#!/usr/bin/env cwl-runner

cwlVersion: v1.0
class: Workflow
label: "exome alignment and somatic variant detection"
requirements:
    - class: SchemaDefRequirement
      types:
          - $import: ../types/labelled_file.yml
          - $import: ../types/sequence_data.yml
          - $import: ../types/trimming_options.yml
    - class: MultipleInputFeatureRequirement
    - class: SubworkflowFeatureRequirement
    - class: StepInputExpressionRequirement
inputs:
    reference:
        type:
            - string
            - File
        secondaryFiles: [.fai, ^.dict, .amb, .ann, .bwt, .pac, .sa]
    tumor_sequence:
        type: ../types/sequence_data.yml#sequence_data[]
        label: "tumor_sequence: MT sequencing data and readgroup information"
        doc: |
          tumor_sequence represents the sequencing data for the MT sample as either FASTQs or BAMs with
          accompanying readgroup information. Note that in the @RG field ID and SM are required.
    tumor_name:
        type: string?
        default: 'tumor'
        label: "tumor_name: String specifying the name of the MT sample"
        doc: |
          tumor_name provides a string for what the MT sample will be referred to in the various
          outputs, for example the VCF files.
    normal_sequence:
        type: ../types/sequence_data.yml#sequence_data[]
        label: "normal_sequence: WT sequencing data and readgroup information"
        doc: |
          normal_sequence represents the sequencing data for the WT sample as either FASTQs or BAMs with
          accompanying readgroup information. Note that in the @RG field ID and SM are required.
    normal_name:
        type: string?
        default: 'normal'
        label: "normal_name: String specifying the name of the WT sample"
        doc: |
          normal_name provides a string for what the WT sample will be referred to in the various
          outputs, for example the VCF files.
    trimming:
        type:
            - ../types/trimming_options.yml#trimming_options
            - "null"
    bait_intervals:
        type: File
    target_intervals:
        type: File
        label: "target_intervals: interval_list file of targets used in the sequencing experiment"
        doc: |
            target_intervals is an interval_list corresponding to the targets for the capture reagent.
            Bed files with this information can be converted to interval_lists with Picard BedToIntervalList.
            In general for a WES exome reagent bait_intervals and target_intervals are the same.
    target_interval_padding:
        type: int
        label: "target_interval_padding: number of bp flanking each target region in which to allow variant calls"
        doc: |
            The effective coverage of capture products generally extends out beyond the actual regions
            targeted. This parameter allows variants to be called in these wingspan regions, extending
            this many base pairs from each side of the target regions.
        default: 100
    per_base_intervals:
        type: ../types/labelled_file.yml#labelled_file[]
    per_target_intervals:
        type: ../types/labelled_file.yml#labelled_file[]
    summary_intervals:
        type: ../types/labelled_file.yml#labelled_file[]
    picard_metric_accumulation_level:
        type: string
    qc_minimum_mapping_quality:
        type: int?
        default: 0
    qc_minimum_base_quality:
        type: int?
        default: 0
    strelka_cpu_reserved:
        type: int?
        default: 8
    scatter_count:
        type: int
        doc: "scatters each supported variant detector (varscan, pindel, mutect) into this many parallel jobs"
    varscan_strand_filter:
        type: int?
        default: 0
    varscan_min_coverage:
        type: int?
        default: 8
    varscan_min_var_freq:
        type: float?
        default: 0.05
    varscan_p_value:
        type: float?
        default: 0.99
    varscan_max_normal_freq:
        type: float?
    pindel_insert_size:
        type: int
        default: 400
    vep_cache_dir:
        type:
            - string
            - Directory
    vep_ensembl_assembly:
        type: string
        doc: "genome assembly to use in vep. Examples: GRCh38 or GRCm38"
    vep_ensembl_version:
        type: string
        doc: "ensembl version - Must be present in the cache directory. Example: 95"
    vep_ensembl_species:
        type: string
        doc: "ensembl species - Must be present in the cache directory. Examples: homo_sapiens or mus_musculus"
    synonyms_file:
        type: File?
    annotate_coding_only:
        type: boolean?
    vep_pick:
        type:
            - "null"
            - type: enum
              symbols: ["pick", "flag_pick", "pick_allele", "per_gene", "pick_allele_gene", "flag_pick_allele", "flag_pick_allele_gene"]
    cle_vcf_filter:
        type: boolean
        default: false
    filter_somatic_llr_threshold:
        type: float
        default: 5
        doc: "Sets the stringency (log-likelihood ratio) used to filter out non-somatic variants.  Typical values are 10=high stringency, 5=normal, 3=low stringency. Low stringency may be desirable when read depths are low (as in WGS) or when tumor samples are impure."
    filter_somatic_llr_tumor_purity:
        type: float
        default: 1
        doc: "Sets the purity of the tumor used in the somatic llr filter, used to remove non-somatic variants. Probably only needs to be adjusted for low-purity (< 50%).  Range is 0 to 1"
    filter_somatic_llr_normal_contamination_rate:
        type: float
        default: 0
        doc: "Sets the fraction of tumor present in the normal sample (range 0 to 1), used in the somatic llr filter. Useful for heavily contaminated adjacent normals. Range is 0 to 1"
    variants_to_table_fields:
        type: string[]
        default: [CHROM,POS,ID,REF,ALT,set,AC,AF]
    variants_to_table_genotype_fields:
        type: string[]
        default: [GT,AD]
    vep_to_table_fields:
        type: string[]
        default: ['Consequence','SYMBOL','Feature']
    tumor_sample_name:
        type: string
    normal_sample_name:
        type: string
    cnvkit_target_average_size:
        type: int?
        doc: "approximate size of split target bins for CNVkit; if not set a suitable window size will be set by CNVkit automatically"
outputs:
    tumor_cram:
        type: File
        outputSource: tumor_index_cram/indexed_cram
    tumor_mark_duplicates_metrics:
        type: File
        outputSource: tumor_alignment_and_qc/mark_duplicates_metrics
    tumor_insert_size_metrics:
        type: File
        outputSource: tumor_alignment_and_qc/insert_size_metrics
    tumor_alignment_summary_metrics:
        type: File
        outputSource: tumor_alignment_and_qc/alignment_summary_metrics
    tumor_hs_metrics:
        type: File
        outputSource: tumor_alignment_and_qc/hs_metrics
    tumor_per_target_coverage_metrics:
        type: File[]
        outputSource: tumor_alignment_and_qc/per_target_coverage_metrics
    tumor_per_target_hs_metrics:
        type: File[]
        outputSource: tumor_alignment_and_qc/per_target_hs_metrics
    tumor_per_base_coverage_metrics:
        type: File[]
        outputSource: tumor_alignment_and_qc/per_base_coverage_metrics
    tumor_per_base_hs_metrics:
        type: File[]
        outputSource: tumor_alignment_and_qc/per_base_hs_metrics
    tumor_summary_hs_metrics:
        type: File[]
        outputSource: tumor_alignment_and_qc/summary_hs_metrics
    tumor_flagstats:
        type: File
        outputSource: tumor_alignment_and_qc/flagstats
    normal_cram:
        type: File
        outputSource: normal_index_cram/indexed_cram
    normal_mark_duplicates_metrics:
        type: File
        outputSource: normal_alignment_and_qc/mark_duplicates_metrics
    normal_insert_size_metrics:
        type: File
        outputSource: normal_alignment_and_qc/insert_size_metrics
    normal_alignment_summary_metrics:
        type: File
        outputSource: normal_alignment_and_qc/alignment_summary_metrics
    normal_hs_metrics:
        type: File
        outputSource: normal_alignment_and_qc/hs_metrics
    normal_per_target_coverage_metrics:
        type: File[]
        outputSource: normal_alignment_and_qc/per_target_coverage_metrics
    normal_per_target_hs_metrics:
        type: File[]
        outputSource: normal_alignment_and_qc/per_target_hs_metrics
    normal_per_base_coverage_metrics:
        type: File[]
        outputSource: normal_alignment_and_qc/per_base_coverage_metrics
    normal_per_base_hs_metrics:
        type: File[]
        outputSource: normal_alignment_and_qc/per_base_hs_metrics
    normal_summary_hs_metrics:
        type: File[]
        outputSource: normal_alignment_and_qc/summary_hs_metrics
    normal_flagstats:
        type: File
        outputSource: normal_alignment_and_qc/flagstats
    mutect_unfiltered_vcf:
        type: File
        outputSource: detect_variants/mutect_unfiltered_vcf
        secondaryFiles: [.tbi]
    mutect_filtered_vcf:
        type: File
        outputSource: detect_variants/mutect_filtered_vcf
        secondaryFiles: [.tbi]
    strelka_unfiltered_vcf:
        type: File
        outputSource: detect_variants/strelka_unfiltered_vcf
        secondaryFiles: [.tbi]
    strelka_filtered_vcf:
        type: File
        outputSource: detect_variants/strelka_filtered_vcf
        secondaryFiles: [.tbi]
    varscan_unfiltered_vcf:
        type: File
        outputSource: detect_variants/varscan_unfiltered_vcf
        secondaryFiles: [.tbi]
    varscan_filtered_vcf:
        type: File
        outputSource: detect_variants/varscan_filtered_vcf
        secondaryFiles: [.tbi]
    pindel_unfiltered_vcf:
        type: File
        outputSource: detect_variants/pindel_unfiltered_vcf
        secondaryFiles: [.tbi]
    pindel_filtered_vcf:
        type: File
        outputSource: detect_variants/pindel_filtered_vcf
        secondaryFiles: [.tbi]
    final_vcf:
        type: File
        outputSource: detect_variants/final_vcf
        secondaryFiles: [.tbi]
    final_filtered_vcf:
        type: File
        outputSource: detect_variants/final_filtered_vcf
        secondaryFiles: [.tbi]
    final_tsv:
        type: File
        outputSource: detect_variants/final_tsv
    vep_summary:
        type: File
        outputSource: detect_variants/vep_summary
    tumor_snv_bam_readcount_tsv:
        type: File
        outputSource: detect_variants/tumor_snv_bam_readcount_tsv
    tumor_indel_bam_readcount_tsv:
        type: File
        outputSource: detect_variants/tumor_indel_bam_readcount_tsv
    normal_snv_bam_readcount_tsv:
        type: File
        outputSource: detect_variants/normal_snv_bam_readcount_tsv
    normal_indel_bam_readcount_tsv:
        type: File
        outputSource: detect_variants/normal_indel_bam_readcount_tsv
steps:
    tumor_alignment_and_qc:
        run: alignment_exome_nonhuman.cwl
        in:
            reference: reference
            sequence: tumor_sequence
            trimming: trimming
            bait_intervals: bait_intervals
            target_intervals: target_intervals
            per_base_intervals: per_base_intervals
            per_target_intervals: per_target_intervals
            summary_intervals: summary_intervals
            picard_metric_accumulation_level: picard_metric_accumulation_level   
            qc_minimum_mapping_quality: qc_minimum_mapping_quality
            qc_minimum_base_quality: qc_minimum_base_quality
            final_name:
                source: tumor_name
                valueFrom: "$(self).bam"
        out:
            [bam, mark_duplicates_metrics, insert_size_metrics, alignment_summary_metrics, hs_metrics, per_target_coverage_metrics, per_target_hs_metrics, per_base_coverage_metrics, per_base_hs_metrics, summary_hs_metrics, flagstats]
    normal_alignment_and_qc:
        run: alignment_exome_nonhuman.cwl
        in:
            reference: reference
            sequence: normal_sequence
            trimming: trimming
            bait_intervals: bait_intervals
            target_intervals: target_intervals
            per_base_intervals: per_base_intervals
            per_target_intervals: per_target_intervals
            summary_intervals: summary_intervals
            picard_metric_accumulation_level: picard_metric_accumulation_level   
            qc_minimum_mapping_quality: qc_minimum_mapping_quality
            qc_minimum_base_quality: qc_minimum_base_quality
            final_name:
                source: normal_name
                valueFrom: "$(self).bam"
        out:
            [bam, mark_duplicates_metrics, insert_size_metrics, alignment_summary_metrics, hs_metrics, per_target_coverage_metrics, per_target_hs_metrics, per_base_coverage_metrics, per_base_hs_metrics, summary_hs_metrics, flagstats]
    pad_target_intervals:
        run: ../tools/interval_list_expand.cwl
        in:
            interval_list: target_intervals
            roi_padding: target_interval_padding
        out:
            [expanded_interval_list]
    detect_variants:
        run: detect_variants_nonhuman.cwl
        in:
            reference: reference
            tumor_bam: tumor_alignment_and_qc/bam
            normal_bam: normal_alignment_and_qc/bam
            roi_intervals: pad_target_intervals/expanded_interval_list
            strelka_exome_mode:
                default: true
            strelka_cpu_reserved: strelka_cpu_reserved
            scatter_count: scatter_count
            varscan_strand_filter: varscan_strand_filter
            varscan_min_coverage: varscan_min_coverage
            varscan_min_var_freq: varscan_min_var_freq
            varscan_p_value: varscan_p_value
            varscan_max_normal_freq: varscan_max_normal_freq
            pindel_insert_size: pindel_insert_size
            vep_cache_dir: vep_cache_dir
            synonyms_file: synonyms_file
            annotate_coding_only: annotate_coding_only
            vep_pick: vep_pick
            cle_vcf_filter: cle_vcf_filter
            filter_somatic_llr_threshold: filter_somatic_llr_threshold
            filter_somatic_llr_tumor_purity: filter_somatic_llr_tumor_purity
            filter_somatic_llr_normal_contamination_rate: filter_somatic_llr_normal_contamination_rate
            variants_to_table_fields: variants_to_table_fields
            variants_to_table_genotype_fields: variants_to_table_genotype_fields
            vep_ensembl_assembly: vep_ensembl_assembly
            vep_ensembl_version: vep_ensembl_version
            vep_ensembl_species: vep_ensembl_species
            vep_to_table_fields: vep_to_table_fields
            tumor_sample_name: tumor_sample_name
            normal_sample_name: normal_sample_name
        out:
            [mutect_unfiltered_vcf, mutect_filtered_vcf, strelka_unfiltered_vcf, strelka_filtered_vcf, varscan_unfiltered_vcf, varscan_filtered_vcf, pindel_unfiltered_vcf, pindel_filtered_vcf, final_vcf, final_filtered_vcf, final_tsv, vep_summary, tumor_snv_bam_readcount_tsv, tumor_indel_bam_readcount_tsv, normal_snv_bam_readcount_tsv, normal_indel_bam_readcount_tsv]
    cnvkit:
        run: ../tools/cnvkit_batch.cwl
        in:
            tumor_bam: tumor_alignment_and_qc/bam
            reference:
                source: [normal_alignment_and_qc/bam, reference]
                valueFrom: |
                    ${
                      var normal = self[0];
                      var fasta = self[1];
                      return {'normal_bam': normal, 'fasta_file': fasta};
                    }
            bait_intervals: bait_intervals
            cnvkit_target_average_size: cnvkit_target_average_size
        out:
            [intervals_antitarget, intervals_target, normal_antitarget_coverage, normal_target_coverage, reference_coverage, cn_diagram, cn_scatter_plot, tumor_antitarget_coverage, tumor_target_coverage, tumor_bin_level_ratios, tumor_segmented_ratios]
    tumor_bam_to_cram:
        run: ../tools/bam_to_cram.cwl
        in:
            bam: tumor_alignment_and_qc/bam
            reference: reference
        out:
            [cram]
    tumor_index_cram:
         run: ../tools/index_cram.cwl
         in:
            cram: tumor_bam_to_cram/cram
         out:
            [indexed_cram]
    normal_bam_to_cram:
        run: ../tools/bam_to_cram.cwl
        in:
            bam: normal_alignment_and_qc/bam
            reference: reference
        out:
            [cram]
    normal_index_cram:
         run: ../tools/index_cram.cwl
         in:
            cram: normal_bam_to_cram/cram
         out:
            [indexed_cram]