gistfile1.txt

## - Reference genome must be Hg38 with ALT contigs
##
## Runtime parameters are optimized for Broad's Google Cloud Platform implementation.
## For program versions, see docker containers.
##
## LICENSING :
## This script is released under the WDL source code license (BSD-3) (see LICENSE in
## https://github.com/broadinstitute/wdl). Note however that the programs it calls may
## be subject to different licenses. Users are responsible for checking that they are
## authorized to run all programs before running this script. Please see the docker
## page at https://hub.docker.com/r/broadinstitute/genomes-in-the-cloud/ for detailed
## licensing information pertaining to the included programs.

# Local import
import "../../../../pipelines/dna_seq/UnmappedBamToAlignedBam.wdl" as ToBam
import "../../../../tasks/AggregatedBamQC.wdl" as AggregatedQC
import "../../../../tasks/GermlineVariantDiscovery.wdl" as Calling
import "../../../../tasks/Qc.wdl" as QC
import "../../../../tasks/Utilities.wdl" as Utils
import "../../../../tasks/BamToCram.wdl" as ToCram
import "../../../../tasks/VariantCalling.wdl" as ToGvcf
import "../../../../structs/dna_seq/germline/GermlineStructs.wdl"

# Git URL import
#import "https://raw.githubusercontent.com/gatk-workflows/five-dollar-genome-analysis-pipeline/1.2.0/tasks/UnmappedBamToAlignedBam.wdl" as ToBam
#import "https://raw.githubusercontent.com/gatk-workflows/five-dollar-genome-analysis-pipeline/1.2.0/tasks/AggregatedBamQC.wdl" as AggregatedQC
#import "https://raw.githubusercontent.com/gatk-workflows/five-dollar-genome-analysis-pipeline/1.2.0/tasks/GermlineVariantDiscovery.wdl" as Calling
#import "https://raw.githubusercontent.com/gatk-workflows/five-dollar-genome-analysis-pipeline/1.2.0/tasks/Qc.wdl" as QC
#import "https://raw.githubusercontent.com/gatk-workflows/five-dollar-genome-analysis-pipeline/1.2.0/tasks/Utilities.wdl" as Utils
#import "https://raw.githubusercontent.com/gatk-workflows/five-dollar-genome-analysis-pipeline/1.2.0/tasks/BamToCram.wdl" as ToCram
#import "https://raw.githubusercontent.com/gatk-workflows/five-dollar-genome-analysis-pipeline/1.2.0/tasks/VariantCalling.wdl" as ToGvcf
#import "https://raw.githubusercontent.com/gatk-workflows/five-dollar-genome-analysis-pipeline/1.2.0/structs/GermlineStructs.wdl"

# WORKFLOW DEFINITION
workflow WholeGenomeGermlineSingleSample {
  input {
    SampleAndUnmappedBams sample_and_unmapped_bams
    GermlineSingleSampleReferences references
    PapiSettings papi_settings
    File wgs_coverage_interval_list

    File? haplotype_database_file
    Boolean provide_bam_output = false
    Boolean use_gatk3_haplotype_caller = true
  }

  # Not overridable:
  Int read_length = 250
  Float lod_threshold = -20.0
  String cross_check_fingerprints_by = "READGROUP"
  String recalibrated_bam_basename = sample_and_unmapped_bams.base_file_name + ".aligned.duplicates_marked.recalibrated"

  call ToBam.UnmappedBamToAlignedBam {
    input:
      sample_and_unmapped_bams    = sample_and_unmapped_bams,
      references                  = references,
      papi_settings               = papi_settings,

      cross_check_fingerprints_by = cross_check_fingerprints_by,
      haplotype_database_file     = haplotype_database_file,
      lod_threshold               = lod_threshold,
      recalibrated_bam_basename   = recalibrated_bam_basename
  }

  call AggregatedQC.AggregatedBamQC {
    input:
      base_recalibrated_bam = UnmappedBamToAlignedBam.output_bam,
      base_recalibrated_bam_index = UnmappedBamToAlignedBam.output_bam_index,
      base_name = sample_and_unmapped_bams.base_file_name,
      sample_name = sample_and_unmapped_bams.sample_name,
      recalibrated_bam_base_name = recalibrated_bam_basename,
      haplotype_database_file = haplotype_database_file,
      references = references,
      papi_settings = papi_settings
  }

  call ToCram.BamToCram as BamToCram {
    input:
      input_bam = UnmappedBamToAlignedBam.output_bam,
      ref_fasta = references.reference_fasta.ref_fasta,
      ref_fasta_index = references.reference_fasta.ref_fasta_index,
      ref_dict = references.reference_fasta.ref_dict,
      duplication_metrics = UnmappedBamToAlignedBam.duplicate_metrics,
      chimerism_metrics = AggregatedBamQC.agg_alignment_summary_metrics,
      base_file_name = sample_and_unmapped_bams.base_file_name,
      agg_preemptible_tries = papi_settings.agg_preemptible_tries
  }

  # QC the sample WGS metrics (stringent thresholds)
  call QC.CollectWgsMetrics as CollectWgsMetrics {
    input:
      input_bam = UnmappedBamToAlignedBam.output_bam,
      input_bam_index = UnmappedBamToAlignedBam.output_bam_index,
      metrics_filename = sample_and_unmapped_bams.base_file_name + ".wgs_metrics",
      ref_fasta = references.reference_fasta.ref_fasta,
      ref_fasta_index = references.reference_fasta.ref_fasta_index,
      wgs_coverage_interval_list = wgs_coverage_interval_list,
      read_length = read_length,
      preemptible_tries = papi_settings.agg_preemptible_tries
  }

  # QC the sample raw WGS metrics (common thresholds)
  call QC.CollectRawWgsMetrics as CollectRawWgsMetrics {
    input:
      input_bam = UnmappedBamToAlignedBam.output_bam,
      input_bam_index = UnmappedBamToAlignedBam.output_bam_index,
      metrics_filename = sample_and_unmapped_bams.base_file_name + ".raw_wgs_metrics",
      ref_fasta = references.reference_fasta.ref_fasta,
      ref_fasta_index = references.reference_fasta.ref_fasta_index,
      wgs_coverage_interval_list = wgs_coverage_interval_list,
      read_length = read_length,
      preemptible_tries = papi_settings.agg_preemptible_tries
  }

  call ToGvcf.VariantCalling as BamToGvcf {
    input:
      calling_interval_list = references.calling_interval_list,
      evaluation_interval_list = references.evaluation_interval_list,
      haplotype_scatter_count = references.haplotype_scatter_count,
      break_bands_at_multiples_of = references.break_bands_at_multiples_of,
      contamination = UnmappedBamToAlignedBam.contamination,
      input_bam = UnmappedBamToAlignedBam.output_bam,
      ref_fasta = references.reference_fasta.ref_fasta,
      ref_fasta_index = references.reference_fasta.ref_fasta_index,
      ref_dict = references.reference_fasta.ref_dict,
      dbsnp_vcf = references.dbsnp_vcf,
      dbsnp_vcf_index = references.dbsnp_vcf_index,
      base_file_name = sample_and_unmapped_bams.base_file_name,
      final_vcf_base_name = sample_and_unmapped_bams.final_gvcf_base_name,
      agg_preemptible_tries = papi_settings.agg_preemptible_tries,
      use_gatk3_haplotype_caller = use_gatk3_haplotype_caller
  }

  if (provide_bam_output) {
    File provided_output_bam = UnmappedBamToAlignedBam.output_bam
    File provided_output_bam_index = UnmappedBamToAlignedBam.output_bam_index
  }

  # Outputs that will be retained when execution is complete
  output {
    Array[File] quality_yield_metrics = UnmappedBamToAlignedBam.quality_yield_metrics

    Array[File] unsorted_read_group_base_distribution_by_cycle_pdf = UnmappedBamToAlignedBam.unsorted_read_group_base_distribution_by_cycle_pdf
    Array[File] unsorted_read_group_base_distribution_by_cycle_metrics = UnmappedBamToAlignedBam.unsorted_read_group_base_distribution_by_cycle_metrics
    Array[File] unsorted_read_group_insert_size_histogram_pdf = UnmappedBamToAlignedBam.unsorted_read_group_insert_size_histogram_pdf
    Array[File] unsorted_read_group_insert_size_metrics = UnmappedBamToAlignedBam.unsorted_read_group_insert_size_metrics
    Array[File] unsorted_read_group_quality_by_cycle_pdf = UnmappedBamToAlignedBam.unsorted_read_group_quality_by_cycle_pdf
    Array[File] unsorted_read_group_quality_by_cycle_metrics = UnmappedBamToAlignedBam.unsorted_read_group_quality_by_cycle_metrics
    Array[File] unsorted_read_group_quality_distribution_pdf = UnmappedBamToAlignedBam.unsorted_read_group_quality_distribution_pdf
    Array[File] unsorted_read_group_quality_distribution_metrics = UnmappedBamToAlignedBam.unsorted_read_group_quality_distribution_metrics

    File read_group_alignment_summary_metrics = AggregatedBamQC.read_group_alignment_summary_metrics
    File read_group_gc_bias_detail_metrics = AggregatedBamQC.read_group_gc_bias_detail_metrics
    File read_group_gc_bias_pdf = AggregatedBamQC.read_group_gc_bias_pdf
    File read_group_gc_bias_summary_metrics = AggregatedBamQC.read_group_gc_bias_summary_metrics

    File? cross_check_fingerprints_metrics = UnmappedBamToAlignedBam.cross_check_fingerprints_metrics

    File selfSM = UnmappedBamToAlignedBam.selfSM
    Float contamination = UnmappedBamToAlignedBam.contamination

    File calculate_read_group_checksum_md5 = AggregatedBamQC.calculate_read_group_checksum_md5

    File agg_alignment_summary_metrics = AggregatedBamQC.agg_alignment_summary_metrics
    File agg_bait_bias_detail_metrics = AggregatedBamQC.agg_bait_bias_detail_metrics
    File agg_bait_bias_summary_metrics = AggregatedBamQC.agg_bait_bias_summary_metrics
    File agg_gc_bias_detail_metrics = AggregatedBamQC.agg_gc_bias_detail_metrics
    File agg_gc_bias_pdf = AggregatedBamQC.agg_gc_bias_pdf
    File agg_gc_bias_summary_metrics = AggregatedBamQC.agg_gc_bias_summary_metrics
    File agg_insert_size_histogram_pdf = AggregatedBamQC.agg_insert_size_histogram_pdf
    File agg_insert_size_metrics = AggregatedBamQC.agg_insert_size_metrics
    File agg_pre_adapter_detail_metrics = AggregatedBamQC.agg_pre_adapter_detail_metrics
    File agg_pre_adapter_summary_metrics = AggregatedBamQC.agg_pre_adapter_summary_metrics
    File agg_quality_distribution_pdf = AggregatedBamQC.agg_quality_distribution_pdf
    File agg_quality_distribution_metrics = AggregatedBamQC.agg_quality_distribution_metrics
    File agg_error_summary_metrics = AggregatedBamQC.agg_error_summary_metrics

    File? fingerprint_summary_metrics = AggregatedBamQC.fingerprint_summary_metrics
    File? fingerprint_detail_metrics = AggregatedBamQC.fingerprint_detail_metrics

    File wgs_metrics = CollectWgsMetrics.metrics
    File raw_wgs_metrics = CollectRawWgsMetrics.metrics

    File duplicate_metrics = UnmappedBamToAlignedBam.duplicate_metrics
    File output_bqsr_reports = UnmappedBamToAlignedBam.output_bqsr_reports

    File gvcf_summary_metrics = BamToGvcf.vcf_summary_metrics
    File gvcf_detail_metrics = BamToGvcf.vcf_detail_metrics

    File? output_bam = provided_output_bam
    File? output_bam_index = provided_output_bam_index

    File output_cram = BamToCram.output_cram
    File output_cram_index = BamToCram.output_cram_index
    File output_cram_md5 = BamToCram.output_cram_md5

    File validate_cram_file_report = BamToCram.validate_cram_file_report

    File output_vcf = BamToGvcf.output_vcf
    File output_vcf_index = BamToGvcf.output_vcf_index
  }
}