Added a boatload of new case-control association modules. Switched the U-test to use longs rather than ints (it just so happened that I overflowed and started getting negative U statistics. Not good.) Added the ALL association type for ease of specifying that we want to throw the book at something. Added an svn-commit.tmp~ because i can't get rid of it even with --force. Hopefully I can remove it after.

git-svn-id: file:///humgen/gsa-scr1/gsa-engineering/svn_contents/trunk@5386 348d0f76-0448-11de-a6fe-93d51630548a

java/src/org/broadinstitute/sting/oneoffprojects/walkers/association/AssociationTestRunner.java

@@ -10,6 +10,7 @@ import cern.jet.random.StudentT;
 import org.broadinstitute.sting.oneoffprojects.walkers.association.statistics.casecontrol.*;
 import org.broadinstitute.sting.utils.MannWhitneyU;
 import org.broadinstitute.sting.utils.MathUtils;
+import org.broadinstitute.sting.utils.QualityUtils;
 import org.broadinstitute.sting.utils.WilcoxonRankSum;
 import org.broadinstitute.sting.utils.collections.Pair;
 
@@ -53,11 +54,14 @@ public class AssociationTestRunner {
         Pair<Double,Double> stats = testStudentT(context);
         double t = stats.first;
         double p = stats.second;
-        return String.format("T: %.2f\tP: %.2e",t,p);
+        return String.format("T: %.2f\tP: %.2e\tQ: %d",t,p,(int)Math.floor(QualityUtils.phredScaleErrorRate(p)));
     }
 
     public static Pair<Double,Double> testStudentT(TStatistic context) {
         Map<CaseControl.Cohort,Collection<Number>> caseControlVectors = context.getCaseControl();
+        if ( caseControlVectors == null || caseControlVectors.get(CaseControl.Cohort.CASE) == null || caseControlVectors.get(CaseControl.Cohort.CONTROL) == null ) {
+            return new Pair<Double,Double>(Double.NaN,Double.NaN);
+        }
         double meanCase = MathUtils.average(caseControlVectors.get(CaseControl.Cohort.CASE));
         double varCase = MathUtils.variance(caseControlVectors.get(CaseControl.Cohort.CASE),meanCase);
         double nCase =  caseControlVectors.get(CaseControl.Cohort.CASE).size();
@@ -79,11 +83,14 @@ public class AssociationTestRunner {
         Pair<Double,Double> stats = testZ(context);
         double z = stats.first;
         double p = stats.second;
-        return String.format("Z: %.2f\tP: %.2e",z,p);
+        return String.format("Z: %.2f\tP: %.2e\tQ: %d",z,p,(int)Math.floor(QualityUtils.phredScaleErrorRate(p)));
     }
 
     public static Pair<Double,Double> testZ(ZStatistic context) {
         Map<CaseControl.Cohort,Pair<Number,Number>> caseControlCounts = context.getCaseControl();
+        if ( caseControlCounts == null || caseControlCounts.get(CaseControl.Cohort.CASE) == null || caseControlCounts.get(CaseControl.Cohort.CONTROL) == null ) {
+            return new Pair<Double,Double>(Double.NaN,Double.NaN);
+        }
         double pCase = caseControlCounts.get(CaseControl.Cohort.CASE).first.doubleValue()/caseControlCounts.get(CaseControl.Cohort.CASE).second.doubleValue();
         double pControl = caseControlCounts.get(CaseControl.Cohort.CONTROL).first.doubleValue()/caseControlCounts.get(CaseControl.Cohort.CONTROL).second.doubleValue();
         double nCase = caseControlCounts.get(CaseControl.Cohort.CASE).second.doubleValue();
@@ -100,12 +107,15 @@ public class AssociationTestRunner {
     }
 
     public static String runU(UStatistic context) {
-        Pair<Integer,Double> results = mannWhitneyUTest(context);
-        return String.format("U: %d\tP: %.2e",results.first,results.second);
+        Pair<Long,Double> results = mannWhitneyUTest(context);
+        return String.format("U: %d\tP: %.2e\tQ: %d",results.first,results.second,(int)Math.floor(QualityUtils.phredScaleErrorRate(results.second)));
     }
 
-    public static Pair<Integer,Double> mannWhitneyUTest(UStatistic context) {
+    public static Pair<Long,Double> mannWhitneyUTest(UStatistic context) {
         Map<CaseControl.Cohort,Collection<Number>> caseControlVectors = context.getCaseControl();
+        if ( caseControlVectors == null || caseControlVectors.get(CaseControl.Cohort.CASE) == null || caseControlVectors.get(CaseControl.Cohort.CONTROL) == null ) {
+            return new Pair<Long,Double>(-1l,Double.NaN);
+        }
         MannWhitneyU mwu = new MannWhitneyU();
         for ( Number n : caseControlVectors.get(CaseControl.Cohort.CASE) ) {
             mwu.add(n, MannWhitneyU.USet.SET1);

java/src/org/broadinstitute/sting/oneoffprojects/walkers/association/RegionalAssociationHandler.java

@@ -49,7 +49,7 @@ public class RegionalAssociationHandler {
         for ( AssociationContext w : associations ) {
             if ( w.isFull() ) {
                 testResults.put(w,String.format("%s\t%d\t%d\t%s",maps.getReferenceContext().getLocus().getContig(),
-                        maps.getReferenceContext().getLocus().getStart(),maps.getReferenceContext().getLocus().getStop(),AssociationTestRunner.runTests(w)));
+                        maps.getReferenceContext().getLocus().getStart(),maps.getReferenceContext().getLocus().getStart()+1,AssociationTestRunner.runTests(w)));
                 w.slide();
             }
         }

java/src/org/broadinstitute/sting/oneoffprojects/walkers/association/RegionalAssociationMultiplexer.java

@@ -33,6 +33,11 @@ public class RegionalAssociationMultiplexer implements Multiplexer<Class<? exten
 
     private Set<Class<? extends AssociationContext>> getAssociations(String[] associationsToUse) {
         List<Class<? extends AssociationContext>> contexts = new PluginManager<AssociationContext>(AssociationContext.class).getPlugins();
+
+        if ( associationsToUse.length > 0 && associationsToUse[0].equals("ALL") ) {
+            return new HashSet<Class<? extends AssociationContext>>((Collection)contexts);
+        }
+
         Map<String,Class<? extends AssociationContext>> classNameToClass = new HashMap<String,Class<? extends AssociationContext>>(contexts.size());
         for ( Class<? extends AssociationContext> clazz : contexts ) {
             classNameToClass.put(clazz.getSimpleName(),clazz);

java/src/org/broadinstitute/sting/oneoffprojects/walkers/association/RegionalAssociationWalker.java

@@ -62,6 +62,25 @@ public class RegionalAssociationWalker extends LocusWalker<MapHolder, RegionalAs
 
     public Set<AssociationContext> getAssociations() {
         List<Class<? extends AssociationContext>> contexts = new PluginManager<AssociationContext>(AssociationContext.class).getPlugins();
+
+
+
+        if ( associationsToUse.length > 0 && associationsToUse[0].equals("ALL") ) {
+            HashSet<AssociationContext> allAssoc =  new HashSet<AssociationContext>(contexts.size());
+            for ( Class<? extends AssociationContext> clazz : contexts ) {
+                AssociationContext context;
+                try {
+                    context = clazz.newInstance();
+                } catch (Exception e ) {
+                    throw new StingException("The class "+clazz.getSimpleName()+" could not be instantiated",e);
+                }
+                context.init(this);
+                allAssoc.add(context);
+            }
+            return allAssoc;
+        }
+
+
         Map<String,Class<? extends AssociationContext>> classNameToClass = new HashMap<String,Class<? extends AssociationContext>>(contexts.size());
         for ( Class<? extends AssociationContext> clazz : contexts ) {
             classNameToClass.put(clazz.getSimpleName(),clazz);

java/src/org/broadinstitute/sting/oneoffprojects/walkers/association/modules/BaseQualityScore.java

@@ -0,0 +1,31 @@
+package org.broadinstitute.sting.oneoffprojects.walkers.association.modules;
+
+import org.broadinstitute.sting.oneoffprojects.walkers.association.statistics.casecontrol.TStatistic;
+import org.broadinstitute.sting.utils.pileup.PileupElement;
+import org.broadinstitute.sting.utils.pileup.ReadBackedPileup;
+
+import java.util.ArrayList;
+import java.util.Collection;
+
+/**
+ * Created by IntelliJ IDEA.
+ * User: chartl
+ * Date: 3/6/11
+ * Time: 1:52 PM
+ * To change this template use File | Settings | File Templates.
+ */
+public class BaseQualityScore extends TStatistic {
+
+    public Collection<Number> map(ReadBackedPileup rbp) {
+        ArrayList<Integer> baseQuals = new ArrayList<Integer>(rbp.size());
+        for (PileupElement e : rbp ) {
+            baseQuals.add((int)e.getQual());
+        }
+
+        return (Collection) baseQuals;
+    }
+
+    public int getWindowSize() { return 5; }
+    public int slideByValue() { return 1; }
+    public boolean usePreviouslySeenReads() { return true; }
+}

java/src/org/broadinstitute/sting/oneoffprojects/walkers/association/modules/InsertSizeDistribution.java

@@ -1,6 +1,7 @@
 package org.broadinstitute.sting.oneoffprojects.walkers.association.modules;
 
 import org.broadinstitute.sting.oneoffprojects.walkers.association.statistics.casecontrol.TStatistic;
+import org.broadinstitute.sting.oneoffprojects.walkers.association.statistics.casecontrol.UStatistic;
 import org.broadinstitute.sting.utils.pileup.PileupElement;
 import org.broadinstitute.sting.utils.pileup.ReadBackedPileup;
 
@@ -11,7 +12,7 @@ import java.util.List;
 /**
  * @author chartl
  */
-public class InsertSizeDistribution extends TStatistic {
+public class InsertSizeDistribution extends UStatistic {
     public int getWindowSize() { return 100; }
     public int slideByValue() { return 10; }
     public boolean usePreviouslySeenReads() { return false; }

java/src/org/broadinstitute/sting/oneoffprojects/walkers/association/modules/MappingQuality0.java

@@ -0,0 +1,33 @@
+package org.broadinstitute.sting.oneoffprojects.walkers.association.modules;
+
+import org.broadinstitute.sting.oneoffprojects.walkers.association.statistics.casecontrol.ZStatistic;
+import org.broadinstitute.sting.utils.collections.Pair;
+import org.broadinstitute.sting.utils.pileup.PileupElement;
+import org.broadinstitute.sting.utils.pileup.ReadBackedPileup;
+
+/**
+ * Created by IntelliJ IDEA.
+ * User: chartl
+ * Date: 3/6/11
+ * Time: 1:29 PM
+ * To change this template use File | Settings | File Templates.
+ */
+public class MappingQuality0 extends ZStatistic {
+
+    public Pair<Number,Number> map(ReadBackedPileup rbp) {
+        int total = 0;
+        int mq0 = 0;
+        for ( PileupElement e : rbp ) {
+            ++total;
+            if (e.getMappingQual() == 0)
+                ++mq0;
+        }
+
+        return new Pair<Number,Number>(mq0,total);
+    }
+
+    public int getWindowSize() { return 50; }
+    public int slideByValue() { return 10; }
+    public boolean usePreviouslySeenReads() { return false; }
+
+}

java/src/org/broadinstitute/sting/oneoffprojects/walkers/association/modules/MateMappingQuality.java

@@ -0,0 +1,33 @@
+package org.broadinstitute.sting.oneoffprojects.walkers.association.modules;
+
+import org.broadinstitute.sting.oneoffprojects.walkers.association.statistics.casecontrol.UStatistic;
+import org.broadinstitute.sting.utils.pileup.PileupElement;
+import org.broadinstitute.sting.utils.pileup.ReadBackedPileup;
+
+import java.util.ArrayList;
+import java.util.Collection;
+
+/**
+ * Created by IntelliJ IDEA.
+ * User: chartl
+ * Date: 3/6/11
+ * Time: 1:43 PM
+ * To change this template use File | Settings | File Templates.
+ */
+public class MateMappingQuality extends UStatistic {
+
+    public Collection<Number> map(ReadBackedPileup rbp) {
+        ArrayList<Integer> mateMapQ = new ArrayList<Integer>(rbp.size());
+        for ( PileupElement e : rbp ) {
+            if ( e.getRead().getReadPairedFlag() && e.getRead().getAttribute("MQ") != null) {
+                mateMapQ.add((Integer) e.getRead().getAttribute("MQ"));
+            }
+        }
+
+        return (Collection) mateMapQ;
+    }
+
+    public int getWindowSize() { return 40; }
+    public int slideByValue() { return 20; }
+    public boolean usePreviouslySeenReads() { return false; }
+}

java/src/org/broadinstitute/sting/oneoffprojects/walkers/association/modules/MateSameStrand.java

@@ -0,0 +1,35 @@
+package org.broadinstitute.sting.oneoffprojects.walkers.association.modules;
+
+import org.broadinstitute.sting.oneoffprojects.walkers.association.statistics.casecontrol.ZStatistic;
+import org.broadinstitute.sting.utils.collections.Pair;
+import org.broadinstitute.sting.utils.pileup.PileupElement;
+import org.broadinstitute.sting.utils.pileup.ReadBackedPileup;
+
+/**
+ * Created by IntelliJ IDEA.
+ * User: chartl
+ * Date: 3/6/11
+ * Time: 1:47 PM
+ * To change this template use File | Settings | File Templates.
+ */
+public class MateSameStrand extends ZStatistic {
+
+    public Pair<Number,Number> map(ReadBackedPileup rbp) {
+        int numPairs = 0;
+        int mateSameStrand = 0;
+        for (PileupElement e : rbp ) {
+            if ( e.getRead().getReadPairedFlag() ) {
+                ++numPairs;
+                if ( e.getRead().getMateNegativeStrandFlag() == e.getRead().getReadNegativeStrandFlag() ) {
+                    ++mateSameStrand;
+                }
+            }
+        }
+
+        return new Pair<Number,Number>(mateSameStrand,numPairs);
+    }
+
+    public int getWindowSize() { return 40; }
+    public int slideByValue() { return 5; }
+    public boolean usePreviouslySeenReads() { return false; }
+}

java/src/org/broadinstitute/sting/oneoffprojects/walkers/association/modules/ProperPairs.java

@@ -0,0 +1,33 @@
+package org.broadinstitute.sting.oneoffprojects.walkers.association.modules;
+
+import org.broadinstitute.sting.oneoffprojects.walkers.association.statistics.casecontrol.ZStatistic;
+import org.broadinstitute.sting.utils.collections.Pair;
+import org.broadinstitute.sting.utils.pileup.PileupElement;
+import org.broadinstitute.sting.utils.pileup.ReadBackedPileup;
+
+/**
+ * Created by IntelliJ IDEA.
+ * User: chartl
+ * Date: 3/6/11
+ * Time: 1:50 PM
+ * To change this template use File | Settings | File Templates.
+ */
+public class ProperPairs extends ZStatistic {
+
+    public Pair<Number,Number> map(ReadBackedPileup rbp) {
+        int numReads = 0;
+        int numPropPair = 0;
+        for (PileupElement e : rbp ) {
+            ++numReads;
+            if ( e.getRead().getReadPairedFlag() && e.getRead().getProperPairFlag() ) {
+                ++numPropPair;
+            }
+        }
+
+        return new Pair<Number,Number>(numPropPair,numReads);
+    }
+
+    public int getWindowSize() { return 30; }
+    public int slideByValue() { return 10; }
+    public boolean usePreviouslySeenReads() { return false; }
+}

java/src/org/broadinstitute/sting/oneoffprojects/walkers/association/modules/ReadClipping.java

@@ -0,0 +1,39 @@
+package org.broadinstitute.sting.oneoffprojects.walkers.association.modules;
+
+import net.sf.samtools.CigarElement;
+import net.sf.samtools.CigarOperator;
+import org.broadinstitute.sting.oneoffprojects.walkers.association.statistics.casecontrol.TStatistic;
+import org.broadinstitute.sting.utils.pileup.PileupElement;
+import org.broadinstitute.sting.utils.pileup.ReadBackedPileup;
+
+import java.util.ArrayList;
+import java.util.Collection;
+
+/**
+ * Created by IntelliJ IDEA.
+ * User: chartl
+ * Date: 3/6/11
+ * Time: 1:31 PM
+ * To change this template use File | Settings | File Templates.
+ */
+public class ReadClipping extends TStatistic {
+
+    public Collection<Number> map(ReadBackedPileup rbp) {
+        ArrayList<Integer> clipping = new ArrayList<Integer>(rbp.size());
+        for ( PileupElement e : rbp ) {
+            int clips = 0;
+            for( CigarElement c : e.getRead().getCigar().getCigarElements() ) {
+                if ( c.getOperator() == CigarOperator.SOFT_CLIP || c.getOperator() == CigarOperator.HARD_CLIP ) {
+                    clips += c.getLength();
+                }
+            }
+            clipping.add(clips);
+        }
+
+        return (Collection) clipping;
+    }
+
+    public int getWindowSize() { return 30; }
+    public int slideByValue() { return 5; }
+    public boolean usePreviouslySeenReads() { return false; }
+}

java/src/org/broadinstitute/sting/oneoffprojects/walkers/association/modules/ReadIndels.java

@@ -0,0 +1,38 @@
+package org.broadinstitute.sting.oneoffprojects.walkers.association.modules;
+
+import net.sf.samtools.CigarElement;
+import net.sf.samtools.CigarOperator;
+import org.broadinstitute.sting.oneoffprojects.walkers.association.statistics.casecontrol.UStatistic;
+import org.broadinstitute.sting.utils.pileup.PileupElement;
+import org.broadinstitute.sting.utils.pileup.ReadBackedPileup;
+
+import java.util.ArrayList;
+import java.util.Collection;
+
+/**
+ * Created by IntelliJ IDEA.
+ * User: chartl
+ * Date: 3/6/11
+ * Time: 1:54 PM
+ * To change this template use File | Settings | File Templates.
+ */
+public class ReadIndels extends UStatistic {
+
+    public Collection<Number> map(ReadBackedPileup rbp) {
+        ArrayList<Integer> indelElements = new ArrayList<Integer>(rbp.size());
+        for (PileupElement e : rbp ) {
+            int indelOps = 0;
+            for ( CigarElement c : e.getRead().getCigar().getCigarElements()) {
+                if ( c.getOperator() == CigarOperator.DELETION || c.getOperator() == CigarOperator.INSERTION )
+                    ++indelOps;
+            }
+            indelElements.add(indelOps);
+        }
+
+        return (Collection) indelElements;
+    }
+
+    public int getWindowSize() { return 50; }
+    public int slideByValue() { return 10; }
+    public boolean usePreviouslySeenReads() { return false; }
+}

java/src/org/broadinstitute/sting/oneoffprojects/walkers/association/modules/ReadMappingQuality.java

@@ -0,0 +1,31 @@
+package org.broadinstitute.sting.oneoffprojects.walkers.association.modules;
+
+import org.broadinstitute.sting.oneoffprojects.walkers.association.statistics.casecontrol.UStatistic;
+import org.broadinstitute.sting.utils.pileup.PileupElement;
+import org.broadinstitute.sting.utils.pileup.ReadBackedPileup;
+
+import java.util.ArrayList;
+import java.util.Collection;
+
+/**
+ * Created by IntelliJ IDEA.
+ * User: chartl
+ * Date: 3/6/11
+ * Time: 1:41 PM
+ * To change this template use File | Settings | File Templates.
+ */
+public class ReadMappingQuality extends UStatistic {
+
+    public Collection<Number> map(ReadBackedPileup rbp) {
+        ArrayList<Integer> mapQuals = new ArrayList<Integer>(rbp.size());
+        for ( PileupElement e : rbp ) {
+            mapQuals.add(e.getMappingQual());
+        }
+
+        return (Collection) mapQuals;
+    }
+
+    public int getWindowSize() { return 40; }
+    public int slideByValue() { return 5; }
+    public boolean usePreviouslySeenReads() { return false; }
+}

java/src/org/broadinstitute/sting/oneoffprojects/walkers/association/modules/SampleDepth.java

@@ -5,6 +5,7 @@ import org.broadinstitute.sting.gatk.walkers.LocusWalker;
 import org.broadinstitute.sting.gatk.walkers.Walker;
 import org.broadinstitute.sting.oneoffprojects.walkers.association.MapExtender;
 import org.broadinstitute.sting.oneoffprojects.walkers.association.RegionalAssociationWalker;
+import org.broadinstitute.sting.oneoffprojects.walkers.association.statistics.casecontrol.TStatistic;
 import org.broadinstitute.sting.oneoffprojects.walkers.association.statistics.casecontrol.UStatistic;
 import org.broadinstitute.sting.utils.MathUtils;
 import org.broadinstitute.sting.utils.collections.Pair;
@@ -16,7 +17,7 @@ import java.util.*;
 /**
  * @author chartl
  */
-public class SampleDepth extends UStatistic {
+public class SampleDepth extends TStatistic {
 
     public Map<Sample,Object> sampleStats = null;
 

java/src/org/broadinstitute/sting/oneoffprojects/walkers/association/modules/svn-commit.tmp~

@@ -0,0 +1,4 @@
+
+--This line, and those below, will be ignored--
+
+AM   SampleDepth.java

java/src/org/broadinstitute/sting/oneoffprojects/walkers/association/statistics/casecontrol/TStatistic.java

@@ -20,8 +20,8 @@ public abstract class TStatistic extends CaseControl<Collection<Number>> {
     public abstract Collection<Number> map(ReadBackedPileup rbp );
 
     public Collection<Number> add(Collection<Number> left, Collection<Number> right) {
-        if ( left instanceof List) {
-            ((List) left).addAll(right);
+        if ( left instanceof ArrayList) {
+            ((ArrayList) left).addAll(right);
             return left;
         } else if ( left instanceof Set ) {
             ((Set) left).addAll(right);

java/src/org/broadinstitute/sting/utils/MannWhitneyU.java

@@ -45,13 +45,13 @@ public class MannWhitneyU {
      * returns the u and p values.
      * @Returns a pair holding the u and p-value.
      */
-    public Pair<Integer,Double> runTwoSidedTest() {
-        Pair<Integer,USet> uPair = calculateTwoSidedU(observations);
-        int u = uPair.first;
+    public Pair<Long,Double> runTwoSidedTest() {
+        Pair<Long,USet> uPair = calculateTwoSidedU(observations);
+        long u = uPair.first;
         int n = uPair.second == USet.SET1 ? sizeSet1 : sizeSet2;
         int m = uPair.second == USet.SET1 ? sizeSet2 : sizeSet1;
         double pval = calculateP(n,m,u,true);
-        return new Pair<Integer,Double>(u,pval);
+        return new Pair<Long,Double>(u,pval);
     }
 
     /**
@@ -61,14 +61,18 @@ public class MannWhitneyU {
      * @param u - the Mann-Whitney U value
      * @param twoSided - is the test twosided
      * @return the (possibly approximate) p-value associated with the MWU test
+     * todo -- there must be an approximation for small m and large n
      */
-    public static double calculateP(int n, int m, int u, boolean twoSided) {
+    public static double calculateP(int n, int m, long u, boolean twoSided) {
         double pval;
         if ( n > 8 && m > 8 ) {
+            // large m and n - normal approx
             pval = calculatePNormalApproximation(n,m,u);
         } else if ( n > 4 && m > 7 ) {
+            // large m, small n - sum uniform approx
             pval = calculatePUniformApproximation(n,m,u);
         } else {
+            // small m [possibly small n] - full approx
             pval = calculatePRecursively(n,m,u);
         }
 
@@ -82,9 +86,9 @@ public class MannWhitneyU {
      * @param u - the Mann-Whitney U value
      * @return p-value associated with the normal approximation
      */
-    public static double calculatePNormalApproximation(int n,int m,int u) {
-        double mean = ((double) m*n+1)/2;
-        double var = (n*m*(n+m+1))/12;
+    public static double calculatePNormalApproximation(int n,int m,long u) {
+        double mean = ( ((long)m)*n+1.0)/2;
+        double var = (((long) n)*m*(n+m+1.0))/12;
         double z = ( u - mean )/Math.sqrt(var);
         return z < 0 ? STANDARD_NORMAL.cdf(z) : 1.0-STANDARD_NORMAL.cdf(z);
     }
@@ -97,8 +101,8 @@ public class MannWhitneyU {
      * @param u -
      * @return
      */
-    public static double calculatePUniformApproximation(int n, int m, int u) {
-        int R = u + (n*(n+1))/2;
+    public static double calculatePUniformApproximation(int n, int m, long u) {
+        long R = u + (n*(n+1))/2;
         double a = Math.sqrt(m*(n+m+1));
         double b = (n/2.0)*(1-Math.sqrt((n+m+1)/m));
         double z = b + R/a;
@@ -130,11 +134,11 @@ public class MannWhitneyU {
      * @param observed
      * @return the minimum of the U counts (set1 dominates 2, set 2 dominates 1)
      */
-    public static Pair<Integer,USet> calculateTwoSidedU(TreeSet<Pair<Number,USet>> observed ) {
+    public static Pair<Long,USet> calculateTwoSidedU(TreeSet<Pair<Number,USet>> observed ) {
         int set1SeenSoFar = 0;
         int set2SeenSoFar = 0;
-        int uSet1DomSet2 = 0;
-        int uSet2DomSet1 = 0;
+        long uSet1DomSet2 = 0;
+        long uSet2DomSet1 = 0;
         USet previous = null;
         for ( Pair<Number,USet> dataPoint : observed ) {
 
@@ -155,7 +159,7 @@ public class MannWhitneyU {
             previous = dataPoint.second;
         }
 
-        return uSet1DomSet2 < uSet2DomSet1 ? new Pair<Integer,USet>(uSet1DomSet2,USet.SET1) : new Pair<Integer,USet>(uSet2DomSet1,USet.SET2);
+        return uSet1DomSet2 < uSet2DomSet1 ? new Pair<Long,USet>(uSet1DomSet2,USet.SET1) : new Pair<Long,USet>(uSet2DomSet1,USet.SET2);
     }
 
     /**
@@ -167,8 +171,8 @@ public class MannWhitneyU {
      * @param u: number of set-two entries that precede set-one entries (e.g. 0,1,0,1,0 -> 3 )
      * @return the probability under the hypothesis that all sequences are equally likely of finding a set-two entry preceding a set-one entry "u" times.
      */
-    public static double calculatePRecursively(int n, int m, int u) {
-        if ( m + n > 16 ) { throw new StingException("Please use the appropriate (normal or sum of uniform) approximation"); }
+    public static double calculatePRecursively(int n, int m, long u) {
+        if ( m > 7 && n > 4 ) { throw new StingException(String.format("Please use the appropriate (normal or sum of uniform) approximation. Values n: %d, m: %d",n,m)); }
         return cpr(n,m,u);
     }
 
@@ -178,7 +182,7 @@ public class MannWhitneyU {
      * @m: number of set-2 entries
      * @u: number of times a set-2 entry as preceded a set-1 entry
      */
-    private static double cpr(int n, int m, int u) {
+    private static double cpr(int n, int m, long u) {
         if ( u < 0 || n == 0 && m == 0 ) {
             return 0.0;
         }

java/test/org/broadinstitute/sting/oneoffprojects/walkers/RegionalAssociationUnitTest.java

@@ -76,22 +76,22 @@ public class RegionalAssociationUnitTest extends BaseTest {
         UTest test1 = new UTest();
         test1.setCaseData((Collection) Arrays.asList(2,4,5,6,8));
         test1.setControlData((Collection) Arrays.asList(1,3,7,9,10,11,12,13));
-        Assert.assertEquals(AssociationTestRunner.mannWhitneyUTest(test1).first,10,0);
+        Assert.assertEquals((long) AssociationTestRunner.mannWhitneyUTest(test1).first,10l);
         Assert.assertEquals(AssociationTestRunner.mannWhitneyUTest(test1).second,0.092292,5e-2); // z-approximation, off by about 0.05
         Assert.assertEquals(AssociationTestRunner.mannWhitneyUTest(test1).second,0.044444,1e-3); // recursive calculation
         UTest test2 = new UTest();
         test2.setCaseData((Collection) Arrays.asList(1,7,8,9,10,11,15,18));
         test2.setControlData((Collection) Arrays.asList(2,3,4,5,6,12,13,14,16,17));
-        Assert.assertEquals(AssociationTestRunner.mannWhitneyUTest(test2).first,37,0);
+        Assert.assertEquals((long) AssociationTestRunner.mannWhitneyUTest(test2).first,37l);
         UTest test3 = new UTest();
         test3.setCaseData((Collection)Arrays.asList(13,14,7,18,5,2,9,17,8,10,3,15,19,6,20,16,11,4,12,1));
         test3.setControlData((Collection) Arrays.asList(29,21,14,10,12,11,28,19,18,13,7,27,20,5,17,16,9,23,22,26));
-        Assert.assertEquals(AssociationTestRunner.mannWhitneyUTest(test3).first,93,0);
+        Assert.assertEquals((long) AssociationTestRunner.mannWhitneyUTest(test3).first,93l);
         Assert.assertEquals(AssociationTestRunner.mannWhitneyUTest(test3).second,2*0.00302,1e-3);
         UTest test4 = new UTest();
         test4.setCaseData((Collection) Arrays.asList(1,2,4,5,6,9));
         test4.setControlData((Collection) Arrays.asList(3,8,11,12,13));
-        Assert.assertEquals(AssociationTestRunner.mannWhitneyUTest(test4).first,5,0);
+        Assert.assertEquals((long) AssociationTestRunner.mannWhitneyUTest(test4).first,5l);
         Assert.assertEquals(AssociationTestRunner.mannWhitneyUTest(test4).second,0.0303,1e-4);
 
     }