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package org.broadinstitute.gatk.tools.walkers.diagnostics.diagnosetargets;

import htsjdk.samtools.util.PeekableIterator;
import org.broadinstitute.gatk.engine.walkers.*;
import org.broadinstitute.gatk.utils.commandline.ArgumentCollection;
import org.broadinstitute.gatk.utils.commandline.Output;
import org.broadinstitute.gatk.engine.CommandLineGATK;
import org.broadinstitute.gatk.utils.contexts.AlignmentContext;
import org.broadinstitute.gatk.utils.contexts.ReferenceContext;
import org.broadinstitute.gatk.utils.downsampling.DownsampleType;
import org.broadinstitute.gatk.utils.refdata.RefMetaDataTracker;
import org.broadinstitute.gatk.utils.GenomeLoc;
import org.broadinstitute.gatk.utils.classloader.PluginManager;
import org.broadinstitute.gatk.utils.exceptions.DynamicClassResolutionException;
import org.broadinstitute.gatk.utils.exceptions.UserException;
import org.broadinstitute.gatk.utils.help.DocumentedGATKFeature;
import org.broadinstitute.gatk.utils.help.HelpConstants;
import htsjdk.variant.variantcontext.*;
import htsjdk.variant.variantcontext.writer.VariantContextWriter;
import htsjdk.variant.vcf.*;
import org.broadinstitute.gatk.utils.sam.ReadUtils;
import org.broadinstitute.gatk.utils.variant.GATKVCFConstants;
import org.broadinstitute.gatk.utils.variant.GATKVCFHeaderLines;

import java.io.PrintStream;
import java.util.*;

/**
 * Analyze coverage distribution and validate read mates per interval and per sample
 *
 * <p>
 * This tool is useful for diagnosing regions with bad coverage, mapping, or read mate pairs. It analyzes each sample
 * independently and aggregates results over intervals of interest.
 * </p>
 * <h3>Input</h3>
 * <ul>
 * <li>A reference file</li>
 * <li>one or more input BAMs</li>
 * <li>One or more intervals</li>
 * </ul>
 * <h3>Output</h3>
 * <p>
 * A modified VCF detailing each interval by sample and information for each interval according to the thresholds used.
 * Interval information includes GC Content, average interval depth, callable status among others. If you use the
 * --missing option, you can get as a second output a intervals file with the loci that have missing data.
 * This file can then be used as input to QualifyMissingIntervals for full qualification and interpretation of why
 * the data is missing.
 * </p>
 * <h3>Usage example</h3>
 * <pre>
 *    java -jar GenomeAnalysisTK.jar
 *              -T DiagnoseTargets \
 *              -R reference.fasta \
 *              -I sample1.bam \
 *              -I sample2.bam \
 *              -I sample3.bam \
 *              -L intervals.interval_list \
 *              -o output.vcf
 *  </pre>
 *
 * @author Mauricio Carneiro, Roger Zurawicki
 * @since 5/8/12
 */
@DocumentedGATKFeature( groupName = HelpConstants.DOCS_CAT_QC, extraDocs = {CommandLineGATK.class} )
@By(value = DataSource.READS)
@PartitionBy(PartitionType.INTERVAL)
@Downsample(by = DownsampleType.NONE)
public class DiagnoseTargets extends LocusWalker<Long, Long> {

    @Output(doc = "File to which interval statistics should be written")
    private VariantContextWriter vcfWriter = null;

    @ArgumentCollection
    private ThresHolder thresholds = new ThresHolder();

    private Map<GenomeLoc, IntervalStratification> intervalMap = null;          // maps each interval => statistics
    private PeekableIterator<GenomeLoc> intervalListIterator;                   // an iterator to go over all the intervals provided as we traverse the genome
    private Set<String> samples = null;                                         // all the samples being processed
    private static final Allele SYMBOLIC_ALLELE = Allele.create("<DT>", false); // avoid creating the symbolic allele multiple times
    private static final Allele UNCOVERED_ALLELE = Allele.create("A", true);    // avoid creating the 'fake' ref allele for uncovered intervals multiple times
    private static final int INITIAL_HASH_SIZE = 50;                            // enough room for potential overlapping intervals plus recently finished intervals

    @Override
    public void initialize() {
        super.initialize();

        if (getToolkit().getIntervals() == null || getToolkit().getIntervals().isEmpty())
            throw new UserException("This tool only works if you provide one or more intervals (use the -L argument). If you want to run whole genome, use -T DepthOfCoverage instead.");

        intervalMap = new LinkedHashMap<>(INITIAL_HASH_SIZE);
        intervalListIterator = new PeekableIterator<>(getToolkit().getIntervals().iterator());

        // get all of the unique sample names for the VCF Header
        samples = ReadUtils.getSAMFileSamples(getToolkit().getSAMFileHeader());
        vcfWriter.writeHeader(new VCFHeader(getHeaderInfo(), samples));

        // pre load all the statistics classes because it is costly to operate on the JVM and we only want to do it once.
        loadAllPlugins(thresholds);
    }

    @Override
    public Long map(final RefMetaDataTracker tracker, final ReferenceContext ref, final AlignmentContext context) {
        GenomeLoc refLocus = ref.getLocus();

        // process and remove any intervals in the map that are don't overlap the current locus anymore
        // and add all new intervals that may overlap this reference locus
        addNewOverlappingIntervals(refLocus);
        outputFinishedIntervals(refLocus, ref.getBase());

        // at this point, all intervals in intervalMap overlap with this locus, so update all of them
        for (IntervalStratification intervalStratification : intervalMap.values())
            intervalStratification.addLocus(context, ref);

        return 1L;
    }

    @Override
    public Long reduceInit() {
        return 0L;
    }

    /**
     * Not sure what we are going to do here
     *
     * @param value result of the map.
     * @param sum   accumulator for the reduce.
     * @return a long
     */
    @Override
    public Long reduce(Long value, Long sum) {
        return sum + value;
    }

    /**
     * Process all remaining intervals
     *
     * @param result number of loci processed by the walker
     */
    @Override
    public void onTraversalDone(final Long result) {
        for (GenomeLoc interval : intervalMap.keySet())
            outputStatsToVCF(intervalMap.get(interval), UNCOVERED_ALLELE);

        GenomeLoc interval = intervalListIterator.peek();
        while (interval != null) {
            outputStatsToVCF(createIntervalStatistic(interval), UNCOVERED_ALLELE);
            intervalListIterator.next();
            interval = intervalListIterator.peek();
        }

        if (thresholds.missingTargets != null) {
            thresholds.missingTargets.close();
        }
    }

    /**
     * Outputs all intervals that are behind the current reference locus
     *
     * @param refLocus the current reference locus
     * @param refBase  the reference allele
     */
    private void outputFinishedIntervals(final GenomeLoc refLocus, final byte refBase) {
        // output any intervals that were finished
        final List<GenomeLoc> toRemove = new LinkedList<>();
        for (GenomeLoc key : intervalMap.keySet()) {
            if (key.isBefore(refLocus)) {
                final IntervalStratification intervalStats = intervalMap.get(key);
                outputStatsToVCF(intervalStats, Allele.create(refBase, true));
                if (hasMissingLoci(intervalStats)) {
                    outputMissingInterval(intervalStats);
                }
                toRemove.add(key);
            }
        }
        for (GenomeLoc key : toRemove) {
            intervalMap.remove(key);
        }
    }

    /**
     * Adds all intervals that overlap the current reference locus to the intervalMap
     *
     * @param refLocus the current reference locus
     */
    private void addNewOverlappingIntervals(final GenomeLoc refLocus) {
        GenomeLoc interval = intervalListIterator.peek();
        while (interval != null && !interval.isPast(refLocus)) {
            intervalMap.put(interval, createIntervalStatistic(interval));
            intervalListIterator.next();
            interval = intervalListIterator.peek();
        }
    }

    /**
     * Takes the interval, finds it in the stash, prints it to the VCF
     *
     * @param stats     The statistics of the interval
     * @param refAllele the reference allele
     */
    private void outputStatsToVCF(final IntervalStratification stats, final Allele refAllele) {
        GenomeLoc interval = stats.getInterval();

        final List<Allele> alleles = new ArrayList<>();
        final Map<String, Object> attributes = new HashMap<>();
        final ArrayList<Genotype> genotypes = new ArrayList<>();

        for (String sample : samples) {
            final GenotypeBuilder gb = new GenotypeBuilder(sample);

            SampleStratification sampleStat = stats.getSampleStatistics(sample);
            gb.attribute(GATKVCFConstants.AVG_INTERVAL_DP_BY_SAMPLE_KEY, sampleStat.averageCoverage(interval.size()));
            gb.attribute(GATKVCFConstants.LOW_COVERAGE_LOCI, sampleStat.getNLowCoveredLoci());
            gb.attribute(GATKVCFConstants.ZERO_COVERAGE_LOCI, sampleStat.getNUncoveredLoci());
            gb.filters(statusToStrings(stats.getSampleStatistics(sample).callableStatuses(), false));

            genotypes.add(gb.make());
        }
        alleles.add(refAllele);
        alleles.add(SYMBOLIC_ALLELE);
        VariantContextBuilder vcb = new VariantContextBuilder("DiagnoseTargets", interval.getContig(), interval.getStart(), interval.getStop(), alleles);

        vcb = vcb.log10PError(VariantContext.NO_LOG10_PERROR);
        vcb.filters(new LinkedHashSet<>(statusToStrings(stats.callableStatuses(), true)));

        attributes.put(VCFConstants.END_KEY, interval.getStop());
        attributes.put(GATKVCFConstants.AVG_INTERVAL_DP_KEY, stats.averageCoverage(interval.size()));
        attributes.put(GATKVCFConstants.INTERVAL_GC_CONTENT_KEY, stats.gcContent());

        vcb = vcb.attributes(attributes);
        vcb = vcb.genotypes(genotypes);

        vcfWriter.add(vcb.make());
    }

    private boolean hasMissingStatuses(AbstractStratification stats) {
        return !stats.callableStatuses().isEmpty();
    }

    private boolean hasMissingLoci(final IntervalStratification stats) {
        return thresholds.missingTargets != null && hasMissingStatuses(stats);
    }

    private void outputMissingInterval(final IntervalStratification stats) {
        final GenomeLoc interval = stats.getInterval();
        final boolean missing[] = new boolean[interval.size()];
        Arrays.fill(missing, true);
        for (AbstractStratification sample : stats.getElements()) {
            if (hasMissingStatuses(sample)) {
                int pos = 0;
                for (AbstractStratification locus : sample.getElements()) {
                    if (locus.callableStatuses().isEmpty()) {
                        missing[pos] = false;
                    }
                    pos++;
                }
            }
        }
        int start = -1;
        boolean insideMissing = false;
        for (int i = 0; i < missing.length; i++) {
            if (missing[i] && !insideMissing) {
                start = interval.getStart() + i;
                insideMissing = true;
            } else if (!missing[i] && insideMissing) {
                final int stop = interval.getStart() + i - 1;
                outputMissingInterval(interval.getContig(), start, stop);
                insideMissing = false;
            }
        }
        if (insideMissing) {
            outputMissingInterval(interval.getContig(), start, interval.getStop());
        }
    }

    private void outputMissingInterval(final String contig, final int start, final int stop) {
        final PrintStream out = thresholds.missingTargets;
            out.println(String.format("%s:%d-%d", contig, start, stop));
    }

    /**
     * Function that process a set of statuses into strings
     *
     * @param statuses the set of statuses to be converted
     * @return a matching set of strings
     */
    private List<String> statusToStrings(Iterable<CallableStatus> statuses, final boolean isInfoField) {
        List<String> output = new LinkedList<>();

        for (CallableStatus status : statuses)
            if ( isInfoField || status != CallableStatus.PASS )
                output.add(status.name());

        return output;
    }

    private IntervalStratification createIntervalStatistic(GenomeLoc interval) {
        return new IntervalStratification(samples, interval, thresholds);
    }

    protected static void loadAllPlugins(final ThresHolder thresholds) {
        for (Class<?> stat : new PluginManager<LocusMetric>(LocusMetric.class).getPlugins()) {
            try {
                final LocusMetric stats = (LocusMetric) stat.newInstance();
                stats.initialize(thresholds);
                thresholds.locusMetricList.add(stats);
            } catch (Exception e) {
                throw new DynamicClassResolutionException(stat, e);
            }
        }

        for (Class<?> stat : new PluginManager<SampleMetric>(SampleMetric.class).getPlugins()) {
            try {
                final SampleMetric stats = (SampleMetric) stat.newInstance();
                stats.initialize(thresholds);
                thresholds.sampleMetricList.add(stats);
            } catch (Exception e) {
                throw new DynamicClassResolutionException(stat, e);
            }
        }

        for (Class<?> stat : new PluginManager<IntervalMetric>(IntervalMetric.class).getPlugins()) {
            try {
                final IntervalMetric stats = (IntervalMetric) stat.newInstance();
                stats.initialize(thresholds);
                thresholds.intervalMetricList.add(stats);
            } catch (Exception e) {
                throw new DynamicClassResolutionException(stat, e);
            }
        }
    }

    /**
     * Gets the header lines for the VCF writer
     *
     * @return A set of VCF header lines
     */
    private static Set<VCFHeaderLine> getHeaderInfo() {
        Set<VCFHeaderLine> headerLines = new HashSet<>();

        // INFO fields for overall data
        headerLines.add(VCFStandardHeaderLines.getInfoLine(VCFConstants.END_KEY));
        headerLines.add(GATKVCFHeaderLines.getInfoLine(GATKVCFConstants.AVG_INTERVAL_DP_KEY));
        headerLines.add(GATKVCFHeaderLines.getInfoLine(GATKVCFConstants.INTERVAL_GC_CONTENT_KEY));
        headerLines.add(new VCFInfoHeaderLine("Diagnose Targets", 0, VCFHeaderLineType.Flag, "DiagnoseTargets mode"));

        // FORMAT fields for each genotype
        headerLines.add(VCFStandardHeaderLines.getFormatLine(VCFConstants.GENOTYPE_FILTER_KEY));
        headerLines.add(GATKVCFHeaderLines.getFormatLine(GATKVCFConstants.AVG_INTERVAL_DP_BY_SAMPLE_KEY));
        headerLines.add(GATKVCFHeaderLines.getFormatLine(GATKVCFConstants.LOW_COVERAGE_LOCI));
        headerLines.add(GATKVCFHeaderLines.getFormatLine(GATKVCFConstants.ZERO_COVERAGE_LOCI));

        // FILTER fields
        for (CallableStatus stat : CallableStatus.values())
            headerLines.add(new VCFFilterHeaderLine(stat.name(), stat.description));

        return headerLines;
    }

}
