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package org.broadinstitute.gatk.tools.walkers.validation.validationsiteselector;

import org.broadinstitute.gatk.utils.commandline.*;
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.refdata.RefMetaDataTracker;
import org.broadinstitute.gatk.engine.walkers.RodWalker;
import org.broadinstitute.gatk.utils.GenomeLocParser;
import org.broadinstitute.gatk.engine.SampleUtils;
import org.broadinstitute.gatk.utils.help.HelpConstants;
import org.broadinstitute.gatk.utils.variant.GATKVariantContextUtils;
import htsjdk.variant.vcf.VCFHeader;
import htsjdk.variant.vcf.VCFHeaderLine;
import org.broadinstitute.gatk.engine.GATKVCFUtils;
import org.broadinstitute.gatk.utils.help.DocumentedGATKFeature;
import htsjdk.variant.variantcontext.VariantContext;
import htsjdk.variant.variantcontext.writer.VariantContextWriter;

import java.io.File;
import java.util.*;


/**
 * Randomly select variant records according to specified options
 *
 * <p>
 * This tool is intended for use in experiments where we sample data randomly from a set of variants, for example
 * in order to choose sites for a follow-up validation study.</p>
 *
 * <p>Sites are selected randomly but within certain restrictions. There are two main sources of restrictions:</p>
 * <ul>
 *     <li><b>Sample restrictions:</b> A user can specify a set of samples, and we will only consider sites which are
 *     polymorphic within the given sample subset. These sample restrictions can be given as a set of individual
 *     samples, a text file (each line containing a sample name), or a regular expression. A user can additionally
 *     specify whether samples will be considered based on their genotypes (a non-reference genotype means that the
 *     sample is polymorphic in that variant, and hence that variant will be considered for inclusion in set), or
 *     based on their PLs.</li>
 *     <li><b>Sampling methods:</b>
 *          <ol>
 *              <li>Uniform sampling will just sample uniformly from variants that are polymorphic in selected samples</li>
 *              <li>Sampling based on Allele Frequency spectrum will ensure that output sites have the same AF distribution as the input set</li>
 *          </ol>
 *     </li>
 *     <li>Variant type (SNP, Indel, etc.)</li>
 * </ul>
 *
 * <h3>Input</h3>
 * <p>
 * One or more variant sets to choose from.
 * </p>
 *
 * <h3>Output</h3>
 * <p>
 * A sites-only VCF with the desired number of randomly selected sites.
 * </p>
 *
 * <h3>Usage examples</h3>
 * <pre>
 * java -jar GenomeAnalysisTK.jar \
 *   -T ValidationSiteSelectorWalker \
 *   -R reference.fasta \
 *   -V input1.vcf \
 *   -V input2.vcf \
 *   -sn NA12878 \
 *   -o output.vcf \
 *   --numValidationSites 200   \
 *   -sampleMode POLY_BASED_ON_GT \
 *   -freqMode KEEP_AF_SPECTRUM
 * </pre>
 * <pre>
 * java -jar GenomeAnalysisTK.jar \
 *   -T ValidationSiteSelectorWalker \
 *   -R reference.fasta \
 *   -V:foo input1.vcf \
 *   -V:bar input2.vcf \
 *   --numValidationSites 200 \
 *   -sf samples.txt \
 *   -o output.vcf \
 *   -sampleMode  POLY_BASED_ON_GT \
  *   -freqMode UNIFORM \
 *   -selectType INDEL
 * </pre>
 *
 */
@DocumentedGATKFeature( groupName = HelpConstants.DOCS_CAT_VALIDATION, extraDocs = {CommandLineGATK.class} )
public class ValidationSiteSelector extends RodWalker<Integer, Integer> {

    public enum AF_COMPUTATION_MODE {
        KEEP_AF_SPECTRUM,
        UNIFORM
    }

    public enum SAMPLE_SELECTION_MODE {
        NONE,
        POLY_BASED_ON_GT,
        POLY_BASED_ON_GL
    }

    /**
     * The input VCF file
     */
    @Input(fullName="variant", shortName = "V", doc="Input VCF file, can be specified multiple times", required=true)
    public List<RodBinding<VariantContext>> variants;

    /**
     * The output VCF file
     */
    @Output(doc="File to which variants should be written")
    protected VariantContextWriter vcfWriter = null;

    /**
     * Sample name(s) to subset the input VCF to, prior to selecting variants. -sn A -sn B subsets to samples A and B.
     */
    @Argument(fullName="sample_name", shortName="sn", doc="Include genotypes from this sample. Can be specified multiple times", required=false)
    public Set<String> sampleNames = new HashSet<String>(0);

    /**
     * Sample regexps to subset the input VCF to, prior to selecting variants. -sn NA12* subsets to all samples with prefix NA12
     */
    @Argument(fullName="sample_expressions", shortName="se", doc="Regular expression to select many samples from the ROD tracks provided. Can be specified multiple times", required=false)
    public Set<String> sampleExpressions ;

    /**
     * File containing a list of sample names to subset the input vcf to. Equivalent to specifying the contents of the file separately with -sn
     */
    @Input(fullName="sample_file", shortName="sf", doc="File containing a list of samples (one per line) to include. Can be specified multiple times", required=false)
    public Set<File> sampleFiles;

    /**
     * A mode for selecting sites based on sample-level data. See the wiki documentation for more information.
     */
    @Argument(fullName="sampleMode", shortName="sampleMode", doc="Sample selection mode", required=false)
    private SAMPLE_SELECTION_MODE sampleMode = SAMPLE_SELECTION_MODE.NONE;

    /**
     * An P[nonref] threshold for SAMPLE_SELECTION_MODE=POLY_BASED_ON_GL. See the wiki documentation for more information.
     */
    @Argument(shortName="samplePNonref",fullName="samplePNonref", doc="GL-based selection mode only: the probability" +
            " that a site is non-reference in the samples for which to include the site",required=false)
    private double samplePNonref = 0.99;

    /**
     * The number of sites in your validation set
     */
    @Argument(fullName="numValidationSites", shortName="numSites", doc="Number of output validation sites", required=true)
    private int numValidationSites;

    /**
     * Do not exclude filtered sites (e.g. not PASS or .) from consideration for validation
     */
    @Argument(fullName="includeFilteredSites", shortName="ifs", doc="If true, will include filtered sites in set to choose variants from", required=false)
    private boolean INCLUDE_FILTERED_SITES = false;

    /**
     * Argument for the frequency selection mode. (AC/AF/AN) are taken from VCF info field, not recalculated. Typically specified for sites-only VCFs that still have AC/AF/AN information.
     */
    @Argument(fullName="ignoreGenotypes", shortName="ignoreGenotypes", doc="If true, will ignore genotypes in VCF, will take AC,AF from annotations and will make no sample selection", required=false)
    private boolean IGNORE_GENOTYPES = false;

    /**
     * Argument for the frequency selection mode. Allows reference (non-polymorphic) sites to be included in the validation set.
     */
    @Argument(fullName="ignorePolymorphicStatus", shortName="ignorePolymorphicStatus", doc="If true, will ignore polymorphic status in VCF, and will take VCF record directly without pre-selection", required=false)
    private boolean IGNORE_POLYMORPHIC = false;

    @Hidden
    @Argument(fullName="numFrequencyBins", shortName="numBins", doc="Number of frequency bins if we're to match AF distribution", required=false)
    private int numFrequencyBins = 20;

    /**
      * This argument selects allele frequency selection mode. See the wiki for more information.
      */
    @Argument(fullName="frequencySelectionMode", shortName="freqMode", doc="Allele Frequency selection mode", required=false)
    private AF_COMPUTATION_MODE freqMode = AF_COMPUTATION_MODE.KEEP_AF_SPECTRUM;

    /**
      * This argument selects particular kinds of variants (i.e. SNP, INDEL) out of a list. If left unspecified, all types are considered.
      */
     @Argument(fullName="selectTypeToInclude", shortName="selectType", doc="Select only a certain type of variants from the input file. Valid types are INDEL, SNP, MIXED, MNP, SYMBOLIC, NO_VARIATION. Can be specified multiple times", required=false)
     private List<VariantContext.Type> TYPES_TO_INCLUDE = new ArrayList<VariantContext.Type>();


    private TreeSet<String> samples = new TreeSet<String>();
    SampleSelector sampleSelector = null;
    FrequencyModeSelector frequencyModeSelector = null;
    private ArrayList<VariantContext.Type> selectedTypes = new ArrayList<VariantContext.Type>();

    public void initialize() {
         // Get list of samples to include in the output
         Map<String, VCFHeader> vcfRods = GATKVCFUtils.getVCFHeadersFromRods(getToolkit());
         TreeSet<String> vcfSamples = new TreeSet<String>(SampleUtils.getSampleList(vcfRods, GATKVariantContextUtils.GenotypeMergeType.REQUIRE_UNIQUE));

         Collection<String> samplesFromFile = SampleUtils.getSamplesFromFiles(sampleFiles);
         Collection<String> samplesFromExpressions = SampleUtils.matchSamplesExpressions(vcfSamples, sampleExpressions);

         // first, add any requested samples
         samples.addAll(samplesFromFile);
         samples.addAll(samplesFromExpressions);
         samples.addAll(sampleNames);

         // if none were requested, we want all of them
         if ( samples.isEmpty() ) {
             samples.addAll(vcfSamples);

         }

         sampleSelector = getSampleSelectorObject(sampleMode, samples);

        // initialize frequency mode selector
        frequencyModeSelector = getFrequencyModeSelectorObject(freqMode, getToolkit().getGenomeLocParser());

        // if user specified types to include, add these, otherwise, add all possible variant context types to list of vc types to include
        if (TYPES_TO_INCLUDE.isEmpty()) {

            for (VariantContext.Type t : VariantContext.Type.values())
                selectedTypes.add(t);

        }
        else {
            for (VariantContext.Type t : TYPES_TO_INCLUDE)
                selectedTypes.add(t);

        }

        Set<VCFHeaderLine> headerLines = new HashSet<VCFHeaderLine>();
        headerLines.add(new VCFHeaderLine("source", "ValidationSiteSelector"));
        vcfWriter.writeHeader(new VCFHeader(headerLines));

    }


    @Override
     public Integer map(RefMetaDataTracker tracker, ReferenceContext ref, AlignmentContext context) {
         if ( tracker == null )
             return 0;

        Collection<VariantContext> vcs = tracker.getValues(variants, context.getLocation());

         if ( vcs == null || vcs.size() == 0) {
             return 0;
         }


        for (VariantContext vc : vcs) {
            if (!selectedTypes.contains(vc.getType()))
                continue;

            // skip if site isn't polymorphic and if user didn't request to ignore polymorphic status
            if (!vc.isPolymorphicInSamples() && !IGNORE_POLYMORPHIC)
                continue;

            if (!INCLUDE_FILTERED_SITES && vc.filtersWereApplied() && vc.isFiltered())
                continue;


            // does this site pass the criteria for the samples we are interested in?
            boolean passesSampleSelectionCriteria;
            if (samples.isEmpty())
                passesSampleSelectionCriteria = true;
            else
                passesSampleSelectionCriteria = sampleSelector.selectSiteInSamples(vc);

            frequencyModeSelector.logCurrentSiteData(vc,passesSampleSelectionCriteria,IGNORE_GENOTYPES,IGNORE_POLYMORPHIC);
        }
        return 1;
    }

    @Override
    public Integer reduceInit() { return 0; }

    @Override
    public Integer reduce(Integer value, Integer sum) { return value + sum; }

    public void onTraversalDone(Integer result) {
        logger.info("Outputting validation sites...");
        ArrayList<VariantContext> selectedSites = frequencyModeSelector.selectValidationSites(numValidationSites);

        for (VariantContext vc : selectedSites) {
            vcfWriter.add(vc);
        }
        logger.info(result + " records processed.");

    }

    private SampleSelector getSampleSelectorObject(SAMPLE_SELECTION_MODE sampleMode, TreeSet<String> samples) {
        SampleSelector sm;
         switch ( sampleMode ) {
             case POLY_BASED_ON_GL:
                 sm = new GLBasedSampleSelector(samples, Math.log10(1.0-samplePNonref));
                 break;
             case POLY_BASED_ON_GT:
                 sm = new GTBasedSampleSelector(samples);
                 break;
             case NONE:
                 sm = new NullSampleSelector(samples);
                 break;
             default:
                 throw new IllegalArgumentException("Unsupported Sample Selection Mode: " + sampleMode);
         }

         return sm;
    }

    private FrequencyModeSelector getFrequencyModeSelectorObject (AF_COMPUTATION_MODE freqMode, GenomeLocParser parser) {
        FrequencyModeSelector fm;

        switch (freqMode) {
            case KEEP_AF_SPECTRUM:
                fm = new KeepAFSpectrumFrequencySelector(numFrequencyBins, parser);
                break;
            case UNIFORM:
                fm = new UniformSamplingFrequencySelector(parser);
                break;
            default: throw new IllegalArgumentException("Unexpected Frequency Selection Mode: "+ freqMode);

        }
        return fm;
    }
}
