KN adding WDLs to github from terra data repository

Calculate_Proband_AC

@@ -0,0 +1,205 @@
+version 1.0
+
+## ProbandCohortAC.wdl
+##
+## Recalculates AC/AN/AF using only proband samples from a PED file,
+## and annotates these values into the INFO field of the full VCF as
+## PROBAND_AC, PROBAND_AN, PROBAND_AF.
+##
+## Inputs:
+##   vcf          - Input VCF (indexed, bgzipped)
+##   vcf_index    - Corresponding .tbi index
+##   ped_file     - PED file (cols: family_id, sample_id, paternal_id, maternal_id, sex, phenotype)
+##                  phenotype: 2 = proband, 1 = unaffected, 0 = unknown
+##
+## Outputs:
+##   annotated_vcf             - VCF with PROBAND_AC, PROBAND_AN, PROBAND_AF in INFO
+##   annotated_vcf_index       - Corresponding .tbi index
+##   proband_list              - All proband sample IDs from PED
+##   proband_list_in_vcf       - Proband sample IDs that were actually found in VCF header
+
+workflow ProbandCohortAC {
+
+    input {
+        File   vcf
+        File   vcf_index
+        File   ped_file
+
+        String docker      = "us.gcr.io/broad-gatk/gatk:4.5.0.0"
+        Int    mem_gb      = 16
+        Int    disk_gb     = 200
+        Int    cpu         = 4
+        Int    preemptible = 3
+    }
+
+    call ExtractProbands {
+        input:
+            ped_file    = ped_file,
+            docker      = docker,
+            mem_gb      = mem_gb,
+            disk_gb     = disk_gb,
+            cpu         = cpu,
+            preemptible = preemptible
+    }
+
+    call CalculateAndAnnotateProbandAC {
+        input:
+            vcf          = vcf,
+            vcf_index    = vcf_index,
+            proband_list = ExtractProbands.proband_list,
+            docker       = docker,
+            mem_gb       = mem_gb,
+            disk_gb      = disk_gb,
+            cpu          = cpu,
+            preemptible  = preemptible
+    }
+
+    output {
+        File annotated_vcf       = CalculateAndAnnotateProbandAC.annotated_vcf
+        File annotated_vcf_index = CalculateAndAnnotateProbandAC.annotated_vcf_index
+        File proband_list        = ExtractProbands.proband_list
+        File proband_list_in_vcf = CalculateAndAnnotateProbandAC.proband_list_in_vcf
+    }
+}
+
+# ---------------------------------------------------------------------------
+# Task 1: Parse PED file to extract proband sample IDs (phenotype == 2)
+#         Strips Windows-style carriage returns (\r) before parsing
+# ---------------------------------------------------------------------------
+task ExtractProbands {
+
+    input {
+        File   ped_file
+        String docker
+        Int    mem_gb
+        Int    disk_gb
+        Int    cpu
+        Int    preemptible
+    }
+
+    command <<<
+        set -euo pipefail
+
+        # Strip carriage returns (\r) to handle Windows-formatted PED files,
+        # then skip header (NR>1) and extract samples where phenotype == 2
+        tr -d '\r' < ~{ped_file} \
+            | awk 'NR>1 && $6 == 2 {print $2}' \
+            | sort -u > proband_list.txt
+
+        echo "Found $(wc -l < proband_list.txt) probands in PED"
+        head -5 proband_list.txt
+    >>>
+
+    output {
+        File proband_list = "proband_list.txt"
+    }
+
+    runtime {
+        docker:      docker
+        memory:      "~{mem_gb} GB"
+        disks:       "local-disk ~{disk_gb} HDD"
+        cpu:         cpu
+        preemptible: preemptible
+    }
+}
+
+# ---------------------------------------------------------------------------
+# Task 2: Calculate proband-only AC/AN/AF and annotate into full VCF
+# ---------------------------------------------------------------------------
+task CalculateAndAnnotateProbandAC {
+
+    input {
+        File   vcf
+        File   vcf_index
+        File   proband_list
+        String docker
+        Int    mem_gb
+        Int    disk_gb
+        Int    cpu
+        Int    preemptible
+    }
+
+    String vcf_basename = basename(vcf, ".vcf.gz")
+
+    command <<<
+        set -euo pipefail
+
+        which bcftools || apt-get install -y bcftools
+
+        # Step 1: Filter proband list to only samples present in VCF header
+        bcftools query -l ~{vcf} > vcf_samples.txt
+
+        comm -12 \
+            <(sort ~{proband_list}) \
+            <(sort vcf_samples.txt) \
+            > proband_list_in_vcf.txt
+
+        echo "Probands in PED:      $(wc -l < ~{proband_list})"
+        echo "Probands in VCF:      $(wc -l < proband_list_in_vcf.txt)"
+        echo "Probands not in VCF (skipped):"
+        comm -23 \
+            <(sort ~{proband_list}) \
+            <(sort vcf_samples.txt)
+
+        if [[ $(wc -l < proband_list_in_vcf.txt) -eq 0 ]]; then
+            echo "ERROR: No proband samples found in VCF header. Check sample name formatting."
+            exit 1
+        fi
+
+        # Step 2: Subset to probands present in VCF and compute AC/AN/AF,
+        # then extract CHROM/POS/ID/REF/ALT + computed tags for annotation file
+        bcftools view \
+            --samples-file proband_list_in_vcf.txt \
+            ~{vcf} | \
+        bcftools +fill-tags -- -t AC,AN,AF | \
+        bcftools query \
+            -f '%CHROM\t%POS\t%ID\t%REF\t%ALT\t%INFO/AC\t%INFO/AN\t%INFO/AF\n' \
+            > proband_annot_raw.txt
+
+        echo "Computed AC/AN/AF for $(wc -l < proband_annot_raw.txt) variants"
+
+        # Step 3: Sort, bgzip, and index the annotation file
+        sort -k1,1V -k2,2n proband_annot_raw.txt \
+            | bgzip -c > proband_annot.txt.gz
+        tabix -s1 -b2 -e2 proband_annot.txt.gz
+
+        # Step 4: Create header lines for the new INFO fields
+        cat > proband_ac_header.txt << 'EOF'
+##INFO=<ID=PROBAND_AC,Number=A,Type=Integer,Description="Allele count in proband samples only (phenotype=2 in PED)">
+##INFO=<ID=PROBAND_AN,Number=1,Type=Integer,Description="Total allele number in proband samples only (phenotype=2 in PED)">
+##INFO=<ID=PROBAND_AF,Number=A,Type=Float,Description="Allele frequency in proband samples only (phenotype=2 in PED)">
+EOF
+
+        # Step 5: Annotate the full VCF with proband AC/AN/AF
+        bcftools annotate \
+            -a proband_annot.txt.gz \
+            -h proband_ac_header.txt \
+            -c CHROM,POS,ID,REF,ALT,PROBAND_AC,PROBAND_AN,PROBAND_AF \
+            ~{vcf} \
+            -Oz -o ~{vcf_basename}.proband_ac.vcf.gz
+
+        bcftools index -t ~{vcf_basename}.proband_ac.vcf.gz
+
+        # Sanity check
+        echo "Spot check first 5 annotated variants:"
+        bcftools query \
+            -f '%ID\t%INFO/PROBAND_AC\t%INFO/PROBAND_AN\t%INFO/PROBAND_AF\n' \
+            -r chr1 \
+            ~{vcf_basename}.proband_ac.vcf.gz | head -5 || true
+
+    >>>
+
+    output {
+        File annotated_vcf       = "~{vcf_basename}.proband_ac.vcf.gz"
+        File annotated_vcf_index = "~{vcf_basename}.proband_ac.vcf.gz.tbi"
+        File proband_list_in_vcf = "proband_list_in_vcf.txt"
+    }
+
+    runtime {
+        docker:      docker
+        memory:      "~{mem_gb} GB"
+        disks:       "local-disk ~{disk_gb} HDD"
+        cpu:         cpu
+        preemptible: preemptible
+    }
+}