Adress #939 #940

.github/workflows/stale_bot.yaml

@@ -0,0 +1,22 @@
+name: Close inactive issues
+on:
+  schedule:
+    - cron: "30 1 * * *"
+
+jobs:
+  close-issues:
+    runs-on: ubuntu-latest
+    permissions:
+      issues: write
+      pull-requests: write
+    steps:
+      - uses: actions/stale@v5
+        with:
+          days-before-issue-stale: 60
+          days-before-issue-close: 14
+          stale-issue-label: "stale"
+          stale-issue-message: "This issue is stale because it has been open for 30 days with no activity."
+          close-issue-message: "This issue was closed because it has been inactive for 14 days since being marked as stale."
+          days-before-pr-stale: -1
+          days-before-pr-close: -1
+          repo-token: ${{ secrets.GITHUB_TOKEN }}

R/annovarToMaf.R

@@ -117,24 +117,16 @@ annovarToMaf = function(annovar, Center = NULL, refBuild = 'hg19', tsbCol = NULL
       ncRNA_splicing = "RNA"
     )
 
-    ann_exonic = ann[Func.refGene %in% 'exonic']
-    ann_res = ann[!Func.refGene %in% 'exonic']
-    if(nrow(ann_exonic) ==0 & nrow(ann_res) == 0){
-      stop("No suitable exonic or intronic variants found!")
-    }
-
-    #Exonic variants
-    if(nrow(ann_exonic) > 0){
-      cat("-Processing Exonic variants\n")
+    #Choose first entry for mixed annotations (e.g; exonic;splicing)
+    ann[, Func.refGene := unlist(data.table::tstrsplit(x = as.character(Func.refGene), split = ";", keep = 1))]
+    ann[, ExonicFunc.refGene := unlist(data.table::tstrsplit(x = as.character(ExonicFunc.refGene), split = ";", keep = 1))]
+    ann$Variant_Classification = ifelse(is.na(ann$ExonicFunc.refGene), annovar_values[ann$Func.refGene], annovar_values[ann$ExonicFunc.refGene])
 
-      #Choose first entry for mixed annotations (e.g; exonic;splicing)
-      ann_exonic[, Func.refGene := data.table::tstrsplit(x = as.character(ann_exonic$Func.refGene), split = ";", keep = 1)]
-      cat("--Adding Variant_Classification\n")
-      ann_exonic[,Variant_Classification := annovar_values[ExonicFunc.refGene]]
+    if(nrow(ann[!is.na(AAChange.refGene)]) > 0){
+      cat("--Extracting tx, exon, txchange and aa-change\n")
+      ann_change = ann[!is.na(AAChange.refGene)]
+      aa_change = unlist(data.table::tstrsplit(x = as.character(ann_change$AAChange.refGene),split = ',', fixed = TRUE, keep = 1))
 
-      #Parse aa-change for exonic variants
-      cat("--Parsing aa-change\n")
-      aa_change = unlist(data.table::tstrsplit(x = as.character(ann_exonic$AAChange.refGene),split = ',', fixed = TRUE, keep = 1))
       aa_tbl = lapply(aa_change, function(x){
         x = unlist(strsplit(x = x, split = ":", fixed = TRUE))
 
@@ -155,80 +147,34 @@ annovarToMaf = function(annovar, Center = NULL, refBuild = 'hg19', tsbCol = NULL
         data.table::data.table(tx, exon, txChange, aaChange)
       })
       aa_tbl = data.table::rbindlist(l = aa_tbl)
-
-      if(length(aa_change) != nrow(ann_exonic)){
-        stop("Something went wrong parsing aa-change")
+      if(length(aa_change) != nrow(ann_change)){
+        stop("Something went wrong while parsing aa-change")
       }
-      ann_exonic = cbind(ann_exonic, aa_tbl)
-    }
-
-    #Non-exonic variants
-    if(nrow(ann_res) > 0){
-      cat("-Processing Non-exonic variants\n")
-      ann_res[, Func.refGene := data.table::tstrsplit(x = as.character(ann_res$Func.refGene), split = ";", keep = 1)]
-      cat("--Adding Variant_Classification\n")
-      ann_res[,Variant_Classification := annovar_values[Func.refGene]]
-      #Merge exonic and non-exonic variants
-      ann = data.table::rbindlist(l = list(ann_exonic, ann_res), use.names = TRUE, fill = TRUE)
-    }else{
-      ann = ann_exonic
+      ann_change = cbind(ann_change, aa_tbl)
+      ann = data.table::rbindlist(l = list(ann_change, ann[is.na(AAChange.refGene)]), use.names = TRUE, fill = TRUE)
     }
 
     #Add Variant-type annotations based on difference between ref and alt alleles
     cat("-Adding Variant_Type\n")
-    ann[,ref_alt_diff := nchar(Ref) - nchar(Alt)]
-    ann[, Variant_Type := ifelse(
-      ref_alt_diff == 0 ,
-      yes = ifelse(test = Ref != "-" & Alt != "-", yes = "SNP",
-      no = ifelse(ref_alt_diff < 0 , yes = "INS", no = "DEL")), no = NA)
-    ]
-
-    #Check for MNPs (they are neither INDELS nor SNPs)
-    ann$Variant_Type = ifelse(
-        test = ann$Variant_Type == "SNP",
-        yes = ifelse(
-          test = nchar(ann$Ref) > 1,
-          yes = "MNP",
-          no = "SNP"
-        ),
-        no = ann$Variant_Type
-      )
+    ann$Variant_Type = ifelse(endsWith(x = ann$Variant_Classification, suffix = "_Del"), yes = "DEL", no = NA)
+    ann$Variant_Type = ifelse(endsWith(x = ann$Variant_Classification, suffix = "_Ins"), yes = "INS", no = ann$Variant_Type)
+    ann$Variant_Type = ifelse(ann$Variant_Classification %in% c("Missense_Mutation", "Silent") , yes = "SNP", no = ann$Variant_Type)
 
-    #Annotate MNPs as Unknown VC
-    ann_mnps = ann[Variant_Type %in% "MNP"]
-    if(nrow(ann_mnps) > 0){
-      ann = ann[!Variant_Type %in% "MNP"]
-      ann_mnps[,Variant_Classification := "Unknown"]
-      ann = rbind(ann, ann_mnps)
-      rm(ann_mnps)
-    }
-
-    #Frameshift_INDEL, Inframe_INDEL are annotated by annovar without INS or DEL status
-    #Parse this based on difference between ref and alt alleles
-    ann_indel = ann[Variant_Classification %in% c("Frameshift_INDEL", "Inframe_INDEL")]
-    if(nrow(ann_indel) > 0){
-      cat("-Fixing ambiguous INDEL annotations\n")
-      ann = ann[!Variant_Classification %in% c("Frameshift_INDEL", "Inframe_INDEL")]
-      vc_fixed = lapply(1:nrow(ann_indel), function(i) {
-        x = ann_indel[i, Variant_Classification]
-        if (x == "Frameshift_INDEL") {
-          if (ann_indel[i, ref_alt_diff] > 0) {
-            return("Frame_Shift_Del")
-          } else{
-            return("Frame_Shift_Ins")
-          }
-        } else if (x == "Inframe_INDEL") {
-          if (ann_indel[i, ref_alt_diff] > 0) {
-            return("In_Frame_Del")
-          } else{
-            return("In_Frame_Ins")
-          }
-        } else{
-          return(x)
-        }
-      })
-      ann_indel[,Variant_Classification := unlist(vc_fixed)]
-      ann = rbind(ann, ann_indel)
+    ann[,ref_alt_len := nchar(Ref) + nchar(Alt)]
+    ann[,ref_alt_diff := nchar(Ref) - nchar(Alt)]
+    ann$Variant_Type = ifelse(ann$ref_alt_diff < 0 , yes = "INS", no = ann$Variant_Type)
+    ann$Variant_Type = ifelse(ann$ref_alt_diff > 0 , yes = "DEL", no = ann$Variant_Type)
+
+     #For ambiguous variants such as DNPs, TNPs and ONPs
+    if(nrow(ann[is.na(Variant_Type)]) > 0){
+      ann[, ref_alt := paste(Ref, Alt, sep = ">")]
+      ann_na = ann[is.na(Variant_Type)]
+      ann_na$Variant_Type = ifelse(test = ann_na$ref_alt %in% paste("-", c("A", "T", "G", "C"), sep = ">"), yes = "INS",
+                                   no = ifelse(test = ann_na$ref_alt %in% paste(c("A", "T", "G", "C"), "-", sep = ">"), yes = "DEL",
+                                               no = ifelse(ann_na$ref_alt_len == 2, yes = "SNP", no = ifelse(test = ann_na$ref_alt_len == 4, yes = "DNP",
+                                                                                                             no = "ONP"))))
+      ann[, ref_alt := NULL]
+      ann = data.table::rbindlist(l = list(ann[!is.na(Variant_Type)], ann_na), use.names = TRUE, fill = TRUE)
     }
 
   #Annovar ensGene doesn't provide HGNC gene symbols as Hugo_Symbol. We will change them manually.
@@ -246,14 +192,18 @@ annovarToMaf = function(annovar, Center = NULL, refBuild = 'hg19', tsbCol = NULL
     }
   }
     ann[, ref_alt_diff := NULL]
+    ann[, ref_alt_len := NULL]
+
+    #MAF requires Hugo_Symbols to be set to Unknown in case of IGR mutations
+    ann$Hugo_Symbol = ifelse(ann$Variant_Classification == "IGR", yes = "Unknown", no = ann$Hugo_Symbol)
+    ann$Hugo_Symbol = ifelse(is.na(ann$Hugo_Symbol), yes = "Unknown", no = ann$Hugo_Symbol)
 
   #Re-roganize columns
   colnames(ann)[match(c("Chr", "Start", "End", "Ref", "Alt"), colnames(ann))] = c("Chromosome", "Start_Position", "End_Position", "Reference_Allele", "Tumor_Seq_Allele2")
   ord1 = colnames(x = ann)[colnames(x = ann) %in% c("Hugo_Symbol", "Chromosome", "Start_Position", "End_Position", "Reference_Allele", "Tumor_Seq_Allele2", "Variant_Classification", "Variant_Type", "Tumor_Sample_Barcode", "tx", "exon", "txChange", "aaChange")]
   ord2 = colnames(x = ann)[!colnames(x = ann) %in% c("Hugo_Symbol", "Chromosome", "Start_Position", "End_Position", "Reference_Allele", "Tumor_Seq_Allele2", "Variant_Classification", "Variant_Type", "Tumor_Sample_Barcode", "tx", "exon", "txChange", "aaChange")]
   ann = ann[,c(ord1, ord2), with = FALSE]
 
-
   if(!is.null(basename)){
     data.table::fwrite(x = ann, file = paste(basename, 'maf', sep='.'), sep='\t')
   }

R/extractSignatures.R

@@ -68,17 +68,17 @@ extractSignatures = function(mat, n = NULL, plotBestFitRes = FALSE, parallel = 4
     colnames(w) = paste('Signature', 1:ncol(w),sep='_')
 
     #Contribution
-    h = NMF::coef(conv.mat.nmf)
-    colnames(h) = colnames(mat) #correct colnames (seems to be mssing with low mutation load)
+    h_abs = NMF::coef(conv.mat.nmf)
+    colnames(h_abs) = colnames(mat) #correct colnames (seems to be mssing with low mutation load)
     #For single signature, contribution will be 100% per sample
     if(n == 1){
-      h = h/h
+      h = h_abs/h_abs
       rownames(h) = paste('Signature', '1', sep = '_')
     }else{
-      h = apply(h, 2, function(x) x/sum(x)) #Scale contributions (coefs)
-      rownames(h) = paste('Signature', 1:nrow(h),sep='_')
+      h = apply(h_abs, 2, function(x) x/sum(x)) #Scale contributions (coefs)
+      rownames(h_abs) = rownames(h) = paste('Signature', 1:nrow(h),sep='_')
     }
 
     message("-Finished in",data.table::timetaken(start_time))
-    return(list(signatures = w, contributions = h, nmfObj = conv.mat.nmf))
+    return(list(signatures = w, contributions = h, nmfObj = conv.mat.nmf, contributions_abs = h_abs))
 }

R/plotSignatures.R

@@ -4,11 +4,12 @@
 #'
 #' @param nmfRes results from \code{\link{extractSignatures}}
 #' @param contributions If TRUE plots contribution of signatures in each sample.
+#' @param absolute Whether to plot absolute contributions. Default FALSE.
 #' @param color colors for each Ti/Tv conversion class. Default NULL
 #' @param patient_order User defined ordering of samples. Default NULL.
 #' @param title_size size of title. Default 1.3
 #' @param axis_lwd axis width. Default 2.
-#' @param font_size font size. Default 1.2
+#' @param font_size font size. Default 0.6
 #' @param show_title If TRUE compares signatures to COSMIC signatures and prints them as title
 #' @param sig_db Only applicable if show_title is TRUE. Can be \code{legacy} or \code{SBS}. Default \code{legacy}
 #' @param show_barcodes Default FALSE
@@ -18,11 +19,16 @@
 #' @seealso \code{\link{trinucleotideMatrix}} \code{\link{plotSignatures}}
 #' @export
 #'
-plotSignatures = function(nmfRes = NULL, contributions = FALSE, color = NULL, patient_order = NULL,
-                          font_size = 1.2, show_title = TRUE, sig_db = "legacy", axis_lwd = 2, title_size = 0.9, show_barcodes = FALSE, yaxisLim = 0.3, ...){
+plotSignatures = function(nmfRes = NULL, contributions = FALSE, absolute = FALSE, color = NULL, patient_order = NULL,
+                          font_size = 0.6, show_title = TRUE, sig_db = "legacy", axis_lwd = 2, title_size = 0.9, show_barcodes = FALSE, yaxisLim = 0.3, ...){
 
   conv.mat.nmf.signatures = nmfRes$signatures
-  contrib = nmfRes$contributions
+  if(absolute){
+    contrib = nmfRes$contributions_abs
+  }else{
+    contrib = nmfRes$contributions
+  }
+
   coSineMat = nmfRes$coSineSimMat
 
   if(contributions){
@@ -45,7 +51,7 @@ plotSignatures = function(nmfRes = NULL, contributions = FALSE, color = NULL, pa
       b = barplot(contrib, axes = FALSE, horiz = FALSE, col = cols, border = NA, names.arg = rep("", ncol(contrib)))
       axis(side = 1, at = b, labels = colnames(contrib), lwd = 2, cex.axis = font_size,
            las = 2, line = 0.2, hadj = 0.8, font = 1, tick = FALSE)
-      axis(side = 2, at = seq(0, 1, 0.25), lwd = 3, font = 1, las = 2, cex.axis = 0.9)
+      axis(side = 2, at = pretty(contrib), lwd = 1, font = 1, las = 2, cex.axis = 0.9)
       mtext(text = "Signature exposures", side = 2, font = 1, cex = 1, line = 2.8)
       plot.new()
       par(mar = c(2, 3, 0, 0))
@@ -56,7 +62,7 @@ plotSignatures = function(nmfRes = NULL, contributions = FALSE, color = NULL, pa
       lo = graphics::layout(mat = matrix(data = c(1, 2), nrow = 2), heights = c(6, 2))
       par(mar = c(3, 4, 2, 1))
       b = barplot(contrib, axes = FALSE, horiz = FALSE, col = cols, border = NA, names.arg = rep("", ncol(contrib)))
-      axis(side = 2, at = seq(0, 1, 0.25), lwd = 3, font = 1, las = 2, cex.axis = 0.9)
+      axis(side = 2, at = pretty(contrib), lwd = 1, font = 1, las = 2, cex.axis = 0.9)
       mtext(text = "Signature exposure", side = 2, font = 1, cex = 1, line = 2.8)
       plot.new()
       par(mar = c(2, 3, 0, 0))

R/validateMaf.R

@@ -37,18 +37,18 @@ validateMaf = function(maf, rdup = TRUE, isTCGA = isTCGA, chatty = TRUE){
     if(chatty){
       cat('--Found ', nrow(maf[Hugo_Symbol %in% ""]), ' variants with no Gene Symbols\n')
       #print(maf[Hugo_Symbol %in% "", required.fields, with = FALSE])
-      cat("--Annotating them as 'UnknownGene' for convenience\n")
+      cat("--Annotating them as 'Unknown' for convenience\n")
     }
-    maf$Hugo_Symbol = ifelse(test = maf$Hugo_Symbol == "", yes = 'UnknownGene', no = maf$Hugo_Symbol)
+    maf$Hugo_Symbol = ifelse(test = maf$Hugo_Symbol == "", yes = 'Unknown', no = maf$Hugo_Symbol)
   }
 
   if(nrow(maf[is.na(Hugo_Symbol)]) > 0){
     if(chatty){
       cat('--Found ', nrow(maf[is.na(Hugo_Symbol) > 0]), ' variants with no Gene Symbols\n')
       #print(maf[is.na(Hugo_Symbol), required.fields, with =FALSE])
-      cat("--Annotating them as 'UnknownGene' for convenience\n")
+      cat("--Annotating them as 'Unknown' for convenience\n")
     }
-    maf$Hugo_Symbol = ifelse(test = is.na(maf$Hugo_Symbol), yes = 'UnknownGene', no = maf$Hugo_Symbol)
+    maf$Hugo_Symbol = ifelse(test = is.na(maf$Hugo_Symbol), yes = 'Unknown', no = maf$Hugo_Symbol)
   }
 
   if(isTCGA){

inst/NEWS.md

@@ -2,15 +2,20 @@
 (GitHub master branch)
 
 ## NEW FUNCTIONS
-- `coGisticChromPlot` for plotting two GISTIC objects side-by-side. [954](https://github.com/PoisonAlien/maftools/pull/954)
+- `coGisticChromPlot` for plotting two GISTIC objects side-by-side. PR by [biosunsci](https://github.com/biosunsci) [954](https://github.com/PoisonAlien/maftools/pull/954)
+- `readGistic` can take gistic output directory as an input. PR by [biosunsci](https://github.com/biosunsci) [954](https://github.com/PoisonAlien/maftools/pull/954)
 
 ## BUG FIXES
+- Bug fix in `oncoplot` for drawing borders. [958](https://github.com/PoisonAlien/maftools/issues/958)
 - Bug fix in `plotSignatures` for hardcoded axis limits. [949](https://github.com/PoisonAlien/maftools/issues/949)
 - Bug fix in `subsetMaf` while handling only CNV events. [908](https://github.com/PoisonAlien/maftools/issues/908)
 - Error handling when no deep/shallow CNV events found. [899](https://github.com/PoisonAlien/maftools/issues/899)
 - Bug fix in `oncoplot` for duplicated values in gene list. [889](https://github.com/PoisonAlien/maftools/issues/889)
 
 ## ENHANCEMENTS
+- Improved `annovarToMaf` with better handling of indels and `Variant_Type`. Issue: [940](https://github.com/PoisonAlien/maftools/issues/940)
+- Include absolute contribution of each signature in `extractSignatures` output. Issue: [939](https://github.com/PoisonAlien/maftools/issues/939)
+- Added `DSEL` protein to the database. Issue: [933](https://github.com/PoisonAlien/maftools/issues/933)
 - Added `showOnlyPathway` argument to `oncoplot`
 - Added `pathdb` argument to `PlotOncogenicPathways`. Issue: [923](https://github.com/PoisonAlien/maftools/issues/923)
 - Emit warnings when fishers test can not be performed during `somaticInteractions`. Issue: [921](https://github.com/PoisonAlien/maftools/issues/921)