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#' compare two GISTIC objects | ||
#' @details Performs fisher test on 2x2 contingency table generated from two GISTIC objects | ||
#' | ||
#' @param g1 first \code{\link{GISTIC}} object | ||
#' @param g2 second \code{\link{GISTIC}} object | ||
#' @param g1Name optional name for first cohort | ||
#' @param g2Name optional name for second cohort | ||
#' @param minEvent Consider only cytobands with minimum this number of samples altered in at least one of the cohort for analysis. Helpful to ignore single mutated genes. Default 5. | ||
#' @param pseudoCount If TRUE, adds 1 to the contingency table with 0's to avoid `Inf` values in the estimated odds-ratio. | ||
#' @return result list | ||
#' @export | ||
#' @seealso \code{\link{forestPlot}} | ||
#' @seealso \code{\link{lollipopPlot2}} | ||
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gisticCompare = function(g1, g2, g1Name = NULL, g2Name = NULL, minEvent = 5, pseudoCount = FALSE){ | ||
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g1.gs <- getCytobandSummary(x = g1) | ||
g2.gs <- getCytobandSummary(x = g2) | ||
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if(is.null(g1Name)){ | ||
g1Name = 'G1' | ||
} | ||
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if(is.null(g2Name)){ | ||
g2Name = 'G2' | ||
} | ||
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g1.sampleSize = as.numeric(g1@summary[ID %in% "Samples", summary]) | ||
g2.sampleSize = as.numeric(g2@summary[ID %in% "Samples", summary]) | ||
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g1_nums = .getAmpDelCounts(g = g1) | ||
g2_nums = .getAmpDelCounts(g = g2) | ||
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amptbl = merge(g1_nums[Variant_Classification %in% "Amp", .N , .(Cytoband)], g2_nums[Variant_Classification %in% "Amp", .N , .(Cytoband)], by = "Cytoband", all = TRUE) | ||
colnames(amptbl) = c("Cytoband", "G1", "G2") | ||
amptbl[is.na(amptbl)] = 0 | ||
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deltbl = merge(g1_nums[Variant_Classification %in% "Del", .N , .(Cytoband)], g2_nums[Variant_Classification %in% "Del", .N , .(Cytoband)], by = "Cytoband", all = TRUE) | ||
colnames(deltbl) = c("Cytoband", "G1", "G2") | ||
deltbl[is.na(deltbl)] = 0 | ||
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cnvtbl = data.table::rbindlist(l = list(Amp = amptbl, Del = deltbl), idcol = "CNV") | ||
cnvtbl[,G1_wt := g1.sampleSize - G1] | ||
cnvtbl[,G2_wt := g2.sampleSize - G2] | ||
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fisherTable = lapply(seq_len(nrow(cnvtbl)), function(i){ | ||
gene = cnvtbl[i, 1] | ||
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ft_mat = matrix(c(cnvtbl[i, G1], cnvtbl[i, G1_wt], cnvtbl[i, G2], cnvtbl[i, G2_wt]), | ||
byrow = TRUE, nrow = 2) | ||
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if(length(which(x = ft_mat == 0)) > 0){ | ||
if(pseudoCount){ | ||
ft_mat = ft_mat + 1 | ||
} | ||
} | ||
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xf = fisher.test(ft_mat, conf.int = TRUE, conf.level = 0.95) | ||
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pval = xf$p.value | ||
or = xf$estimate | ||
ci.up = xf$conf.int[2] | ||
ci.low = xf$conf.int[1] | ||
tdat = data.table::data.table(pval = pval, or = or, ci.up = ci.up, ci.low = ci.low) | ||
tdat | ||
}) | ||
fisherTable = data.table::rbindlist(fisherTable, use.names = TRUE, fill = TRUE) | ||
fisherTable = cbind(cnvtbl, fisherTable) | ||
fisherTable = fisherTable[order(pval)] | ||
fisherTable[,adjPval := p.adjust(p = pval, method = 'fdr')] | ||
colnames(fisherTable)[3:6] = c(g1Name, g2Name, paste0(g1Name, "_wt"), paste0(g2Name, "_wt")) | ||
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fisherTable | ||
} | ||
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.getAmpDelCounts = function(g){ | ||
gs <- getCytobandSummary(x = g) | ||
amp_bands = gs[Variant_Classification %in% "Amp"] | ||
del_bands = gs[Variant_Classification %in% "Del"] | ||
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amp_bands_samps = lapply(split(amp_bands, amp_bands$Cytoband), function(cb){ | ||
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cb_tsbs = lapply(cb$Unique_Name, function(b){ | ||
b_samps = g@cnMatrix[b,] | ||
names(b_samps[b_samps != ""]) | ||
}) | ||
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cb_tsbs = unique(unlist(cb_tsbs, use.names = FALSE)) | ||
data.table::data.table(Cytoband = unique(cb$Cytoband), Tumor_Sample_Barcode = cb_tsbs) | ||
}) | ||
amp_bands_samps_tbl = data.table::rbindlist(amp_bands_samps) | ||
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del_bands_samps = lapply(split(del_bands, del_bands$Cytoband), function(cb){ | ||
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cb_tsbs = lapply(cb$Unique_Name, function(b){ | ||
b_samps = g@cnMatrix[b,] | ||
names(b_samps[b_samps != ""]) | ||
}) | ||
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cb_tsbs = unique(unlist(cb_tsbs, use.names = FALSE)) | ||
data.table::data.table(Cytoband = unique(cb$Cytoband), Tumor_Sample_Barcode = cb_tsbs) | ||
}) | ||
del_bands_samps_tbl = data.table::rbindlist(del_bands_samps) | ||
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data.table::rbindlist(list(Amp = amp_bands_samps_tbl, Del= del_bands_samps_tbl), idcol = "Variant_Classification") | ||
} |
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