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This Agreement shall be construed, governed, interpreted and applied in accordance with the internal laws of the Commonwealth of Massachusetts, U.S.A., without regard to conflict of laws principles. */ package org.broadinstitute.sting.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.sting.utils.collections.Pair; import org.broadinstitute.sting.utils.exceptions.ReviewedStingException; 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 ReviewedStingException("chi2 value is " + chi2PValue + " at " + getRecalDatum()); return penalty; } catch (MathException e) { throw new ReviewedStingException("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); } } }