changeset 18:8d9f31389f33 draft

"planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit 1cb9c8fd0c74943a8e6de4c63ac5e4a84ef27430"
author artbio
date Sun, 17 Oct 2021 15:51:05 +0000
parents 8c6ee1c2248f
children 69f09dff98f9
files mutational_patterns.R mutational_patterns.xml test-data/cosmic_output1.pdf test-data/cosmic_output_v3.pdf test-data/denovo_1.RData test-data/denovo_output1.pdf test-data/sig_contrib_table.tsv test-data/sig_contrib_table_user_defined.tsv test-data/sig_contrib_table_v3.tsv test-data/spectrum_output1.pdf test-data/user_defined_signature.tsv test-data/user_output.pdf
diffstat 12 files changed, 294 insertions(+), 114 deletions(-) [+]
line wrap: on
line diff
--- a/mutational_patterns.R	Tue Oct 05 22:28:34 2021 +0000
+++ b/mutational_patterns.R	Sun Oct 17 15:51:05 2021 +0000
@@ -35,15 +35,21 @@
   ),
   make_option(
     "--cosmic_version",
-    default = "v2",
+    default = NA,
     type = "character",
-    help = "Version of the Cosmic Signature set to be used to express mutational patterns"
+    help = "Version of the Cosmic Signature set to be used to express mutational profiles"
+  ),
+  make_option(
+    "--own_signatures",
+    default = NA,
+    type = "character",
+    help = "Path to the user-defined signature matrix"
   ),
   make_option(
     "--signum",
     default = 2,
     type = "integer",
-    help = "selects the N most significant signatures in samples to express mutational patterns"
+    help = "selects the N most significant signatures in samples to express mutational profiles"
   ),
   make_option(
     "--nrun",
@@ -82,7 +88,7 @@
     help = "path to signature matrix"
   ),
   make_option(
-    "--output_cosmic",
+    "--output_sigpattern",
     default = NA,
     type = "character",
     help = "path to output dataset"
@@ -141,8 +147,6 @@
 ##### This is done for any section ######
 mut_mat <- mut_matrix(vcf_list = vcfs, ref_genome = ref_genome)
 qual_col_pals <- brewer.pal.info[brewer.pal.info$category == "qual", ]
-col_vector <- unique(unlist(mapply(brewer.pal, qual_col_pals$maxcolors, rownames(qual_col_pals))))
-col_vector <- col_vector[c(-32, -34, -39)] # 67-color palette
 
 ###### Section 1 Mutation characteristics and spectrums #############
 if (!is.na(opt$output_spectrum)[1]) {
@@ -221,53 +225,75 @@
                           condensed = TRUE)
     dev.off()
     }
-##### Section 3: Find optimal contribution of known signatures: COSMIC mutational signatures ####
 
-if (!is.na(opt$output_cosmic)[1]) {
+##### Section 3: Find optimal contribution of known signatures: COSMIC or OWN mutational signatures ####
+
+if (!is.na(opt$output_sigpattern)[1]) {
     # Prepare cosmic signatures
-    cosmic_urls <- read.delim(paste0(opt$tooldir, "cosmic_urls.tsv"), sep = "\t", header = TRUE)
-    cosmic_sbs_file <- cosmic_urls$url[cosmic_urls$genome == opt$genome &
-                                       cosmic_urls$cosmic_version == opt$cosmic_version]
-    cancer_sbs_signatures <- read.table(paste0(opt$tooldir, cosmic_sbs_file),
-                                        sep = "\t", header = TRUE)
-    row.names(cancer_sbs_signatures) <- cancer_sbs_signatures$Type
-    new_order <- match(row.names(mut_mat), cancer_sbs_signatures$Type)
-    cancer_sbs_signatures <- cancer_sbs_signatures[as.numeric(new_order), ]
-    cosmic_tag <- paste(opt$genome, "COSMIC", opt$cosmic_version, sep = " ")
-    cosmic_colors <- col_vector[seq_len(ncol(cancer_sbs_signatures) - 1)]
-    names(cosmic_colors) <- colnames(cancer_sbs_signatures[2:length(cancer_sbs_signatures)])
-    cancer_sbs_matrix <- as.matrix(cancer_sbs_signatures[, 2:length(cancer_sbs_signatures)])
+    if (!is.na(opt$cosmic_version)) {
+        cosmic_urls <- read.delim(paste0(opt$tooldir, "cosmic_urls.tsv"), sep = "\t", header = TRUE)
+        cosmic_sbs_file <- cosmic_urls$url[cosmic_urls$genome == opt$genome &
+                                           cosmic_urls$cosmic_version == opt$cosmic_version]
+        sbs_signatures <- read.table(paste0(opt$tooldir, cosmic_sbs_file),
+                                            sep = "\t", header = TRUE)
+        tag <- paste(opt$genome, "COSMIC", opt$cosmic_version, sep = " ")
+    }
+    # Prepare user-defined signatures
+    if (!is.na(opt$own_signatures)) {
+        sbs_signatures <- read.table(opt$own_signatures, sep = "\t", header = TRUE)
+        tag <- paste(opt$genome, "User-Defined Signatures", sep = " ")
+    }
+    row.names(sbs_signatures) <- sbs_signatures$Type
+    # drop column Type of sbs_signatures
+    sbs_signatures <- subset(sbs_signatures, select = -c(Type))
+    # reorder substitutions of sbs_signatures to match mut_mat
+    sbs_signatures <- sbs_signatures[match(row.names(mut_mat), row.names(sbs_signatures)), ]
+    colnames(sbs_signatures) <- gsub("SBS", "", colnames(sbs_signatures))
+    # arrange signature colors
+    signature_colors <- c("#3f4100", "#6f53ff", "#6dc400", "#9d1fd7", "#009c06", "#001fae", "#8adb4d", "#5a67ff", "#d8c938", "#024bc3", "#d2ab00",
+                          "#e36eff", "#00ac44", "#d000b0", "#01b071", "#ff64e2", "#006b21", "#b70090", "#60dc9f", "#5f0083", "#c0ce67", "#002981",
+                          "#ffb53e", "#44005f", "#b59600", "#7d95ff", "#f47600", "#017bc4", "#ff2722", "#02cfec", "#ff233f", "#01b7b4", "#fd005c",
+                          "#019560", "#ff57a9", "#88d896", "#b80067", "#abd27f", "#dc8eff", "#667b00", "#fba3ff", "#093f00", "#ff6494", "#009791",
+                          "#c93200", "#4ac8ff", "#a60005", "#8fd4b6", "#ce0036", "#00634d", "#ff6035", "#2d1956", "#f0be6d", "#6a0058", "#957a00",
+                          "#e4b4ff", "#4a5500", "#abc7fe", "#c95900", "#003d27", "#b10043", "#d5c68e", "#3e163e", "#b36b00", "#debaeb", "#605400",
+                          "#7a0044", "#ffa06d", "#4c0d21", "#ff9cb5", "#3f1d02", "#ff958f", "#634a66", "#775500", "#6e0028", "#717653",
+                          "#6c1000", "#693600")
+    signature_colors <- signature_colors[seq_len(ncol(sbs_signatures))]
+    names(signature_colors) <- colnames(sbs_signatures)
+    # To drop signature_colors <- signature_colors[colnames(sbs_signatures)]
+    # This is IMPORTANT since in Galaxy we do not use the embeded function get_known_signatures()
+    sbs_signatures <- as.matrix(sbs_signatures)
 
 
     # Plot mutational profiles of the COSMIC signatures
-    pdf(opt$output_cosmic, paper = "special", width = 11.69, height = 11.69)
-    if (opt$cosmic_version == "v2") {
-        p6 <- plot_96_profile(cancer_sbs_matrix, condensed = TRUE, ymax = 0.3)
-        grid.arrange(p6, top = textGrob("COSMIC SBS signature profiles", gp = gpar(fontsize = 12, font = 3)))
-    } else {
-        p6 <- plot_96_profile(cancer_sbs_matrix[, 1:trunc(ncol(cancer_sbs_matrix) / 2)], condensed = TRUE, ymax = 0.3)
-        p6bis <- plot_96_profile(cancer_sbs_matrix[, (trunc(ncol(cancer_sbs_matrix) / 2) + 1):ncol(cancer_sbs_matrix)],
-                                 condensed = TRUE, ymax = 0.3)
-        grid.arrange(p6, top = textGrob("COSMIC signature profiles (on two pages)",
-                     gp = gpar(fontsize = 12, font = 3)))
-        grid.arrange(p6bis, top = textGrob("COSMIC signature profiles (continued)",
-                     gp = gpar(fontsize = 12, font = 3)))
+
+    # to do: this is largely optional and should be graphically improved anyway
+
+    pdf(opt$output_sigpattern, paper = "special", width = 11.69, height = 11.69)
+    for (i in head(seq(1, ncol(sbs_signatures), by = 20), -1)) {
+        p6 <- plot_96_profile(sbs_signatures[, i:(i + 19)], condensed = TRUE, ymax = 0.3)
+        grid.arrange(p6, top = textGrob(paste0(tag, " profiles (", trunc((i + 1) / 20) + 1, " of ",
+                                               trunc(ncol(sbs_signatures) / 20) + 1, " pages)"),
+                                        gp = gpar(fontsize = 12, font = 3)))
     }
-
-
+    p6 <- plot_96_profile(sbs_signatures[, (trunc(ncol(sbs_signatures) / 20) * 20):(ncol(sbs_signatures))],
+                          condensed = TRUE, ymax = 0.3)
+    grid.arrange(p6, top = textGrob(paste0(tag, " profiles (", trunc(ncol(sbs_signatures) / 20) + 1, " of ",
+                                               trunc(ncol(sbs_signatures) / 20) + 1, " pages)"),
+                                        gp = gpar(fontsize = 12, font = 3)))
     # Find optimal contribution of COSMIC signatures to reconstruct 96 mutational profiles
     pseudo_mut_mat <- mut_mat + 0.0001 # First add a small pseudocount to the mutation count matrix
-    fit_res <- fit_to_signatures(pseudo_mut_mat, cancer_sbs_matrix)
+    fit_res <- fit_to_signatures(pseudo_mut_mat, sbs_signatures)
 
     # Plot contribution barplots
-    pc3 <- plot_contribution(fit_res$contribution, cancer_sbs_matrix, coord_flip = T, mode = "absolute")
-    pc4 <- plot_contribution(fit_res$contribution, cancer_sbs_matrix, coord_flip = T, mode = "relative")
+    pc3 <- plot_contribution(fit_res$contribution, sbs_signatures, coord_flip = T, mode = "absolute")
+    pc4 <- plot_contribution(fit_res$contribution, sbs_signatures, coord_flip = T, mode = "relative")
     if (is.na(opt$levels)[1]) {  # if there are NO levels to display in graphs
         pc3_data <- pc3$data
         pc3 <- ggplot(pc3_data, aes(x = Sample, y = Contribution, fill = as.factor(Signature))) +
                geom_bar(stat = "identity", position = "stack") +
                coord_flip() +
-               scale_fill_manual(name = "Cosmic\nSignatures", values = cosmic_colors) +
+               scale_fill_manual(name = "Cosmic\nSignatures", values = signature_colors[]) +
                labs(x = "Samples", y = "Absolute contribution") + theme_bw() +
                theme(panel.grid.minor.x = element_blank(),
                      panel.grid.major.x = element_blank(),
@@ -278,7 +304,7 @@
         pc4 <- ggplot(pc4_data, aes(x = Sample, y = Contribution, fill = as.factor(Signature))) +
                geom_bar(stat = "identity", position = "fill") +
                coord_flip() +
-               scale_fill_manual(name = "Cosmic\nSignatures", values = cosmic_colors) +
+               scale_fill_manual(name = "Cosmic\nSignatures", values = signature_colors) +
                scale_y_continuous(labels = scales::percent_format(accuracy = 1)) +
                labs(x = "Samples", y = "Relative contribution") + theme_bw() +
                theme(panel.grid.minor.x = element_blank(), panel.grid.major.x = element_blank(), legend.position = "right",
@@ -292,7 +318,7 @@
         pc3_data <- merge(pc3_data, metadata_table[, c(1, 3)], by.x = "Sample", by.y = "element_identifier")
         pc3 <- ggplot(pc3_data, aes(x = Sample, y = Contribution, fill = as.factor(Signature))) +
                geom_bar(stat = "identity", position = "stack") +
-               scale_fill_manual(name = "Cosmic\nSignatures", values = cosmic_colors) +
+               scale_fill_manual(name = "Cosmic\nSignatures", values = signature_colors) +
                labs(x = "Samples", y = "Absolute contribution") + theme_bw() +
                theme(panel.grid.minor.x = element_blank(),
                      panel.grid.major.x = element_blank(),
@@ -304,7 +330,7 @@
         pc4_data <- merge(pc4_data, metadata_table[, c(1, 3)], by.x = "Sample", by.y = "element_identifier")
         pc4 <- ggplot(pc4_data, aes(x = Sample, y = Contribution, fill = as.factor(Signature))) +
                geom_bar(stat = "identity", position = "fill") +
-               scale_fill_manual(name = "Cosmic\nSignatures", values = cosmic_colors) +
+               scale_fill_manual(name = "Cosmic\nSignatures", values = signature_colors) +
                scale_y_continuous(labels = scales::percent_format(accuracy = 1)) +
                labs(x = "Samples", y = "Relative contribution") + theme_bw() +
                theme(panel.grid.minor.x = element_blank(),
@@ -316,7 +342,7 @@
     }
     # Combine the two plots:
     grid.arrange(pc3, pc4,
-                 top = textGrob("Absolute and Relative Contributions of Cosmic signatures to mutational patterns",
+                 top = textGrob("Absolute and Relative Contributions of elementary signatures to mutational profiles",
                  gp = gpar(fontsize = 12, font = 3)))
 
     #### pie charts of comic signatures contributions in samples ###
@@ -356,9 +382,10 @@
               geom_bar(width = 1, stat = "identity") +
               geom_text(aes(label = label), position = position_stack(vjust = 0.5), color = "black", size = 3) +
               coord_polar("y", start = 0) + facet_wrap(.~sample) +
-              labs(x = "", y = "Samples", fill = cosmic_tag) +
+              labs(x = "", y = "Samples", fill = tag) +
               scale_fill_manual(name = paste0(opt$signum, " most contributing\nsignatures\n(in each label/tissue)"),
-                                values = cosmic_colors[levels(worklist$signature)]) +
+                                values = signature_colors[levels(worklist$signature)],
+                                labels = names(signature_colors[levels(worklist$signature)])) +
               theme(axis.text = element_blank(),
                     axis.ticks = element_blank(),
                     panel.grid  = element_blank())
@@ -377,8 +404,10 @@
             output_table <- data.frame(sample = paste0(metadata_table[metadata_table$element_identifier == colnames(fit_res$contribution),
                                                                     3], "-", colnames(fit_res$contribution)),
                                        output_table)
+            colnames(output_table) <- gsub("X", "SBS", colnames(output_table))
             } else {
-        output_table <- data.frame(sample = rownames(output_table), output_table)
+            output_table <- data.frame(sample = rownames(output_table), output_table)
+            colnames(output_table) <- gsub("X", "SBS", colnames(output_table))
         }
         write.table(output_table, file = opt$sig_contrib_matrix, sep = "\t", quote = F, row.names = F)
     }
@@ -412,7 +441,7 @@
                       panel.grid.major.y = element_blank()) +
                       # Add cut.off line
                       geom_hline(aes(yintercept = .95))
-    grid.arrange(p9, top = textGrob("Similarity between true and reconstructed profiles (with all Cosmic sig.)", gp = gpar(fontsize = 12, font = 3)))
+    grid.arrange(p9, top = textGrob("Similarity between true profiles and profiles reconstructed with elementary signatures", gp = gpar(fontsize = 12, font = 3)))
     dev.off()
 }
 
--- a/mutational_patterns.xml	Tue Oct 05 22:28:34 2021 +0000
+++ b/mutational_patterns.xml	Sun Oct 17 15:51:05 2021 +0000
@@ -1,7 +1,9 @@
-<tool id="mutational_patterns" name="Analyse Mutational Patterns/Signatures" version="3.2.0+galaxy2">
+<tool id="mutational_patterns" name="Analyse Mutational Patterns/Signatures" version="3.2.0+galaxy3">
     <description>from genomic variations in vcf files</description>
     <requirements>
         <requirement type="package" version="3.2.0=r41hdfd78af_0">bioconductor-mutationalpatterns</requirement>
+        <requirement type="package" version="1.1.1l=h7f98852_0">openssl</requirement>
+        <requirement type="package" version="3.3.5=r41hc72bb7e_0">r-ggplot2</requirement>
         <requirement type="package" version="1.6.6=r41hc72bb7e_1">r-optparse</requirement>
         <requirement type="package" version="0.2.20=r41h03ef668_1002">r-rjson</requirement>
         <requirement type="package" version="0.21.0=r41h03ef668_1004">r-nmf</requirement>
@@ -9,10 +11,6 @@
         <requirement type="package" version="1.4.3=r41hdfd78af_3">bioconductor-bsgenome.hsapiens.ucsc.hg19</requirement>
         <requirement type="package" version="1.4.3=r41hdfd78af_3">bioconductor-bsgenome.hsapiens.ucsc.hg38</requirement>
 <!--
-        <requirement type="package" version="1.3.1000=r40_4">bioconductor-bsgenome.hsapiens.ncbi.grch38</requirement>
-        <requirement type="package" version="0.99.1=r40_4">bioconductor-bsgenome.hsapiens.1000genomes.hs37d5</requirement>
--->
-<!--
 install more bioconda genomes
 bioconductor-bsgenome.mmusculus.ucsc.mm9
 bioconductor-bsgenome.mmusculus.ucsc.mm10
@@ -50,13 +48,23 @@
         --sigmatrix $sigmatrix
     #end if
 
-    #if $set_cosmic.choices == 'yes':
-        --cosmic_version '$set_cosmic.cosmic_version'
-        --signum '$set_cosmic.signum'
-        --output_cosmic $cosmic
-        #if $set_cosmic.contrib_matrix_out == 'yes'
+    #if $set_preset.choices == 'yes':
+
+        #if $set_preset.set_signature_input.input_signature_choices == 'cosmic'
+            --cosmic_version '$set_preset.set_signature_input.cosmic_version'
+        #end if
+
+        #if $set_preset.set_signature_input.input_signature_choices == 'user_signatures'
+            --own_signatures '$set_preset.set_signature_input.own_matrix'
+        #end if
+       
+        --signum '$set_preset.signum'
+        --output_sigpattern $sig_contrib
+
+        #if $set_preset.contrib_matrix_out == 'yes'
             --sig_contrib_matrix $sig_contrib_matrix
         #end if
+
     #end if
             
     #if $rdata_out
@@ -69,12 +77,8 @@
     <inputs>
         <param name="vcfs" type="data_collection" format="vcf" label="VCF file(s) collection" multiple="true"/>
         <param name="genome" type="select" label="Reference Genome">
-            <!-- <option value="BSgenome.Hsapiens.1000genomes.hs37d5">BSgenome.Hsapiens.1000genomes.hs37d5</option> -->
-            <!-- <option value="BSgenome.Hsapiens.NCBI.GRCh38">BSgenome.Hsapiens.NCBI.GRCh38</option> -->
             <option value="BSgenome.Hsapiens.UCSC.hg19">BSgenome.Hsapiens.UCSC.hg19</option>
             <option value="BSgenome.Hsapiens.UCSC.hg38" selected="true">BSgenome.Hsapiens.UCSC.hg38</option>
-            <!--<option value="BSgenome.Mmusculus.UCSC.mm10">BSgenome.Mmusculus.UCSC.mm10</option>
-            <option value="BSgenome.Mmusculus.UCSC.mm9">BSgenome.Mmusculus.UCSC.mm9</option>-->
         </param>
         <conditional name="set_levels">
             <param name="choices" type="select" label="samples have levels/labels for grouping them in the analysis" display="radio"
@@ -108,8 +112,8 @@
 
         <conditional name="set_denovo">
             <param name="choices" type="select" label="Extract de novo signatures with MutationalPatterns" display="radio">
-                <option value="yes" selected="true">Yes</option>
-                <option value="no">No</option>
+                <option value="yes">Yes</option>
+                <option value="no" selected="true">No</option>
             </param>
             <when value="yes">
                 <param name="nrun" type="integer" value="10" min="10" max="200"
@@ -125,28 +129,41 @@
             <when value="no" />
         </conditional>
 
-        <conditional name="set_cosmic">
-            <param name="choices" type="select" label="Decompose with Cosmic signatures" display="radio">
+        <conditional name="set_preset">
+            <param name="choices" type="select" label="Decompose with preset signatures" display="radio">
                 <option value="yes" selected="true">Yes</option>
                 <option value="no">No</option>
             </param>
             <when value="yes">
+                <conditional name="set_signature_input">
+                    <param name="input_signature_choices" type="select" label="type of signatures" display="radio">
+                        <option value="cosmic" selected="true">COSMIC signatures</option>
+                        <option value="user_signatures">Use your own signature matrix</option>
+                    </param>
+                    <when value="cosmic">
+                        <param name="cosmic_version" type="select" label="Version of the Cosmic signature set">
+                            <option value="v2" selected="true">Cosmic v2, March 2015</option>
+                            <option value="v3">Cosmic v3, May 2019</option>
+                            <option value="v3.1">Cosmic v3.1, June 2020</option>
+                            <option value="v3.2">Cosmic v3.2, March 2021</option>
+                        </param>
+                    </when>
+                    <when value="user_signatures">
+                        <param name="own_matrix" type="data" format="tabular"
+                               label="A tab-separated matrix describing elementary signatures"
+                               help="see https://cancer.sanger.ac.uk/signatures/documents/453/COSMIC_v3.2_SBS_GRCh38.txt for the required format" />
+                    </when>
+                </conditional>
                 <param name="signum" type="integer" value="3" min="2" max="30"
                        label="selects the N most significant signatures in samples to express mutational patterns"
-                       help="an integer between 2 and 30 signature types from cosmic"/>
-                <param name="cosmic_version" type="select" label="Version of the Cosmic signature set">
-                    <option value="v2" selected="true">Cosmic v2, March 2015</option>
-                    <option value="v3">Cosmic v3, May 2019</option>
-                    <option value="v3.1">Cosmic v3.1, June 2020</option>
-                    <option value="v3.2">Cosmic v3.2, March 2021</option>
-                </param>
+                       help="an integer between 2 and the number of elementary signatures in your signature matrix"/>
                 <param name="contrib_matrix_out" type="select" label="Output Signature Contribution table ?"
                        help="Output the normalized signatures contributions for further visualization" >
                     <option value="no" selected="true">No</option>
                     <option value="yes">Yes</option>
                 </param>
             </when>
-             <when value="no" />
+            <when value="no" />
         </conditional>
         <param name="rdata_out" type="boolean" checked="false" label="Output RData file?" help="Output all the data used by R to construct the tables and plots, can be loaded into R" />
     </inputs>
@@ -160,11 +177,11 @@
         <data name="sigmatrix" format="tabular" label="De novo signatures probability matrix">
             <filter>set_denovo['choices'] == "yes"</filter>
         </data>
-        <data name="cosmic" format="pdf" label="Cosmic signatures">
-            <filter>set_cosmic['choices'] == "yes"</filter>
+        <data name="sig_contrib" format="pdf" label="Signature contributions">
+            <filter>set_preset['choices'] == "yes"</filter>
         </data>
         <data name="sig_contrib_matrix" format="tabular" label="${tool.name}: Signature contribution table">
-            <filter>set_cosmic['choices'] == "yes" and set_cosmic['contrib_matrix_out'] == "yes"</filter>
+            <filter>set_preset['choices'] == "yes" and set_preset['contrib_matrix_out'] == "yes"</filter>
         </data>
 
         <data name="rdata" format="rdata" label="${tool.name}: RData file">
@@ -173,7 +190,7 @@
 
     </outputs>
     <tests>
-         <!-- cosmic signatures with cosmic V3 -->
+         <!-- user defined (v3.2 restricted 30 minus 27) -->
         <test>
             <param name="vcfs">
                 <collection type="list">
@@ -191,17 +208,19 @@
             <conditional name="set_denovo">
                 <param name="choices" value="no"/>
             </conditional>
-            <conditional name="set_cosmic">
+            <conditional name="set_preset">
                 <param name="choices" value="yes"/>
+                <conditional name="set_signature_input">
+                    <param name="input_signature_choices" value="user_signatures" />
+                    <param name="own_matrix" value="user_defined_signature.tsv" ftype="tabular"/>
+                </conditional>
                 <param name="contrib_matrix_out"  value="yes" />
-                <param name="cosmic_version" value="v3"/>
             </conditional>
-            <param name="signum" value="3" />
-            <output name="cosmic" file="cosmic_output_v3.pdf" compare="sim_size"/>
-            <output name="sig_contrib_matrix" file="sig_contrib_table_v3.tsv" compare="sim_size"/>
+            <param name="signum" value="4" />
+            <output name="sig_contrib" file="user_output.pdf" compare="sim_size"/>
+            <output name="sig_contrib_matrix" file="sig_contrib_table_user_defined.tsv" compare="sim_size"/>
         </test>
-
-         <!-- cosmic signatures -->
+         <!-- cosmic v3.2 -->
         <test>
             <param name="vcfs">
                 <collection type="list">
@@ -219,37 +238,49 @@
             <conditional name="set_denovo">
                 <param name="choices" value="no"/>
             </conditional>
-            <conditional name="set_cosmic">
+            <conditional name="set_preset">
                 <param name="choices" value="yes"/>
+                <conditional name="set_signature_input">
+                    <param name="input_signature_choices" value="cosmic" />
+                    <param name="cosmic_version" value="v3.2"/>
+                </conditional>
                 <param name="contrib_matrix_out"  value="yes" />
             </conditional>
             <param name="signum" value="3" />
-            <output name="cosmic" file="cosmic_output1.pdf" compare="sim_size"/>
-            <output name="sig_contrib_matrix" file="sig_contrib_table.tsv" compare="sim_size"/>
+            <output name="sig_contrib" file="cosmic_output_v3.pdf" compare="sim_size"/>
+            <output name="sig_contrib_matrix" file="sig_contrib_table_v3.tsv" compare="sim_size"/>
         </test>
-
-        <!-- cosmic signature on single sample -->
+         <!-- cosmic v2 -->
         <test>
             <param name="vcfs">
                 <collection type="list">
-                    <element name="1" value="G.vcf"/>
+                    <element name="6" value="F.vcf"/>
+                    <element name="7" value="G.vcf"/>
+                    <element name="8" value="H.vcf"/>
+                    <element name="9" value="I.vcf"/>
                 </collection>
             </param>
             <param name="genome" value="BSgenome.Hsapiens.UCSC.hg38"/>
+            <param name="levels" value="FGHI_levels.tab" ftype="tabular"/>
             <conditional name="set_spectrum">
                 <param name="choices" value="no"/>
             </conditional>
             <conditional name="set_denovo">
                 <param name="choices" value="no"/>
             </conditional>
-            <conditional name="set_cosmic">
+            <conditional name="set_preset">
                 <param name="choices" value="yes"/>
+                <conditional name="set_signature_input">
+                    <param name="input_signature_choices" value="cosmic" />
+                    <param name="cosmic_version" value="v2"/>
+                </conditional>
+                <param name="contrib_matrix_out"  value="yes" />
             </conditional>
-            <param name="signum" value="5" />
-            <output name="cosmic" file="cosmic_output2.pdf" compare="sim_size" delta="50000"/>
+            <param name="signum" value="3" />
+            <output name="sig_contrib" file="cosmic_output1.pdf" compare="sim_size"/>
+            <output name="sig_contrib_matrix" file="sig_contrib_table.tsv" compare="sim_size"/>
         </test>
-
-        <!-- simple profile -->
+        <!-- simple spectrum -->
         <test>
             <param name="vcfs">
                 <collection type="list">
@@ -268,12 +299,11 @@
             <conditional name="set_denovo">
                 <param name="choices" value="no"/>
             </conditional>
-            <conditional name="set_cosmic">
+            <conditional name="set_preset">
                 <param name="choices" value="no"/>
             </conditional>
             <output name="spectrum" file="spectrum_output1.pdf" compare="sim_size"/>
         </test>
-
          <!-- de novo signatures -->
         <test>
             <param name="vcfs">
@@ -291,7 +321,7 @@
             <conditional name="set_denovo">
                 <param name="choices" value="yes"/>
             </conditional>
-            <conditional name="set_cosmic">
+            <conditional name="set_preset">
                 <param name="choices" value="no"/>
             </conditional>
             <param name="nrun" value="10" />
@@ -307,27 +337,46 @@
 
 **What it does**
 
-Takes as inputs
+This tool implement the R package MutationalPatterns to decompose mutations found in cancers
+in a linear combination of elementary mutational signatures, as first described by
+Alexandrov_ et al (2013) and recently improved in an update_ published in 2020.
+
+.. _Alexandrov: https://www.nature.com/articles/nature12477
+.. _update: https://www.nature.com/articles/s41586-020-1943-3
 
-* a collection of n vcf files corresponding to n samples.
-* a tabular table describing the correspondance of sample names to levels (tissues, ages, sexes, etc.)
-* the number of cosmic signatures to decompose mutational patterns of samples
+Sets of elementary signatures found by analyzing large cohortes of patients are published
+in the COSMIC databases v2_ to v3.2_. You can choose among these COSMIC signature sets to
+analyse your own VCFs.
 
+In addition, you can use your own signature sets (or filtered COSMIC signature sets)
+since MutationalPatterns implements a method to extract elementary signatures from
+user-provided VCFs.
+
+**Inputs**
 
-This tool returns a pdf file with the visualisation :
+* a collection of VCF files with somatic mutations calls from analysis of samples.
+* a tabular table describing the correspondance of sample names to levels of a factor
+(tissues, ages, sexes, etc.)
+
+**Outputs**
+
+This tool returns pdf files with various visualisations of :
 
-* the Cosine similarity of samples when decomposed over the 30 signatures of cosmic_
-* the absolute contribution of the n most contributing cosmic_ signatures in the samples mutational patterns (to be set by the user, between 2 and 30)
-* the relative contribution of the n most contributing cosmic_ signatures in the samples mutational patterns  (to be set by the user, between 2 and 30)
-* a clustering of the samples with respect to the relative contribution of their cosmic_ signatures
-* pie charts of the samples displaying for each sample the relative contribution of the n most contributing cosmic_ signatures to their mutational pattern
+* the spectrum of single nucleotide mutation types
+* the absolute contribution of the elementary signatures in the samples
+* the relative contribution of the elementary signatures in the samples
+* an unrooted hierarchical clustering of the reconstructed samples with respect to the relative contribution of elementary signatures
+* the Cosine similarity between true samples and samples reconstructed with elementary signatures
+* pie charts displaying the relative contribution of the n most contributing elementary signatures in the reconstructed sample profiles
 
-.. _cosmic: https://cancer.sanger.ac.uk/cosmic/signatures_v2.tt
+.. _v2: https://cancer.sanger.ac.uk/signatures/signatures_v2/
+.. _v3.2: https://cancer.sanger.ac.uk/signatures/sbs/
 
     </help>
     <citations>
         <citation type="doi">10.18129/B9.bioc.MutationalPatterns</citation>
         <citation type="doi">10.1186/s13073-018-0539-0</citation>
         <citation type="doi">10.1038/nature12477</citation>
+        <citation type="doi">10.1038/s41586-020-1943-3</citation>
     </citations>
 </tool>
Binary file test-data/cosmic_output1.pdf has changed
Binary file test-data/cosmic_output_v3.pdf has changed
Binary file test-data/denovo_1.RData has changed
Binary file test-data/denovo_output1.pdf has changed
--- a/test-data/sig_contrib_table.tsv	Tue Oct 05 22:28:34 2021 +0000
+++ b/test-data/sig_contrib_table.tsv	Sun Oct 17 15:51:05 2021 +0000
@@ -1,4 +1,4 @@
-sample	s1	s2	s3	s4	s5	s6	s7	s8	s9	s10	s11	s12	s13	s14	s15	s16	s17	s18	s19	s20	s21	s22	s23	s24	s25	s26	s27	s28	s29	s30
+sample	SBS1	SBS2	SBS3	SBS4	SBS5	SBS6	SBS7	SBS8	SBS9	SBS10	SBS11	SBS12	SBS13	SBS14	SBS15	SBS16	SBS17	SBS18	SBS19	SBS20	SBS21	SBS22	SBS23	SBS24	SBS25	SBS26	SBS27	SBS28	SBS29	SBS30
 ovary-I.vcf	0.107676737465178	0.0107477401085281	0.263118370815298	0	0.0975192598491968	0.00654300960428024	0	0.121325654310372	0.0675812234604709	0	0.0475946682228466	0.0483240788134274	0.00116766365611527	0	0.0195773794486755	0.128367970358363	0	0	0	0	0	0	0	0	0.0564468988265929	0	0.000297382010539655	0.0237119630501146	0	0
 ovary-H.vcf	0.105483533021363	0.0160722050763363	0.220294683323486	0	0.270646531625838	0	0	0.0632630764001629	0.0651960109780565	0	0.0265849338024135	0	0.00937728828228106	0	0	0.169077458531394	0	0	0	0	0	0	0	0	0.0141372418969508	0	0.0064233897483352	0.0334436473133834	0	0
 lung-G.vcf	0.210828794798222	0.0160042182355152	0.174216713183146	0	0.248848735805233	0	0	0.0079146795135654	0.122852241624819	0	0.0316731744534412	0.0400882001887818	0	0	0	0.0415901687752403	0	0	0.0349534584507835	0	0	0	0	0	0.0686079325155911	0	0.0013880107407027	0.00103367171495887	0	0
--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/test-data/sig_contrib_table_user_defined.tsv	Sun Oct 17 15:51:05 2021 +0000
@@ -0,0 +1,5 @@
+sample	SBS1	SBS2	SBS3	SBS4	SBS5	SBS6	SBS7a	SBS8	SBS9	SBS10a	SBS11	SBS12	SBS13	SBS14	SBS15	SBS16	SBS17a	SBS18	SBS19	SBS20	SBS21	SBS22	SBS23	SBS24	SBS25	SBS26	SBS28	SBS29	SBS30
+ovary-I.vcf	0.044741393105028	0.011069018301987	0.187803779081214	0	0.307576392721694	0.0390017684003016	0	0.133709187523867	0.0763944509288322	0	0.0336042710599181	0.00220624140261095	0.0127873005328564	0	0	0.02020342244349	0.00211060816974033	0	0.00943263947590895	0	0	0	0	0	0.0617812132959067	0.0360554090047252	0.0193480376106478	0	0.00217486694127118
+ovary-H.vcf	0.0553256363614375	0.0124754288752531	0.172657307861813	0	0.390049768714777	0	0	0.0896595811464236	0.064875377225018	0.0002310155419569	0.0154421351083386	0	0.0177741353898114	0	0	0.03211663626174	0.0016974261829219	0	0.01130045225648	0.00706360420658175	0	0	0	0	0.0511061356153333	0.0334989901908753	0.0301573738491178	0	0.014568995212121
+lung-G.vcf	0.100607683465906	0.00885784389158831	0.091705156107157	0	0.388761692211351	0.0185902394159154	0	0.0790841986452702	0.104477088095262	0	0.0248378551618795	0	0.00785386622534465	0	0	0.00158790002897007	0.00587634748109639	0	0.0340439376359571	0	0.000644451383999199	0	0	0	0.0781129677262457	0.0319243418807398	0.00678144834422734	0	0.0162529822990906
+lung-F.vcf	0.130476654237574	0.00697559248767266	0.122146706678661	0	0.427134248306192	0	0	0.106255839292615	0.0369879379068786	0	0.0223610787636894	0	0	0	0	0.0200543223993699	0	0	0.0126155822640537	0	0	0	0	0	0.0504488522544811	0.0125177073155609	0.0278975294535814	0	0.0241279486396702
--- a/test-data/sig_contrib_table_v3.tsv	Tue Oct 05 22:28:34 2021 +0000
+++ b/test-data/sig_contrib_table_v3.tsv	Sun Oct 17 15:51:05 2021 +0000
@@ -1,5 +1,5 @@
-sample	s1	s2	s3	s4	s5	s6	s7a	s7b	s7c	s7d	s8	s9	s10a	s10b	s11	s12	s13	s14	s15	s16	s17a	s17b	s18	s19	s20	s21	s22	s23	s24	s25	s26	s27	s28	s29	s30	s31	s32	s33	s34	s35	s36	s37	s38	s39	s40	s41	s42	s43	s44	s45	s46	s47	s48	s49	s50	s51	s52	s53	s54	s55	s56	s57	s58	s59	s60	s84	s85
-ovary-I.vcf	0.0261662312700287	0	0	0.00540922040548445	0	0.0554522494221051	0.0015054005135302	0	0.0527698220499384	0	0.0887078997707257	0	0.000907076161215129	0	0	0	0.00816538925821039	0	0.0128589414347678	0.0380260440755711	0	0	0.0173905924247456	0.001707488229021	0	0.010276473882261	0	0	0.00537132652951311	0.0418328062226971	0.011268103748697	0	0.013513567633232	0	0.0299817999935266	0.0290828169035887	0.0455904351684802	0.00911446107696196	0.0142491074457184	0	0	0.0828680955875177	0	0.137846212289707	0	0	0	0.00955362702540194	0.0176518216878586	0	0	0	0	0	0.00791168443668074	0.023401746173643	0	0	0.0142889494092746	0	0	0.0589804306629367	0.127565493753874	0.00058468535308627	0	0	0
-ovary-H.vcf	0.0514943738497272	0	0	0.0087020810819626	0	0	0.00236410365956529	0	0.0283100865280861	0.00330015778410193	0.0876336183320928	0	0.00461986640013499	0	0	0	0.0149334722781705	0	0	0.0575304849089614	0	0.00251629772375885	0	0.0165652645823303	0	0.000624306444994269	0	0	0.00504372393616242	0.00966085594196363	0.00415555408979927	0.00663515443687386	0.0171493644187634	0	0.0481611871648976	0.00444934777109341	0.0328633359412982	0.0116426528342991	0.0171447988100082	0	0	0.0946683632396481	0	0.137633236641122	0	0	0	0	0.0602320275961475	0	0	0	0	0	0.0124382204627417	0.0101014447648236	0	0.00234093513264533	0.0255780469333522	0.0118621125591813	0	0.0844080841563258	0.123178981782342	0.00205845781262428	0	0	0
-lung-G.vcf	0.0835415571466835	0	0	0	0	0.0531396303027374	0.00733219232339216	0	0.0313762292215084	0	0.0606428164890939	0.0176603522234399	0	0.000123110879620826	0	0	0.00735095968187644	0	0	0.0290566556597906	0.00029875750108526	0	0.0203972540873668	0.0355580201715423	0	0.0123438369843411	0.00148831528108934	0	0.00702152929618746	0.0500581225968108	0	0	0	0	0.0483376674495861	0.00503826980581789	0.0375230365596794	0.000365640786534471	0.0173540188566111	0	0	0.119562508095986	0	0.0922495052872749	0	0	0.00186662484782185	0	0.00198383177758492	0	0	0.0016907139525808	0	0	0	0.0339551728551291	0	0.000506019602171982	0.0354612532013092	0	0	0.0800934470527665	0.0943176689178333	0	0.00204207638725024	0.0102632047174961	0
-lung-F.vcf	0.129733671535086	0	0.0756510632174742	0	0	0	0	0	0.0340346028561247	0	0.0771217892059738	0	0.00227780162121716	0.00924261610588687	0	0	0	0	0	0.0465201871969074	0	0	0.0110305938436319	0.0158255469126101	0	0.00374844346904832	0.00146787555295699	0	0.00847802739839135	0.0105235337001421	0	0.000114895596046716	0.0236577247003424	0	0.0645253165188412	0.00780877511904059	0.0367599879858517	0.00522232526398284	0.0100399736075406	0	0	0.087309725420689	0	0.0759894281641185	0	0	0.000534487830683315	0.00298777004029269	0.0229584360721825	0	0	0.0217298493319228	0	0.00070999042925293	0	0.0141214288614859	0	0.00249376674671315	0.0393307390657661	0	0	0.0241692429399726	0.120513106763722	0.00304686844730181	0	0.0103204084787993	0
+sample	SBS1	SBS2	SBS3	SBS4	SBS5	SBS6	SBS7a	SBS7b	SBS7c	SBS7d	SBS8	SBS9	SBS10a	SBS10b	SBS10c	SBS10d	SBS11	SBS12	SBS13	SBS14	SBS15	SBS16	SBS17a	SBS17b	SBS18	SBS19	SBS20	SBS21	SBS22	SBS23	SBS24	SBS25	SBS26	SBS27	SBS28	SBS29	SBS30	SBS31	SBS32	SBS33	SBS34	SBS35	SBS36	SBS37	SBS38	SBS39	SBS40	SBS41	SBS42	SBS43	SBS44	SBS45	SBS46	SBS47	SBS48	SBS49	SBS50	SBS51	SBS52	SBS53	SBS54	SBS55	SBS56	SBS57	SBS58	SBS59	SBS60	SBS84	SBS85	SBS86	SBS87	SBS88	SBS89	SBS90	SBS91	SBS92	SBS93	SBS94
+ovary-I.vcf	0.0248743382983054	0	0	0	0	0.0382804313784858	0.000279867877099847	0	0.0523368831013261	0	0.0882193437709409	0	0.00105713908429325	0	0	0	0	0	0.00790452113929918	0	0.0228952649764221	0.035824437322864	0	0	0.0157694785042366	0.00112106011995225	0	0.00901729432205061	0	0	0.0067314503274015	0.0424173427597118	0.00897709595233141	0	0.0134288190900345	0	0.0315118740824124	0.0274274413781644	0.0459722043929115	0.00919119609371442	0.0135875438956959	0	0	0.0813737079036436	0	0.134441510514793	0	0	0	0.00968535679523162	0.0232988957406608	0	0	0	0	0	0.00901138983347702	0.0232219272273402	0	0	0.0140535953847184	0	0	0.0588372989742489	0.126837942673735	0.000414033475201199	0	0	0	0	0.0123975208041955	0	0	0	0	0.00960179280510004	0	0
+ovary-H.vcf	0.0526112623195139	0	0	0.00259659019141931	0	0	0.00441492436160073	0	0.028442412784458	0.00371282908990969	0.0771150268514295	0	0.00469080414948085	0	0	0	0	0	0.0131075005010316	0	0	0.0564087542136608	0	0.00228775187171679	0	0.0197458393231762	0	0.00177238312166065	0	0	0.00886883514891954	0	0.00387092295756819	0.0034150231168899	0.0174808677883371	0	0.0435652656329046	0.001821180738257	0.0264091265962629	0.0107100101651646	0.0174453430547186	0	0	0.0961708355601418	0	0.121116601538177	0	0	0	0	0.0571796516660221	0	0	0	0	0.000214057521674493	0.0111211317159625	0.00829256700318903	0	0.00164798457109997	0.0258483341879308	0.00644458809280953	0	0.0846638702721653	0.122478370005574	0.00222471578608652	0	0.000420172000753205	0	0.00163043517541805	0.000141322538953654	0	0.0574873294316273	0.00242537895433406	0	0	0	0
+lung-G.vcf	0.0823617355865553	0	0	0	0	0.0525713539199432	0.00861488625601096	0	0.0339595873379564	0	0.0456255244916971	0.0145585252714382	0	0.000421381081383047	0	0	0	0	0.00522670784278192	0	0	0.0293382321445568	0.00139649570607906	0	0.0194196611974925	0.0386127956083362	0	0.013789732383022	0	0	0.0100733150661604	0.0349706130241875	0	0	0	0	0.0434093655847984	0.00181825891236839	0.0303474622606777	0	0.0187029901709085	0	0	0.120376065787024	0	0.0599280433448042	0	0	0.00132966985611013	0	0	0	0	0.0039271065334873	0	0	0	0.0280674592931216	0	0	0.035137879879521	0	0	0.0812463129866582	0.0917684488653737	0	0	0.0124734516843239	0	0.00901316909994899	0.00681265646517624	0	0.0647011123580966	0	0	0	0	0
+lung-F.vcf	0.125106083697333	0	0.0894527459328343	0	0	0	0	0	0.0324668080771622	0	0.0672874649502956	0	0.00268401866175131	0.00917023093306937	0	0	0	0	0	0	0	0.0451906045983062	0	0	0.00910592930802089	0.0167722110675364	0	0.0038298515888168	0	0	0.009531234514015	0	0	0	0.0232363343868912	0	0.062330351090351	0.00493364473237903	0.0324520312030243	0.00486738928923164	0.0100557162196348	0	0	0.0888476521405422	0	0.0556313157931215	0	0	0	0	0.020753584501296	0	0	0.0183541664469706	0	0.000330058861573153	0.00181335415290947	0.0123934694096205	0	0.00196180738612452	0.0392499133494657	0	0	0.0247940538178981	0.120319900452309	0.00358101555748017	0	0.0122742608109216	0.000420655172516775	0	0.0145849808127487	0	0.0316331756761206	0.00458398540772828	0	0	0	0
Binary file test-data/spectrum_output1.pdf has changed
--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/test-data/user_defined_signature.tsv	Sun Oct 17 15:51:05 2021 +0000
@@ -0,0 +1,97 @@
+Type	SBS1	SBS2	SBS3	SBS4	SBS5	SBS6	SBS7a	SBS8	SBS9	SBS10a	SBS11	SBS12	SBS13	SBS14	SBS15	SBS16	SBS17a	SBS18	SBS19	SBS20	SBS21	SBS22	SBS23	SBS24	SBS25	SBS26	SBS28	SBS29	SBS30
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