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package org.broadinstitute.gatk.utils.recalibration;
import com.google.java.contract.Ensures;
import com.google.java.contract.Requires;
import org.apache.commons.math.MathException;
import org.apache.commons.math.stat.inference.ChiSquareTestImpl;
import org.apache.log4j.Logger;
import org.broadinstitute.gatk.utils.collections.Pair;
import org.broadinstitute.gatk.utils.exceptions.ReviewedGATKException;
import java.util.Collection;
import java.util.HashSet;
import java.util.LinkedList;
import java.util.Set;
/**
* A tree of recal datum, where each contains a set of sub datum representing sub-states of the higher level one
*
* @author Mark DePristo
* @since 07/27/12
*/
public class RecalDatumNode<T extends RecalDatum> {
private final static double SMALLEST_CHI2_PVALUE = 1e-300;
protected static final Logger logger = Logger.getLogger(RecalDatumNode.class);
/**
* fixedPenalty is this value if it's considered fixed
*/
private final static double UNINITIALIZED = Double.NEGATIVE_INFINITY;
private final T recalDatum;
private double fixedPenalty = UNINITIALIZED;
private final Set<RecalDatumNode<T>> subnodes;
@Requires({"recalDatum != null"})
public RecalDatumNode(final T recalDatum) {
this(recalDatum, new HashSet<RecalDatumNode<T>>());
}
@Override
public String toString() {
return recalDatum.toString();
}
@Requires({"recalDatum != null", "subnodes != null"})
public RecalDatumNode(final T recalDatum, final Set<RecalDatumNode<T>> subnodes) {
this(recalDatum, UNINITIALIZED, subnodes);
}
@Requires({"recalDatum != null"})
protected RecalDatumNode(final T recalDatum, final double fixedPenalty) {
this(recalDatum, fixedPenalty, new HashSet<RecalDatumNode<T>>());
}
@Requires({"recalDatum != null", "subnodes != null"})
protected RecalDatumNode(final T recalDatum, final double fixedPenalty, final Set<RecalDatumNode<T>> subnodes) {
this.recalDatum = recalDatum;
this.fixedPenalty = fixedPenalty;
this.subnodes = new HashSet<RecalDatumNode<T>>(subnodes);
}
/**
* Get the recal data associated with this node
* @return
*/
@Ensures("result != null")
public T getRecalDatum() {
return recalDatum;
}
/**
* The set of all subnodes of this tree. May be modified.
* @return
*/
@Ensures("result != null")
public Set<RecalDatumNode<T>> getSubnodes() {
return subnodes;
}
/**
* Return the fixed penalty, if set, or else the the calculated penalty for this node
* @return
*/
public double getPenalty() {
if ( fixedPenalty != UNINITIALIZED )
return fixedPenalty;
else
return calcPenalty();
}
/**
* Set the fixed penalty for this node to a fresh calculation from calcPenalty
*
* This is important in the case where you want to compute the penalty from a full
* tree and then chop the tree up afterwards while considering the previous penalties.
* If you don't call this function then manipulating the tree may result in the
* penalty functions changing with changes in the tree.
*
* @param doEntireTree recurse into all subnodes?
* @return the fixed penalty for this node
*/
public double calcAndSetFixedPenalty(final boolean doEntireTree) {
fixedPenalty = calcPenalty();
if ( doEntireTree )
for ( final RecalDatumNode<T> sub : subnodes )
sub.calcAndSetFixedPenalty(doEntireTree);
return fixedPenalty;
}
/**
* Add node to the set of subnodes of this node
* @param sub
*/
@Requires("sub != null")
public void addSubnode(final RecalDatumNode<T> sub) {
subnodes.add(sub);
}
/**
* Is this a leaf node (i.e., has no subnodes)?
* @return
*/
public boolean isLeaf() {
return subnodes.isEmpty();
}
/**
* Is this node immediately above only leaf nodes?
*
* @return
*/
public boolean isAboveOnlyLeaves() {
for ( final RecalDatumNode<T> sub : subnodes )
if ( ! sub.isLeaf() )
return false;
return true;
}
/**
* What's the immediate number of subnodes from this node?
* @return
*/
@Ensures("result >= 0")
public int getNumSubnodes() {
return subnodes.size();
}
/**
* Total penalty is the sum of leaf node penalties
*
* This algorithm assumes that penalties have been fixed before pruning, as leaf nodes by
* definition have 0 penalty unless they represent a pruned tree with underlying -- but now
* pruned -- subtrees
*
* @return
*/
public double totalPenalty() {
if ( isLeaf() )
return getPenalty();
else {
double sum = 0.0;
for ( final RecalDatumNode<T> sub : subnodes )
sum += sub.totalPenalty();
return sum;
}
}
/**
* The maximum penalty among all nodes
* @return
*/
public double maxPenalty(final boolean leafOnly) {
double max = ! leafOnly || isLeaf() ? getPenalty() : Double.MIN_VALUE;
for ( final RecalDatumNode<T> sub : subnodes )
max = Math.max(max, sub.maxPenalty(leafOnly));
return max;
}
/**
* The minimum penalty among all nodes
* @return
*/
public double minPenalty(final boolean leafOnly) {
double min = ! leafOnly || isLeaf() ? getPenalty() : Double.MAX_VALUE;
for ( final RecalDatumNode<T> sub : subnodes )
min = Math.min(min, sub.minPenalty(leafOnly));
return min;
}
/**
* What's the longest branch from this node to any leaf?
* @return
*/
public int maxDepth() {
int subMax = 0;
for ( final RecalDatumNode<T> sub : subnodes )
subMax = Math.max(subMax, sub.maxDepth());
return subMax + 1;
}
/**
* What's the shortest branch from this node to any leaf? Includes this node
* @return
*/
@Ensures("result > 0")
public int minDepth() {
if ( isLeaf() )
return 1;
else {
int subMin = Integer.MAX_VALUE;
for ( final RecalDatumNode<T> sub : subnodes )
subMin = Math.min(subMin, sub.minDepth());
return subMin + 1;
}
}
/**
* Return the number of nodes, including this one, reachable from this node
* @return
*/
@Ensures("result > 0")
public int size() {
int size = 1;
for ( final RecalDatumNode<T> sub : subnodes )
size += sub.size();
return size;
}
/**
* Count the number of leaf nodes reachable from this node
*
* @return
*/
@Ensures("result >= 0")
public int numLeaves() {
if ( isLeaf() )
return 1;
else {
int size = 0;
for ( final RecalDatumNode<T> sub : subnodes )
size += sub.numLeaves();
return size;
}
}
/**
* Calculate the phred-scaled p-value for a chi^2 test for independent among subnodes of this node.
*
* The chi^2 value indicates the degree of independence of the implied error rates among the
* immediate subnodes
*
* @return the phred-scaled p-value for chi2 penalty, or 0.0 if it cannot be calculated
*/
private double calcPenalty() {
if ( isLeaf() || freeToMerge() )
return 0.0;
else if ( subnodes.size() == 1 )
// only one value, so its free to merge away
return 0.0;
else {
final long[][] counts = new long[subnodes.size()][2];
int i = 0;
for ( final RecalDatumNode<T> subnode : subnodes ) {
// use the yates correction to help avoid all zeros => NaN
counts[i][0] = Math.round(subnode.getRecalDatum().getNumMismatches()) + 1L;
counts[i][1] = subnode.getRecalDatum().getNumObservations() + 2L;
i++;
}
try {
final double chi2PValue = new ChiSquareTestImpl().chiSquareTest(counts);
final double penalty = -10.0 * Math.log10(Math.max(chi2PValue, SMALLEST_CHI2_PVALUE));
// make sure things are reasonable and fail early if not
if (Double.isInfinite(penalty) || Double.isNaN(penalty))
throw new ReviewedGATKException("chi2 value is " + chi2PValue + " at " + getRecalDatum());
return penalty;
} catch ( MathException e ) {
throw new ReviewedGATKException("Failed in calculating chi2 value", e);
}
}
}
/**
* Is this node free to merge because its rounded Q score is the same as all nodes below
* @return
*/
private boolean freeToMerge() {
if ( isLeaf() ) // leaves are free to merge
return true;
else {
final byte myQual = getRecalDatum().getEmpiricalQualityAsByte();
for ( final RecalDatumNode<T> sub : subnodes )
if ( sub.getRecalDatum().getEmpiricalQualityAsByte() != myQual )
return false;
return true;
}
}
/**
* Calculate the penalty of this interval, given the overall error rate for the interval
*
* If the globalErrorRate is e, this value is:
*
* sum_i |log10(e_i) - log10(e)| * nObservations_i
*
* each the index i applies to all leaves of the tree accessible from this interval
* (found recursively from subnodes as necessary)
*
* @param globalErrorRate overall error rate in real space against which we calculate the penalty
* @return the cost of approximating the bins in this interval with the globalErrorRate
*/
@Requires("globalErrorRate >= 0.0")
@Ensures("result >= 0.0")
private double calcPenaltyLog10(final double globalErrorRate) {
if ( globalErrorRate == 0.0 ) // there were no observations, so there's no penalty
return 0.0;
if ( isLeaf() ) {
// this is leave node
return (Math.abs(Math.log10(recalDatum.getEmpiricalErrorRate()) - Math.log10(globalErrorRate))) * (double)recalDatum.getNumObservations();
// TODO -- how we can generalize this calculation?
// if ( this.qEnd <= minInterestingQual )
// // It's free to merge up quality scores below the smallest interesting one
// return 0;
// else {
// return (Math.abs(Math.log10(getEmpiricalErrorRate()) - Math.log10(globalErrorRate))) * getNumObservations();
// }
} else {
double sum = 0;
for ( final RecalDatumNode<T> hrd : subnodes)
sum += hrd.calcPenaltyLog10(globalErrorRate);
return sum;
}
}
/**
* Return a freshly allocated tree prunes to have no more than maxDepth from the root to any leaf
*
* @param maxDepth
* @return
*/
public RecalDatumNode<T> pruneToDepth(final int maxDepth) {
if ( maxDepth < 1 )
throw new IllegalArgumentException("maxDepth < 1");
else {
final Set<RecalDatumNode<T>> subPruned = new HashSet<RecalDatumNode<T>>(getNumSubnodes());
if ( maxDepth > 1 )
for ( final RecalDatumNode<T> sub : subnodes )
subPruned.add(sub.pruneToDepth(maxDepth - 1));
return new RecalDatumNode<T>(getRecalDatum(), fixedPenalty, subPruned);
}
}
/**
* Return a freshly allocated tree with to no more than maxElements in order of penalty
*
* Note that nodes must have fixed penalties to this algorithm will fail.
*
* @param maxElements
* @return
*/
public RecalDatumNode<T> pruneByPenalty(final int maxElements) {
RecalDatumNode<T> root = this;
while ( root.size() > maxElements ) {
// remove the lowest penalty element, and continue
root = root.removeLowestPenaltyNode();
}
// our size is below the target, so we are good, return
return root;
}
/**
* Return a freshly allocated tree where all mergable nodes with < maxPenalty are merged
*
* Note that nodes must have fixed penalties to this algorithm will fail.
*
* @param maxPenaltyIn the maximum penalty we are allowed to incur for a merge
* @param applyBonferroniCorrection if true, we will adjust penalty by the phred-scaled bonferroni correction
* for the size of the initial tree. That is, if there are 10 nodes in the
* tree and maxPenalty is 20 we will actually enforce 10^-2 / 10 = 10^-3 = 30
* penalty for multiple testing
* @return
*/
public RecalDatumNode<T> pruneToNoMoreThanPenalty(final double maxPenaltyIn, final boolean applyBonferroniCorrection) {
RecalDatumNode<T> root = this;
final double bonferroniCorrection = 10 * Math.log10(this.size());
final double maxPenalty = applyBonferroniCorrection ? maxPenaltyIn + bonferroniCorrection : maxPenaltyIn;
if ( applyBonferroniCorrection )
logger.info(String.format("Applying Bonferroni correction for %d nodes = %.2f to initial penalty %.2f for total " +
"corrected max penalty of %.2f", this.size(), bonferroniCorrection, maxPenaltyIn, maxPenalty));
while ( true ) {
final Pair<RecalDatumNode<T>, Double> minPenaltyNode = root.getMinPenaltyAboveLeafNode();
if ( minPenaltyNode == null || minPenaltyNode.getSecond() > maxPenalty ) {
// nothing to merge, or the best candidate is above our max allowed
if ( minPenaltyNode == null ) {
if ( logger.isDebugEnabled() ) logger.debug("Stopping because no candidates could be found");
} else {
if ( logger.isDebugEnabled() ) logger.debug("Stopping because node " + minPenaltyNode.getFirst() + " has penalty " + minPenaltyNode.getSecond() + " > max " + maxPenalty);
}
break;
} else {
// remove the lowest penalty element, and continue
if ( logger.isDebugEnabled() ) logger.debug("Removing node " + minPenaltyNode.getFirst() + " with penalty " + minPenaltyNode.getSecond());
root = root.removeLowestPenaltyNode();
}
}
// no more candidates exist with penalty < maxPenalty
return root;
}
/**
* Find the lowest penalty above leaf node in the tree, and return a tree without it
*
* Note this excludes the current (root) node
*
* @return
*/
private RecalDatumNode<T> removeLowestPenaltyNode() {
final Pair<RecalDatumNode<T>, Double> nodeToRemove = getMinPenaltyAboveLeafNode();
if ( logger.isDebugEnabled() )
logger.debug("Removing " + nodeToRemove.getFirst() + " with penalty " + nodeToRemove.getSecond());
final Pair<RecalDatumNode<T>, Boolean> result = removeNode(nodeToRemove.getFirst());
if ( ! result.getSecond() )
throw new IllegalStateException("Never removed any node!");
final RecalDatumNode<T> oneRemoved = result.getFirst();
if ( oneRemoved == null )
throw new IllegalStateException("Removed our root node, wow, didn't expect that");
return oneRemoved;
}
/**
* Finds in the tree the node with the lowest penalty whose subnodes are all leaves
*
* @return the node and its penalty, or null if no such node exists
*/
private Pair<RecalDatumNode<T>, Double> getMinPenaltyAboveLeafNode() {
if ( isLeaf() )
// not allowed to remove leafs directly
return null;
if ( isAboveOnlyLeaves() )
// we only consider removing nodes above all leaves
return new Pair<RecalDatumNode<T>, Double>(this, getPenalty());
else {
// just recurse, taking the result with the min penalty of all subnodes
Pair<RecalDatumNode<T>, Double> minNode = null;
for ( final RecalDatumNode<T> sub : subnodes ) {
final Pair<RecalDatumNode<T>, Double> subFind = sub.getMinPenaltyAboveLeafNode();
if ( subFind != null && (minNode == null || subFind.getSecond() < minNode.getSecond()) ) {
minNode = subFind;
}
}
return minNode;
}
}
/**
* Return a freshly allocated tree without the node nodeToRemove
*
* @param nodeToRemove
* @return
*/
private Pair<RecalDatumNode<T>, Boolean> removeNode(final RecalDatumNode<T> nodeToRemove) {
if ( this == nodeToRemove ) {
if ( isLeaf() )
throw new IllegalStateException("Trying to remove a leaf node from the tree! " + this + " " + nodeToRemove);
// node is the thing we are going to remove, but without any subnodes
final RecalDatumNode<T> node = new RecalDatumNode<T>(getRecalDatum(), fixedPenalty);
return new Pair<RecalDatumNode<T>, Boolean>(node, true);
} else {
// did we remove something in a sub branch?
boolean removedSomething = false;
// our sub nodes with the penalty node removed
final Set<RecalDatumNode<T>> sub = new HashSet<RecalDatumNode<T>>(getNumSubnodes());
for ( final RecalDatumNode<T> sub1 : subnodes ) {
if ( removedSomething ) {
// already removed something, just add sub1 back to sub
sub.add(sub1);
} else {
// haven't removed anything yet, so try
final Pair<RecalDatumNode<T>, Boolean> maybeRemoved = sub1.removeNode(nodeToRemove);
removedSomething = maybeRemoved.getSecond();
sub.add(maybeRemoved.getFirst());
}
}
final RecalDatumNode<T> node = new RecalDatumNode<T>(getRecalDatum(), fixedPenalty, sub);
return new Pair<RecalDatumNode<T>, Boolean>(node, removedSomething);
}
}
/**
* Return a collection of all of the data in the leaf nodes of this tree
*
* @return
*/
public Collection<T> getAllLeaves() {
final LinkedList<T> list = new LinkedList<T>();
getAllLeavesRec(list);
return list;
}
/**
* Helpful recursive function for getAllLeaves()
*
* @param list the destination for the list of leaves
*/
private void getAllLeavesRec(final LinkedList<T> list) {
if ( isLeaf() )
list.add(getRecalDatum());
else {
for ( final RecalDatumNode<T> sub : subnodes )
sub.getAllLeavesRec(list);
}
}
}