/*
 * The MIT License
 *
 * Copyright (c) 2010-2018 The 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.
 */

package picard.fingerprint;

import com.google.cloud.storage.contrib.nio.SeekableByteChannelPrefetcher;
import com.google.common.annotations.VisibleForTesting;
import htsjdk.samtools.SAMFileHeader;
import htsjdk.samtools.SAMReadGroupRecord;
import htsjdk.samtools.SAMRecord;
import htsjdk.samtools.SAMSequenceDictionary;
import htsjdk.samtools.SamFiles;
import htsjdk.samtools.SamInputResource;
import htsjdk.samtools.SamReader;
import htsjdk.samtools.SamReaderFactory;
import htsjdk.samtools.ValidationStringency;
import htsjdk.samtools.filter.SamRecordFilter;
import htsjdk.samtools.filter.SecondaryAlignmentFilter;
import htsjdk.samtools.util.Interval;
import htsjdk.samtools.util.IntervalList;
import htsjdk.samtools.util.Log;
import htsjdk.samtools.util.SamLocusIterator;
import htsjdk.samtools.util.SequenceUtil;
import htsjdk.samtools.util.StringUtil;
import htsjdk.variant.variantcontext.Allele;
import htsjdk.variant.variantcontext.Genotype;
import htsjdk.variant.variantcontext.GenotypeLikelihoods;
import htsjdk.variant.variantcontext.VariantContext;
import htsjdk.variant.vcf.VCFFileReader;
import picard.PicardException;
import picard.util.AlleleSubsettingUtils;
import picard.util.MathUtil;
import picard.util.ThreadPoolExecutorWithExceptions;

import java.io.File;
import java.io.IOException;
import java.nio.channels.SeekableByteChannel;
import java.nio.file.Path;
import java.util.ArrayList;
import java.util.Collection;
import java.util.Collections;
import java.util.HashMap;
import java.util.HashSet;
import java.util.LinkedList;
import java.util.List;
import java.util.Map;
import java.util.NoSuchElementException;
import java.util.OptionalInt;
import java.util.Random;
import java.util.Set;
import java.util.SortedSet;
import java.util.TreeSet;
import java.util.concurrent.ConcurrentHashMap;
import java.util.concurrent.ExecutionException;
import java.util.concurrent.ExecutorCompletionService;
import java.util.concurrent.ExecutorService;
import java.util.concurrent.TimeUnit;
import java.util.concurrent.atomic.AtomicInteger;
import java.util.function.Function;
import java.util.stream.Collectors;

/**
 * Major class that coordinates the activities involved in comparing genetic fingerprint
 * data whether the source is from a genotyping platform or derived from sequence data.
 *
 * @author Tim Fennell
 */
public class FingerprintChecker {
    public static final double DEFAULT_GENOTYPING_ERROR_RATE = 0.01;
    public static final int DEFAULT_MINIMUM_MAPPING_QUALITY = 10;
    public static final int DEFAULT_MINIMUM_BASE_QUALITY = 20;

    // used sometimes to subset loci. Fix the random seed so that the results are deterministic
    private static final Random random = new Random(42);

    private final HaplotypeMap haplotypes;
    private int minimumBaseQuality = DEFAULT_MINIMUM_BASE_QUALITY;
    private int minimumMappingQuality = DEFAULT_MINIMUM_MAPPING_QUALITY;
    private double genotypingErrorRate = DEFAULT_GENOTYPING_ERROR_RATE;
    private File referenceFasta;

    public ValidationStringency getValidationStringency() {
        return validationStringency;
    }

    public void setValidationStringency(final ValidationStringency validationStringency) {
        this.validationStringency = validationStringency;
    }

    public File getReferenceFasta() {
        return referenceFasta;
    }

    private ValidationStringency validationStringency = ValidationStringency.DEFAULT_STRINGENCY;

    private boolean allowDuplicateReads = false;
    private double pLossofHet = 0;
    private int locusMaxReads = 0;
    private String defaultSampleID = "<UNKNOWN>";

    private final Set<Path> missingRGFiles = new HashSet<>();

    private final Log log = Log.getInstance(FingerprintChecker.class);

    /**
     * Creates a fingerprint checker that will work with the set of haplotypes stored in
     * the supplied file.
     */
    public FingerprintChecker(final File haplotypeData) {
        this.haplotypes = new HaplotypeMap(haplotypeData);
    }

    /**
     * Creates a fingerprint checker that will work with the set of haplotyped provided.
     */
    public FingerprintChecker(final HaplotypeMap haplotypes) {
        this.haplotypes = haplotypes;
    }

    /**
     * Sets the minimum base quality for bases used when computing a fingerprint from sequence data.
     */
    public void setMinimumBaseQuality(final int minimumBaseQuality) {
        this.minimumBaseQuality = minimumBaseQuality;
    }

    /**
     * Sets the minimum mapping quality for reads used when computing fingerprints from sequence data.
     */
    public void setMinimumMappingQuality(final int minimumMappingQuality) {
        this.minimumMappingQuality = minimumMappingQuality;
    }

    /**
     * Sets the assumed genotyping error rate used when accurate error rates are not available.
     */
    public void setGenotypingErrorRate(final double genotypingErrorRate) {
        this.genotypingErrorRate = genotypingErrorRate;
    }

    public SAMFileHeader getHeader() {
        return haplotypes.getHeader();
    }

    /**
     * Sets whether duplicate reads should be allowed when calling genotypes from SAM files. This is
     * useful when comparing read groups within a SAM file and individual read groups show artifactually
     * high duplication (e.g. a single-ended read group mixed in with paired-end read groups).
     *
     * @param allowDuplicateReads should fingerprinting use duplicate reads?
     */
    public void setAllowDuplicateReads(final boolean allowDuplicateReads) {
        this.allowDuplicateReads = allowDuplicateReads;
    }

    //sets the value of the probability that a genotype underwent a Loss of Hetrozygosity (for Tumors)
    public void setpLossofHet(final double pLossofHet) {
        this.pLossofHet = pLossofHet;
    }

    /**
     * Loads VCF reader from path, and checks if index available when forced.
     */
    @VisibleForTesting
    static VCFFileReader getVCFReader(final Path vcfPath, final Path indexPath, final boolean forceIndex) {
        VCFFileReader reader = indexPath != null ? new VCFFileReader(vcfPath, indexPath) : new VCFFileReader(vcfPath, forceIndex);

        if (forceIndex && !reader.isQueryable()) {
            throw new PicardException("Input VCF file " + vcfPath + " has no index while user required index to proceed.");
        }

        return reader;
    }

    /**
     * Loads genotypes from the supplied file into one or more Fingerprint objects and returns them in a
     * Map of Sample->Fingerprint.
     *
     * @param fingerprintFile - VCF file containing genotypes for one or more samples
     * @param specificSample  - null to load genotypes for all samples contained in the file or the name
     *                        of an individual sample to load (and exclude all others).
     * @return a Map of Sample name to Fingerprint
     */
    public Map<String, Fingerprint> loadFingerprints(final Path fingerprintFile, final Path indexPath, final boolean forceIndex, final String specificSample) {
        final VCFFileReader reader = getVCFReader(fingerprintFile, indexPath, forceIndex);
        checkDictionaryGoodForFingerprinting(reader.getFileHeader().getSequenceDictionary());

        final Map<String, Fingerprint> fingerprints;
        if (reader.isQueryable()) {
            fingerprints = loadFingerprintsFromQueriableReader(reader, specificSample, fingerprintFile);
        } else {
            log.warn("Couldn't find index for file " + fingerprintFile + " going to read through it all.");
            fingerprints = loadFingerprintsFromVariantContexts(reader, specificSample, fingerprintFile);
        }
        //add an entry for each sample which was not fingerprinted
        reader.getFileHeader().getGenotypeSamples().forEach(sample -> fingerprints.computeIfAbsent(sample, s -> new Fingerprint(s, fingerprintFile, null)));

        return fingerprints;
    }

    private void checkDictionaryGoodForFingerprinting(final SAMSequenceDictionary sequenceDictionaryToCheck) {
        final SAMSequenceDictionary activeDictionary = getActiveDictionary(haplotypes);

        if (sequenceDictionaryToCheck.getSequences().size() < activeDictionary.size()) {
            throw new SequenceUtil.SequenceListsDifferException("Dictionary on fingerprinted file smaller than that on Haplotype Database!");
        }
        try {
            SequenceUtil.assertSequenceDictionariesEqual(activeDictionary, sequenceDictionaryToCheck, true);
        } catch (final SequenceUtil.SequenceListsDifferException e) {
            throw new PicardException("Dictionary on fingerprinted file does not match dictionary in Haplotype Database.", e);
        }
    }

    private static SAMSequenceDictionary getActiveDictionary(final HaplotypeMap haplotypes) {
        final SAMSequenceDictionary origSequenceDictionary = haplotypes.getHeader().getSequenceDictionary();

        final OptionalInt maxSequenceIndex = haplotypes.getAllSnps().stream()
                .map(Snp::getChrom)
                .mapToInt(origSequenceDictionary::getSequenceIndex)
                .max();
        if (!maxSequenceIndex.isPresent()) {
            return origSequenceDictionary;
        }
        //plus one since sublist is exclusive of the end.
        return new SAMSequenceDictionary(origSequenceDictionary.getSequences().subList(0, maxSequenceIndex.getAsInt() + 1));
    }

    /**
     * Loads genotypes from the supplied file into one or more Fingerprint objects and returns them in a
     * Map of Sample->Fingerprint.
     *
     * @param fingerprintFile - VCF file containing genotypes for one or more samples
     * @param specificSample  - null to load genotypes for all samples contained in the file or the name
     *                        of an individual sample to load (and exclude all others).
     * @return a Map of Sample name to Fingerprint
     */
    public Map<String, Fingerprint> loadFingerprintsFromNonIndexedVcf(final Path fingerprintFile, final String specificSample) {
        final VCFFileReader reader = new VCFFileReader(fingerprintFile, false);
        checkDictionaryGoodForFingerprinting(reader.getFileHeader().getSequenceDictionary());

        return loadFingerprintsFromVariantContexts(reader, specificSample, fingerprintFile);
    }

    /**
     * Loads genotypes from the supplied file into one or more Fingerprint objects and returns them in a
     * Map of Sample->Fingerprint.
     *
     * @param iterable       - an iterable over variantContexts containing genotypes for one or more samples
     * @param specificSample - null to load genotypes for all samples contained in the file or the name
     *                       of an individual sample to load (and exclude all others).
     * @param source         The path of the source file used. used to emit errors, and annotate the fingerprints.
     * @return a Map of Sample name to Fingerprint
     */
    public Map<String, Fingerprint> loadFingerprintsFromVariantContexts(final Iterable<VariantContext> iterable, final String specificSample, final Path source) {

        final Map<String, Fingerprint> fingerprints = new HashMap<>();
        Set<String> samples = null;

        for (final VariantContext ctx : iterable) {
            // Setup the sample names set if needed
            if (ctx == null) {
                continue;
            }

            if (samples == null) {
                if (specificSample != null) {
                    samples = new HashSet<>();
                    samples.add(specificSample);
                } else {
                    samples = ctx.getSampleNames();
                    if (samples == null) {
                        log.warn("No samples found in file: " + source.toUri().toString() + ". Skipping.");
                        return Collections.emptyMap();
                    }
                }

                samples.forEach(s -> fingerprints.put(s, new Fingerprint(s, source, null)));
            }
            try {
                getFingerprintFromVc(fingerprints, ctx);
            } catch (final IllegalArgumentException e) {
                log.warn(e, "There was a genotyping error in File: " + source.toUri().toString() + "\n" + e.getMessage());
            }
        }

        return fingerprints;
    }

    /**
     * Loads genotypes from the supplied file into one or more Fingerprint objects and returns them in a
     * Map of Sample->Fingerprint.
     *
     * @param fingerprintFile - VCF file containing genotypes for one or more samples
     * @param specificSample  - null to load genotypes for all samples contained in the file or the name
     *                        of an individual sample to load (and exclude all others).
     * @return a Map of Sample name to Fingerprint
     */
    public Map<String, Fingerprint> loadFingerprintsFromIndexedVcf(final Path fingerprintFile, final String specificSample) {
        final VCFFileReader reader = new VCFFileReader(fingerprintFile, true);
        return loadFingerprintsFromQueriableReader(reader, specificSample, fingerprintFile);
    }

    /**
     * Loads genotypes from the supplied reader into one or more Fingerprint objects and returns them in a
     * Map of Sample->Fingerprint.
     *
     * @param reader         - VCF reader containing genotypes for one or more samples
     * @param specificSample - null to load genotypes for all samples contained in the file or the name
     *                       of an individual sample to load (and exclude all others).
     * @param source         The path of the source file used. used to emit errors.
     * @return a Map of Sample name to Fingerprint
     */
    public Map<String, Fingerprint> loadFingerprintsFromQueriableReader(final VCFFileReader reader, final String specificSample, final Path source) {

        checkDictionaryGoodForFingerprinting(reader.getFileHeader().getSequenceDictionary());

        final SortedSet<Snp> snps = new TreeSet<>(haplotypes.getAllSnps());

        return loadFingerprintsFromVariantContexts(() ->
                        snps.stream().map(snp -> {
                            try {
                                return reader.query(snp.getChrom(), snp.getPos(), snp.getPos()).next();
                            } catch (NoSuchElementException e) {
                                return null;
                            }
                        }).iterator(),
                specificSample, source);
    }

    /**
     * Adds the fingerprints found in the variant Context to the map.
     *
     * @param fingerprints a map from Sample to fingerprint
     * @param ctx          the VC from which to extract (part of ) a fingerprint
     */
    private void getFingerprintFromVc(final Map<String, Fingerprint> fingerprints, final VariantContext ctx) throws IllegalArgumentException {
        final HaplotypeBlock h = this.haplotypes.getHaplotype(ctx.getContig(), ctx.getStart());
        if (h == null) {
            return;
        }

        final Snp snp = this.haplotypes.getSnp(ctx.getContig(), ctx.getStart());

        final VariantContext usableSnp = AlleleSubsettingUtils.subsetVCToMatchSnp(ctx, snp);
        if (usableSnp == null) {
            return;
        }

        // Check the alleles from the file against the expected set of genotypes
        {
            boolean allelesOk = true;
            for (final Allele allele : usableSnp.getAlleles()) {
                final byte[] bases = allele.getBases();
                if (bases.length > 1 || (bases[0] != snp.getAllele1() && bases[0] != snp.getAllele2())) {
                    allelesOk = false;
                }
            }
            if (!allelesOk) {

                log.warn("Problem with genotype file: Alleles "
                        + usableSnp.getAlleles() + " do not match to alleles for SNP " + snp
                        + " with alleles " + snp.getAlleleString());
                throw new IllegalArgumentException("Alleles do not match between database and file");
            }
        }

        for (final String sample : fingerprints.keySet()) {
            final Fingerprint fp = fingerprints.get(sample);

            //PLs are preferred over GTs
            //TODO: this code is replicated in various places (ReconstructTriosFromVCF for example). Needs refactoring.
            //TODO: add a way to force using GTs when both are available (why?)

            // Get the genotype for the sample and check that it is useful
            final Genotype genotype = usableSnp.getGenotype(sample);
            if (genotype == null) {
                throw new IllegalArgumentException("Cannot find sample " + sample + " in provided file. ");
            }
            if (genotype.hasPL()) {

                final HaplotypeProbabilitiesFromGenotypeLikelihoods hFp = new HaplotypeProbabilitiesFromGenotypeLikelihoods(h);
                hFp.addToLogLikelihoods(snp, usableSnp.getAlleles(), GenotypeLikelihoods.fromPLs(genotype.getPL()).getAsVector());
                fp.add(hFp);
            } else {

                if (genotype.isNoCall()) {
                    continue;
                }

                // TODO: when multiple genotypes are available for a Haplotype check that they
                // TODO: agree. Not urgent since DownloadGenotypes already does this.
                // TODO: more urgent now as we convert vcfs to haplotypeProbabilities and
                // TODO: there could be different VCs with information we'd like to use...
                if (fp.containsKey(h)) {
                    continue;
                }

                final boolean hom = genotype.isHom();
                final byte allele = StringUtil.toUpperCase(genotype.getAllele(0).getBases()[0]);

                final double halfError = this.genotypingErrorRate / 2;
                final double accuracy = 1 - this.genotypingErrorRate;
                final double[] probs = new double[]{
                        (hom && allele == snp.getAllele1()) ? accuracy : halfError,
                        (!hom) ? accuracy : halfError,
                        (hom && allele == snp.getAllele2()) ? accuracy : halfError
                };
                fp.add(new HaplotypeProbabilitiesFromGenotype(snp, h, probs[0], probs[1], probs[2]));
            }
        }
    }

    /**
     * Takes a set of fingerprints and returns an IntervalList containing all the loci that
     * can be productively examined in sequencing data to compare to one or more of the
     * fingerprints.
     */
    public IntervalList getLociToGenotype(final Collection<Fingerprint> fingerprints) {
        final IntervalList intervals = new IntervalList(this.haplotypes.getHeader());

        for (final Fingerprint fp : fingerprints) {
            for (final HaplotypeProbabilities genotype : fp.values()) {
                final HaplotypeBlock h = genotype.getHaplotype();
                for (final Snp snp : h.getSnps()) {
                    intervals.add(new Interval(snp.getChrom(), snp.getPos(), snp.getPos(), false, snp.getName()));
                }
            }
        }

        return intervals.uniqued();
    }

    // For backwards compatibility with previous interface
    @Deprecated
    public Map<FingerprintIdDetails, Fingerprint> fingerprintVcf(final Path vcfFile) {
        return fingerprintVcf(vcfFile, null, false);
    }

    public Map<FingerprintIdDetails, Fingerprint> fingerprintVcf(final Path vcfFile, final Path indexPath, final boolean forceIndex) {
        final Map<FingerprintIdDetails, Fingerprint> fpIdMap = new HashMap<>();

        final Map<String, Fingerprint> sampleFpMap = loadFingerprints(vcfFile, indexPath, forceIndex, null);

        sampleFpMap.forEach((key, value) -> {
            final FingerprintIdDetails fpId = new FingerprintIdDetails();
            fpId.sample = key;
            fpId.file = vcfFile.toUri().toString();

            fpIdMap.put(fpId, value);
        });
        return fpIdMap;
    }

    private static final Function<SeekableByteChannel, SeekableByteChannel> seekableChannelFunction = (chan) -> {
        try {
            return SeekableByteChannelPrefetcher.addPrefetcher(1, chan);
        } catch (IOException e) {
            throw new RuntimeException("Trouble wrapping seekable stream with prefetcher.", e);
        }
    };

    /**
     * Does same thing as {@link #fingerprintSamFile(Path, Path, boolean, Function)} but in the old way that required that you pass in the loci of interest.
     * Since the loci are always the same as in {@link #haplotypes} there's no need for this method signature anymore
     *
     * @deprecated use {@link #fingerprintSamFile(Path, Path, boolean, Function)} instead.
     */
    @Deprecated
    public Map<FingerprintIdDetails, Fingerprint> fingerprintSamFile(final Path samFile, final IntervalList loci) {
        return fingerprintSamFile(samFile, null, false, HaplotypeProbabilitiesFromSequence::new);
    }

    @VisibleForTesting
    SamReader getSamReader(final Path samFile, final Path indexPath, final boolean forceIndex) {
        final SamInputResource samResource = SamInputResource.of(samFile);
        if (indexPath != null) {
            // Use of seekableChannelFunction here avoids issue: https://github.com/broadinstitute/picard/issues/1175
            samResource.index(indexPath, seekableChannelFunction);
        } else {
            final Path indexMaybe = SamFiles.findIndex(samFile);
            if (indexMaybe != null) samResource.index(indexMaybe, seekableChannelFunction);
        }

        final SamReader reader = SamReaderFactory.makeDefault()
                .enable(SamReaderFactory.Option.CACHE_FILE_BASED_INDEXES)
                .referenceSequence(referenceFasta)
                .open(samResource);
        if (forceIndex && !reader.isQueryable()) {
            throw new PicardException("Input SAM file " + samFile + " has no index while user required index to proceed.");
        }

        return reader;
    }

    /**
     * Generates a Fingerprint per read group in the supplied SAM file using the loci provided in
     * the interval list.
     */

    // Keeping old method for backwards compatibility
    @Deprecated
    public Map<FingerprintIdDetails, Fingerprint> fingerprintSamFile(final Path samFile, final Function<HaplotypeBlock, HaplotypeProbabilities> blockToProbMapper) {
        return fingerprintSamFile(samFile, null, false, blockToProbMapper);
    }

    public Map<FingerprintIdDetails, Fingerprint> fingerprintSamFile(final Path samFile, final Path indexPath, final boolean forceIndex,
                                                                     final Function<HaplotypeBlock, HaplotypeProbabilities> blockToProbMapper) {
        final SamReader in = getSamReader(samFile, indexPath, forceIndex);
        checkDictionaryGoodForFingerprinting(in.getFileHeader().getSequenceDictionary());

        if (!in.hasIndex()) {
            log.warn(String.format("Operating without an index! We could be here for a while. (%s)", samFile.toUri().toString()));
        } else {
            log.info(String.format("Reading an indexed file (%s)", samFile.toUri().toString()));
        }

        // fingerprinting allows that headers differ, but SamLocusIterator doesn't allow the dictionary of the query
        // interval list to differ from that of the samfile, leading to an exception thrown.
        // At this point we already know that the dictionary of the haplotypes is a proper prefix of that of the sam file
        // So we just swap out the header in the interval list.
        final IntervalList il = this.haplotypes.getIntervalList();
        final IntervalList newIl = new IntervalList(in.getFileHeader());
        newIl.addall(il.getIntervals());

        final SamLocusIterator iterator = new SamLocusIterator(in, newIl, in.hasIndex());
        iterator.setEmitUncoveredLoci(true);
        iterator.setMappingQualityScoreCutoff(this.minimumMappingQuality);
        iterator.setQualityScoreCutoff(this.minimumBaseQuality);

        // In some cases it is useful to allow duplicate reads to be used - the most common is in single-end
        // sequence data where the duplicate marking may have been overly aggressive, and there is useful
        // non-redundant data in the reads marked as "duplicates'.
        if (this.allowDuplicateReads) {
            final List<SamRecordFilter> filters = new ArrayList<>(1);
            filters.add(new SecondaryAlignmentFilter());
            iterator.setSamFilters(filters);
        }

        final Map<SAMReadGroupRecord, FingerprintIdDetails> fingerprintIdDetailsMap = new HashMap<>();
        final Map<FingerprintIdDetails, Fingerprint> fingerprintsByReadGroup = new HashMap<>();

        for (final SAMReadGroupRecord rg : in.getFileHeader().getReadGroups()) {
            final FingerprintIdDetails id = new FingerprintIdDetails(rg.getPlatformUnit(), samFile.toUri().toString());
            id.library = rg.getLibrary();
            id.sample = rg.getSample();
            fingerprintIdDetailsMap.put(rg, id);

            final Fingerprint fingerprint = new Fingerprint(id.sample,
                    samFile,
                    id.platformUnit);
            fingerprintsByReadGroup.put(id, fingerprint);

            for (final HaplotypeBlock h : this.haplotypes.getHaplotypes()) {
                fingerprint.add(blockToProbMapper.apply(h));
            }
        }

        // Set of read/template names from which we have already sampled a base and a qual. Since we assume
        // that all evidence for a haplotype is independent we can't sample two or more bases from a single
        // read or read-pair because they would not be independent!
        final Set<String> usedReadNames = new HashSet<>(10000);

        // Now go through the data at each locus and figure stuff out!
        boolean foundALocus = false;
        for (final SamLocusIterator.LocusInfo info : iterator) {
            log.debug(() -> "At locus " + info);

            // TODO: Filter out the locus if the allele balance doesn't make sense for either a
            // TODO: 50/50 het or a hom with some errors; in HS data with deep coverage any base
            // TODO: with major strand bias could cause errors

            // Find the matching Snp and HaplotypeProbs
            final HaplotypeBlock haplotypeBlock = this.haplotypes.getHaplotype(info.getSequenceName(), info.getPosition());
            final Snp snp = this.haplotypes.getSnp(info.getSequenceName(), info.getPosition());

            // randomly select locusMaxReads elements from the list
            final List<SamLocusIterator.RecordAndOffset> recordAndOffsetList = locusMaxReads == 0 ?
                    info.getRecordAndOffsets() :
                    MathUtil.randomSublist(info.getRecordAndOffsets(), locusMaxReads, random);

            for (final SamLocusIterator.RecordAndOffset rec : recordAndOffsetList) {
                final SAMReadGroupRecord rg = rec.getRecord().getReadGroup();
                final FingerprintIdDetails details;

                // if there's a missing rg tag, add the unknown FP id to the map
                if (rg == null && !fingerprintIdDetailsMap.containsKey(null)) {

                    final FingerprintIdDetails unknownFPDetails = createUnknownFP(samFile, rec.getRecord());

                    fingerprintIdDetailsMap.put(null, unknownFPDetails);

                    final Fingerprint fp = new Fingerprint(unknownFPDetails.sample, samFile, unknownFPDetails.platformUnit);
                    fingerprintsByReadGroup.put(unknownFPDetails, fp);

                    for (final HaplotypeBlock h : this.haplotypes.getHaplotypes()) {
                        fp.add(blockToProbMapper.apply(h));
                    }
                }

                if (fingerprintIdDetailsMap.containsKey(rg)) {
                    foundALocus = true;
                    details = fingerprintIdDetailsMap.get(rg);

                    final String readName = rec.getRecord().getReadName();
                    if (!usedReadNames.contains(readName)) {
                        final HaplotypeProbabilitiesFromSequence probs = (HaplotypeProbabilitiesFromSequence) fingerprintsByReadGroup.get(details).get(haplotypeBlock);
                        final byte base = StringUtil.toUpperCase(rec.getReadBase());
                        final byte qual = rec.getBaseQuality();

                        probs.addToProbs(snp, base, qual);
                        usedReadNames.add(readName);
                    }
                } else {
                    throw new PicardException("Unknown read group: " + rg + " in file: " + samFile);
                }
            }
        }

        if (!foundALocus && in.getFileHeader().getSortOrder() != SAMFileHeader.SortOrder.coordinate) {
            throw new PicardException(String.format("Couldn't even find one locus with reads to fingerprint in file %s, which in addition isn't coordinate-sorted. Please sort the file and try again.", samFile));
        }

        return fingerprintsByReadGroup;
    }

    private FingerprintIdDetails createUnknownFP(final Path samFile, final SAMRecord rec) {
        final PicardException e = new PicardException("Found read with no readgroup: " + rec.getReadName() + " in file: " + samFile);
        if (validationStringency != ValidationStringency.STRICT) {
            final SAMReadGroupRecord readGroupRecord = new SAMReadGroupRecord("<UNKNOWN>:::" + samFile.toUri().toString());
            readGroupRecord.setLibrary("<UNKNOWN>");
            readGroupRecord.setSample(defaultSampleID);
            readGroupRecord.setPlatformUnit("<UNKNOWN>.0.ZZZ");

            if (validationStringency != ValidationStringency.SILENT && missingRGFiles.add(samFile)) {
                log.warn(e.getMessage());
                log.warn("further messages from this file will be suppressed");
            }

            return new FingerprintIdDetails(readGroupRecord, samFile.toUri().toString());
        } else {
            log.error(e.getMessage());
            throw e;
        }
    }

    /**
     * Generates a per-sample Fingerprint for the contaminant in the supplied SAM file.
     * Data is aggregated by sample, not read-group.
     */
    public Map<String, Fingerprint> identifyContaminant(final Path samFile, final double contamination) {

        final Map<FingerprintIdDetails, Fingerprint> fpIdDetailsMap = this.fingerprintSamFile(samFile, h -> new HaplotypeProbabilitiesFromContaminatorSequence(h, contamination));

        final Map<FingerprintIdDetails, Fingerprint> fpIdDetailsBySample = Fingerprint.mergeFingerprintsBy(fpIdDetailsMap,
                Fingerprint.getFingerprintIdDetailsStringFunction(CrosscheckMetric.DataType.SAMPLE));

        return fpIdDetailsBySample.entrySet().stream()
                .collect(Collectors.toMap(e -> e.getKey().sample, Map.Entry::getValue));
    }

    /**
     * Fingerprints one or more SAM/BAM/VCF files at all available loci within the haplotype map, using multiple threads
     * to speed up the processing.
     */

    // If no indexPathMap provided, set to null & forceIndex to false; for backwards compatibility with other methods using this
    @Deprecated
    public Map<FingerprintIdDetails, Fingerprint> fingerprintFiles(final Collection<Path> files, final int threads, final int waitTime, final TimeUnit waitTimeUnit) {
        return fingerprintFiles(files, null, false, threads, waitTime, waitTimeUnit);
    }

    public Map<FingerprintIdDetails, Fingerprint> fingerprintFiles(final Collection<Path> files, final Map<Path, Path> indexPathMap, final Boolean forceIndex,
                                                                   final int threads, final int waitTime, final TimeUnit waitTimeUnit) {
        // Generate fingerprints from each file
        final AtomicInteger filesRead = new AtomicInteger(0);

        final ExecutorService executor = new ThreadPoolExecutorWithExceptions(threads);
        final ExecutorCompletionService<Path> executorCompletionService = new ExecutorCompletionService<>(executor);
        final Map<FingerprintIdDetails, Fingerprint> retval = new ConcurrentHashMap<>(files.size());

        for (final Path p : files) {
            executorCompletionService.submit(() -> {

                final Map<FingerprintIdDetails, Fingerprint> oneFileFingerprints;
                log.debug("Processed file: " + p.toUri().toString() + " (" + filesRead.get() + ")");

                // Determine whether valid index path given for this file
                final Path indexPath = (indexPathMap != null) ? indexPathMap.get(p) : null;
                if (indexPathMap != null && indexPath == null) {
                    log.warn("Index map file provided, but no explicit index provided for " + p);
                } else if (indexPath != null) {
                    log.info("Using explicit index provided for " + p);
                }

                // Perform fingerprinting on SAM or VCF file
                if (CheckFingerprint.fileContainsReads(p)) {
                    oneFileFingerprints = fingerprintSamFile(p, indexPath, forceIndex, HaplotypeProbabilitiesFromSequence::new);
                } else {
                    oneFileFingerprints = fingerprintVcf(p, indexPath, forceIndex);
                }

                if (oneFileFingerprints.isEmpty()) {
                    log.warn("No fingerprint data was found in file:" + p);
                }
                retval.putAll(oneFileFingerprints);

                if (filesRead.incrementAndGet() % 100 == 0) {
                    log.info("Processed " + filesRead.get() + " out of " + files.size());
                }
            }, p);
        }

        executor.shutdown();
        try {
            executor.awaitTermination(waitTime, waitTimeUnit);
        } catch (final InterruptedException ie) {
            throw new PicardException("Interrupted while waiting for executor to terminate.", ie);
        }

        for (int i = 0; i < files.size(); i++) {
            try {
                executorCompletionService.take().get();
            } catch (InterruptedException | ExecutionException e) {
                throw new PicardException("Failed to fingerprint", e);
            }
        }

        log.info("Processed files. " + retval.size() + " fingerprints found in map.");

        return retval;
    }

    /**
     * Top level method to take a set of one or more SAM files and one or more Genotype files and compare
     * each read group in each SAM file to each set of fingerprint genotypes.
     *
     * @param samFiles         the list of SAM files to fingerprint
     * @param genotypeFiles    the list of genotype files from which to pull fingerprint genotypes
     * @param specificSample   an optional single sample who's genotypes to load from the supplied files
     * @param ignoreReadGroups aggregate data into one fingerprint per file, instead of splitting by RG
     */
    public List<FingerprintResults> checkFingerprints(final List<Path> samFiles,
                                                      final List<Path> genotypeFiles,
                                                      final String specificSample,
                                                      final boolean ignoreReadGroups) {
        // Load the fingerprint genotypes
        final List<Fingerprint> expectedFingerprints = new LinkedList<>();
        for (final Path p : genotypeFiles) {
            expectedFingerprints.addAll(loadFingerprints(p, null, false, specificSample).values());
        }

        if (expectedFingerprints.isEmpty()) {
            throw new IllegalStateException("Could not find any fingerprints in: " + genotypeFiles);
        }

        final List<FingerprintResults> resultsList = new ArrayList<>();

        // Fingerprint the SAM files and calculate the results
        for (final Path p : samFiles) {
            final Map<FingerprintIdDetails, Fingerprint> fingerprintsByReadGroup = fingerprintSamFile(p, null, false, HaplotypeProbabilitiesFromSequence::new);

            if (ignoreReadGroups) {
                final Fingerprint combinedFp = new Fingerprint(specificSample, p, null);
                fingerprintsByReadGroup.values().forEach(combinedFp::merge);

                final FingerprintResults results = new FingerprintResults(p, null, specificSample);
                for (final Fingerprint expectedFp : expectedFingerprints) {
                    final MatchResults result = calculateMatchResults(combinedFp, expectedFp, pLossofHet);
                    results.addResults(result);
                }

                resultsList.add(results);

            } else {
                for (final FingerprintIdDetails rg : fingerprintsByReadGroup.keySet()) {
                    final FingerprintResults results = new FingerprintResults(p, rg.platformUnit, rg.sample);
                    for (final Fingerprint expectedFp : expectedFingerprints) {
                        final MatchResults result = calculateMatchResults(fingerprintsByReadGroup.get(rg), expectedFp, pLossofHet);
                        results.addResults(result);
                    }

                    resultsList.add(results);
                }
            }
        }

        return resultsList;
    }

    /**
     * Top level method to take a set of one or more observed genotype (VCF) files and one or more expected genotype (VCF) files and compare
     * one or more sample in the observed genotype file with one or more in the expected file and generate results for each set.
     *
     * @param observedGenotypeFiles The list of genotype files containing observed calls, from which to pull fingerprint genotypes
     * @param expectedGenotypeFiles The list of genotype files containing expected calls, from which to pull fingerprint genotypes
     * @param observedSample        an optional single sample whose genotypes to load from the observed genotype file (if null, use all)
     * @param expectedSample        an optional single sample whose genotypes to load from the expected genotype file (if null, use all)
     */
    public List<FingerprintResults> checkFingerprintsFromPaths(final List<Path> observedGenotypeFiles,
                                                               final List<Path> expectedGenotypeFiles,
                                                               final String observedSample,
                                                               final String expectedSample) {

        // Load the expected fingerprint genotypes
        final List<Fingerprint> expectedFingerprints = new ArrayList<>();
        for (final Path p : expectedGenotypeFiles) {
            expectedFingerprints.addAll(loadFingerprints(p, null, false, expectedSample).values());
        }

        if (expectedFingerprints.isEmpty()) {
            throw new IllegalStateException("Could not find any fingerprints in: " + expectedGenotypeFiles);
        }

        final List<FingerprintResults> resultsList = new ArrayList<>();

        for (final Path p : observedGenotypeFiles) {
            final Map<String, Fingerprint> observedFingerprintsBySample = loadFingerprints(p, null, false, observedSample);
            if (observedFingerprintsBySample.isEmpty()) {
                throw new IllegalStateException("Found no fingerprints in observed genotypes file: " + observedGenotypeFiles);
            }

            for (final String sample : observedFingerprintsBySample.keySet()) {
                final FingerprintResults results = new FingerprintResults(p, null, sample);
                for (final Fingerprint expectedFp : expectedFingerprints) {
                    final MatchResults result = calculateMatchResults(observedFingerprintsBySample.get(sample), expectedFp, pLossofHet);
                    results.addResults(result);
                }
                resultsList.add(results);
            }
        }
        return resultsList;
    }

    public static MatchResults calculateMatchResults(final Fingerprint observedFp, final Fingerprint expectedFp, final double pLoH) {
        return calculateMatchResults(observedFp, expectedFp, pLoH, true, true);

    }

    /**
     * Compares two fingerprints and calculates a MatchResults object which contains detailed
     * information about the match (or mismatch) between fingerprints including the LOD score
     * for whether or not the two are likely from the same sample.
     * <p>
     * If comparing sequencing data to genotype data then the sequencing data should be passed
     * as the observedFp and the genotype data as the expectedFp in order to get the best output.
     * <p>
     * In the cases where the most likely genotypes from the two fingerprints do not match the
     * lExpectedSample is Max(actualpExpectedSample, minPExpected).
     */
    public static MatchResults calculateMatchResults(final Fingerprint observedFp, final Fingerprint expectedFp, final double pLoH, final boolean calculateLocusInfo, final boolean calculateTumorAwareLod) {
        final List<LocusResult> locusResults = calculateLocusInfo ? new ArrayList<>() : null;

        double llNoSwapModel = 0;
        double llSwapModel = 0;

        double lodExpectedSampleTumorNormal = 0;
        double lodExpectedSampleNormalTumor = 0;

        for (final HaplotypeProbabilities probs2 : expectedFp.values()) {
            final HaplotypeBlock haplotypeBlock = probs2.getHaplotype();
            final HaplotypeProbabilities probs1 = observedFp.get(haplotypeBlock);
            if (probs1 == null) {
                continue;
            }

            final HaplotypeProbabilityOfNormalGivenTumor prob1AssumingDataFromTumor;
            final HaplotypeProbabilityOfNormalGivenTumor prob2AssumingDataFromTumor;
            if (calculateTumorAwareLod) {
                prob1AssumingDataFromTumor = new HaplotypeProbabilityOfNormalGivenTumor(probs1, pLoH);
                prob2AssumingDataFromTumor = new HaplotypeProbabilityOfNormalGivenTumor(probs2, pLoH);
            } else {
                prob1AssumingDataFromTumor = null;
                prob2AssumingDataFromTumor = null;
            }

            // If one is from genotype data we'd like to report the output relative
            // to the genotyped SNP instead of against a random SNP from the haplotype
            final Snp snp = probs2.getRepresentativeSnp();
            if (calculateLocusInfo) {
                final DiploidGenotype externalGenotype = probs2.getMostLikelyGenotype(snp);
                final LocusResult lr = new LocusResult(snp,
                        externalGenotype,
                        probs1.getMostLikelyGenotype(snp),
                        probs1.getObsAllele1(),
                        probs1.getObsAllele2(),
                        probs1.getLodMostProbableGenotype(),
                        // expected sample log-likelihood
                        probs1.shiftedLogEvidenceProbabilityGivenOtherEvidence(probs2),
                        // random sample log-likelihood
                        probs1.shiftedLogEvidenceProbability(),

                        // probs1 is tumor probs2 is normal, correct sample lod
                        calculateTumorAwareLod ? prob1AssumingDataFromTumor.shiftedLogEvidenceProbabilityGivenOtherEvidence(probs2) -
                                prob1AssumingDataFromTumor.shiftedLogEvidenceProbability() : 0,
                        // probs1 is normal probs2 is tumor, correct sample lod
                        calculateTumorAwareLod ? probs1.shiftedLogEvidenceProbabilityGivenOtherEvidence(prob2AssumingDataFromTumor) -
                                probs1.shiftedLogEvidenceProbability() : 0);

                locusResults.add(lr);
            }
            if (probs1.hasEvidence() && probs2.hasEvidence()) {
                llNoSwapModel += probs1.shiftedLogEvidenceProbabilityGivenOtherEvidence(probs2);
                llSwapModel += probs1.shiftedLogEvidenceProbability() + probs2.shiftedLogEvidenceProbability();

                if (calculateTumorAwareLod) {
                    lodExpectedSampleTumorNormal += prob1AssumingDataFromTumor.shiftedLogEvidenceProbabilityGivenOtherEvidence(probs2) -
                            prob1AssumingDataFromTumor.shiftedLogEvidenceProbability() - probs2.shiftedLogEvidenceProbability();
                    lodExpectedSampleNormalTumor += prob2AssumingDataFromTumor.shiftedLogEvidenceProbabilityGivenOtherEvidence(probs1) -
                            prob2AssumingDataFromTumor.shiftedLogEvidenceProbability() - probs1.shiftedLogEvidenceProbability();

                }
            }
        }

        // TODO: prune the set of LocusResults for things that are too close together?
        return new MatchResults(expectedFp.getSource(), expectedFp.getSample(), llNoSwapModel, llSwapModel, lodExpectedSampleTumorNormal, lodExpectedSampleNormalTumor, locusResults);
    }

    /**
     * Compares two fingerprints and calculates a MatchResults object which contains detailed
     * information about the match (or mismatch) between fingerprints including the LOD score
     * for whether or not the two are likely from the same sample.
     * <p>
     * If comparing sequencing data to genotype data then the sequencing data should be passed
     * as the observedFp and the genotype data as the expectedFp in order to get the best output.
     */
    public static MatchResults calculateMatchResults(final Fingerprint observedFp, final Fingerprint expectedFp) {
        return calculateMatchResults(observedFp, expectedFp, 0);
    }

    public void setReferenceFasta(final File referenceFasta) {
        this.referenceFasta = referenceFasta;
    }

    public int getLocusMaxReads() {
        return locusMaxReads;
    }

    public void setLocusMaxReads(final int locusMaxReads) {
        this.locusMaxReads = locusMaxReads;
    }

    public String getDefaultSampleID() {
        return defaultSampleID;
    }

    public void setDefaultSampleID(final String defaultSampleID) {
        this.defaultSampleID = defaultSampleID;
    }
}
