Major refactoring of association testing framework. New modules are now beyond trivial to implement. One hurdle remains which is how to deal with statistics that ought to be sample-normalized (e.g. depth, insert-size [when multiple libraries are used], and possibly others).

git-svn-id: file:///humgen/gsa-scr1/gsa-engineering/svn_contents/trunk@5366 348d0f76-0448-11de-a6fe-93d51630548a

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

@@ -1,42 +1,74 @@
 package org.broadinstitute.sting.oneoffprojects.walkers.association;
 
-import java.lang.reflect.InvocationTargetException;
+import org.broadinstitute.sting.gatk.datasources.sample.Sample;
-import java.util.*;
+import org.broadinstitute.sting.utils.pileup.ReadBackedPileup;
+
+import java.util.ArrayList;
+import java.util.HashMap;
+import java.util.List;
+import java.util.Map;
 
 /**
- * @Author chartl
+ * Created by IntelliJ IDEA.
- * @Date 2011-02-23
+ * User: chartl
- * A general context for windowed association
+ * Date: 3/2/11
+ * Time: 11:58 AM
+ * To change this template use File | Settings | File Templates.
  */
-public abstract class AssociationContext<X extends AssociationContextAtom> {
+public abstract class AssociationContext<X> {
-    protected Class<? extends AssociationContextAtom> clazz;
-    protected List<X> window;
 
-    public AssociationContext( Class<X> zclaz ) {
+    protected List<Map<Sample,Object>> window;
-        window = new ArrayList<X>(getWindowSize());
+
-        clazz = zclaz;
+    public AssociationContext() {
+        window = new ArrayList<Map<Sample,Object>>(getWindowSize());
     }
 
-    public X map(MapExtender e) throws NoSuchMethodException, InstantiationException, IllegalAccessException, InvocationTargetException, ClassCastException {
+    // specifies size of window
-        return (X) clazz.getConstructor(new Class[] {MapExtender.class}).newInstance(new Object[] {e});
+    public abstract int getWindowSize();
-    }
 
+    // specifies how many bases to wait until next test
+    public abstract int slideByValue();
+
+    // specifies whether to use previously seen reads
+    public abstract boolean usePreviouslySeenReads();
+
+    // specifies the map from a sample's pileup to the data we want to test
+    public abstract Object map(ReadBackedPileup rbp);
+
+    // specifies how to take the per-sample data and reduce them into testable pairs
+    public abstract Map<?,X> reduce(List<Map<Sample,X>> win);
+
+    // do we filter the current location (e.g. omit from window)
     public boolean filter(MapExtender m) { return true; }
 
-    public void reduce(X context) {
+    public Map<Sample,Object> mapLocus(MapExtender extender) {
-        window.add(context);
+        Map<Sample,ReadBackedPileup> pileups;
+        if ( ! usePreviouslySeenReads() ) {
+            pileups = extender.getReadFilteredPileup();
+        } else {
+            pileups = extender.getFullPileup();
+        }
+        Map<Sample,Object> maps = new HashMap<Sample,Object>(pileups.size());
+        for ( Map.Entry<Sample,ReadBackedPileup> samPileup : pileups.entrySet() ) {
+            maps.put(samPileup.getKey(),map(samPileup.getValue()));
+        }
+
+        return maps;
+    }
+
+
+    public void addData(Map<Sample,Object> sampleData) {
+        window.add(sampleData);
     }
 
-    public abstract int getWindowSize();
-    public abstract int slideByValue();
 
     public boolean isFull() {
         return window.size() >= getWindowSize();
     }
 
     public void slide() {
-        ArrayList<X> newWindow = new ArrayList<X>((window.subList(slideByValue(),window.size())));
+        ArrayList<Map<Sample,Object>> newWindow = new ArrayList<Map<Sample,Object>>((window.subList(slideByValue(),window.size())));
         newWindow.ensureCapacity(getWindowSize());
         window = newWindow;
     }
-}
+}

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

@@ -1,13 +0,0 @@
-package org.broadinstitute.sting.oneoffprojects.walkers.association;
-
-/**
- * @Author chartl
- * @Date 2011-02-23
- * general class for calculating base data for generalized association tests
- */
-public abstract class AssociationContextAtom {
-
-    public AssociationContextAtom(MapExtender e) {
-
-    }
-}

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

@@ -5,7 +5,8 @@ import java.util.List;
 
 import cern.jet.random.Normal;
 import cern.jet.random.StudentT;
-import org.broadinstitute.sting.oneoffprojects.walkers.association.interfaces.*;
+import org.broadinstitute.sting.oneoffprojects.walkers.association.statistics.casecontrol.*;
+import org.broadinstitute.sting.utils.MathUtils;
 
 /**
  * Created by IntelliJ IDEA.
@@ -34,17 +35,19 @@ public class AssociationTestRunner {
         return results;
     }
 
-    public static String runStudentT(TStatistic context) {
+    public static String runStudentT(TStatistic context) { /*
-        double t = context.getTStatistic();
+        StudentT studentT = new StudentT(dfnum/dfdenom,null);
-        StudentT studentT = new StudentT(context.getDegreesOfFreedom(),null);
         double p = t < 0 ? 2*studentT.cdf(t) : 2*(1-studentT.cdf(t));
-        return String.format("T: %.2f\tP: %.2e",t,p);
+        return String.format("T: %.2f\tP: %.2e",t,p);*/
+        return null;
     }
 
-    public static String runZ(ZStatistic context) {
+    public static String runZ(ZStatistic context) { /*
-        double z = context.getZStatistic();
+        double z = num/Math.sqrt(se);
         double p = z < 0 ? 2*standardNormal.cdf(z) : 2*(1-standardNormal.cdf(z));
-        return String.format("Z: %.2f\tP: %.2e",z,p);
+        return String.format("Z: %.2f\tP: %.2e",z,p);*/
+
+        return null;
     }
 
     public static String runFisherExact(AssociationContext context) {

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

@@ -1,11 +1,16 @@
 package org.broadinstitute.sting.oneoffprojects.walkers.association;
 
+import net.sf.samtools.SAMRecord;
+import org.broadinstitute.sting.gatk.contexts.AlignmentContext;
 import org.broadinstitute.sting.gatk.contexts.ReferenceContext;
 import org.broadinstitute.sting.gatk.contexts.StratifiedAlignmentContext;
 import org.broadinstitute.sting.gatk.datasources.sample.Sample;
 import org.broadinstitute.sting.gatk.refdata.RefMetaDataTracker;
+import org.broadinstitute.sting.utils.pileup.PileupElement;
+import org.broadinstitute.sting.utils.pileup.ReadBackedPileup;
+import org.broadinstitute.sting.utils.pileup.ReadBackedPileupImpl;
 
-import java.util.Map;
+import java.util.*;
 
 /**
  * @Author chartl
@@ -13,9 +18,12 @@ import java.util.Map;
  * Holds multiple map contexts for use in the regional association walker
  */
 public class MapExtender {
-
+    static StratifiedAlignmentContext.StratifiedContextType TYPE = StratifiedAlignmentContext.StratifiedContextType.COMPLETE;
+    // hold on to these -- atoms may want access to the tracker or other context types
     private MapHolder previous = null;
     private MapHolder current = null;
+    private Map<Sample,ReadBackedPileup> fullPileup = null;
+    private Map<Sample,ReadBackedPileup> readFilteredPileup = null;
 
     public MapExtender() {
         // no need to do anything
@@ -24,8 +32,41 @@ public class MapExtender {
     public void set(MapHolder holder) {
         previous = current;
         current = holder;
+
+        Map<Sample,ReadBackedPileup> prevPileup = fullPileup;
+        fullPileup = new HashMap<Sample,ReadBackedPileup>();
+        readFilteredPileup = new HashMap<Sample,ReadBackedPileup>();
+
+        if ( current != null ) {
+            for ( Map.Entry<Sample,StratifiedAlignmentContext> sac : current.getContext().entrySet() ) {
+                AlignmentContext context = sac.getValue().getContext(TYPE);
+                if ( context.hasBasePileup() ) {
+                    fullPileup.put(sac.getKey(),context.getBasePileup());
+                } else if ( context.hasExtendedEventPileup() ) {
+                    fullPileup.put(sac.getKey(),context.getExtendedEventPileup());
+                }
+
+                if ( prevPileup != null ) {
+
+                    List<PileupElement> filtElems = new ArrayList<PileupElement>(fullPileup.get(sac.getKey()).size());
+                    Set<SAMRecord> seenReads = prevPileup.containsKey(sac.getKey()) ? new HashSet<SAMRecord>(prevPileup.get(sac.getKey()).getReads()) : new HashSet<SAMRecord>(0);
+                    for ( PileupElement e : fullPileup.get(sac.getKey()) ) {
+                        if ( ! seenReads.contains(e.getRead()) ) {
+                            filtElems.add(e);
+                        }
+                    }
+
+                    readFilteredPileup.put(sac.getKey(),new ReadBackedPileupImpl(current.getRef().getLocus(),filtElems));
+                } else {
+                    readFilteredPileup = fullPileup;
+                }
+            }
+        }
     }
 
+    public Map<Sample,ReadBackedPileup> getFullPileup() { return fullPileup; }
+    public Map<Sample,ReadBackedPileup> getReadFilteredPileup(){ return readFilteredPileup; }
+
     public Map<Sample,StratifiedAlignmentContext> getPreviousContext() {
         return previous != null ? previous.getContext() : null;
     }

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

@@ -2,7 +2,6 @@ package org.broadinstitute.sting.oneoffprojects.walkers.association;
 
 import org.broadinstitute.sting.utils.GenomeLoc;
 
-import java.lang.reflect.InvocationTargetException;
 import java.util.*;
 
 /**
@@ -31,10 +30,10 @@ public class RegionalAssociationHandler {
      * @reduce: (List<AssociationContext>,AssociationContext) --> List<AssociationContextAtom>
      *  @implementation: just append
      */
-    public void runMapReduce() throws NoSuchMethodException, IllegalAccessException, InstantiationException, InvocationTargetException {
+    public void runMapReduce() {
         for ( AssociationContext w : associations ) {
             if ( w.filter(maps) ) {
-                w.reduce(w.map(maps));
+                w.addData(w.mapLocus(maps));
             }
         }
     }

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

@@ -7,8 +7,6 @@ import org.broadinstitute.sting.gatk.contexts.ReferenceContext;
 import org.broadinstitute.sting.gatk.refdata.RefMetaDataTracker;
 import org.broadinstitute.sting.gatk.walkers.LocusWalker;
 import org.broadinstitute.sting.gatk.walkers.TreeReducible;
-import org.broadinstitute.sting.oneoffprojects.walkers.association.modules.LowMappingQuality;
-import org.broadinstitute.sting.oneoffprojects.walkers.association.modules.LowMappingQualityAtom;
 import org.broadinstitute.sting.utils.exceptions.StingException;
 import org.broadinstitute.sting.utils.exceptions.UserException;
 
@@ -59,11 +57,8 @@ public class RegionalAssociationWalker extends LocusWalker<MapHolder, RegionalAs
     }
 
     private AssociationContext stringToAssociationContext(String s) {
-        if ( s.equals("LowMappingQuality") ) {
-            return new LowMappingQuality();
-        }
 
-        throw new UserException(String.format("AssociationContext type %s not found.",s));
+        throw new UserException(String.format("AssociationContextOld type %s not found.",s));
     }
 
     private Set<AssociationContext> getAssociations() {

java/src/org/broadinstitute/sting/oneoffprojects/walkers/association/interfaces/TStatistic.java

@@ -1,15 +0,0 @@
-package org.broadinstitute.sting.oneoffprojects.walkers.association.interfaces;
-
-import org.broadinstitute.sting.utils.collections.Pair;
-
-/**
- * Created by IntelliJ IDEA.
- * User: chartl
- * Date: Feb 24, 2011
- * Time: 12:58:16 PM
- * To change this template use File | Settings | File Templates.
- */
-public interface TStatistic {
-    public abstract double getTStatistic();
-    public abstract double getDegreesOfFreedom();
-}

java/src/org/broadinstitute/sting/oneoffprojects/walkers/association/interfaces/ZStatistic.java

@@ -1,12 +0,0 @@
-package org.broadinstitute.sting.oneoffprojects.walkers.association.interfaces;
-
-/**
- * Created by IntelliJ IDEA.
- * User: chartl
- * Date: Feb 24, 2011
- * Time: 12:58:38 PM
- * To change this template use File | Settings | File Templates.
- */
-public interface ZStatistic {
-    public abstract double getZStatistic();
-}

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

@@ -0,0 +1,28 @@
+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;
+import java.util.List;
+
+/**
+ * @author chartl
+ */
+public class InsertSizeDistribution extends TStatistic {
+    public int getWindowSize() { return 100; }
+    public int slideByValue() { return 10; }
+    public boolean usePreviouslySeenReads() { return false; }
+
+    public Collection<Number> map(ReadBackedPileup pileup) {
+        List<Integer> insertSizes = new ArrayList<Integer>(pileup.size());
+        for ( PileupElement e : pileup ) {
+            insertSizes.add(e.getRead().getInferredInsertSize());
+        }
+
+        return (Collection) insertSizes;
+    }
+
+}

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

@@ -1,89 +0,0 @@
-package org.broadinstitute.sting.oneoffprojects.walkers.association.modules;
-
-import org.broadinstitute.sting.gatk.datasources.sample.Sample;
-import org.broadinstitute.sting.oneoffprojects.walkers.association.AssociationContext;
-import org.broadinstitute.sting.oneoffprojects.walkers.association.AssociationContextAtom;
-import org.broadinstitute.sting.oneoffprojects.walkers.association.interfaces.TStatistic;
-import org.broadinstitute.sting.oneoffprojects.walkers.association.interfaces.ZStatistic;
-import org.broadinstitute.sting.utils.MathUtils;
-import org.broadinstitute.sting.utils.collections.Pair;
-
-import java.util.*;
-
-/**
- * Created by IntelliJ IDEA.
- * User: chartl
- * Date: Feb 24, 2011
- * Time: 1:49:37 PM
- * To change this template use File | Settings | File Templates.
- */
-public class LowMappingQuality extends AssociationContext<LowMappingQualityAtom> implements ZStatistic, TStatistic {
-    private double df = -1;
-
-    public LowMappingQuality(Class<LowMappingQualityAtom> atomClass ) {
-        super(atomClass);
-    }
-
-    public LowMappingQuality() {
-        this(LowMappingQualityAtom.class);
-    }
-
-    public int getWindowSize() { return 20; }
-    public int slideByValue() { return 5; }
-
-    public double getZStatistic() {
-        int case_low= 0;
-        int case_tot = 0;
-        int ctrl_low = 0;
-        int ctrl_tot = 0;
-        for ( LowMappingQualityAtom atom : window ) {
-            Map<String, Pair<Integer,Integer>> ccc = atom.getCaseControlCounts();
-            case_low += ccc.get("case").first;
-            case_tot += ccc.get("case").second;
-            ctrl_low += ccc.get("control").first;
-            ctrl_tot += ccc.get("control").second;
-        }
-        double p_case = ( (double) case_low)/case_tot;
-        double p_ctrl = ((double) ctrl_low)/ctrl_tot;
-        double p_pool = ( (double) case_low + (double) ctrl_low )/(case_tot+ctrl_tot);
-        double SE = Math.sqrt( p_pool*(1-p_pool)*( 1/((double)ctrl_tot) + 1/((double)case_tot) ));
-        return (p_case - p_ctrl)/SE;
-    }
-
-    public double getTStatistic() {
-        // todo -- running average is unnecessary and inefficient here, but was quick to write
-        MathUtils.RunningAverage cases =  new MathUtils.RunningAverage();
-        MathUtils.RunningAverage controls = new MathUtils.RunningAverage();
-        Set<Sample> caseSamples = new HashSet<Sample>();
-        Set<Sample> controlSamples = new HashSet<Sample>();
-        for ( LowMappingQualityAtom atom : window ) {
-            Map<String,List<Integer>> caseControlQuals = atom.getCaseControlMappingQuals();
-            cases.addAll((Collection) caseControlQuals.get("case"));
-            controls.addAll((Collection) caseControlQuals.get("control"));
-            for ( Sample s : atom.getSamples() ) {
-                if ( s.getProperty("cohort").equals("case") ) {
-                    caseSamples.add(s);
-                }
-                if ( s.getProperty("cohort").equals("control")) {
-                    controlSamples.add(s);
-                }
-            }
-        }
-        double a = cases.var()/caseSamples.size();
-        double b = controls.var()/controlSamples.size();
-
-        df = ( a + b )/( a*a/(caseSamples.size()-1) + b*b/(controlSamples.size()-1));
-
-        return ( cases.mean() - controls.mean() )/Math.sqrt( (cases.var()/caseSamples.size()) + (controls.var()/controlSamples.size()));
-    }
-
-    // todo -- this is super hacky
-    public double getDegreesOfFreedom() {
-        if ( df < 0 ) {
-            getTStatistic();
-        }
-        double holder = df;
-        df = -1;
-        return holder;
-    }
-}

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

@@ -1,143 +0,0 @@
-package org.broadinstitute.sting.oneoffprojects.walkers.association.modules;
-
-import org.broadinstitute.sting.gatk.contexts.StratifiedAlignmentContext;
-import org.broadinstitute.sting.gatk.datasources.sample.Sample;
-import org.broadinstitute.sting.oneoffprojects.walkers.association.AssociationContextAtom;
-import org.broadinstitute.sting.oneoffprojects.walkers.association.MapExtender;
-import org.broadinstitute.sting.oneoffprojects.walkers.association.MapHolder;
-import org.broadinstitute.sting.utils.collections.Pair;
-import org.broadinstitute.sting.utils.pileup.PileupElement;
-
-import java.util.*;
-
-/**
- * Created by IntelliJ IDEA.
- * User: chartl
- * Date: Feb 24, 2011
- * Time: 1:49:55 PM
- * To change this template use File | Settings | File Templates.
- */
-public class LowMappingQualityAtom extends AssociationContextAtom {
-    private static int LOW_THRESH = 5;
-    private static StratifiedAlignmentContext.StratifiedContextType TYPE = StratifiedAlignmentContext.StratifiedContextType.COMPLETE;
-
-    protected Map<Sample, Pair<Integer,Integer>> stratifiedCounts;
-    protected Map<Sample,List<Integer>> mappingQualities;
-
-    public LowMappingQualityAtom(MapExtender e) {
-        super(e);
-        stratifiedCounts = new HashMap<Sample,Pair<Integer,Integer>>();
-        mappingQualities = new HashMap<Sample,List<Integer>>();
-        for ( Sample s : e.getContext().keySet() ) {
-            makeCounts(s,e.getPreviousContext(),e.getContext());
-        }
-    }
-
-    public void makeCounts( Sample sample, Map<Sample, StratifiedAlignmentContext> prev, Map<Sample,StratifiedAlignmentContext> cur ) {
-        int low = 0;
-        int tot = 0;
-        if ( cur != null && cur.get(sample) != null && cur.get(sample).getContext(TYPE) != null) {
-            HashSet<String> rnames;
-            List<Integer> mapQuals = new ArrayList<Integer>(cur.size());
-            if ( prev != null && prev.get(sample) != null && prev.get(sample).getContext(TYPE) != null) {
-                rnames = new HashSet<String>(prev.get(sample).getContext(TYPE).size());
-                if ( prev.get(sample).getContext(TYPE).hasBasePileup()) {
-                    for ( PileupElement e : prev.get(sample).getContext(TYPE).getBasePileup() ) {
-                        rnames.add(e.getRead().getReadName());
-                    }
-                }
-                if ( prev.get(sample).getContext(TYPE).hasExtendedEventPileup()) {
-                    for ( PileupElement e : prev.get(sample).getContext(TYPE).getExtendedEventPileup() ) {
-                        rnames.add(e.getRead().getReadName());
-                    }
-                }
-            } else {
-                rnames = new HashSet<String>(0);
-            }
-            if ( cur.get(sample).getContext(TYPE).hasBasePileup()) {
-                for ( PileupElement e : cur.get(sample).getContext(TYPE).getBasePileup() ) {
-                    if ( ! rnames.contains(e.getRead().getReadName()) ) {
-                        ++tot;
-                        if ( e.getMappingQual() < LOW_THRESH ) {
-                            ++low;
-                        }
-                        mapQuals.add(e.getMappingQual());
-                    }
-                }
-            }
-            if ( cur.get(sample).getContext(TYPE).hasExtendedEventPileup()) {
-                for ( PileupElement e : cur.get(sample).getContext(TYPE).getExtendedEventPileup() ) {
-                    if ( ! rnames.contains(e.getRead().getReadName()) ) {
-                        ++tot;
-                        if ( e.getMappingQual() < LOW_THRESH ) {
-                            ++low;
-                        }
-                        mapQuals.add(e.getMappingQual());
-                    }
-                }
-            }
-
-            stratifiedCounts.put(sample,new Pair<Integer,Integer>(low,tot));
-            mappingQualities.put(sample,mapQuals);
-        }
-        
-    }
-
-    public Map<Sample,Pair<Integer,Integer>> getCounts() {
-        return stratifiedCounts;
-    }
-
-    public Map<String,Pair<Integer,Integer>> getCaseControlCounts() {
-        Pair<Integer,Integer> cases = new Pair<Integer,Integer>(0,0);
-        Pair<Integer,Integer> controls = new Pair<Integer,Integer>(0,0);
-        for ( Map.Entry<Sample,Pair<Integer,Integer>> e : stratifiedCounts.entrySet() ) {
-            if ( e.getKey().getProperty("cohort").equals("case") ) {
-                cases.first += e.getValue().first;
-                cases.second += e.getValue().second;
-            }
-            if ( e.getKey().getProperty("cohort").equals("control") ) {
-                controls.first += e.getValue().first;
-                controls.second += e.getValue().second;
-            }
-        }
-
-        Map<String,Pair<Integer,Integer>> caseControlCounts= new HashMap<String,Pair<Integer,Integer>>(2);
-        caseControlCounts.put("case",cases);
-        caseControlCounts.put("control",controls);
-        return caseControlCounts;
-    }
-
-    public Map<String,List<Integer>> getCaseControlMappingQuals() {
-        int caseSize = 0;
-        int controlSize = 0;
-        for ( Map.Entry<Sample,List<Integer>> v : mappingQualities.entrySet() ) {
-            if ( v.getKey().getProperty("cohort").equals("case") ) {
-                caseSize += v.getValue().size();
-            }
-            if ( v.getKey().getProperty("cohort").equals("control") ) {
-                controlSize += v.getValue().size();
-            }
-        }
-        List<Integer> caseQuals = new ArrayList<Integer>(caseSize);
-        List<Integer> controlQuals = new ArrayList<Integer>(controlSize);
-        for ( Map.Entry<Sample,List<Integer>> v : mappingQualities.entrySet() ) {
-            if ( v.getKey().getProperty("cohort").equals("case") ) {
-                caseQuals.addAll(v.getValue());
-            }
-
-            if ( v.getKey().getProperty("cohort").equals("control")) {
-                controlQuals.addAll(v.getValue());
-            }
-        }
-
-        Map<String,List<Integer>> caseControlQuals = new HashMap<String,List<Integer>>(2);
-        caseControlQuals.put("case",caseQuals);
-        caseControlQuals.put("control",controlQuals);
-        return caseControlQuals;
-    }
-
-    public Set<Sample> getSamples() {
-        return stratifiedCounts.keySet();
-    }
-
-}

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

@@ -0,0 +1,36 @@
+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: 3/1/11
+ * Time: 3:00 PM
+ * To change this template use File | Settings | File Templates.
+ */
+public class MateOtherContig extends ZStatistic {
+
+    public int getWindowSize() { return 50; }
+    public int slideByValue() { return 25; }
+    public boolean usePreviouslySeenReads() { return false; }
+
+    public Pair<Number,Number> map(ReadBackedPileup pileup) {
+        int tot = 0;
+        int otherCon = 0;
+        for ( PileupElement e : pileup ) {
+            if ( e.getRead().getReadPairedFlag() ) {
+                ++tot;
+                if ( ! e.getRead().getMateReferenceIndex().equals(e.getRead().getReferenceIndex()) ) {
+                    ++otherCon;
+                }
+            }
+        }
+
+        return new Pair<Number,Number>(tot,otherCon);
+    }
+
+}

java/src/org/broadinstitute/sting/oneoffprojects/walkers/association/modules/MateUnmapped.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: 3/2/11
+ * Time: 2:09 PM
+ * To change this template use File | Settings | File Templates.
+ */
+public class MateUnmapped extends ZStatistic  {
+
+    public Pair<Number,Number> map(ReadBackedPileup pileup) {
+        int numMatedReads = 0;
+        int numPairUnmapped = 0;
+        for (PileupElement e : pileup ) {
+            if ( e.getRead().getProperPairFlag() ) {
+                ++numMatedReads;
+                if ( e.getRead().getMateUnmappedFlag() ) {
+                    ++numPairUnmapped;
+                }
+            }
+        }
+
+        return new Pair<Number,Number>(numMatedReads,numPairUnmapped);
+    }
+
+    public int getWindowSize() { return 100; }
+    public int slideByValue() { return 25; }
+    public boolean usePreviouslySeenReads() { return false; }
+}

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

@@ -0,0 +1,50 @@
+package org.broadinstitute.sting.oneoffprojects.walkers.association.statistics.casecontrol;
+
+import org.broadinstitute.sting.gatk.datasources.sample.Sample;
+import org.broadinstitute.sting.oneoffprojects.walkers.association.AssociationContext;
+import org.broadinstitute.sting.utils.pileup.ReadBackedPileup;
+
+import java.util.HashMap;
+import java.util.List;
+import java.util.Map;
+
+/**
+ * Created by IntelliJ IDEA.
+ * @author chartl
+ */
+public abstract class CaseControl<X> extends AssociationContext<X> {
+
+    public Map<Cohort,X> reduce(List<Map<Sample,X>> window) {
+        X accumCase = null;
+        X accumControl = null;
+        for ( Map<Sample,X> sampleXMap : window ) {
+            for ( Map.Entry<Sample,X> entry : sampleXMap.entrySet() ) {
+                if ( entry.getKey().getProperty("cohort").equals("case") ) {
+                    accum(accumCase, entry.getValue());
+                } else if ( entry.getKey().getProperty("cohort").equals("control") ) {
+                    accum(accumControl,entry.getValue());
+                }
+            }
+        }
+
+        Map<Cohort,X> cohortMap = new HashMap<Cohort,X>(2);
+        cohortMap.put(Cohort.CASE,accumCase);
+        cohortMap.put(Cohort.CONTROL,accumControl);
+        return cohortMap;
+    }
+
+    protected X accum(X left, X right) {
+        if ( left == null ) {
+            return right;
+        }
+        if ( right == null ) {
+            return left;
+        }
+        return add(left,right);
+    }
+
+    public abstract X map(ReadBackedPileup rbp);
+    public abstract X add(X left, X right);
+
+    public enum Cohort { CASE,CONTROL }
+}

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

@@ -1,4 +1,4 @@
-package org.broadinstitute.sting.oneoffprojects.walkers.association.interfaces;
+package org.broadinstitute.sting.oneoffprojects.walkers.association.statistics.casecontrol;
 
 /**
  * Created by IntelliJ IDEA.

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

@@ -0,0 +1,37 @@
+package org.broadinstitute.sting.oneoffprojects.walkers.association.statistics.casecontrol;
+
+import org.broadinstitute.sting.utils.collections.Pair;
+import org.broadinstitute.sting.utils.pileup.ReadBackedPileup;
+
+import java.util.ArrayList;
+import java.util.Collection;
+import java.util.List;
+import java.util.Set;
+
+/**
+ * Created by IntelliJ IDEA.
+ * User: chartl
+ * Date: Feb 24, 2011
+ * Time: 12:58:16 PM
+ * To change this template use File | Settings | File Templates.
+ */
+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);
+            return left;
+        } else if ( left instanceof Set ) {
+            ((Set) left).addAll(right);
+            return left;
+        } else {
+            List<Number> newList = new ArrayList<Number>(left.size()+right.size());
+            newList.addAll(left);
+            newList.addAll(right);
+            return newList;
+        }
+    }
+
+}

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

@@ -0,0 +1,36 @@
+package org.broadinstitute.sting.oneoffprojects.walkers.association.statistics.casecontrol;
+
+import org.broadinstitute.sting.utils.pileup.ReadBackedPileup;
+
+import java.util.ArrayList;
+import java.util.Collection;
+import java.util.List;
+import java.util.Set;
+
+/**
+ * Created by IntelliJ IDEA.
+ * User: chartl
+ * Date: 3/2/11
+ * Time: 1:53 PM
+ * To change this template use File | Settings | File Templates.
+ */
+public abstract class UStatistic 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);
+            return left;
+        } else if ( left instanceof Set) {
+            ((Set) left).addAll(right);
+            return left;
+        } else {
+            List<Number> newList = new ArrayList<Number>(left.size()+right.size());
+            newList.addAll(left);
+            newList.addAll(right);
+            return newList;
+        }
+    }
+
+}

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

@@ -0,0 +1,26 @@
+package org.broadinstitute.sting.oneoffprojects.walkers.association.statistics.casecontrol;
+
+import org.broadinstitute.sting.utils.collections.Pair;
+import org.broadinstitute.sting.utils.pileup.ReadBackedPileup;
+
+import java.util.ArrayList;
+import java.util.Collection;
+import java.util.List;
+import java.util.Set;
+
+/**
+ * Created by IntelliJ IDEA.
+ * User: chartl
+ * Date: Feb 24, 2011
+ * Time: 12:58:38 PM
+ * To change this template use File | Settings | File Templates.
+ */
+public abstract class ZStatistic extends CaseControl<Pair<Number,Number>> {
+    public abstract Pair<Number,Number> map(ReadBackedPileup rbp );
+
+    public Pair<Number,Number> add(Pair<Number,Number> left, Pair<Number,Number> right) {
+        return new Pair<Number,Number>(left.first.doubleValue()+right.first.doubleValue(),
+                                       left.second.doubleValue()+right.second.doubleValue());
+    }
+
+}