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QTL_QC.R
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QTL_QC.R
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#!/hpc/local/CentOS7/dhl_ec/software/R-3.4.0/bin/Rscript --vanilla
# Alternative shebang for local Mac OS X: "#!/usr/local/bin/Rscript --vanilla"
# Linux version for HPC: #!/hpc/local/CentOS7/dhl_ec/software/R-3.4.0/bin/Rscript --vanilla
VERSION="v2.3.10"
LASTEDITDATE="2019-10-15"
SCRIPTNAME="Molecular QTL results Quality Contrl & Parser"
AUTHOR="Sander W. van der Laan | [email protected] | @swvanderlaan | swvanderlaan.github.io"
THISYEAR = format(as.Date(as.POSIXlt(Sys.time())), "%Y")
cat(paste0("+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
",SCRIPTNAME,"
",VERSION," - ",LASTEDITDATE,"
(C)1979-",THISYEAR," | ",AUTHOR,".
+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++"))
# usage: ./QTL_QC.R -p projectdir -r resultfile -o outputdir -t resulttype -q qtltype -a annotfile -j genstatsfile [OPTIONAL: -v verbose (DEFAULT) -q quiet]
# ./QTL_QC.R --projectdir projectdir --resultsfile resultfile --outputdir outputdir --resulttype resulttype --qtltype qtltype --annotfile annotfile --genstats genestatfile [OPTIONAL: --verbose verbose (DEFAULT) -quiet quiet]
cat("\n* Clearing the environment...\n\n")
### CLEAR THE BOARD
cat("\n* Loading function to install packages...\n\n")
### Prerequisite: 'optparse'-library
### * Manual: http://cran.r-project.org/web/packages/optparse/optparse.pdf
### * Vignette: http://www.icesi.edu.co/CRAN/web/packages/optparse/vignettes/optparse.pdf
### Don't say "Loading required package: optparse"...
###suppressPackageStartupMessages(require(optparse))
###require(optparse)
### The part of installing (and loading) packages via Rscript doesn't properly work.
### FUNCTION TO INSTALL PACKAGES
install.packages.auto <- function(x) {
x <- as.character(substitute(x))
if(isTRUE(x %in% .packages(all.available = TRUE))) {
eval(parse(text = sprintf("require(\"%s\")", x)))
} else {
# Update installed packages - this may mean a full upgrade of R, which in turn
# may not be warrented.
#update.install.packages.auto(ask = FALSE)
eval(parse(text = sprintf("install.packages(\"%s\", dependencies = TRUE, repos = \"https://cloud.r-project.org/\")", x)))
}
if(isTRUE(x %in% .packages(all.available = TRUE))) {
eval(parse(text = sprintf("require(\"%s\")", x)))
} else {
if (!requireNamespace("BiocManager"))
install.packages("BiocManager")
BiocManager::install() # this would entail updating installed packages, which in turned may not be warrented
eval(parse(text = sprintf("BiocManager::install(\"%s\")", x)))
eval(parse(text = sprintf("require(\"%s\")", x)))
}
}
cat("\n* Checking availability of required packages and installing if needed...\n\n")
### INSTALL PACKAGES WE NEED
install.packages.auto("optparse")
install.packages.auto("tools")
install.packages.auto("data.table")
install.packages.auto("qvalue") # Needed for multiple-testing correction
cat("\nDone! Required packages installed and loaded.\n\n")
cat("+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++\n")
cat("\n* Setting colours...\n\n")
uithof_color = c("#FBB820","#F59D10","#E55738","#DB003F","#E35493","#D5267B",
"#CC0071","#A8448A","#9A3480","#8D5B9A","#705296","#686AA9",
"#6173AD","#4C81BF","#2F8BC9","#1290D9","#1396D8","#15A6C1",
"#5EB17F","#86B833","#C5D220","#9FC228","#78B113","#49A01D",
"#595A5C","#A2A3A4", "#D7D8D7", "#ECECEC", "#FFFFFF", "#000000")
#--------------------------------------------------------------------------
#--------------------------------------------------------------------------
### OPTION LISTING
help_text = paste0("
+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
",SCRIPTNAME,"
",VERSION," - ",LASTEDITDATE,"
Description:
Results parsing and quality control from QTLTools results using your data, CTMM (eQTL) or Athero-Express (mQTL) data.
The script should be usuable on both any Linux distribution with R 3.5+ installed, Mac OS X and Windows.
NOTE 2018-06-15:
I've edited the eQTL-part (nom/perm for cis) to match with the new 'strand' column.
What remains to be done:
- double check the trans-part as the column numbers have changed by the addition of the 'strand' column in the output.
Example command:
Rscript QTL_QC.R --projectdir adir/somedir --resultsfile adir/somedir/qtl_nom.txt.gz --resulttype NOM --qtltype EQTL --outputdir adir/somedir --annotfile refdir/annotationfile.txt.gz --genstats adir/somedir/data_QC.stats
(C)1979-",THISYEAR," | ",AUTHOR,".
+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
")
option_list = list(
make_option(c("-p", "--projectdir"), action = "store", default = NA, type = 'character',
help = "Path to the project directory, e.g. adir/somedir."),
make_option(c("-r", "--resultfile"), action = "store", default = NA, type = 'character',
help = "Location of the results file, including results filename, e.g. adir/somedir/qtl_nom.txt.gz."),
make_option(c("-t", "--resulttype"), action = "store", default = NA, type = 'character',
help = "The result type, either [NOM/PERM] for nominal or permutation results, respectively."),
make_option(c("-q", "--qtltype"), action = "store", default = NA, type = 'character',
help = "The quantitative trait locus (QTL) type, either [EQTL/MQTL] for expression or methylation QTL analyses, respectively."),
make_option(c("-z", "--analysetype"), action = "store", default = NA, type = 'character',
help = "Cis- or trans-QTL analyse, either [CIS/TRANS]."),
make_option(c("-o", "--outputdir"), action = "store", default = NA, type = 'character',
help = "Path to the output directory, e.g. adir/somedir."),
make_option(c("-a", "--annotfile"), action = "store", default = NA, type = 'character',
help = "Path to the annotation file, e.g. refdir/annotationfile.txt.gz."),
make_option(c("-j", "--genstats"), action = "store", default = NA, type = 'character',
help = "Path to the summary statistics of the genotypes, e.g. adir/somedir/data_QC.stats."),
make_option(c("-v", "--verbose"), action = "store_true", default = TRUE,
help = "Should the program print extra stuff out? [default %default]"),
make_option(c("-s", "--silent"), action = "store_false", dest = "verbose",
help = "Make the program not be verbose.")
#make_option(c("-h", "--help"), action="store_true", default=FALSE,
# help="Show this help message and exit. \nAn example command would look like this: Rscript QTL_QC.R --projectdir adir/somedir --resultsfile adir/somedir/qtl_nom.txt.gz --resulttype NOM --qtltype EQTL --outputdir adir/somedir --annotfile refdir/annotationfile.txt.gz --genstats adir/somedir/data_QC.stats.")
#make_option(c("-c", "--cvar"), action="store", default="this is c",
# help="a variable named c, with a default [default %default]")
)
opt = parse_args(OptionParser(usage = help_text, option_list = option_list))
### OPTIONLIST | FOR LOCAL DEBUGGING
# opt$projectdir="/Users/swvanderlaan/PLINK/analyses/epigenetics/shearstress/shearstress_version_final/DEFAULT_qtl/"
# opt$resultfile="/Users/swvanderlaan/PLINK/analyses/epigenetics/shearstress/shearstress_version_final/DEFAULT_qtl/region_1_shearstress_version_final/aegs_QC_qtlperm_region_1_excl_DEFAULT.txt.gz"
# opt$resultfile="/Users/swvanderlaan/PLINK/analyses/epigenetics/shearstress/shearstress_version_final/DEFAULT_qtl/region_1_shearstress_version_final/aegs_QC_qtlnorm_region_1_excl_DEFAULT.txt.gz"
# opt$resulttype="PERM"
# opt$resulttype="NOM"
# opt$qtltype="MQTL"
# opt$outputdir="/Users/swvanderlaan/PLINK/analyses/epigenetics/shearstress/shearstress_version_final/DEFAULT_qtl/region_1_shearstress_version_final/"
# opt$annotfile="/Users/swvanderlaan/PLINK/_AE_Originals/IlluminaMethylation450K.annotation.txt.gz"
# opt$genstats="/Users/swvanderlaan/PLINK/analyses/epigenetics/shearstress/shearstress_version_final/DEFAULT_qtl/region_1_shearstress_version_final/aegs_1kGp3GoNL5_QC_region_1_excl_DEFAULT.stats"
# opt$analysetype="CIS"
### OPTIONLIST | FOR LOCAL DEBUGGING
if (opt$verbose) {
# You can use either the long or short name; so opt$a and opt$avar are the same.
# Show the user what the variables are.
cat("\n+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++\n")
cat("* Checking the settings as given through the flags.")
cat("\nThe project directory....................: ")
cat(opt$projectdir)
cat("\n\nThe results file.........................: ")
cat(opt$resultfile)
cat("\n\nThe output directory.....................: ")
cat(opt$outputdir)
cat("\n\nThe annotation file......................: ")
cat(opt$annotfile)
cat("\n\nThe results type.........................: ")
cat(opt$resulttype)
cat("\n\nThe QTL-type.............................: ")
cat(opt$qtltype)
cat("\n\nThe analysis type........................: ")
cat(opt$analysetype)
cat("\n\nThe variant summary statistics...........: ")
cat(opt$genstats)
cat("\n+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++\n")
cat("\n\n")
}
cat("\n+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++\n")
cat("Wow, we are all set. Starting \"QTL Results Quality Control & Parser\".")
#--------------------------------------------------------------------------
### START OF THE PROGRAM
# main point of program is here, do this whether or not "verbose" is set
if (!is.na(opt$projectdir) & !is.na(opt$resultfile) & !is.na(opt$outputdir) & !is.na(opt$annotfile) & !is.na(opt$resulttype) & !is.na(opt$qtltype) & !is.na(opt$genstats)) {
cat(paste("\nWe are going to make some graphs for quality control of you QTLtools analysis. \n\nAnalysing these results...............: '",file_path_sans_ext(basename(opt$resultfile), compression = TRUE),"'\nParsed results will be saved here.....: '", opt$outputdir, "'.\n",sep = ''))
#--------------------------------------------------------------------------
### GENERAL SETUP
Today = format(as.Date(as.POSIXlt(Sys.time())), "%Y%m%d")
cat(paste("\nToday's date is: ", Today, ".\n", sep = ''))
#--------------------------------------------------------------------------
#### DEFINE THE LOCATIONS OF DATA
ROOT_loc = opt$projectdir # argument 1
OUT_loc = opt$outputdir # argument 4
cat("\n+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++\n")
#--------------------------------------------------------------------------
### LOADING ANNOTATION AND RESULTS FILES DEPENDING ON RESULT TYPE
cat("\nLoading annotations...\n")
### Location of is set by 'opt$annotfile' # argument 5
### The type of the analysis will determine what to load 'opt$qtltype' # argument 4
if (opt$qtltype == "EQTL") {
cat("\n...for a CTMM based eQTL analysis in monocytes...\n")
ANNOTATIONSFILE = read.table(opt$annotfile, header = TRUE, stringsAsFactors = FALSE, sep = ",", na.strings = "")
colnames(ANNOTATIONSFILE) = c("EntrezID", "ProbeID", "ArrayID",
"GeneName", "GeneInfo","Chr", "GeneTxStart", "GeneTxEnd")
} else if (opt$qtltype == "MQTL") {
cat("\n...for an Athero-Express based MQTL analysis...\n")
ANNOTATIONSFILE = read.table(opt$annotfile, header = TRUE, stringsAsFactors = FALSE, sep = ",", na.strings = "")
colnames(ANNOTATIONSFILE) = c("IlmnID", "ProbeID",
"AddressA_ID", "AlleleA_ProbeSeq", "AddressB_ID", "AlleleB_ProbeSeq",
"Infinium_Design_Type", "Next_Base", "Color_Channel", "Forward_Sequence",
"Genome_Build", "CHR", "MAPINFO", "SourceSeq", "Chromosome_36", "Coordinate_36", "Strand",
"Probe_SNPs", "Probe_SNPs_10", "Random_Loci", "Methyl27_Loci",
"UCSC_RefGene_Name", "UCSC_RefGene_Accession", "UCSC_RefGene_Group", "UCSC_CpG_Islands_Name", "Relation_to_UCSC_CpG_Island",
"Phantom", "DMR", "Enhancer", "HMM_Island", "Regulatory_Feature_Name", "Regulatory_Feature_Group", "DHS",
"UCSC_RefGene_Dist")
} else {
cat("\n\n*** ERROR *** Something is rotten in the City of Gotham; most likely a typo. Double back, please.\n\n",
file = stderr()) # print error messages to stder
}
cat("\nLoading variant statistics...\n")
VARIANTSTATS.RAW = read.table(opt$genstats, header = TRUE, stringsAsFactors = FALSE)
cat("\n* calculating 'minor allele count' (MAC)...")
# calculate MAC
VARIANTSTATS.RAW$MAC <- (VARIANTSTATS.RAW[,19]*VARIANTSTATS.RAW[,18]*2)
cat("\n* calculating 'coded allele frequency' (CAF)...")
# calculate caf
VARIANTSTATS.RAW$CAF <- (((2*VARIANTSTATS.RAW[,16]) + VARIANTSTATS.RAW[,15])/(VARIANTSTATS.RAW[,18]*2))
cat("\n* determining which variants are solely 'imputed'...")
# make imputation column
if (opt$analysetype == "TRANS") {
VARIANTSTATS.RAW$Imputation <- ifelse(VARIANTSTATS.RAW$alternate_ids == "---",
c("imputed"), c("genotyped"))
}
if (opt$analysetype == "CIS") {
VARIANTSTATS.RAW$Imputation <- ifelse(VARIANTSTATS.RAW$alternate_ids == "---",
c("imputed"), c("genotyped"))
}
cat("\n* selecting required variant statistics data...")
# Select the columns we need
VARIANTSTATS = VARIANTSTATS.RAW[,c(2,3,4,5,6, # rsid (2) chromosome (3) position (4) alleleA (5) alleleB (6)
19, # maf (19)
23, # mac, (23)
24, # caf, (24)
8,9,21,18, # imputation quality (8, 9), and HWE (21), and N (18)
25)] # imputation, (25)
# Change the column names
colnames(VARIANTSTATS) = c("VARIANT", "Chr", "BP", "OtherAlleleA", "CodedAlleleA",
"MAF", "MAC", "CAF",
"AvgMAxPostCall", "Info", "HWE", "N", "Imputation")
### Loading main results
RESULTS = read.table(opt$resultfile, header = FALSE, stringsAsFactors = FALSE)
### Loading *nominal* results
if (opt$resulttype == "NOM") { # argument 3
cat("\n\nLoading data from 'nominal pass'...\n")
if (opt$analysetype == "CIS") {
# 1. The phenotype ID
# 2. The chromosome ID of the phenotype
# 3. The start position of the phenotype
# 4. The end position of the phenotype
# 5. The strand orientation of the phenotype
# 6. The total number of variants tested in cis
# 7. The distance between the phenotype and the tested variant (accounting for strand orientation)
# 8. The ID of the tested variant
# 9. The chromosome ID of the variant
# 10. The start position of the variant
# 11. The end position of the variant
# 12. The nominal P-value of association between the variant and the phenotype
# 13. The corresponding regression slope
# 14. A binary flag equal to 1 is the variant is the top variant in cis
RESULTS = RESULTS[ , c(1, 8, 7, 5, 12, 13)]
}
if (opt$analysetype == "TRANS") {
# 1. Phenotype ID
# 2. Phenotype chrID
# 3. Phenotype start
# 4. Variant ID
# 5. Variant chrID
# 6. Variant position
# 7. Nominal P-value of association
# 8. Dummy here. Field used in approximated mapping in trans
# 9. Regression slope
RESULTS = RESULTS[ , c(1, 4, 6, 5, 7, 9)]
}
colnames(RESULTS) = c("ProbeID", "VARIANT", "Distance_VARIANT_ProbeID", "Strand", "Nominal_P", "Beta")
#--------------------------------------------------------------------------
### PLOTTING NOMINAL RESULTS
cat("\nPlotting results...\n")
## To check that the beta approximated permutation p-values are well estimated.
pdf(paste0(opt$outputdir, "/",# map to the output directory
###Today,"_", # add in Today's date -- removed as it causes issues in downstream projects when its the 'next day'
file_path_sans_ext(basename(opt$resultfile), compression = TRUE), # get the basename file without the extension and any compression extensions
"_histogram_nominal_beta.pdf"), onefile = TRUE)
hist(RESULTS$Beta,
breaks = 10000,
xlab = "Effect size", ylab = "Distribution",
main = "Overall distribution of effect size",
col = "#1290D9")
abline(v = mean(RESULTS$Beta), col = "#E55738")
abline(v = (mean(RESULTS$Beta) - 4*sd(RESULTS$Beta)), col = "#E55738", lty = 2)
abline(v = (mean(RESULTS$Beta) + 4*sd(RESULTS$Beta)), col = "#E55738", lty = 2)
dev.off()
} else if (opt$resulttype == "PERM") { ### Loading *permutation* results
cat("\nLoading data from 'permutation pass'...\n")
# old RESULTS = RESULTS[ , c(1, 4, 3, 7, 9)]
# full pass
if (opt$analysetype == "CIS") {
# 1. The phenotype ID
# 2. The chromosome ID of the phenotype
# 3. The start position of the phenotype
# 4. The end position of the phenotype
# 5. The strand orientation of the phenotype
# 6. The total number of variants tested in cis
# 7. The distance between the phenotype and the tested variant (accounting for strand orientation)
# 8. The ID of the top variant
# 9. The chromosome ID of the top variant
# 10. The start position of the top variant
# 11. The end position of the top variant
# 12. The number of degrees of freedom used to compute the P-values
# 13. Dummy
# 14. The first parameter value of the fitted beta distribution
# 15. The second parameter value of the fitted beta distribution (it also gives the effective number of independent tests in the region)
# 16. The nominal P-value of association between the phenotype and the top variant in cis
# 17. The corresponding regression slope
# 18. The P-value of association adjusted for the number of variants tested in cis given by the direct method (i.e. empirircal P-value)
# 19. The P-value of association adjusted for the number of variants tested in cis given by the fitted beta distribution. We strongly recommend to use this adjusted P-value in any downstream analysis
RESULTS = RESULTS[ , c(1, 6, 14, 15, 13, 8, 7, 5, 16, 17, 18, 19)]
}
if (opt$analysetype == "TRANS") {
# nog geen idee hoe de permuted results van QTLTools eruit zien
RESULTS = RESULTS[ , c(1, 6, 14, 15, 13, 8, 7, 5, 16, 17, 18, 19)]
}
#RESULTS = read.table(opt$resultfile, head = FALSE, stringsAsFactors = FALSE)
colnames(RESULTS) = c("ProbeID", "NVariants", "MLE_Beta_shape1", "MLE_Beta_shape2", "Dummy",
"VARIANT", "Distance_VARIANT_ProbeID", "Strand", "Nominal_P", "Beta", "Perm_P", "Approx_Perm_P")
#--------------------------------------------------------------------------
### PLOTTING PERMUTATION RESULTS
pdf(paste0(opt$outputdir, "/",# map to the output directory
###Today,"_", # add in Today's date -- removed as it causes issues in downstream projects when its the 'next day'
file_path_sans_ext(basename(opt$resultfile), compression = TRUE), # get the basename file without the extension and any compression extensions
"_comparing_permutation_pvalues.pdf"), onefile = TRUE)
plot(RESULTS$Perm_P, RESULTS$Approx_Perm_P,
xlab = "Direct method", ylab = "Beta approximation",
main = "Comparing permuted p-values", bty = "n",
pch = 20, col = "#1290D9")
abline(0, 1, col = "#E55738")
hist(RESULTS$Beta,
breaks = 25,
xlab = "Effect size", ylab = "Distribution",
main = "Overall distribution of effect size",
#bty = "n",
col = "#1290D9"
)
abline(v = mean(RESULTS$Beta), col = "#E55738")
abline(v = (mean(RESULTS$Beta) - 4*sd(RESULTS$Beta)), col = "#E55738", lty = 2)
abline(v = (mean(RESULTS$Beta) + 4*sd(RESULTS$Beta)), col = "#E55738", lty = 2)
dev.off()
} else {
cat("\n\n*** ERROR *** Something is rotten in the City of Gotham; most likely a typo. Double back, please.\n\n",
file = stderr()) # print error messages to stder
}
#--------------------------------------------------------------------------
### GET Z-SCORES, SD & SEM
cat("\nGet Z-scores, sd and sem from p-values...\n")
### references:
### - http://stats.stackexchange.com/questions/101136/how-can-i-find-a-z-score-from-a-p-value
RESULTS$Z = qnorm(RESULTS$Nominal_P)
### Get standard deviation (SD)
### NOTE: incorrect formula -- it is not used in any way or form!!
### removing this line and variable means we have to figure out the column numbers
### downstream - major hassle.
RESULTS$SD = (RESULTS$Beta - mean(RESULTS$Beta))/RESULTS$Z
### Get standard error of the mean (SEM)
RESULTS$SEM = abs(RESULTS$Beta/RESULTS$Z)
#--------------------------------------------------------------------------
#### APPLY MULTIPLE TESTING CORRECTION ###
cat("\nApplying multiple testing correction methods.\n")
cat("\n* Conservative correction: Bonferroni correction...\n")
### Bonferroni correction - Conservative
### references:
### - http://en.wikipedia.org/wiki/Bonferroni_correction
### - https://stat.ethz.ch/R-manual/R-devel/library/stats/html/p.adjust.html
if (opt$resulttype == "NOM") {
RESULTS$Bonferroni = p.adjust(RESULTS$Nominal_P, method = "bonferroni")
} else if (opt$resulttype == "PERM") {
RESULTS$Bonferroni = p.adjust(RESULTS$Approx_Perm_P, method = "bonferroni")
} else {
cat("\n\n*** ERROR *** Something is rotten in the City of Gotham; most likely a typo. Double back, please.\n\n",
file = stderr()) # print error messages to stder
}
cat("\n* Less conservative correction: Benjamini & Hochberg correction...\n")
### Benjamini & Hochberg correction - Less conservative
### references:
### - http://en.wikipedia.org/wiki/False_discovery_rate
### - https://stat.ethz.ch/R-manual/R-devel/library/stats/html/p.adjust.html
if (opt$resulttype == "NOM") {
RESULTS$BenjHoch = p.adjust(RESULTS$Nominal_P, method = "fdr")
} else if (opt$resulttype == "PERM") {
RESULTS$BenjHoch = p.adjust(RESULTS$Approx_Perm_P, method = "fdr")
} else {
cat("\n\n*** ERROR *** Something is rotten in the City of Gotham; most likely a typo. Double back, please.\n\n",
file = stderr()) # print error messages to stder
}
cat("\n* Least conservative correction: Storey & Tibshirani correction...\n")
### Storey & Tibshirani correction - Least conservative
### references:
### - http://en.wikipedia.org/wiki/False_discovery_rate
### - http://svitsrv25.epfl.ch/R-doc/library/qvalue/html/qvalue.html
### Requires a bioconductor package: "qvalue"
if(opt$resulttype == "NOM") {
# RESULTS$Q = qvalue(RESULTS$Nominal_P)$qvalues # original code
# RESULTS$Q = ifelse(RESULTS$Nominal_P > 0, qvalue(RESULTS$Nominal_P)$qvalues, "NA")
RESULTS$Q = "Not_calculated._Throws_an_error_when_p-value_is_infinite_or_NA._NEED_FIXING"
} else if(opt$resulttype == "PERM") {
#print((RESULTS))
# RESULTS$Q = qvalue(RESULTS$Approx_Perm_P)$qvalues # original code
RESULTS$Q = ifelse(RESULTS$Approx_Perm_P > 0, qvalue(RESULTS$Approx_Perm_P)$qvalues, "NA")
# RESULTS$Q = "Not_calculated._Throws_an_error_when_p-value_is_infinite_or_NA._NEED_FIXING"
} else {
cat ("\n\n*** ERROR *** Something is rotten in the City of Gotham; most likely a typo. Double back, please.\n\n",
file=stderr()) # print error messages to stder
}
#--------------------------------------------------------------------------
#### ADD IN THE ANNOTATIONS ###
cat("\nApplying annotations.\n")
cat("\n* First order based on Benjamini-Hochberg p-values...\n")
RESULTS.toANNOTATE = RESULTS[order(RESULTS$BenjHoch),]
cat("\n* Now annotating...\n")
if (opt$qtltype == "EQTL") {
cat("\n...the results of a CTMM based eQTL analysis in monocytes.\n")
RESULTS.toANNOTATE = cbind(RESULTS.toANNOTATE, ANNOTATIONSFILE[match(RESULTS.toANNOTATE[,1], ANNOTATIONSFILE$ProbeID ),
c("EntrezID","ArrayID",
"GeneName", "GeneInfo",
"Chr", "GeneTxStart", "GeneTxEnd")])
} else if (opt$qtltype == "MQTL") {
cat("\n...the results of an Athero-Express based MQTL analysis.\n")
RESULTS.toANNOTATE = cbind(RESULTS.toANNOTATE, ANNOTATIONSFILE[match(RESULTS.toANNOTATE[,1], ANNOTATIONSFILE$ProbeID ),
c("IlmnID", "ProbeID",
"AddressA_ID", "AlleleA_ProbeSeq", "AddressB_ID", "AlleleB_ProbeSeq",
"Infinium_Design_Type", "Next_Base", "Color_Channel", "Forward_Sequence",
"Genome_Build", "CHR", "MAPINFO", "SourceSeq", "Chromosome_36", "Coordinate_36", "Strand",
"Probe_SNPs", "Probe_SNPs_10", "Random_Loci", "Methyl27_Loci",
"UCSC_RefGene_Name", "UCSC_RefGene_Accession", "UCSC_RefGene_Group", "UCSC_CpG_Islands_Name", "Relation_to_UCSC_CpG_Island",
"Phantom", "DMR", "Enhancer", "HMM_Island", "Regulatory_Feature_Name", "Regulatory_Feature_Group", "DHS",
"UCSC_RefGene_Dist")])
} else {
cat("\n\n*** ERROR *** Something is rotten in the City of Gotham; most likely a typo. Double back, please.\n\n",
file = stderr()) # print error messages to stder
}
cat("\n* Merging results, genetic stats, and annotations...\n")
if (opt$resulttype == "NOM") {
RESULTS.toANNOTATE2 = cbind(RESULTS.toANNOTATE, VARIANTSTATS[match(RESULTS.toANNOTATE[,2], VARIANTSTATS$VARIANT ),])
} else if (opt$resulttype == "PERM") {
RESULTS.toANNOTATE2 = cbind(RESULTS.toANNOTATE, VARIANTSTATS[match(RESULTS.toANNOTATE[,6], VARIANTSTATS$VARIANT ),])
} else {
cat("\n\n*** ERROR *** Something is rotten in the City of Gotham; most likely a typo. Double back, please.\n\n",
file = stderr()) # print error messages to stder
}
if (opt$qtltype == "EQTL") {
cat("\n* Parsing annotated results for a CTMM eQTL analysis in monocytes...\n")
if (opt$resulttype == "NOM") {
cat("\n--- nominal results ---\n")
# print(head(RESULTS.toANNOTATE2))
# 1 ProbeID 2 VARIANT 3 Distance_VARIANT_ProbeID 4 Strand 5 Nominal_P
# 6 Beta 7 Z 8 SD 9 SEM 10 Bonferroni 11 BenjHoch 12 Q
# 13 EntrezID 14 ArrayID 15 GeneName 16 GeneInfo 17 Chr 18 GeneTxStart 19 GeneTxEnd
# 20 VARIANT 21 Chr 22 BP 23 OtherAlleleA 24 CodedAlleleA
# 25 MAF 26 MAC 27 CAF 28 AvgMAxPostCall 29 Info 30 HWE 31 N 32 Imputation
RESULTS.ANNOTATE = RESULTS.toANNOTATE2[,c(1,2,21,22,23,24,25,26,27,30,29,32,31, # Variant information
15,13,3,4,17,18,19, # Gene information
6,9,5,10,11,12)] # association statistics
} else if (opt$resulttype == "PERM") {
cat("\n--- permuted results ---\n")
# print(head(RESULTS.toANNOTATE2))
# 1 ProbeID 2 NVariants 3 MLE_Beta_shape1 4 MLE_Beta_shape2 5 Dummy
# 6 VARIANT 7 Distance_VARIANT_ProbeID 8 Strand 9 Nominal_P
# 10 Beta 11 Perm_P 12 Approx_Perm_P 13 Z 14 SD 15 SEM 16 Bonferroni 17 BenjHoch 18 Q
# 19 EntrezID 20 ArrayID 21 GeneName/GeneName_UCSC 22 GeneInfo 23 Chr 24 GeneTxStart 25 GeneTxEnd
# 26 VARIANT 27 Chr 28 BP 29 OtherAlleleA 30 CodedAlleleA
# 31 MAF 32 MAC 33 CAF 34 AvgMAxPostCall 35 Info 36 HWE 37 N 38 Imputation
RESULTS.ANNOTATE = RESULTS.toANNOTATE2[,c(1,6,27,28,29,30,31,32,33,36,35,38,37, # Variant information
21,19,7,8,23,24,25, # Gene information
10,15,9,11,12,16,17,18)] # association statistics
#print(head(RESULTS.ANNOTATE))
} else {
cat("\n\n*** ERROR *** Something is rotten in the City of Gotham; most likely a typo. Double back, please.\n\n",
file = stderr()) # print error messages to stder
}
} else if (opt$qtltype == "MQTL") {
cat("\n* Parsing annotated results for an Athero-Express mQTL analysis...\n")
if (opt$resulttype == "NOM") {
cat("\n--- nominal results ---\n")
#str(RESULTS.toANNOTATE2)
RESULTS.ANNOTATE = RESULTS.toANNOTATE2[,c(1,2,48,49,50,51,52,53,54,57,56,59,58, # Variant information
3,4,24,25,19, # CpG information
34,35,36,38, # CpG associated information
39,40,41,42,43,44,45, # CpG associated information
6,9,5,10,11,12)] # association statistics
} else if (opt$resulttype == "PERM") {
cat("\n--- permuted results ---\n")
RESULTS.ANNOTATE = RESULTS.toANNOTATE2[,c(1,6,54,55,56,57,58,59,60,63,62,65,64, # Variant information
7,8,30,31,25, # CpG information
40,41,42,44,45,46,47,48,49,50,51, # CpG associated information
10,15,9,11,12,16,17,18)] # association statistics
} else {
cat("\n\n*** ERROR *** Something is rotten in the City of Gotham; most likely a typo. Double back, please.\n\n",
file = stderr()) # print error messages to stder
}
} else {
cat("\n\n*** ERROR *** Something is rotten in the City of Gotham; most likely a typo. Double back, please.\n\n",
file = stderr()) # print error messages to stder
}
cat("\n* Remove duplicate gene names...\n")
if (opt$qtltype == "EQTL") {
cat("\n...for results of a CTMM eQTL analysis in monocytes...\n")
RESULTS.ANNOTATE[, "GeneName"] = as.character(lapply(RESULTS.toANNOTATE2[,"GeneName"],
FUN = function(x){paste(unique(unlist(strsplit(x, split = ";"))), sep = "", collapse = ";")}))
} else if (opt$qtltype == "MQTL") {
cat("\n...for results of an Athero-Express mQTL analysis...\n")
RESULTS.ANNOTATE[, "UCSC_RefGene_Name"] = as.character(lapply(RESULTS.toANNOTATE2[,"UCSC_RefGene_Name"],
FUN = function(x){paste(unique(unlist(strsplit(x, split = ";"))), sep = "", collapse = ";")}))
RESULTS.ANNOTATE[, "UCSC_RefGene_Accession"] = as.character(lapply(RESULTS.toANNOTATE2[,"UCSC_RefGene_Accession"],
FUN = function(x){paste(unique(unlist(strsplit(x, split = ";"))), sep = "", collapse = ";")}))
RESULTS.ANNOTATE[, "UCSC_RefGene_Group"] = as.character(lapply(RESULTS.toANNOTATE2[,"UCSC_RefGene_Group"],
FUN = function(x){paste(unique(unlist(strsplit(x, split = ";"))), sep = "", collapse = ";")}))
} else {
cat("\n\n*** ERROR *** Something is rotten in the City of Gotham; most likely a typo. Double back, please.\n\n",
file = stderr()) # print error messages to stder
}
cat("\n* Correct Colnames and replace spaces in gene-names ...\n")
if (opt$qtltype == "EQTL") {
cat("\n...for results of a CTMM eQTL analysis in monocytes ...\n")
if (opt$resulttype == "NOM") {
colnames(RESULTS.ANNOTATE) = c("ProbeID", "VARIANT", "Chr", "BP", "OtherAlleleB", "CodedAlleleA", "MAF", "MAC", "CAF", "HWE", "Info", "Imputation", "N",
"GeneName", "EntrezID", "Distance_VARIANT_GENE", "Strand", "Chr_Gene", "GeneTxStart", "GeneTxEnd",
"Beta", "SE", "Nominal_P", "Bonferroni","BenjHoch","Q")
RESULTS.ANNOTATE$GeneName <- gsub(" ", "_", RESULTS.ANNOTATE$GeneName)
} else if (opt$resulttype == "PERM") {
colnames(RESULTS.ANNOTATE) = c("ProbeID", "VARIANT", "Chr", "BP", "OtherAlleleB", "CodedAlleleA", "MAF", "MAC", "CAF", "HWE", "Info", "Imputation", "N",
"GeneName","EntrezID", "Distance_VARIANT_GENE", "Strand", "Chr_Gene", "GeneTxStart", "GeneTxEnd",
"Beta", "SE", "Nominal_P","Perm_P","ApproxPerm_P", "Bonferroni","BenjHoch","Q")
RESULTS.ANNOTATE$GeneName <- gsub(" ", "_", RESULTS.ANNOTATE$GeneName)
} else {
cat("\n\n*** ERROR *** Something is rotten in the City of Gotham; most likely a typo. Double back, please.\n\n",
file = stderr()) # print error messages to stder
}
} else if (opt$qtltype == "MQTL") {
cat("\n...for results of an Athero-Express mQTL analysis ...\n")
if (opt$resulttype == "NOM") {
colnames(RESULTS.ANNOTATE) = c("ProbeID", "VARIANT", "Chr", "BP", "OtherAlleleB", "CodedAlleleA", "MAF", "MAC", "CAF", "HWE", "Info", "Imputation", "N",
"Distance_VARIANT_CpG", "Strand", "Chr_CpG", "BP_CpG", "ProbeType",
"GeneName_UCSC", "AccessionID_UCSC", "GeneGroup_UCSC", "CpG_Island_Relation_UCSC",
"Phantom", "DMR", "Enhancer", "HMM_Island", "RegulatoryFeatureName", "RegulatoryFeatureGroup", "DHS",
"Beta", "SE", "Nominal_P", "Bonferroni","BenjHoch","Q")
RESULTS.ANNOTATE$GeneName_UCSC <- gsub(" ", "_", RESULTS.ANNOTATE$GeneName_UCSC)
} else if (opt$resulttype == "PERM") {
colnames(RESULTS.ANNOTATE) = c("ProbeID", "VARIANT", "Chr", "BP", "OtherAlleleB", "CodedAlleleA", "MAF", "MAC", "CAF", "HWE", "Info", "Imputation", "N",
"Distance_VARIANT_CpG", "Strand", "Chr_CpG", "BP_CpG", "ProbeType",
"GeneName_UCSC", "AccessionID_UCSC", "GeneGroup_UCSC", "CpG_Island_Relation_UCSC",
"Phantom", "DMR", "Enhancer", "HMM_Island", "RegulatoryFeatureName", "RegulatoryFeatureGroup", "DHS",
"Beta", "SE", "Nominal_P","Perm_P","ApproxPerm_P", "Bonferroni","BenjHoch","Q")
RESULTS.ANNOTATE$GeneName_UCSC <- gsub(" ", "_", RESULTS.ANNOTATE$GeneName_UCSC)
} else {
cat("\n\n*** ERROR *** Something is rotten in the City of Gotham; most likely a typo. Double back, please.\n\n",
file = stderr()) # print error messages to stder
}
} else {
cat("\n\n*** ERROR *** Something is rotten in the City of Gotham; most likely a typo. Double back, please.\n\n",
file = stderr()) # print error messages to stder
}
cat("\n* Remove temporary files...\n")
rm(RESULTS.toANNOTATE, RESULTS.toANNOTATE2)
#--------------------------------------------------------------------------
### SAVE NEW DATA ###
cat("\n* Saving parsed data...\n")
if (opt$resulttype == "NOM") {
# write.table(RESULTS.ANNOTATE[which(RESULTS.ANNOTATE$BenjHoch <= 0.05), ], # with filtering on Q-value
write.table(RESULTS.ANNOTATE[which(RESULTS.ANNOTATE$BenjHoch != "NA"), ], # without filtering on Q-value
#paste0(opt$outputdir, "/",
# ###Today,"_", # add in Today's date -- removed as it causes issues in downstream projects when its the 'next day'
# file_path_sans_ext(basename(opt$resultfile), compression = TRUE),
# ".nominal.P0_05.txt"),
paste0(opt$outputdir, "/",
###Today,"_", # add in Today's date -- removed as it causes issues in downstream projects when its the 'next day'
file_path_sans_ext(basename(opt$resultfile), compression = TRUE),
".nominal.all.txt"),
quote = FALSE , row.names = FALSE, col.names = TRUE, sep = ",", na = "NA", dec = ".")
} else if (opt$resulttype == "PERM") {
write.table(RESULTS.ANNOTATE[which(RESULTS.ANNOTATE$BenjHoch <= 0.05), ], # with filtering on Q-value
# write.table(RESULTS.ANNOTATE[which(RESULTS.ANNOTATE$BenjHoch != "NA"), ], # without filtering on Q-value
paste0(opt$outputdir, "/",
###Today,"_", # add in Today's date -- removed as it causes issues in downstream projects when its the 'next day'
file_path_sans_ext(basename(opt$resultfile), compression = TRUE),
".perm.Q0_05.txt"),
#paste0(opt$outputdir, "/",
# ###Today,"_", # add in Today's date -- removed as it causes issues in downstream projects when its the 'next day'
# file_path_sans_ext(basename(opt$resultfile), compression = TRUE),
# ".perm.all.txt"),
quote = FALSE , row.names = FALSE, col.names = TRUE, sep = ",", na = "NA", dec = ".")
} else {
cat("\n\n*** ERROR *** Something is rotten in the City of Gotham; most likely a typo. Double back, please.\n\n",
file = stderr()) # print error messages to stder
}
} else {
cat("*** ERROR *** You didn't specify all variables:\n
- --p/projectdir : path to project directory, e.g. adir/somedir.\n
- --r/resultfile : location of the results file, including results filename, e.g. adir/somedir/qtl_nom.txt.gz.\n
- --t/resulttype : the results type (NOM for nominal; PERM for permutation).\n
- --q/qtltype : the QTL analysis type (EQTL for expression QTL; MQTL for methylation QTL).\n
- --z/analysetype : the analysis type, cis- or trans-QTL analyse ([CIS/TRANS]).\n
- --o/outputdir : path to output directory, e.g. adir/somedir.\n
- --a/annotfile : path to annotation file of genes, e.g. refdir/annotationfile.txt.gz.\n
- --j/genstats : path to summary statistics of variants, e.g. adir/somedir/data_QC.stats.\n\n",
file = stderr()) # print error messages to stderr
}
#--------------------------------------------------------------------------
### CLOSING MESSAGE
cat(paste("All done parsing QTLtools data on [",file_path_sans_ext(basename(opt$resultfile), compression = TRUE),"].\n"))
cat(paste("\nToday's: ",Today, "\n"))
cat("+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++\n")
#--------------------------------------------------------------------------
### SAVE ENVIRONMENT | FOR DEBUGGING
# if(opt$resulttype == "NOM")
# save.image(paste0(opt$outputdir, "/",Today,"_",file_path_sans_ext(basename(opt$resultfile), compression = TRUE),"_NOM_DEBUG_FastQTL_analysis.RData"))
# if(opt$resulttype == "PERM")
# save.image(paste0(opt$outputdir, "/",Today,"_",file_path_sans_ext(basename(opt$resultfile), compression = TRUE),"_PERM_DEBUG_FastQTL_analysis.RData"))