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munge_sumstats.wdl
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task clean_filter {
String docker
File sumstat_file
String af_col
String N_col
String Ncontrol_col
String Ncase_col
String info_col
Float min_mac
Float min_info
String outfile = sub(basename(sumstat_file, ".gz"), "\\.bgz$", "") + ".munged.MAC." + min_mac + ".INFO." + min_info + ".gz"
String dollar = "$"
command <<<
#TODO use pandas or something
echo "Biobank meta-analysis - clean and filter sumstats"
echo "${sumstat_file}"
echo ""
echo "`date` original number of variants"
gunzip -c ${sumstat_file} | tail -n+2 | wc -l
chr_col=$(gunzip -c ${sumstat_file} | head -1 | tr '\t ' '\n' | grep -nx "#CHR\|CHR" | head -1 | cut -d ':' -f1)
pos_col=$(gunzip -c ${sumstat_file} | head -1 | tr '\t ' '\n' | grep -nx "POS" | head -1 | cut -d ':' -f1)
N_col_num=$(gunzip -c ${sumstat_file} | head -1 | tr '\t ' '\n' | grep -nx "${N_col}" | head -1 | cut -d ':' -f1)
Ncase_col_num=$(gunzip -c ${sumstat_file} | head -1 | tr '\t ' '\n' | grep -nx "${Ncase_col}" | head -1 | cut -d ':' -f1)
Ncontrol_col_num=$(gunzip -c ${sumstat_file} | head -1 | tr '\t ' '\n' | grep -nx "${Ncontrol_col}" | head -1 | cut -d ':' -f1)
printf "`date` col CHR "${dollar}{chr_col}" col POS "${dollar}{pos_col}"\n"
if [ -z "$N_col_num" ]; then
gunzip -c ${sumstat_file} | awk -v infoHeader=${info_col} ' \
#BEGIN{FS="\t| "; OFS="\t"}
BEGIN{FS="[ \t]+"; OFS="\t"}
NR==1 {
for (i=1;i<=NF;i++) { sub("^CHR", "#CHR", $i); a[$i]=i; if ($i=="POS") pos=i }
gsub("Pvalue", "p.value", $0);
gsub(infoHeader, "imputationInfo", $0)
print $0
} NR>1 {
sub("^0", "", $a["#CHR"]); sub("^chr", "", $a["#CHR"]); sub("^X", "23", $a["#CHR"]);
if ($a["#CHR"] ~ /^[0-9]+$/ && $a["p.value"] != 0 && $a["BETA"] < 1e6 && $a["BETA"] > -1e6 && ($a["${af_col}"]*2*($a["${Ncase_col}"]+$a["${Ncontrol_col}"]))>${min_mac} && (2*($a["${Ncase_col}"]+$a["${Ncontrol_col}"])*(1-$a["${af_col}"]))>${min_mac} && $a["imputationInfo"]>${min_info}) {
printf $1
for (i=2; i<=NF; i++) {
if (i==pos) {
printf "\t%d", $i
} else {
printf "\t"$i
}
}
printf "\n"
}
}' | \
sort -k$chr_col,${dollar}{chr_col}g -k$pos_col,${dollar}{pos_col}g -u | \
bgzip > ${outfile}
else
gunzip -c ${sumstat_file} | awk ' \
BEGIN{FS="\t| "; OFS="\t"}
NR==1 {
for (i=1;i<=NF;i++) { sub("^CHR", "#CHR", $i); a[$i]=i; if ($i=="POS") pos=i }
gsub("Pvalue", "p.value", $0);
print $0
} NR>1 {
sub("^0", "", $a["#CHR"]); sub("^chr", "", $a["#CHR"]); sub("^X", "23", $a["#CHR"]);
if ($a["#CHR"] ~ /^[0-9]+$/ && $a["p.value"] != 0 && $a["BETA"] < 1e6 && $a["BETA"] > -1e6 && (2*$a["${N_col}"]*$a["${af_col}"])>${min_mac} && (2*$a["${N_col}"]*(1-$a["${af_col}"]))>${min_mac} && $a["${info_col}"]>${min_info}) {
printf $1
for (i=2; i<=NF; i++) {
if (i==pos) {
printf "\t%d", $i
} else {
printf "\t"$i
}
}
printf "\n"
}
}' | \
sort -k$chr_col,${dollar}{chr_col}g -k$pos_col,${dollar}{pos_col}g -u | \
bgzip > ${outfile}
fi
tabix -S 1 -s $chr_col -b $pos_col -e $pos_col ${outfile}
echo "`date` new number of variants"
gunzip -c ${outfile} | tail -n+2 | wc -l
echo "`date` headers"
gunzip -c ${outfile} | head -1 | tr '\t' '\n'
gunzip -c ${outfile} | tail -n+2 | cut -f $chr_col | uniq > chr.tmp
echo "`date` $(wc -l chr.tmp | cut -d' ' -f1) chromosomes"
cat chr.tmp
echo "`date` unique number of fields"
gunzip -c ${outfile} | awk 'BEGIN{FS="\t"} {print NF}' | sort -u > n.tmp
cat n.tmp
if [ $(wc -l n.tmp | cut -d' ' -f1) != 1 ]; then echo "file not square"; exit 1; fi
if [ $(wc -l chr.tmp | cut -d' ' -f1) -lt 22 ]; then echo "less than 22 chromosomes"; exit 1; fi
echo "`date` done"
>>>
output {
File out = outfile
File tbi = outfile + ".tbi"
}
runtime {
docker: "${docker}"
cpu: "1"
memory: "2 GB"
disks: "local-disk 200 HDD"
zones: "us-central1-f"
preemptible: 0
noAddress: false
}
}
task lift {
String docker
File sumstat_file
File tbi_file = sumstat_file + ".tbi"
String base = basename(sumstat_file)
File b37_ref
File b38_ref
String dollar = "$"
command <<<
echo "Biobank meta-analysis - lift over sumstats if needed"
echo "${sumstat_file}"
echo "${b37_ref}"
echo "${b38_ref}"
echo ""
mv ${sumstat_file} ${base}
mv ${tbi_file} ${base}.tbi
tabix -R ${b37_ref} ${base} | wc -l > b37.txt
tabix -R ${b38_ref} ${base} | wc -l > b38.txt
echo "`date` `cat b37.txt` chr 21 variants build 37"
echo "`date` `cat b38.txt` chr 21 variants build 38"
if ((`cat b37.txt` == 0 && `cat b38.txt` == 0)); then
echo "`date` no chr 21 variants found in either build, quitting"
exit 1
fi
if ((`cat b37.txt` > `cat b38.txt`)); then
echo "`date` lifting to build 38"
time /META_ANALYSIS/scripts/lift.py -chr "#CHR" -pos POS -ref Allele1 -alt Allele2 \
-chain_file /META_ANALYSIS/data/hg19ToHg38.over.chain.gz -tmp_path /cromwell_root/ \
${base} > ${base}.lift.out 2> ${base}.lift.err
gunzip -c ${base}.lifted.gz | \
cut -f2- | awk '
BEGIN { FS=OFS="\t" }
NR==1 { for (i=1;i<=NF;i++) a[$i]=i; print $0 }
NR>1 {
temp=$a["#CHR"]; $a["#CHR"]=$a["anew_chr"]; $a["anew_chr"]=temp; temp=$a["POS"]; $a["POS"]=$a["anew_pos"]; $a["anew_pos"]=temp;
sub("^0", "", $a["#CHR"]); sub("^chr", "", $a["#CHR"]); sub("^X", "23", $a["#CHR"]);
if ($a["#CHR"] ~ /^[0-9]+$/) {
print $0
}
}' | bgzip > ${base}
else
echo "`date` presumably already in build 38"
fi
>>>
output {
File out = base
}
runtime {
docker: "${docker}"
cpu: "1"
memory: "20 GB"
disks: "local-disk 200 HDD"
zones: "us-central1-f"
preemptible: 0
noAddress: false
}
}
task harmonize {
String docker
File sumstat_file
String base = basename(sumstat_file)
File gnomad_ref
String gnomad_ref_base = basename(gnomad_ref)
Int n
String options
command <<<
echo "Biobank meta-analysis - harmonize sumstats to reference"
echo "${sumstat_file}"
echo "${gnomad_ref}"
echo ""
mv ${sumstat_file} ${base}
mv ${gnomad_ref} ${gnomad_ref_base}
echo "`date` harmonizing stats with gnomAD"
python3 /META_ANALYSIS/scripts/harmonize.py ${base} ${gnomad_ref_base} ${n} ${options}\
| bgzip > ${base}.${gnomad_ref_base} && \
tabix -S 1 -s 1 -b 2 -e 2 ${base}.${gnomad_ref_base} && \
echo "`date` done"
>>>
output {
File out = base + "." + gnomad_ref_base
File out_tbi = base + "." + gnomad_ref_base + ".tbi"
}
runtime {
docker: "${docker}"
cpu: "1"
memory: "2 GB"
disks: "local-disk 200 SSD"
zones: "us-central1-f"
preemptible: 0
noAddress: false
}
}
task plot {
File sumstat_file
String base = basename(sumstat_file)
String pop
String docker
command <<<
mv ${sumstat_file} ${base} && \
Rscript - <<EOF
require(ggplot2)
require(data.table)
options(bitmapType='cairo')
data <- fread("${base}")
png("${base}_AF.png", width=1000, height=1000, units="px")
p <- ggplot(data, aes_string(x="AF_Allele2", y="AF_gnomad_v3_b38_ref_${pop}")) +
geom_point(alpha=0.1) +
xlab("AF_${base}") +
theme_minimal(base_size=18)
print(p)
dev.off()
EOF
echo "`date` QQ plot start"
/plot_scripts/QQplot.r --input=${base} --prefix="${base}" --af=AF_Allele2 --pvalue=p.value
echo "`date` Manhattan plot start"
/plot_scripts/ManhattanPlot.r --input=${base} --PVAL=p.value --knownRegionFlank=1000000 --prefix="${base}" --ismanhattanplot=TRUE --isannovar=FALSE --isqqplot=FALSE --CHR="#CHR" --POS=POS --ALLELE1=Allele1 --ALLELE2=Allele2
>>>
output {
Array[File] pngs = glob("*.png")
File out = base + ".regions.txt"
File out_tophits = base + ".tophits.txt"
}
runtime {
docker: "${docker}"
cpu: "1"
memory: 15*ceil(size(sumstat_file, "G")) + " GB"
disks: "local-disk 200 HDD"
zones: "us-central1-f"
preemptible: 0
noAddress: false
}
}
task plot2 {
File sumstat_file
String base = basename(sumstat_file)
String pop
String docker
command <<<
mv ${sumstat_file} ${base} && \
Rscript - <<EOF
require(ggplot2)
require(data.table)
options(bitmapType='cairo')
data <- fread("${base}")
png("${base}_AF.png", width=1000, height=1000, units="px")
p <- ggplot(data, aes_string(x="AF_Allele2", y="AF_gnomad_v3_b38_ref_${pop}")) +
geom_point(alpha=0.1) +
xlab("AF_${base}") +
theme_minimal(base_size=18)
print(p)
dev.off()
EOF
echo "`date` QQ plot start"
/plot_scripts/QQplot.r --input=${base} --prefix="${base}" --af=AF_Allele2 --pvalue=p.value
echo "`date` Manhattan plot start"
/plot_scripts/ManhattanPlot.r --input=${base} --PVAL=p.value --knownRegionFlank=1000000 --prefix="${base}" --ismanhattanplot=TRUE --isannovar=FALSE --isqqplot=FALSE --CHR="#CHR" --POS=POS --ALLELE1=Allele1 --ALLELE2=Allele2
>>>
output {
Array[File] pngs = glob("*.png")
File out = base + ".regions.txt"
File out_tophits = base + ".tophits.txt"
}
runtime {
docker: "${docker}"
cpu: "1"
memory: 15*ceil(size(sumstat_file, "G")) + " GB"
disks: "local-disk 200 HDD"
zones: "us-central1-f"
preemptible: 0
noAddress: false
}
}
task filterbyfc_comparetoLOCObbk_qc {
String docker
File sumstat_file
String base = basename(sumstat_file)
File rmlistfile
String rmlistfile_base = basename(rmlistfile)
File amlistfile
String amlistfile_base = basename(amlistfile)
String outfile = sub(basename(sumstat_file, ".gz"), "\\.bgz$", "") + ".postGWASQC.gz"
command <<<
echo "Biobank meta-analysis - postGWASQC-filterbyfc_comparetoLOCObbk"
echo "${sumstat_file}"
echo ""
mv ${sumstat_file} ${base}
mv ${rmlistfile} ${rmlistfile_base}
mv ${amlistfile} ${amlistfile_base}
python3 /META_ANALYSIS/scripts/harmonize_postGWASQC.py ${base} ${rmlistfile_base} ${amlistfile_base} \
| bgzip > ${outfile} && \
tabix -S 1 -s 1 -b 2 -e 2 ${outfile} && \
echo "`date` done"
>>>
output {
File out = outfile
File out_tbi = outfile + ".tbi"
}
runtime {
docker: "${docker}"
cpu: "1"
memory: "2 GB"
disks: "local-disk 200 SSD"
zones: "us-central1-f"
preemptible: 0
noAddress: false
}
}
workflow munge_sumstats {
File sumstats_loc
Array[Array[String]] sumstat_files = read_tsv(sumstats_loc)
String gnomad_ref_template
scatter (sumstat_file in sumstat_files) {
call clean_filter {
input: sumstat_file=sumstat_file[0], info_col=sumstat_file[3]
}
call lift {
input: sumstat_file=clean_filter.out
}
call harmonize {
input: sumstat_file=lift.out, gnomad_ref=sub(gnomad_ref_template, "POP", sumstat_file[1]), n=sumstat_file[2]
}
call plot {
#input: sumstat_file=harmonize.out, pop=sumstat_file[1]
}
call filterbyfc_comparetoLOCObbk_qc {
input: sumstat_file=harmonize.out, rmlistfile=sumstat_file[4], amlistfile=sumstat_file[5]
}
call plot2 {
input: sumstat_file=filterbyfc_comparetoLOCObbk_qc.out, pop=sumstat_file[1]
}
}
}