cwlVersion: v1.0
class: Workflow


requirements:
  - class: SubworkflowFeatureRequirement
  - class: StepInputExpressionRequirement
  - class: InlineJavascriptRequirement


inputs:

  indices_folder:
    type: Directory
    label: "BOWTIE indices folder"
    doc: "Path to BOWTIE generated indices folder"

  annotation_file:
    type: File
    label: "Annotation file"
    format: "http://edamontology.org/format_3475"
    doc: "Tab-separated input annotation file"

  genome_size:
    type: string
    label: "Effective genome size"
    doc: "MACS2 effective genome size: hs, mm, ce, dm or number, for example 2.7e9"

  chrom_length:
    type: File
    label: "Chromosome length file"
    format: "http://edamontology.org/format_2330"
    doc: "Chromosome length file"

  control_file:
    type: File?
    default: null
    label: "Control BAM file"
    format: "http://edamontology.org/format_2572"
    doc: "Control BAM file file for MACS2 peak calling"

  broad_peak:
    type: boolean
    label: "Callpeak broad"
    doc: "Set to call broad peak for MACS2"

  fastq_file:
    type: File
    label: "FASTQ input file"
    format: "http://edamontology.org/format_1930"
    doc: "Reads data in a FASTQ format, received after single end sequencing"

  exp_fragment_size:
    type: int?
    default: 150
    label: "Expected fragment size"
    doc: "Expected fragment size for MACS2"

  force_fragment_size:
    type: boolean?
    default: false
    label: "Force fragment size"
    doc: "Force MACS2 to use exp_fragment_size"

  clip_3p_end:
    type: int?
    default: 0
    label: "Clip from 3p end"
    doc: "Number of bases to clip from the 3p end"

  clip_5p_end:
    type: int?
    default: 0
    label: "Clip from 5p end"
    doc: "Number of bases to clip from the 5p end"

  remove_duplicates:
    type: boolean?
    default: false
    label: "Remove duplicates"
    doc: "Calls samtools rmdup to remove duplicates from sortesd BAM file"

  threads:
    type: int?
    default: 2
    doc: "Number of threads for those steps that support multithreading"
    label: "Number of threads"


outputs:

  bigwig:
    type: File
    format: "http://edamontology.org/format_3006"
    label: "BigWig file"
    doc: "Generated BigWig file"
    outputSource: bam_to_bigwig/bigwig_file

  fastx_statistics:
    type: File
    label: "FASTQ statistics"
    format: "http://edamontology.org/format_2330"
    doc: "fastx_quality_stats generated FASTQ file quality statistics file"
    outputSource: fastx_quality_stats/statistics_file

  bowtie_log:
    type: File
    label: "BOWTIE alignment log"
    format: "http://edamontology.org/format_2330"
    doc: "BOWTIE generated alignment log"
    outputSource: bowtie_aligner/log_file

  iaintersect_log:
    type: File
    label: "Island intersect log"
    format: "http://edamontology.org/format_3475"
    doc: "Iaintersect generated log"
    outputSource: island_intersect/log_file

  iaintersect_result:
    type: File
    label: "Island intersect results"
    format: "http://edamontology.org/format_3475"
    doc: "Iaintersect generated results"
    outputSource: island_intersect/result_file

  atdp_log:
    type: File
    label: "ATDP log"
    format: "http://edamontology.org/format_3475"
    doc: "Average Tag Density generated log"
    outputSource: average_tag_density/log_file

  atdp_result:
    type: File
    label: "ATDP results"
    format: "http://edamontology.org/format_3475"
    doc: "Average Tag Density generated results"
    outputSource: average_tag_density/result_file

  samtools_rmdup_log:
    type: File
    label: "Remove duplicates log"
    format: "http://edamontology.org/format_2330"
    doc: "Samtools rmdup generated log"
    outputSource: samtools_rmdup/rmdup_log

  bambai_pair:
    type: File
    format: "http://edamontology.org/format_2572"
    label: "Coordinate sorted BAM alignment file (+index BAI)"
    doc: "Coordinate sorted BAM file and BAI index file"
    outputSource: samtools_sort_index_after_rmdup/bam_bai_pair

  macs2_called_peaks:
    type: File?
    label: "Called peaks"
    format: "http://edamontology.org/format_3468"
    doc: "XLS file to include information about called peaks"
    outputSource: macs2_callpeak/peak_xls_file

  macs2_narrow_peaks:
    type: File?
    label: "Narrow peaks"
    format: "http://edamontology.org/format_3613"
    doc: "Contains the peak locations together with peak summit, pvalue and qvalue"
    outputSource: macs2_callpeak/narrow_peak_file

  macs2_broad_peaks:
    type: File?
    label: "Broad peaks"
    format: "http://edamontology.org/format_3614"
    doc: "Contains the peak locations together with peak summit, pvalue and qvalue"
    outputSource: macs2_callpeak/broad_peak_file

  macs2_peak_summits:
    type: File?
    label: "Peak summits"
    format: "http://edamontology.org/format_3003"
    doc: "Contains the peak summits locations for every peaks"
    outputSource: macs2_callpeak/peak_summits_file

  macs2_moder_r:
    type: File?
    label: "MACS2 generated R script"
    format: "http://edamontology.org/format_2330"
    doc: "R script to produce a PDF image about the model based on your data"
    outputSource: macs2_callpeak/moder_r_file

  macs2_gapped_peak:
    type: File?
    label: "Gapped peak"
    format: "http://edamontology.org/format_3586"
    doc: "Contains both the broad region and narrow peaks"
    outputSource: macs2_callpeak/gapped_peak_file

  macs2_log:
    type: File?
    label: "MACS2 log"
    format: "http://edamontology.org/format_2330"
    doc: "MACS2 output log"
    outputSource: macs2_callpeak/macs_log

  get_stat_log:
    type: File?
    label: "Bowtie & Samtools Rmdup combined log"
    format: "http://edamontology.org/format_2330"
    doc: "Processed and combined Bowtie aligner and Samtools rmdup log"
    outputSource: get_stat/output_file

  macs2_fragment_stat:
    type: File?
    label: "FRAGMENT, FRAGMENTE, ISLANDS"
    format: "http://edamontology.org/format_2330"
    doc: "fragment, calculated fragment, islands count from MACS2 results"
    outputSource: macs2_callpeak/macs2_stat_file

  fastq_compressed:
    type: File
    label: "Compressed FASTQ"
    doc: "bz2 compressed FASTQ file"
    outputSource: bzip/output_file

steps:

  fastx_quality_stats:
    run: ./tools/fastx-quality-stats.cwl
    in:
      input_file: fastq_file
    out: [statistics_file]

  bzip:
    run: ./tools/bzip2-compress.cwl
    in:
      input_file: fastq_file
    out: [output_file]

  bowtie_aligner:
    run: ./tools/bowtie-alignreads.cwl
    in:
      upstream_filelist: fastq_file
      indices_folder: indices_folder
      clip_3p_end: clip_3p_end
      clip_5p_end: clip_5p_end
      v:
        default: 3
      m:
        default: 1
      best:
        default: true
      strata:
        default: true
      sam:
        default: true
      threads: threads
      q:
        default: true
    out: [sam_file, log_file]

  samtools_sort_index:
    run: ./tools/samtools-sort-index.cwl
    in:
      sort_input: bowtie_aligner/sam_file
      threads: threads
    out: [bam_bai_pair]

  samtools_rmdup:
    run: ./tools/samtools-rmdup.cwl
    in:
      trigger: remove_duplicates
      bam_file: samtools_sort_index/bam_bai_pair
      single_end:
        default: true
    out: [rmdup_output, rmdup_log]

  samtools_sort_index_after_rmdup:
    run: ./tools/samtools-sort-index.cwl
    in:
      trigger: remove_duplicates
      sort_input: samtools_rmdup/rmdup_output
      threads: threads
    out: [bam_bai_pair]

  macs2_callpeak:
    run: ./tools/macs2-callpeak-biowardrobe-only.cwl
    in:
      treatment_file: samtools_sort_index_after_rmdup/bam_bai_pair
      control_file: control_file
      nolambda:
        source: control_file
        valueFrom: $(!self)
      genome_size: genome_size
      mfold:
        default: "4 40"
      verbose:
        default: 3
      nomodel: force_fragment_size
      extsize: exp_fragment_size
      bw: exp_fragment_size
      broad: broad_peak
      call_summits:
        source: broad_peak
        valueFrom: $(!self)
      keep_dup:
        default: auto
      q_value:
        default: 0.05
      format_mode:
        default: BAM
      buffer_size:
        default: 10000
    out:
      - peak_xls_file
      - narrow_peak_file
      - peak_summits_file
      - broad_peak_file
      - moder_r_file
      - gapped_peak_file
      - treat_pileup_bdg_file
      - control_lambda_bdg_file
      - macs_log
      - macs2_stat_file
      - macs2_fragments_calculated

  bam_to_bigwig:
    run: ./workflows/bam-bedgraph-bigwig.cwl
    in:
      bam_file: samtools_sort_index_after_rmdup/bam_bai_pair
      chrom_length_file: chrom_length
      mapped_reads_number: get_stat/mapped_reads
      fragment_size: macs2_callpeak/macs2_fragments_calculated
    out: [bigwig_file]

  get_stat:
      run: ./tools/python-get-stat-chipseq.cwl
      in:
        bowtie_log: bowtie_aligner/log_file
        rmdup_log: samtools_rmdup/rmdup_log
      out:
        - output_file
        - mapped_reads

  island_intersect:
      run: ./tools/iaintersect.cwl
      in:
        input_filename: macs2_callpeak/peak_xls_file
        annotation_filename: annotation_file
        promoter_bp:
          default: 1000
      out: [result_file, log_file]

  average_tag_density:
      run: ./tools/atdp.cwl
      in:
        input_file: samtools_sort_index_after_rmdup/bam_bai_pair
        annotation_filename: annotation_file
        fragmentsize_bp: macs2_callpeak/macs2_fragments_calculated
        avd_window_bp:
          default: 5000
        avd_smooth_bp:
          default: 50
        ignore_chr:
          default: chrM
        double_chr:
          default: "chrX chrY"
        avd_heat_window_bp:
          default: 200
        mapped_reads: get_stat/mapped_reads
      out: [result_file, log_file]


$namespaces:
  s: http://schema.org/

$schemas:
- http://schema.org/docs/schema_org_rdfa.html

s:name: "biowardrobe_chipseq_se"
s:downloadUrl: https://raw.githubusercontent.com/Barski-lab/ga4gh_challenge/master/biowardrobe_chipseq_se.cwl
s:codeRepository: https://github.com/Barski-lab/ga4gh_challenge
s:license: http://www.apache.org/licenses/LICENSE-2.0

s:isPartOf:
  class: s:CreativeWork
  s:name: Common Workflow Language
  s:url: http://commonwl.org/

s:creator:
- class: s:Organization
  s:legalName: "Cincinnati Children's Hospital Medical Center"
  s:location:
  - class: s:PostalAddress
    s:addressCountry: "USA"
    s:addressLocality: "Cincinnati"
    s:addressRegion: "OH"
    s:postalCode: "45229"
    s:streetAddress: "3333 Burnet Ave"
    s:telephone: "+1(513)636-4200"
  s:logo: "https://www.cincinnatichildrens.org/-/media/cincinnati%20childrens/global%20shared/childrens-logo-new.png"
  s:department:
  - class: s:Organization
    s:legalName: "Allergy and Immunology"
    s:department:
    - class: s:Organization
      s:legalName: "Barski Research Lab"
      s:member:
      - class: s:Person
        s:name: Michael Kotliar
        s:email: mailto:misha.kotliar@gmail.com
        s:sameAs:
        - id: http://orcid.org/0000-0002-6486-3898

doc: |
  Current workflow is used to run CHIP-Seq basic analysis with single-end input FASTQ file.
  In outputs it returns coordinate sorted BAM file alongside with index BAI file, quality
  statistics of the input FASTQ file, reads coverage in a form of BigWig file, peaks calling
  data in a form of narrowPeak or broadPeak files.

s:about: |
  Current workflow is used to run CHIP-Seq basic analysis with single-end input FASTQ file.
  In outputs it returns coordinate sorted BAM file alongside with index BAI file, quality
  statistics of the input FASTQ file, reads coverage in a form of BigWig file, peaks calling
  data in a form of narrowPeak or broadPeak files.
  Workflow starts with running fastx_quality_stats (Step fastx_quality_stats) from FASTX-Toolkit
  to calculate quality statistics for input FASTQ file. At the same time (Step bowtie_aligner)
  Bowtie is used to align reads from input FASTQ file to reference genome. The output of this step
  is unsorted SAM file which is being sorted and indexed by samtools sort and samtools index
  (Step samtools_sort_index). Depending on workflow’s input parameters indexed the sorted BAM file
  could be processed by samtools rmdup (Step samtools_rmdup) to remove all possible read duplicates.
  In a case when removing duplicates is not necessary the step returns original input BAM and BAI
  files without any processing. If the duplicates were removed the following step
  (Step samtools_sort_index_after_rmdup) reruns samtools sort and samtools index with BAM and BAI files,
  if not - the step returns original unchanged input files. Right after that (Step macs2_callpeak)
  macs2 callpeak performs peak calling. This step also calculates the number of islands and estimated
  fragment size. If the last one is less that 80 (hardcoded in a workflow) macs2 callpeak is rerun again
  with forced fixed fragment size value. If at the very beginning it was set in workflow
  input parameters to run peak calling with fixed fragment size, macs2 peak calling is run only once.
  The following step (Step bam_to_bigwig) is used to calculate read coverage on the base of input BAM file
  and save it in bigWig format. For that purpose the mapped reads number is used as a scaling factor
  by bedtools genomecov when it performs coverage calculation and saves it in BED format. The last one
  is then being sorted and converted to bigWig format by bedGraphToBigWig tool from UCSC utilities.
  The following two steps (Step island_intersect and average_tag_density) define the closest genes to
  the islands received from macs2 peak calling and calculate average tag density.