Nothing
RAVA.FIRST <- function(x, SNVs.scores = NULL, indels.scores = NULL, ref.level, filter = c("whole", "controls", "any"), maf.threshold = 0.01, min.nb.snps = 2, min.cumulative.maf = NULL, group = NULL, cores = 10, burden = TRUE, H0.burden, burden.parameters, SKAT = TRUE, H0.SKAT, SKAT.parameters, verbose = TRUE, path.data){
##Check if good paramters for RVAT are given
if(burden & missing(H0.burden)) stop("'H0.burden should be given if 'burden = TRUE' and can be obtained using 'NullObject.parameters()'")
if(SKAT & missing(H0.SKAT)) stop("'H0.SKAT should be given if 'SKAT = TRUE' and can be obtained using 'NullObject.parameters()'")
###Attribute CADD regions to variants
if(verbose) cat("Attribution of CADD regions\n")
if(missing(path.data)) stop("the directory 'path.data' to download and use the necessary files for RAVA-FIRST analysis should be provided")
x <- set.CADDregions(x, path.data = path.data)
#Importation of CADD regions to give position information in final results
regions <- read.table(gzfile(paste0(path.data, "/CADDRegions.202204.hg19.bed.gz")), header = T, as.is = T)
rownames(regions) <- regions$Name
###Filtering based on CADD scores
x.filter <- filter.adjustedCADD(x, SNVs.scores = SNVs.scores, indels.scores = indels.scores, ref.level = ref.level, filter = filter, maf.threshold = maf.threshold, min.nb.snps = min.nb.snps, min.cumulative.maf = min.cumulative.maf, group = group, path.data = path.data, verbose = verbose)
if(verbose) cat("Filtering of rare variants within CADD regions\n")
###Association
if(burden){
if(missing(burden.parameters)){ burden.parameters <- list(burden.function = WSS, get.effect.size = F) }
if(verbose) cat("Burden test\n")
x.burden <- burden.subscores(x.filter, H0.burden, burden.function = burden.parameters$burden.function, maf.threshold = maf.threshold, get.effect.size = burden.parameters$get.effect.size, alpha = 0.05, cores = cores, verbose = verbose)
#Add information about CADD region
x.burden <- cbind(x.burden, regions[rownames(x.burden),c(1:3,5,7)])
}else{
x.burden <- NULL
}
if(SKAT){
if(missing(SKAT.parameters)){ SKAT.parameters <- list(get.moments = "size.based", estimation.pvalue = "kurtosis", params.sampling = list(perm.target = 100, perm.max = 50000), debug = F) }
if(verbose) cat("SKAT\n")
x.SKAT <- SKAT(x.filter, H0.SKAT, weights = (1 - x.filter@snps$maf)^24, maf.threshold = maf.threshold, get.moments = SKAT.parameters$get.moments, estimation.pvalue = SKAT.parameters$estimation.pvalue, params.sampling = SKAT.parameters$params.sampling, debug = SKAT.parameters$debug)
#Add information about CADD region
x.SKAT <- cbind(x.SKAT, regions[rownames(x.SKAT),c(1:3,5,7)])
}else{
x.SKAT <- NULL
}
return(list(burden = x.burden, SKAT = x.SKAT))
}
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