final int ac;
+    private final int an;
+    private final int homs;
 
     public static Frequency of(FrequencySource source, float value) {
-        return new Frequency(source, value);
+        return new Frequency(source, value, 0, 0, 0);
     }
 
-    private Frequency(FrequencySource source, float value) {
+    public static Frequency of(FrequencySource source, int ac, int an, int homs) {
+        if (an <= 0 || ac > an || homs > ac) {
+            throw new IllegalArgumentException(source + " AN must be > 0, AC must be < AN and HOM must be < AC. Got AC=" + ac + ", AN=" + an + ", hom=" + homs);
+        }
+        return new Frequency(source, percentageFrequency(ac, an), ac, an, homs);
+    }
+
+    // package private to work with FrequencyData *ONLY* where allele frequency has already been calculated and input
+    // values have already been validated
+    static Frequency of(FrequencySource source, float af, int ac, int an, int homs) {
+        return new Frequency(source, af, ac, an, homs);
+    }
+
+    private Frequency(FrequencySource source, float value, int ac, int an, int homs) {
         this.source = source;
         this.value = value;
+        this.ac = ac;
+        this.an = an;
+        this.homs = homs;
+    }
+
+    public FrequencySource source() {
+        return source;
     }
 
-    public float getFrequency() {
+    public float frequency() {
         return value;
     }
 
-    public FrequencySource getSource() {
-        return source;
+    public int ac() {
+        return ac;
+    }
+
+    public int an() {
+        return an;
+    }
+
+    public int homs() {
+        return homs;
     }
-    
+
     public boolean isOverThreshold(float threshold) {
         return value > threshold;
     }
 
     /**
-     * Returns the frequency of ac/an as a percentage value.
+     * Returns the frequency of ac/an as a percentage frequency.
      *
      * @param ac    Allele Count - the number of observed alleles.
      * @param an    Allele Number - size of the population in which the AC was observed.
-     * @return the frequency of ac/an as a percentage value in the range 0..100
+     * @return the frequency of ac/an as a percentage frequency in the range 0..100
      */
     public static float percentageFrequency(int ac, int an) {
         return 100f * (ac / (float) an);
     }
 
+
     @Override
-    public int hashCode() {
-        return Objects.hash(source, value);
+    public boolean equals(Object o) {
+        if (this == o) return true;
+        if (o == null || getClass() != o.getClass()) return false;
+        Frequency frequency = (Frequency) o;
+        return Float.compare(value, frequency.value) == 0 && ac == frequency.ac && an == frequency.an && homs == frequency.homs && source == frequency.source;
     }
 
     @Override
-    public boolean equals(Object o) {
-        if (this == o) {
-            return true;
-        }
-        if (!(o instanceof Frequency)) {
-            return false;
-        }
-        Frequency other = (Frequency) o;
-        if (source != other.source) {
-            return false;
-        }
-        return Float.compare(other.value, value) == 0;
+    public int hashCode() {
+        return Objects.hash(source, value, ac, an, homs);
     }
 
+
     @Override
     public String toString() {
-        return "Frequency{" + source + "=" + value + '}';
+        return "Frequency{" + source +
+               '=' + value + (an > 0 ? formatAcAn() : "") +
+               '}';
     }
 
+    private String formatAcAn() {
+        return "(" + ac + '|' + an + '|' + homs + ')';
+    }
 }