/*
 * The MIT License (MIT)
 *
 * Copyright (c) 2007-2015 Broad Institute
 *
 * Permission is hereby granted, free of charge, to any person obtaining a copy
 * of this software and associated documentation files (the "Software"), to deal
 * in the Software without restriction, including without limitation the rights
 * to use, copy, modify, merge, publish, distribute, sublicense, and/or sell
 * copies of the Software, and to permit persons to whom the Software is
 * furnished to do so, subject to the following conditions:
 *
 * The above copyright notice and this permission notice shall be included in
 * all copies or substantial portions of the Software.
 *
 *
 * THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR
 * IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY,
 * FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL THE
 * AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER
 * LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM,
 * OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN
 * THE SOFTWARE.
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package org.broad.igv.tools;

import htsjdk.samtools.util.CloseableIterator;
import org.apache.commons.math.stat.StatUtils;
import org.apache.log4j.Logger;
import org.broad.igv.sam.Alignment;
import org.broad.igv.sam.ReadMate;
import org.broad.igv.sam.reader.AlignmentReader;
import org.broad.igv.sam.reader.AlignmentReaderFactory;

import java.io.IOException;
import java.util.Iterator;


/**
 * @author jrobinso
 * @date Jan 14, 2011
 */
public class PairedEndStats {

    static private Logger log = Logger.getLogger(PairedEndStats.class);

    private double minPercentileInsertSize;
    private double maxPercentileInsertSize;
    private double averageInsertSize;
    private double medianInsertSize;
    private double stddevInsertSize;
    private double madInsertSize;
    private static final int MAX_PAIRS = 10000;

    public static void main(String[] args) throws IOException {

        AlignmentReader reader = AlignmentReaderFactory.getReader(args[0], false);
        CloseableIterator<Alignment> iter = reader.iterator();
        PairedEndStats stats = compute(iter, .1, 99.9);
        iter.close();
        reader.close();

        System.out.println(args[0] + "\t" + stats.averageInsertSize + "\t" + stats.medianInsertSize +
                "\t" + stats.stddevInsertSize + "\t" + stats.madInsertSize);
    }


    public PairedEndStats(double averageInsertSize, double medianInsertSize, double insertSizeStdev, double madInsertSize, double secondPercentileSize, double maxPercentileInsertSize) {
        this.averageInsertSize = averageInsertSize;
        this.medianInsertSize = medianInsertSize;
        this.stddevInsertSize = insertSizeStdev;
        this.madInsertSize = madInsertSize;
        this.minPercentileInsertSize = secondPercentileSize;
        this.maxPercentileInsertSize = maxPercentileInsertSize;
    }

    public static PairedEndStats compute(String bamFile) {
        AlignmentReader reader = null;
        try {
            reader = AlignmentReaderFactory.getReader(bamFile, false);
            final CloseableIterator<Alignment> alignmentCloseableIterator = reader.iterator();
            PairedEndStats stats = compute(alignmentCloseableIterator, .1, 99.9);
            alignmentCloseableIterator.close();
            return stats;

        } catch (IOException e) {
            log.error("Error reading sam file: " + e.getMessage(), e);
            return null;
        }
        finally {
            try {
                if (reader != null)
                    reader.close();
            } catch (IOException e) {
                log.error(e.getMessage(), e);
            }
        }
    }

    public static PairedEndStats compute(AlignmentReader reader, String chr, int start, int end) {
        try {
            PairedEndStats stats = compute(reader.query(chr, start, end, false), .1, 99.9);
            return stats;
        } catch (IOException e) {
            log.error("Error computing alignment stats: " + e.getMessage(), e);
            return null;
        }
    }

    public static PairedEndStats compute(Iterator<Alignment> alignments, double minPercentile, double maxPercentile) {


        double[] insertSizes = new double[MAX_PAIRS];
        int nPairs = 0;

        while (alignments.hasNext()) {


            Alignment al = alignments.next();

            if (isProperPair(al)) {
                insertSizes[nPairs] = Math.abs(al.getInferredInsertSize());
                nPairs++;
            }


            if (nPairs >= MAX_PAIRS) {
                break;
            }

        }

        if(nPairs == 0) {
            log.error("Error computing insert size distribution. No alignments in sample interval.");
            return null;
        }

        double mean = StatUtils.mean(insertSizes, 0, nPairs);
        double median = StatUtils.percentile(insertSizes, 0, nPairs, 50);
        double stdDev = Math.sqrt(StatUtils.variance(insertSizes, 0, nPairs));

        double[] deviations = new double[nPairs];
        for (int i = 0; i < nPairs; i++) {
            deviations[i] = Math.abs(insertSizes[i] - median);
        }

        // MAD, as defined at http://stat.ethz.ch/R-manual/R-devel/library/stats/html/mad.html
        double mad = 1.4826 * StatUtils.percentile(deviations, 50);

        double sec = StatUtils.percentile(insertSizes, 0, nPairs, minPercentile);
        double max = StatUtils.percentile(insertSizes, 0, nPairs, maxPercentile);

        PairedEndStats stats = new PairedEndStats(mean, median, stdDev, mad, sec, max);

        return stats;
    }


    static boolean isProperPair(Alignment alignment) {
        if (alignment.isMapped() &&
                alignment.isPaired() &&
                alignment.isProperPair() &&
                !alignment.isDuplicate() &&
                alignment.getMappingQuality() > 0 &&
                !alignment.isVendorFailedRead() &&
                alignment.getInferredInsertSize() > 0) {
            ReadMate mate = alignment.getMate();
            boolean mateMapped = mate != null && mate.isMapped();
            boolean sameChromosome = mateMapped && mate.getChr().equals(alignment.getChr());
            return mateMapped && sameChromosome;
        }
        return false;
    }

    public double getAverageInsertSize() {
        return averageInsertSize;
    }

    public double getMedianInsertSize() {
        return medianInsertSize;
    }

    public double getStddevInsertSize() {
        return stddevInsertSize;
    }

    public double getMadInsertSize() {
        return madInsertSize;
    }

    public double getMinPercentileInsertSize() {
        return minPercentileInsertSize;
    }

    public double getMaxPercentileInsertSize() {
        return maxPercentileInsertSize;
    }
}


@@ -6074,17 +6074,18 @@
 tSize() 
-%3E
+!=
  0) %7B%0A  

Fix "is proper pair" test