changeset 3:e332cf9dfa06 draft

"planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit 0f7593f703ba0dfd12aea1c0460e371f08b57d2f"
author artbio
date Thu, 24 Sep 2020 01:32:52 +0000
parents aea952be68cb
children 7ba08c826888
files mutational_patterns.R mutational_patterns.xml sigProfiler_SBS_signatures_2019_05_22.tsv test-data/cosmic_output1.pdf test-data/denovo_1.RData test-data/denovo_output1.pdf test-data/sigmatrix.tab test-data/spectrum_output1.pdf
diffstat 8 files changed, 388 insertions(+), 95 deletions(-) [+]
line wrap: on
line diff
--- a/mutational_patterns.R	Wed Sep 16 22:58:28 2020 +0000
+++ b/mutational_patterns.R	Thu Sep 24 01:32:52 2020 +0000
@@ -29,6 +29,12 @@
     help = "path to the tab separated file describing the levels in function of datasets"
   ),
   make_option(
+    "--cosmic_version",
+    default = "v2",
+    type = 'character',
+    help = "Version of the Cosmic Signature set to be used to express mutational patterns"
+  ),
+  make_option(
     "--signum",
     default = 2,
     type = 'integer',
@@ -52,7 +58,6 @@
     type = 'integer',
     help = "Number of new signatures to be captured"
   ),
-
   make_option(
     "--output_spectrum",
     default = NA,
@@ -66,11 +71,22 @@
     help = "path to output dataset"
   ),
   make_option(
+    "--sigmatrix",
+    default = NA,
+    type = 'character',
+    help = "path to signature matrix"
+  ),
+  make_option(
     "--output_cosmic",
     default = NA,
     type = 'character',
     help = "path to output dataset"
-  )
+  ),
+  make_option(
+    c("-r", "--rdata"),
+    type="character",
+    default=NULL,
+    help="Path to RData output file")
 )
 
 opt = parse_args(OptionParser(option_list = option_list),
@@ -81,28 +97,27 @@
 parser <- newJSONParser()
 parser$addData(json_dict)
 fileslist <- parser$getObject()
-vcf_files <- attr(fileslist, "names")
-sample_names <- unname(unlist(fileslist))
+vcf_paths <- attr(fileslist, "names")
+element_identifiers <- unname(unlist(fileslist))
 ref_genome <- opt$genome
-vcf_table <- data.frame(sample_name=sample_names, path=vcf_files)
+vcf_table <- data.frame(element_identifier=element_identifiers, path=vcf_paths)
 
 library(MutationalPatterns)
 library(ref_genome, character.only = TRUE)
+library(ggplot2)
 
 # Load the VCF files into a GRangesList:
-vcfs <- read_vcfs_as_granges(vcf_files, sample_names, ref_genome)
+vcfs <- read_vcfs_as_granges(vcf_paths, element_identifiers, ref_genome)
 if (!is.na(opt$levels)[1]) {  # manage levels if there are
-    levels_table  <- read.delim(opt$levels, header=FALSE, col.names=c("sample_name","level"))
-    library(dplyr)
-    metadata_table <- left_join(vcf_table, levels_table, by = "sample_name")
-#    detach("package:dplyr", unload=TRUE)
-    tissue <- metadata_table$level
+    levels_table  <- read.delim(opt$levels, header=FALSE, col.names=c("element_identifier","level"))
+    library(plyr)
+    metadata_table <- join(vcf_table, levels_table, by = "element_identifier")
+    tissue <- as.vector(metadata_table$level)
 }
 
 ##### This is done for any section ######
 mut_mat <- mut_matrix(vcf_list = vcfs, ref_genome = ref_genome)
 
-
 ###### Section 1 Mutation characteristics and spectrums #############
 if (!is.na(opt$output_spectrum)[1]) {
     pdf(opt$output_spectrum, paper = "special", width = 11.69, height = 11.69)
@@ -114,34 +129,41 @@
         p1 <- plot_spectrum(type_occurrences, CT = TRUE, legend=TRUE)
         plot(p1)
     } else {
-        p2 <- plot_spectrum(type_occurrences, by = tissue, CT=TRUE, legend=TRUE) # by sample
+        p2 <- plot_spectrum(type_occurrences, by = tissue, CT=TRUE) # by levels
         p3 <- plot_spectrum(type_occurrences, CT=TRUE, legend=TRUE) # total
         grid.arrange(p2, p3, ncol=2, widths=c(4,2.3), heights=c(4,1))
-    }
+   }
     plot_96_profile(mut_mat, condensed = TRUE)
     dev.off()
 }
 
 ###### Section 2: De novo mutational signature extraction using NMF #######
 if (!is.na(opt$output_denovo)[1]) {
-    mut_mat <- mut_mat + 0.0001 # First add a small psuedocount to the mutation count matrix
+    # opt$rank cannot be higher than the number of samples
+    if (opt$rank > length(element_identifiers)) {opt$rank <-length(element_identifiers)}
+    # likewise, opt$signum cannot be higher thant the number of samples
+    if (opt$signum > length(element_identifiers)) {opt$signum <-length(element_identifiers)}
+    pseudo_mut_mat <- mut_mat + 0.0001 # First add a small pseudocount to the mutation count matrix
     # Use the NMF package to generate an estimate rank plot
     library("NMF")
-    estimate <- nmf(mut_mat, rank=1:opt$rank+1, method="brunet", nrun=opt$nrun, seed=123456)
+    estimate <- nmf(pseudo_mut_mat, rank=1:opt$rank, method="brunet", nrun=opt$nrun, seed=123456)
     # And plot it
     pdf(opt$output_denovo, paper = "special", width = 11.69, height = 11.69)
-    p.trans <- plot(estimate)
-    grid.arrange(p.trans)
+    p4 <- plot(estimate)
+    grid.arrange(p4)
     # Extract 4 (PARAMETIZE) mutational signatures from the mutation count matrix with extract_signatures
     # (For larger datasets it is wise to perform more iterations by changing the nrun parameter
     # to achieve stability and avoid local minima)
-    nmf_res <- extract_signatures(mut_mat, rank=opt$rank, nrun=opt$nrun)
+    nmf_res <- extract_signatures(pseudo_mut_mat, rank=opt$newsignum, nrun=opt$nrun)
     # Assign signature names
-    colnames(nmf_res$signatures) <- paste0("NewSig_", 1:opt$rank)
-    rownames(nmf_res$contribution) <- paste0("NewSig_", 1:opt$rank)
+    colnames(nmf_res$signatures) <- paste0("NewSig_", 1:opt$newsignum)
+    rownames(nmf_res$contribution) <- paste0("NewSig_", 1:opt$newsignum)
     # Plot the 96-profile of the signatures:
-    p.trans <- plot_96_profile(nmf_res$signatures, condensed = TRUE)
-    grid.arrange(p.trans)
+    p5 <- plot_96_profile(nmf_res$signatures, condensed = TRUE)
+    new_sig_matrix <- reshape2::dcast(p5$data, substitution + context ~ variable, value.var = "value")
+    new_sig_matrix = format(new_sig_matrix, scientific=TRUE)
+    write.table(new_sig_matrix, file=opt$sigmatrix, quote = FALSE, row.names = FALSE, sep="\t") 
+    grid.arrange(p5)
     # Visualize the contribution of the signatures in a barplot
     pc1 <- plot_contribution(nmf_res$contribution, nmf_res$signature, mode="relative", coord_flip = TRUE)
     # Visualize the contribution of the signatures in absolute number of mutations
@@ -155,14 +177,14 @@
     # can be plotted in a user-specified order.
     # Plot signature contribution as a heatmap with sample clustering dendrogram and a specified signature order:
     pch1 <- plot_contribution_heatmap(nmf_res$contribution,
-                                      sig_order = paste0("NewSig_", 1:opt$rank))
+                                      sig_order = paste0("NewSig_", 1:opt$newsignum))
     # Plot signature contribution as a heatmap without sample clustering:
     pch2 <- plot_contribution_heatmap(nmf_res$contribution, cluster_samples=FALSE)
     #Combine the plots into one figure:
     grid.arrange(pch1, pch2, ncol = 2, widths = c(2,1.6))
     
     # Compare the reconstructed mutational profile with the original mutational profile:   
-    plot_compare_profiles(mut_mat[,1],
+    plot_compare_profiles(pseudo_mut_mat[,1],
                           nmf_res$reconstructed[,1],
                           profile_names = c("Original", "Reconstructed"),
                           condensed = TRUE)
@@ -172,18 +194,38 @@
 
 if (!is.na(opt$output_cosmic)[1]) {
     pdf(opt$output_cosmic, paper = "special", width = 11.69, height = 11.69)
-    sp_url <- paste("https://cancer.sanger.ac.uk/cancergenome/assets/", "signatures_probabilities.txt", sep = "")
-    cancer_signatures = read.table(sp_url, sep = "\t", header = TRUE)
-    mut_mat <- mut_mat + 0.0001 # First add a small psuedocount to the mutation count matrix
-    new_order = match(row.names(mut_mat), cancer_signatures$Somatic.Mutation.Type)
-    cancer_signatures = cancer_signatures[as.vector(new_order),]
-    row.names(cancer_signatures) = cancer_signatures$Somatic.Mutation.Type
-    cancer_signatures = as.matrix(cancer_signatures[,4:33])
+    pseudo_mut_mat <- mut_mat + 0.0001 # First add a small psuedocount to the mutation count matrix
+    if (opt$cosmic_version == "v2") {
+        sp_url <- paste("https://cancer.sanger.ac.uk/cancergenome/assets/", "signatures_probabilities.txt", sep = "")
+        cancer_signatures = read.table(sp_url, sep = "\t", header = TRUE)
+        new_order = match(row.names(pseudo_mut_mat), cancer_signatures$Somatic.Mutation.Type)
+        cancer_signatures = cancer_signatures[as.vector(new_order),]
+        row.names(cancer_signatures) = cancer_signatures$Somatic.Mutation.Type
+        cancer_signatures = as.matrix(cancer_signatures[,4:33])
+        colnames(cancer_signatures) <- gsub("Signature.", "", colnames(cancer_signatures)) # shorten signature labels
+        cosmic_tag <- "Signatures (Cosmic v2, March 2015)"
+        } else {
+        sp_url <- "https://raw.githubusercontent.com/ARTbio/startbio/master/sigProfiler_SBS_signatures_2019_05_22.tsv"
+        cancer_signatures = read.table(sp_url, sep = "\t", header = TRUE)
+        new_order = match(row.names(pseudo_mut_mat), cancer_signatures$Somatic.Mutation.Type)
+        cancer_signatures = cancer_signatures[as.vector(new_order),]
+        row.names(cancer_signatures) = cancer_signatures$Somatic.Mutation.Type
+        cancer_signatures = as.matrix(cancer_signatures[,4:70])        
+        colnames(cancer_signatures) <- gsub("SBS", "", colnames(cancer_signatures)) # shorten signature labels
+        cosmic_tag <- "Signatures (Cosmic v3, May 2019)"
+        }
     
     # Plot mutational profiles of the COSMIC signatures
-    colnames(cancer_signatures) <- gsub("Signature.", "", colnames(cancer_signatures)) # shorten signature labels
-    p.trans <- plot_96_profile(cancer_signatures, condensed = TRUE, ymax = 0.3)
-    grid.arrange(p.trans, top = textGrob("COSMIC signature profiles",gp=gpar(fontsize=12,font=3)))
+    if (opt$cosmic_version == "v2") {
+        p6 <- plot_96_profile(cancer_signatures, condensed = TRUE, ymax = 0.3)
+        grid.arrange(p6, top = textGrob("COSMIC signature profiles",gp=gpar(fontsize=12,font=3)))
+    } else {
+        print(length(cancer_signatures))
+        p6 <- plot_96_profile(cancer_signatures[,1:33], condensed = TRUE, ymax = 0.3)
+        p6bis <- plot_96_profile(cancer_signatures[,34:67], 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)))
+    }
 
     # Hierarchically cluster the COSMIC signatures based on their similarity with average linkage
     # hclust_cosmic = cluster_signatures(cancer_signatures, method = "average")
@@ -211,16 +253,37 @@
     # grid.arrange(p.trans)
     
     # Find optimal contribution of COSMIC signatures to reconstruct 96 mutational profiles
-    fit_res <- fit_to_signatures(mut_mat, cancer_signatures)
+    fit_res <- fit_to_signatures(pseudo_mut_mat, cancer_signatures)
 
     # Select signatures with some contribution (above a threshold)
     threshold <- tail(sort(unlist(rowSums(fit_res$contribution), use.names = FALSE)), opt$signum)[1]
     select <- which(rowSums(fit_res$contribution) >= threshold) # ensure opt$signum best signatures in samples are retained, the others discarded
     # Plot contribution barplots
-    pc1 <- plot_contribution(fit_res$contribution[select,], cancer_signatures[,select], coord_flip = T, mode = "absolute")
-    pc2 <- plot_contribution(fit_res$contribution[select,], cancer_signatures[,select], coord_flip = T, mode = "relative")
+    pc3 <- plot_contribution(fit_res$contribution[select,], cancer_signatures[,select], coord_flip = T, mode = "absolute")
+    pc4 <- plot_contribution(fit_res$contribution[select,], cancer_signatures[,select], coord_flip = T, mode = "relative")
+    #####
+    # ggplot2 alternative
+    if (!is.na(opt$levels)[1]) {  # if there are levels to display in graphs
+        pc3_data <- pc3$data
+        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_discrete(name="Cosmic\nSignature") +
+               labs(x = "Samples", y = "Absolute contribution") + theme_bw() + 
+               theme(panel.grid.minor.x = element_blank(), panel.grid.major.x = element_blank()) + 
+               facet_grid(~level, scales = "free_x")
+        pc4_data <- pc4$data
+        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_discrete(name="Cosmic\nSignature") +
+               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()) + 
+               facet_grid(~level, scales = "free_x")
+    }
     # Combine the two plots:
-    grid.arrange(pc1, pc2)
+    grid.arrange(pc3, pc4, top = textGrob("Absolute and Relative Contributions of Cosmic signatures to mutational patterns",gp=gpar(fontsize=12,font=3)))
     ## pie charts of comic signatures contributions in samples
     
     sig_data_pie <- as.data.frame(t(head(fit_res$contribution[select,])))
@@ -231,20 +294,19 @@
     melted_sig_data_pie_percents <-melt(data=sig_data_pie_percents)
     melted_sig_data_pie_percents$label <- sub("Sig.", "", melted_sig_data_pie_percents$variable)
     melted_sig_data_pie_percents$pos <- cumsum(melted_sig_data_pie_percents$value) - melted_sig_data_pie_percents$value/2
-    library(ggplot2)
-    p.trans <-  ggplot(melted_sig_data_pie_percents, aes(x="", y=value, group=variable, fill=variable)) +
+    p7 <-  ggplot(melted_sig_data_pie_percents, aes(x="", y=value, group=variable, fill=variable)) +
                        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 = "Signatures (Cosmic_v2,March 2015)") +
+                       labs(x="", y="Samples", fill = cosmic_tag) +
                        theme(axis.text = element_blank(),
                              axis.ticks = element_blank(),
                              panel.grid  = element_blank())
-    grid.arrange(p.trans)
+    grid.arrange(p7)
 
     # Plot relative contribution of the cancer signatures in each sample as a heatmap with sample clustering
-    p.trans <- plot_contribution_heatmap(fit_res$contribution, cluster_samples = TRUE, method = "complete")
-    grid.arrange(p.trans)
+    p8 <- plot_contribution_heatmap(fit_res$contribution, cluster_samples = TRUE, method = "complete")
+    grid.arrange(p8)
 
     # Compare the reconstructed mutational profile of sample 1 with its original mutational profile
     # plot_compare_profiles(mut_mat[,1], fit_res$reconstructed[,1],
@@ -255,7 +317,7 @@
     # `cos_sim_matrix`
     
     # calculate all pairwise cosine similarities
-    cos_sim_ori_rec <- cos_sim_matrix(mut_mat, fit_res$reconstructed)
+    cos_sim_ori_rec <- cos_sim_matrix(pseudo_mut_mat, fit_res$reconstructed)
     # extract cosine similarities per sample between original and reconstructed
     cos_sim_ori_rec <- as.data.frame(diag(cos_sim_ori_rec))
     
@@ -270,7 +332,7 @@
     colnames(cos_sim_ori_rec) = "cos_sim"
     cos_sim_ori_rec$sample = row.names(cos_sim_ori_rec)
     # Make barplot
-    p.trans <- ggplot(cos_sim_ori_rec, aes(y=cos_sim, x=sample)) +
+    p9 <- ggplot(cos_sim_ori_rec, aes(y=cos_sim, x=sample)) +
                       geom_bar(stat="identity", fill = "skyblue4") +
                       coord_cartesian(ylim=c(0.8, 1)) +
                       # coord_flip(ylim=c(0.8,1)) +
@@ -283,7 +345,12 @@
                       panel.grid.major.y=element_blank()) +
                       # Add cut.off line
                       geom_hline(aes(yintercept=.95))
-    grid.arrange(p.trans, top = textGrob("Similarity between true and reconstructed profiles (with all Cosmic sig.)",gp=gpar(fontsize=12,font=3)))    
-    
+    grid.arrange(p9, top = textGrob("Similarity between true and reconstructed profiles (with all Cosmic sig.)",gp=gpar(fontsize=12,font=3)))    
     dev.off()
 }
+
+
+# Output RData file
+if (!is.null(opt$rdata)) {
+  save.image(file=opt$rdata)
+}
--- a/mutational_patterns.xml	Wed Sep 16 22:58:28 2020 +0000
+++ b/mutational_patterns.xml	Thu Sep 24 01:32:52 2020 +0000
@@ -1,4 +1,4 @@
-<tool id="mutational_patterns" name="Analyse Mutational Patters/Signatures" version="2.0.0+galaxy3">
+<tool id="mutational_patterns" name="Analyse Mutational Patterns/Signatures" version="2.0.0+galaxy4">
     <description>from genomic variations in vcf files</description>
     <requirements>
         <requirement type="package" version="2.0.0=r40_0">bioconductor-mutationalpatterns</requirement>
@@ -43,13 +43,19 @@
         --rank $set_denovo.rank
         --newsignum $set_denovo.newsignum
         --output_denovo $denovo
+        --sigmatrix $sigmatrix
     #end if
 
     #if $set_cosmic.choices == 'yes':
+        --cosmic_version $set_cosmic.cosmic_version
         --signum '$set_cosmic.signum'
         --output_cosmic $cosmic
     #end if
             
+    #if $rdata_out
+        --rdata '$rdata'
+    #end if
+
 ]]></command>
     <inputs>
         <param name="vcfs" type="data_collection" format="vcf" label="VCF file(s) collection" multiple="true"/>
@@ -90,6 +96,7 @@
             <when value="yes" />
             <when value="no" />
         </conditional>
+
         <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>
@@ -101,10 +108,10 @@
                        help="High values extend the computational time"/>
                 <param name="rank" type="integer" value="4" min="3" max="30"
                        label="Number of ranks to be displayed for control of optimal number of signature"
-                       help="High values extend the computational time"/>
+                       help="High values extend the computational time. In addition the number of ranks cannot be greater than the number of available samples in the study"/>
                 <param name="newsignum" type="integer" value="4" min="2" max="30"
                        label="Number of de novo signatures to capture"
-                       help="High values extend the computational time"/>
+                       help="High values extend the computational time. Note also that you cannot extract more signature than the number of available samples in the study"/>
             </when>
             <when value="no" />
         </conditional>
@@ -118,9 +125,14 @@
                 <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>
+                </param>
             </when>
              <when value="no" />
-       </conditional>
+        </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>
     <outputs>
         <data name="spectrum" format="pdf" label="Mutational Spectrum">
@@ -129,53 +141,19 @@
         <data name="denovo" format="pdf" label="De novo signatures">
             <filter>set_denovo['choices'] == "yes"</filter>
         </data>
+        <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>
+        <data name="rdata" format="rdata" label="${tool.name}: RData file">
+            <filter>rdata_out</filter>
+        </data>
+
     </outputs>
     <tests>
-        <test>
-            <param name="vcfs">
-                <collection type="list">
-                    <element name="1" ftype="vcf" value="G.vcf"/>
-                    <element name="2" ftype="vcf" value="H.vcf"/>
-                </collection>
-            </param>
-            <param name="genome" value="BSgenome.Hsapiens.UCSC.hg38"/>
-            <param name="levels" value="GH_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">
-                <param name="choices" value="yes"/>
-            </conditional>
-            <param name="signum" value="3" />
-            <output name="cosmic" file="cosmic_output1.pdf" compare="sim_size" ftype="pdf"/>
-        </test>
-        <test>
-            <param name="vcfs">
-                <collection type="list">
-                    <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"/>
-            <conditional name="set_spectrum">
-                <param name="choices" value="no"/>
-            </conditional>
-            <conditional name="set_denovo">
-                <param name="choices" value="yes"/>
-            </conditional>
-            <conditional name="set_cosmic">
-                <param name="choices" value="no"/>
-            </conditional>
-            <output name="denovo" file="denovo_output1.pdf" compare="sim_size" ftype="pdf"/>
-        </test>
+        <!-- simple profile -->
         <test>
             <param name="vcfs">
                 <collection type="list">
@@ -199,6 +177,60 @@
             </conditional>
             <output name="spectrum" file="spectrum_output1.pdf" compare="sim_size" ftype="pdf"/>
         </test>
+
+         <!-- de novo signatures -->
+        <test>
+            <param name="vcfs">
+                <collection type="list">
+                    <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"/>
+            <conditional name="set_spectrum">
+                <param name="choices" value="no"/>
+            </conditional>
+            <conditional name="set_denovo">
+                <param name="choices" value="yes"/>
+            </conditional>
+            <conditional name="set_cosmic">
+                <param name="choices" value="no"/>
+            </conditional>
+            <param name="nrun" value="10" />
+            <param name="rank" value="4" />
+            <param name="newsignum" value="4" />
+            <param name="rdata_out" value="true" />
+            <output name="denovo" file="denovo_output1.pdf" compare="sim_size" ftype="pdf"/>
+            <output name="sigmatrix" file="sigmatrix.tab" ftype="tabular" compare="sim_size"/>
+            <output name="rdata" file="denovo_1.RData" compare="sim_size" delta="400000"/> <!--  delta="170000" -->
+        </test>
+
+         <!-- cosmic signatures -->
+        <test>
+            <param name="vcfs">
+                <collection type="list">
+                    <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="GH_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">
+                <param name="choices" value="yes"/>
+            </conditional>
+            <param name="signum" value="3" />
+            <output name="cosmic" file="cosmic_output1.pdf" compare="sim_size" ftype="pdf"/>
+        </test>
     </tests>
     <help>
 
--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/sigProfiler_SBS_signatures_2019_05_22.tsv	Thu Sep 24 01:32:52 2020 +0000
@@ -0,0 +1,97 @@
+Type	SubType	Somatic Mutation Type	SBS1	SBS2	SBS3	SBS4	SBS5	SBS6	SBS7a	SBS7b	SBS7c	SBS7d	SBS8	SBS9	SBS10a	SBS10b	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
+C>A	ACA	A[C>A]A	8.86E-04	5.80E-07	2.08E-02	4.22E-02	1.20E-02	4.25E-04	6.70E-05	2.33E-03	4.83E-03	4.04E-05	4.41E-02	5.58E-04	2.19E-03	1.82E-04	1.46E-04	4.52E-03	1.82E-03	1.12E-03	9.44E-04	1.60E-02	2.07E-03	6.08E-04	5.15E-02	1.27E-03	6.19E-04	1.57E-04	6.01E-03	8.35E-04	3.64E-02	9.90E-03	8.73E-04	5.21E-03	7.84E-04	6.32E-02	1.80E-03	9.54E-03	2.23E-02	3.11E-03	4.87E-03	8.83E-03	2.52E-02	3.95E-03	1.28E-02	1.17E-02	2.82E-02	2.11E-03	1.16E-03	2.95E-02	7.68E-18	9.11E-03	4.40E-03	6.78E-02	8.55E-04	2.51E-02	1.19E-01	1.41E-01	1.52E-02	5.38E-03	2.16E-03	5.88E-03	1.26E-02	1.23E-02	5.89E-02	3.59E-03	6.15E-03	0.003471994832	0.006080257390
+C>A	ACC	A[C>A]C	2.28E-03	1.48E-04	1.65E-02	3.33E-02	9.44E-03	5.24E-04	1.79E-04	4.61E-04	1.15E-03	7.65E-04	4.78E-02	4.09E-03	1.77E-03	6.54E-03	5.52E-04	1.13E-03	7.21E-04	1.31E-02	4.97E-04	2.90E-03	9.18E-04	1.29E-04	1.58E-02	6.41E-04	1.39E-03	2.36E-03	9.54E-05	3.99E-04	2.65E-02	7.00E-03	5.28E-04	4.74E-03	2.53E-03	5.12E-02	5.06E-04	1.85E-02	1.88E-02	2.23E-03	6.96E-03	4.62E-02	8.32E-03	1.45E-03	1.01E-02	7.15E-03	1.34E-02	1.22E-03	2.06E-02	5.90E-03	1.50E-04	2.85E-03	4.70E-03	2.97E-02	8.41E-04	7.03E-03	1.27E-01	1.69E-03	6.54E-03	1.96E-03	7.96E-04	2.05E-03	1.57E-02	1.43E-03	6.75E-03	2.37E-03	7.79E-04	0.005007308997	0.000879936873
+C>A	ACG	A[C>A]G	1.77E-04	5.23E-05	1.75E-03	1.56E-02	1.85E-03	5.20E-05	7.12E-05	1.86E-04	3.77E-04	2.50E-04	4.62E-03	4.26E-04	1.50E-04	5.35E-05	9.41E-05	5.40E-04	2.64E-04	4.13E-04	4.61E-05	1.02E-03	4.76E-05	5.82E-05	2.43E-03	2.46E-04	2.18E-05	2.94E-04	7.65E-04	9.85E-08	1.48E-02	1.45E-03	1.14E-04	7.83E-04	3.53E-04	1.92E-02	9.13E-05	1.66E-03	4.46E-03	4.14E-04	5.20E-05	1.39E-03	2.24E-03	1.06E-03	1.90E-03	2.67E-03	2.92E-03	6.14E-05	3.34E-05	6.26E-04	9.16E-07	1.66E-03	3.00E-04	1.38E-03	2.58E-04	7.11E-03	5.77E-03	4.80E-03	4.14E-03	3.81E-02	1.64E-03	4.49E-05	2.06E-04	3.33E-03	8.25E-04	1.42E-04	2.23E-16	0.000452641972	0.000306011349
+C>A	ACT	A[C>A]T	1.28E-03	9.78E-05	1.22E-02	2.95E-02	6.61E-03	1.80E-04	2.48E-04	7.10E-04	1.96E-03	4.05E-03	4.70E-02	3.05E-03	1.70E-02	1.63E-05	2.66E-04	1.22E-03	3.48E-04	8.26E-02	1.11E-03	1.06E-02	6.18E-05	4.56E-04	2.14E-02	5.71E-04	1.24E-03	6.21E-04	1.72E-03	5.61E-18	2.20E-02	4.97E-03	6.19E-04	2.72E-03	3.97E-03	3.56E-02	5.56E-04	6.28E-03	1.46E-02	1.90E-03	1.23E-03	2.16E-02	1.79E-02	1.85E-03	8.85E-03	7.40E-03	1.48E-02	1.33E-03	7.97E-03	2.07E-03	5.78E-03	9.64E-03	3.40E-03	1.19E-02	3.89E-05	7.97E-03	8.32E-02	2.12E-02	9.24E-03	1.71E-05	4.14E-04	1.17E-03	2.30E-02	8.64E-03	5.58E-03	1.45E-02	4.44E-04	0.009295948365	0.002717279233
+C>A	CCA	C[C>A]A	3.12E-04	2.08E-04	2.25E-02	8.07E-02	7.43E-03	1.82E-03	4.55E-04	1.14E-03	1.09E-04	1.45E-02	4.01E-02	4.80E-03	3.18E-03	5.21E-04	6.18E-04	5.42E-03	1.40E-03	1.63E-02	4.18E-02	1.04E-02	2.95E-04	2.71E-04	7.40E-02	1.32E-03	3.76E-02	2.22E-16	1.83E-03	1.51E-04	2.54E-02	1.48E-02	1.41E-03	5.07E-03	2.03E-03	5.42E-02	7.68E-04	1.07E-02	1.24E-03	2.70E-03	1.95E-03	2.99E-02	5.58E-02	3.22E-03	3.81E-01	1.01E-02	2.08E-02	2.38E-03	1.16E-02	6.63E-03	2.84E-05	2.38E-01	1.56E-02	2.46E-02	1.18E-03	2.29E-01	2.25E-02	6.98E-03	5.74E-02	3.34E-01	6.32E-05	6.25E-03	2.48E-03	8.70E-03	6.18E-03	2.23E-03	1.18E-03	0.000000000000	0.004264235123
+C>A	CCC	C[C>A]C	1.79E-03	9.53E-05	2.53E-02	7.97E-02	6.14E-03	4.09E-03	2.40E-04	1.55E-03	3.09E-03	3.22E-03	3.88E-02	1.92E-03	2.02E-04	3.18E-03	9.86E-04	4.28E-03	9.68E-04	1.97E-02	5.05E-03	9.03E-03	1.16E-03	4.11E-05	1.96E-02	7.67E-04	9.89E-02	2.60E-03	4.43E-03	6.30E-04	3.49E-02	7.82E-03	1.51E-03	2.23E-03	1.09E-04	3.69E-02	3.88E-04	1.16E-02	4.92E-03	1.91E-03	3.67E-05	3.30E-02	2.02E-02	8.14E-04	6.95E-02	9.06E-03	1.47E-02	9.19E-04	3.28E-02	8.20E-05	3.03E-02	1.51E-01	7.20E-03	5.27E-03	3.57E-05	2.86E-02	2.89E-03	3.17E-03	1.90E-02	3.55E-03	2.57E-03	3.75E-03	6.68E-03	3.94E-03	1.83E-03	5.93E-03	2.53E-04	0.005218571801	0.000306234865
+C>A	CCG	C[C>A]G	9.32E-05	2.23E-16	2.51E-03	2.45E-02	3.46E-03	1.65E-03	2.23E-16	4.08E-04	1.91E-03	8.51E-05	3.41E-03	1.37E-03	4.64E-05	8.38E-05	9.20E-06	1.17E-03	4.33E-06	1.38E-03	6.62E-05	1.74E-03	2.22E-16	2.23E-16	1.20E-02	2.36E-04	7.43E-03	1.98E-03	1.36E-04	1.30E-04	1.60E-02	1.28E-03	3.62E-04	2.66E-04	2.22E-16	1.48E-02	4.07E-04	3.29E-04	1.66E-05	3.71E-04	2.98E-04	2.20E-03	7.10E-03	7.47E-04	5.10E-02	5.74E-03	2.54E-03	2.61E-04	1.88E-03	2.56E-05	3.74E-03	6.79E-02	4.50E-03	2.71E-04	1.37E-01	5.15E-01	5.18E-18	4.30E-03	1.36E-02	6.77E-02	5.93E-03	6.41E-04	6.72E-18	1.07E-03	1.46E-03	8.15E-04	3.79E-04	0.000069231298	0.000157256840
+C>A	CCT	C[C>A]T	2.23E-16	4.21E-04	1.54E-02	6.90E-02	6.49E-03	9.60E-03	3.72E-04	1.49E-03	1.35E-02	1.17E-04	3.30E-02	3.06E-03	1.73E-02	8.33E-03	1.50E-04	1.10E-03	2.22E-16	2.60E-01	2.87E-02	2.49E-03	1.37E-04	1.82E-04	3.63E-02	3.44E-05	2.52E-01	1.91E-02	1.10E-04	5.80E-04	1.71E-02	1.26E-02	7.14E-03	3.10E-03	2.03E-04	5.19E-02	2.97E-04	2.79E-02	2.67E-03	2.53E-03	6.20E-04	8.25E-02	6.05E-02	1.77E-03	1.84E-01	6.03E-03	1.47E-02	2.65E-03	2.11E-02	5.22E-18	8.67E-02	1.94E-01	8.30E-03	6.82E-04	8.45E-04	4.90E-02	1.15E-03	5.07E-03	1.88E-02	4.92E-03	5.53E-03	2.84E-05	7.13E-02	8.21E-03	1.96E-03	2.02E-03	5.41E-05	0.005640381180	0.000860850681
+C>A	GCA	G[C>A]A	1.58E-03	8.62E-05	7.13E-03	3.16E-02	1.02E-02	4.27E-04	4.06E-05	7.46E-04	1.05E-03	1.68E-04	2.42E-02	7.72E-03	1.21E-03	7.31E-04	1.65E-04	1.98E-03	9.49E-04	2.08E-03	2.29E-03	8.61E-03	1.78E-03	9.98E-04	1.09E-01	8.14E-04	1.08E-02	2.14E-03	2.23E-03	3.37E-04	6.22E-02	1.35E-02	4.96E-04	1.08E-02	1.56E-04	9.71E-02	9.43E-04	1.31E-02	4.51E-03	4.41E-03	2.81E-03	9.87E-03	6.77E-02	2.04E-03	1.20E-02	6.88E-03	1.42E-02	3.09E-03	7.71E-03	9.30E-03	7.68E-18	7.55E-03	7.20E-03	1.11E-02	7.52E-04	7.88E-03	1.42E-02	3.94E-03	8.24E-03	4.32E-04	5.19E-03	8.55E-04	2.17E-04	1.89E-03	2.74E-03	1.03E-01	5.17E-04	0.002703472389	0.001439703098
+C>A	GCC	G[C>A]C	3.39E-04	2.23E-16	1.09E-02	3.48E-02	7.65E-03	9.13E-04	1.38E-04	2.15E-04	7.42E-04	2.22E-16	2.62E-02	6.68E-03	4.41E-04	2.55E-03	4.05E-04	4.17E-04	4.51E-04	2.24E-02	2.49E-03	4.25E-03	1.28E-03	2.78E-06	1.73E-02	2.72E-04	5.65E-03	7.07E-03	1.73E-03	5.41E-04	1.28E-01	6.47E-03	6.66E-04	1.24E-02	1.02E-03	9.03E-02	4.94E-04	2.15E-02	3.62E-03	9.68E-04	4.68E-04	5.02E-02	1.92E-02	6.29E-04	6.28E-03	6.95E-03	1.02E-02	7.23E-04	2.68E-02	1.69E-03	4.67E-03	5.73E-03	3.00E-03	3.48E-03	3.46E-04	2.48E-03	7.58E-03	3.28E-03	7.32E-03	3.44E-03	9.13E-03	1.92E-04	7.34E-03	7.52E-04	1.08E-03	1.29E-01	8.66E-04	0.010228858800	0.000504268015
+C>A	GCG	G[C>A]G	5.87E-04	1.39E-05	1.43E-03	1.53E-02	2.34E-03	3.57E-04	4.25E-05	7.29E-05	2.22E-16	1.82E-05	2.74E-03	1.71E-04	1.05E-05	8.52E-05	1.39E-05	4.47E-04	1.64E-04	1.11E-03	4.04E-04	1.36E-03	1.06E-04	9.24E-05	7.56E-03	2.05E-04	1.57E-03	1.69E-03	5.15E-04	1.19E-04	6.59E-02	6.58E-04	1.29E-04	1.63E-03	3.95E-05	2.30E-02	2.22E-16	9.72E-04	8.77E-04	3.42E-04	2.27E-04	5.07E-04	4.83E-03	5.06E-04	1.37E-03	4.53E-03	2.55E-03	2.20E-04	1.06E-03	1.77E-04	6.05E-04	2.09E-03	4.00E-04	7.83E-04	7.39E-04	6.83E-03	2.44E-04	4.28E-03	4.04E-03	5.08E-02	5.64E-03	7.72E-05	9.79E-06	6.57E-18	2.73E-03	1.21E-02	3.90E-04	0.000763601342	0.000362282705
+C>A	GCT	G[C>A]T	2.23E-16	5.12E-05	1.00E-02	2.12E-02	6.82E-03	1.23E-03	2.23E-16	1.47E-04	3.63E-04	7.40E-05	2.69E-02	8.56E-03	1.11E-02	2.80E-03	2.22E-16	2.75E-05	6.15E-05	1.26E-01	1.82E-02	5.80E-03	4.70E-05	5.34E-04	6.23E-02	2.73E-04	2.49E-03	8.90E-03	5.51E-04	3.09E-05	5.44E-02	1.05E-02	8.17E-04	7.41E-03	1.58E-04	8.46E-02	8.62E-04	3.51E-03	3.27E-03	3.19E-03	1.35E-05	2.29E-02	6.90E-02	1.29E-03	9.09E-03	5.89E-03	1.08E-02	1.95E-03	1.81E-02	1.39E-03	1.13E-02	6.99E-03	2.40E-03	1.41E-03	1.99E-05	5.84E-03	2.04E-03	3.45E-03	4.21E-03	1.14E-03	6.73E-03	7.38E-04	1.57E-02	1.95E-03	3.50E-04	4.99E-01	1.33E-04	0.010179165989	0.000762947056
+C>A	TCA	T[C>A]A	6.58E-05	6.39E-04	8.41E-03	3.98E-02	7.86E-03	3.56E-04	3.90E-04	2.90E-03	2.52E-03	1.14E-02	2.98E-02	1.70E-02	9.40E-02	4.46E-04	1.80E-04	3.48E-03	7.90E-02	3.47E-04	1.72E-02	1.08E-02	1.90E-04	1.24E-05	7.38E-02	1.38E-03	1.71E-03	1.46E-03	7.84E-04	2.13E-03	2.98E-02	6.94E-03	9.38E-04	7.08E-03	1.43E-02	4.52E-02	6.96E-04	1.86E-03	9.73E-03	1.19E-02	4.27E-03	5.27E-03	1.41E-01	2.00E-03	1.77E-02	5.98E-03	2.60E-02	3.31E-03	5.10E-03	6.30E-03	8.53E-04	6.40E-02	1.23E-02	1.69E-02	1.24E-01	3.29E-02	1.90E-02	3.57E-02	4.64E-01	2.67E-03	6.69E-04	1.74E-03	2.19E-01	1.43E-02	7.37E-03	2.37E-05	2.02E-03	0.002083564327	0.001944387330
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+T>A	GTC	G[T>A]C	1.29E-04	1.31E-04	7.48E-03	3.60E-03	2.91E-03	4.89E-04	2.24E-04	2.56E-04	2.27E-03	1.12E-04	1.35E-02	2.12E-03	2.23E-16	1.23E-04	3.75E-04	1.81E-03	1.30E-04	2.73E-03	5.89E-04	6.08E-04	3.40E-03	3.47E-04	1.95E-03	7.78E-05	2.56E-03	3.26E-03	1.02E-02	1.40E-04	2.35E-03	5.85E-03	1.15E-03	2.35E-05	1.18E-04	7.89E-04	1.82E-04	2.91E-03	8.22E-03	3.62E-04	2.42E-03	5.56E-03	6.31E-04	7.74E-04	1.12E-03	3.52E-03	3.43E-03	2.29E-03	1.84E-03	1.33E-03	2.36E-03	6.38E-04	1.00E-03	2.28E-04	1.24E-04	9.10E-05	1.05E-03	3.85E-03	3.99E-04	2.70E-03	8.99E-03	1.85E-04	2.37E-03	5.97E-04	6.26E-04	1.98E-03	1.10E-04	0.000065576983	0.001005109264
+T>A	GTG	G[T>A]G	2.46E-04	6.38E-05	1.16E-02	1.31E-02	4.11E-03	1.95E-04	2.90E-04	6.56E-04	2.22E-16	1.35E-03	1.56E-02	7.88E-04	7.30E-05	2.22E-16	1.19E-04	2.51E-03	4.70E-05	1.20E-04	1.87E-04	5.55E-03	6.95E-04	2.41E-04	1.83E-03	4.86E-04	2.13E-03	7.42E-04	3.75E-02	4.68E-18	2.49E-03	3.82E-02	6.08E-04	1.57E-03	7.17E-05	3.66E-03	9.86E-05	5.77E-03	1.31E-02	8.27E-04	6.53E-03	1.12E-03	1.17E-03	1.08E-03	1.21E-03	6.67E-03	4.41E-03	1.43E-03	7.77E-03	4.50E-03	2.21E-03	1.03E-03	2.40E-03	1.31E-05	1.43E-04	1.10E-04	1.99E-04	4.29E-03	1.29E-03	3.96E-03	2.64E-03	1.25E-02	4.36E-04	2.46E-03	2.04E-02	5.05E-04	3.60E-04	0.000337380913	0.003520166086
+T>A	GTT	G[T>A]T	2.58E-04	6.28E-05	1.23E-02	5.52E-03	3.22E-03	2.48E-04	3.06E-04	5.59E-05	2.03E-02	8.76E-03	2.81E-02	2.56E-03	4.26E-04	1.08E-04	1.64E-04	9.15E-04	3.58E-04	8.57E-04	8.40E-04	9.66E-04	4.80E-03	1.58E-03	3.46E-03	2.83E-04	4.30E-03	9.37E-04	9.32E-03	5.78E-18	1.31E-03	2.02E-02	8.34E-04	0.00E+00	3.24E-04	1.07E-03	1.91E-04	7.89E-04	6.16E-03	1.76E-03	7.48E-03	2.86E-03	1.12E-03	1.68E-03	1.84E-03	4.09E-03	5.77E-03	4.52E-03	3.25E-03	1.31E-03	3.18E-03	5.10E-04	1.20E-03	3.28E-06	2.31E-04	1.31E-04	7.86E-04	1.46E-04	8.11E-04	3.11E-03	1.85E-03	5.12E-03	5.37E-03	7.93E-03	2.77E-03	1.51E-03	6.37E-04	0.000135756563	0.011658501206
+T>A	TTA	T[T>A]A	6.72E-03	4.22E-04	6.51E-03	8.88E-03	6.31E-03	4.54E-04	3.56E-04	3.24E-03	1.54E-02	1.67E-02	1.15E-02	2.60E-02	2.04E-03	3.06E-03	1.86E-04	3.75E-03	2.96E-04	2.00E-04	1.09E-03	1.23E-02	1.19E-04	1.19E-03	1.08E-02	4.94E-04	1.20E-02	2.57E-04	7.18E-02	7.77E-18	4.12E-03	2.18E-02	1.13E-03	5.28E-02	1.88E-04	7.64E-04	2.82E-04	6.70E-03	5.12E-04	4.10E-03	2.72E-01	4.30E-03	2.46E-03	2.45E-03	2.44E-03	6.69E-03	7.13E-03	8.06E-02	8.50E-03	7.63E-05	6.96E-03	4.07E-04	4.50E-03	1.56E-01	2.35E-05	4.20E-04	1.69E-03	2.01E-02	1.05E-03	3.10E-03	1.55E-03	3.61E-03	9.42E-03	3.02E-03	1.19E-02	2.09E-03	1.13E-03	0.006569907486	0.060179901809
+T>A	TTC	T[T>A]C	2.23E-16	1.92E-04	1.05E-02	4.31E-03	4.14E-03	1.14E-04	3.89E-04	2.24E-03	3.42E-02	1.23E-03	1.95E-02	1.85E-03	3.60E-04	6.65E-04	2.02E-04	6.45E-03	2.32E-04	1.73E-03	1.57E-04	4.67E-03	5.70E-03	2.42E-04	2.73E-03	4.75E-04	3.18E-04	7.95E-04	2.36E-02	5.27E-18	3.27E-03	3.41E-03	1.26E-03	4.71E-05	1.25E-03	1.93E-03	2.41E-04	3.75E-03	2.45E-03	2.17E-04	2.22E-16	5.30E-03	1.02E-03	1.13E-03	9.28E-04	3.69E-03	1.03E-02	1.43E-02	2.26E-03	9.38E-04	2.07E-05	2.62E-04	4.30E-03	1.23E-05	7.64E-06	5.70E-05	6.64E-04	2.58E-03	4.69E-04	3.56E-03	1.79E-04	6.95E-05	8.05E-04	9.23E-03	8.98E-04	1.86E-03	2.23E-16	0.000864507132	0.007794895232
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+T>A	TTT	T[T>A]T	2.25E-03	2.05E-04	1.30E-02	5.62E-03	8.75E-03	4.26E-04	7.98E-04	2.22E-16	2.79E-01	2.73E-02	3.79E-02	1.70E-02	5.29E-03	1.52E-03	6.74E-04	5.25E-03	6.20E-05	1.82E-03	4.75E-04	7.16E-03	1.98E-03	1.31E-03	7.10E-03	6.73E-04	6.71E-03	7.64E-05	3.01E-02	7.32E-18	2.19E-03	1.45E-02	1.31E-03	1.93E-03	5.72E-03	1.20E-03	7.01E-04	8.88E-03	7.11E-04	2.72E-03	4.60E-02	5.41E-03	2.70E-03	1.95E-03	2.50E-03	1.07E-02	2.10E-02	5.35E-02	3.52E-03	8.77E-18	1.39E-02	1.39E-03	3.40E-03	4.35E-03	4.26E-04	3.31E-04	2.95E-03	6.38E-03	1.34E-03	5.08E-03	7.45E-18	2.10E-03	7.44E-04	2.89E-02	1.46E-02	2.99E-03	5.30E-04	0.007059955557	0.062798279518
+T>C	ATA	A[T>C]A	1.09E-03	6.17E-05	1.65E-02	7.95E-03	4.62E-02	2.21E-03	4.90E-04	1.02E-03	2.88E-04	4.36E-03	9.77E-03	2.03E-02	7.45E-04	9.35E-03	1.14E-03	7.36E-02	1.91E-03	1.26E-02	3.89E-03	2.42E-01	9.65E-05	9.73E-05	2.02E-03	2.59E-03	1.07E-02	1.67E-02	2.50E-02	8.86E-04	6.40E-03	2.07E-02	8.48E-02	5.05E-03	5.49E-04	1.96E-03	6.11E-04	2.04E-02	9.36E-04	1.25E-02	4.62E-03	2.04E-03	5.25E-03	7.33E-02	2.79E-03	1.12E-02	1.87E-02	1.44E-02	1.16E-02	8.88E-06	1.93E-02	1.37E-03	1.85E-02	2.83E-03	1.10E-03	6.13E-04	2.63E-03	2.59E-03	3.75E-03	1.13E-02	2.92E-02	4.35E-03	1.25E-02	2.66E-02	8.05E-02	9.95E-03	1.29E-03	0.000000000000	0.029567020575
+T>C	ATC	A[T>C]C	3.04E-03	2.15E-05	7.76E-03	7.15E-04	1.34E-02	1.13E-03	2.27E-04	4.56E-04	5.33E-04	3.93E-03	5.01E-03	1.05E-02	3.62E-03	5.10E-04	9.38E-04	4.03E-02	1.42E-04	6.30E-03	1.96E-03	1.29E-02	1.27E-02	2.52E-04	2.09E-03	5.94E-04	4.55E-03	1.00E-02	8.99E-04	1.78E-04	2.18E-03	9.50E-03	2.61E-02	1.85E-03	4.41E-04	2.29E-03	4.58E-04	7.40E-03	7.01E-04	3.75E-03	1.23E-03	8.21E-04	1.69E-03	3.84E-02	1.64E-03	5.64E-03	7.34E-03	5.79E-03	3.51E-03	3.13E-02	3.24E-03	4.18E-04	4.78E-02	5.67E-03	1.89E-04	8.14E-05	9.28E-03	1.93E-02	1.88E-03	3.70E-03	7.75E-03	3.36E-06	6.16E-03	9.66E-03	4.93E-03	2.61E-03	2.77E-04	0.000323133451	0.020410486307
+T>C	ATG	A[T>C]G	1.06E-04	1.32E-05	1.23E-02	5.00E-03	3.82E-02	4.24E-03	1.87E-04	1.50E-03	1.07E-03	9.19E-03	6.98E-03	1.43E-02	2.14E-03	5.31E-04	3.20E-04	7.05E-02	4.28E-04	1.24E-02	2.40E-04	6.39E-02	3.76E-04	2.23E-16	2.08E-03	2.31E-03	1.86E-02	3.88E-03	7.75E-03	4.70E-04	1.76E-03	1.99E-02	7.85E-02	5.69E-03	4.05E-04	2.75E-03	2.77E-04	8.12E-03	1.09E-03	7.34E-02	1.95E-05	9.20E-04	3.84E-03	1.68E-02	2.17E-03	9.64E-03	1.55E-02	8.04E-03	8.56E-03	5.86E-04	2.72E-02	2.07E-03	3.29E-02	2.09E-03	2.85E-04	2.00E-04	1.13E-03	3.95E-03	2.62E-03	8.25E-03	2.02E-01	4.02E-03	9.55E-03	1.03E-02	6.75E-03	3.52E-03	3.52E-06	0.000011504801	0.005070940432
+T>C	ATT	A[T>C]T	5.74E-03	1.55E-04	1.73E-02	1.56E-03	3.83E-02	5.02E-04	6.15E-04	2.15E-03	2.65E-03	5.10E-02	1.49E-02	2.90E-02	3.36E-03	1.50E-04	1.19E-03	6.38E-02	9.59E-04	5.97E-03	9.29E-04	1.36E-01	7.79E-03	5.44E-04	4.24E-03	1.74E-03	1.03E-04	2.56E-02	7.55E-04	2.61E-04	2.44E-03	1.45E-02	3.72E-02	2.59E-03	5.95E-04	1.15E-03	5.45E-04	8.47E-03	6.10E-04	9.21E-03	2.34E-03	2.03E-03	5.12E-03	4.80E-02	3.49E-03	1.36E-02	1.94E-02	1.77E-02	2.70E-03	8.80E-03	2.67E-04	1.46E-03	3.06E-02	1.30E-03	1.11E-03	4.82E-04	4.92E-03	1.87E-03	4.92E-03	7.18E-03	7.83E-03	1.37E-02	1.24E-02	1.79E-02	8.16E-03	1.08E-02	3.63E-05	0.009382160052	0.059234079950
+T>C	CTA	C[T>C]A	2.23E-16	3.02E-04	8.83E-03	5.18E-03	1.33E-02	1.66E-03	4.51E-04	1.53E-03	7.57E-03	1.02E-02	2.39E-03	1.37E-02	1.22E-04	1.32E-03	3.28E-04	4.54E-02	4.74E-05	3.16E-03	7.50E-04	1.07E-02	1.11E-02	6.47E-04	3.86E-04	4.52E-04	1.17E-02	1.15E-02	6.74E-03	6.86E-18	2.27E-03	9.03E-03	5.20E-02	4.90E-03	1.32E-03	1.18E-03	1.27E-03	8.15E-03	5.93E-04	1.51E-02	5.94E-04	1.33E-03	1.50E-03	5.00E-02	1.95E-03	7.34E-03	1.09E-02	1.03E-02	3.54E-03	2.72E-03	1.46E-02	1.11E-03	2.23E-02	1.91E-03	1.45E-04	1.21E-04	8.39E-04	4.18E-03	2.39E-03	1.01E-02	1.14E-02	4.18E-03	3.37E-03	1.20E-02	3.92E-03	2.20E-03	8.79E-04	0.002269665991	0.007184033893
+T>C	CTC	C[T>C]C	2.50E-03	2.85E-05	1.45E-02	2.36E-03	1.04E-02	1.03E-03	2.59E-04	8.40E-04	3.58E-03	8.89E-05	7.00E-03	1.53E-02	4.12E-05	1.24E-04	7.13E-04	4.97E-02	1.22E-04	5.34E-03	2.15E-03	3.17E-03	1.73E-01	6.46E-03	2.46E-03	8.14E-05	4.83E-03	2.82E-03	1.34E-03	4.47E-18	2.24E-03	1.08E-02	3.12E-02	5.72E-03	2.62E-03	1.84E-03	1.38E-03	9.91E-03	9.27E-04	3.01E-02	4.04E-05	2.02E-03	1.88E-03	2.18E-02	2.32E-03	7.91E-03	9.87E-03	5.25E-03	3.13E-03	1.05E-01	3.20E-03	2.87E-03	8.34E-02	6.28E-03	4.50E-04	1.78E-04	1.77E-02	7.11E-02	1.31E-03	4.07E-03	1.70E-02	4.98E-03	2.64E-03	4.56E-03	9.50E-03	5.73E-03	2.79E-03	0.000003247249	0.006209066076
+T>C	CTG	C[T>C]G	3.60E-04	2.23E-16	1.01E-02	5.50E-03	2.08E-02	5.32E-03	1.04E-04	7.30E-04	2.17E-03	9.35E-04	1.26E-03	1.54E-02	1.05E-03	2.53E-05	1.31E-04	3.74E-02	2.22E-16	4.47E-03	1.39E-03	9.61E-03	8.73E-02	3.92E-03	1.62E-03	4.98E-04	2.61E-02	1.44E-02	2.03E-03	3.89E-04	4.22E-03	1.34E-02	7.87E-02	5.66E-03	2.49E-03	3.91E-03	1.27E-03	4.46E-03	1.84E-03	4.00E-02	8.11E-04	1.56E-03	1.85E-03	9.95E-03	2.54E-03	7.77E-03	1.05E-02	5.57E-03	3.56E-03	9.25E-03	3.38E-02	1.56E-03	5.04E-02	3.10E-03	3.21E-05	1.08E-04	2.42E-03	2.93E-03	1.23E-03	8.49E-03	1.93E-01	9.49E-04	4.81E-04	8.30E-03	5.93E-03	1.64E-03	5.80E-04	0.003628314755	0.000839951905
+T>C	CTT	C[T>C]T	4.26E-05	1.86E-04	1.58E-02	2.56E-03	1.49E-02	1.27E-03	1.82E-03	5.73E-03	4.31E-02	3.97E-02	6.46E-03	3.29E-02	2.44E-06	8.15E-04	8.45E-05	4.59E-02	1.12E-04	2.06E-03	1.75E-03	1.55E-02	4.26E-01	1.83E-02	2.56E-03	3.91E-04	6.90E-03	2.17E-02	5.36E-04	4.71E-05	3.63E-03	8.96E-03	5.55E-02	3.90E-03	3.67E-04	1.78E-03	4.10E-03	1.38E-02	1.09E-03	3.07E-03	1.59E-03	3.18E-03	2.16E-03	5.04E-02	4.27E-03	8.59E-03	1.36E-02	7.87E-03	3.24E-03	9.45E-03	7.71E-03	6.02E-04	9.58E-02	5.45E-03	6.77E-05	9.74E-05	1.38E-03	6.64E-03	2.34E-03	5.42E-03	2.69E-02	6.84E-04	2.06E-04	2.43E-02	2.82E-02	1.22E-02	2.10E-03	0.000918581801	0.016913140039
+T>C	GTA	G[T>C]A	1.05E-03	2.23E-16	9.98E-03	2.90E-03	1.41E-02	2.57E-03	1.01E-04	2.66E-04	2.22E-16	8.00E-04	2.60E-03	9.52E-03	2.20E-03	1.47E-02	8.09E-04	7.11E-02	2.87E-04	1.10E-02	1.29E-02	2.06E-03	1.23E-04	5.95E-05	7.08E-04	9.54E-04	2.76E-03	2.23E-01	7.21E-04	2.18E-04	3.70E-03	1.75E-02	8.35E-02	4.78E-03	4.91E-04	1.08E-03	9.35E-04	4.53E-03	9.14E-03	1.22E-02	1.09E-04	5.65E-04	2.34E-03	3.07E-02	1.70E-03	7.47E-03	6.01E-03	6.06E-03	5.82E-03	7.50E-18	2.70E-02	6.54E-04	2.21E-02	4.17E-04	1.57E-04	6.59E-05	1.38E-03	1.18E-03	2.42E-03	5.61E-03	1.14E-02	2.61E-03	7.30E-04	3.86E-03	2.18E-03	7.10E-04	7.61E-04	0.000000000000	0.021590706956
+T>C	GTC	G[T>C]C	1.90E-03	2.74E-05	5.64E-03	1.18E-03	7.94E-03	1.11E-03	7.41E-05	2.22E-16	4.23E-04	2.32E-03	2.62E-03	9.78E-03	6.28E-03	5.33E-03	8.60E-04	3.04E-02	1.82E-04	6.54E-03	1.16E-02	1.19E-03	1.49E-02	1.50E-03	2.26E-03	3.71E-04	2.26E-03	6.63E-02	1.24E-03	4.18E-04	3.65E-03	4.05E-03	2.48E-02	1.96E-03	5.87E-04	3.59E-03	5.55E-04	6.57E-03	7.67E-03	7.94E-03	6.46E-04	2.03E-03	1.40E-03	1.82E-02	2.16E-03	6.89E-03	4.58E-03	3.74E-03	3.31E-03	2.19E-02	1.16E-03	5.70E-04	5.76E-02	1.09E-03	1.29E-04	1.51E-04	5.38E-03	2.27E-03	2.05E-03	6.68E-03	4.43E-03	3.17E-03	2.73E-05	2.29E-03	7.80E-04	3.18E-03	6.35E-04	0.000865945066	0.011606134984
+T>C	GTG	G[T>C]G	1.17E-03	1.07E-04	1.09E-02	2.37E-03	1.50E-02	2.45E-03	7.25E-05	5.29E-04	2.32E-04	2.57E-03	2.81E-03	6.31E-03	2.23E-16	1.38E-03	5.61E-04	4.15E-02	1.95E-04	1.10E-02	5.95E-03	4.28E-03	3.57E-03	1.01E-03	3.98E-03	9.53E-04	4.06E-03	1.17E-01	5.81E-04	4.68E-18	2.67E-03	1.34E-02	7.12E-02	1.23E-03	7.31E-04	2.99E-03	5.01E-04	5.13E-03	9.62E-03	2.07E-01	4.40E-04	1.91E-04	1.84E-03	9.83E-03	1.87E-03	5.74E-03	5.65E-03	3.51E-03	3.21E-03	1.20E-03	1.73E-02	9.07E-04	3.53E-02	3.10E-03	4.67E-05	6.53E-05	3.71E-03	4.56E-03	9.14E-04	2.56E-03	1.21E-01	6.01E-03	1.65E-03	4.72E-03	1.11E-02	9.86E-04	5.00E-04	0.000197907041	0.006462687955
+T>C	GTT	G[T>C]T	7.13E-05	1.25E-05	1.02E-02	7.55E-04	1.37E-02	9.06E-04	8.11E-04	6.85E-03	7.07E-03	3.18E-01	6.29E-03	9.86E-03	5.29E-03	1.15E-02	2.37E-04	4.63E-02	2.22E-16	1.12E-02	5.86E-03	2.40E-03	5.24E-03	1.47E-03	3.15E-03	2.36E-03	9.28E-04	1.33E-01	8.34E-04	7.99E-04	3.99E-03	1.42E-02	5.52E-02	3.75E-03	8.51E-04	1.55E-03	4.45E-04	4.69E-03	1.29E-02	9.71E-03	2.22E-16	4.21E-04	2.65E-03	4.00E-02	3.05E-03	7.51E-03	7.31E-03	3.89E-03	2.39E-03	5.18E-04	1.11E-02	1.39E-03	6.07E-02	3.19E-03	1.10E-04	1.75E-04	1.17E-03	4.01E-03	3.11E-03	6.99E-03	5.41E-03	1.26E-02	2.58E-03	5.36E-03	2.02E-03	1.19E-03	6.96E-04	0.003662473198	0.054089001127
+T>C	TTA	T[T>C]A	2.55E-04	2.23E-16	1.52E-02	2.41E-03	1.80E-02	1.48E-03	2.15E-03	6.00E-03	3.02E-02	8.12E-02	2.08E-03	1.40E-02	7.30E-04	8.86E-03	1.13E-04	8.61E-02	2.21E-05	6.27E-03	3.42E-03	1.30E-02	2.09E-03	1.06E-03	1.80E-03	1.24E-03	1.38E-02	8.42E-02	4.63E-03	7.77E-18	1.46E-03	1.45E-02	4.23E-02	1.72E-03	1.31E-03	2.59E-03	5.44E-04	4.59E-03	8.97E-04	1.10E-02	1.40E-03	3.68E-04	2.97E-03	4.77E-02	2.11E-03	5.94E-03	1.02E-02	6.36E-02	6.82E-03	1.37E-04	1.99E-02	1.28E-03	9.30E-03	1.37E-03	6.05E-04	1.73E-04	1.09E-03	4.46E-03	2.77E-03	7.11E-03	4.73E-03	4.88E-03	5.68E-04	4.90E-03	3.31E-03	2.05E-03	2.40E-04	0.000432939443	0.012963549217
+T>C	TTC	T[T>C]C	3.39E-03	4.35E-05	8.99E-03	5.03E-04	9.71E-03	1.09E-03	5.96E-04	1.73E-03	2.09E-02	1.43E-02	2.64E-03	1.36E-02	5.17E-03	8.10E-05	4.67E-04	4.63E-02	2.49E-05	2.88E-03	5.92E-03	3.67E-03	1.53E-02	1.10E-03	6.18E-03	5.53E-04	1.66E-02	5.48E-02	2.22E-16	1.90E-04	3.00E-03	7.41E-03	3.14E-02	3.49E-03	2.05E-03	1.50E-03	2.86E-04	1.03E-02	1.22E-03	1.25E-02	6.24E-03	8.22E-04	2.28E-03	4.51E-02	2.19E-03	6.44E-03	7.55E-03	2.68E-02	3.03E-03	3.59E-02	1.05E-02	1.10E-03	5.43E-02	1.75E-02	4.04E-04	8.47E-05	2.90E-02	3.93E-03	2.18E-03	5.03E-03	8.19E-03	9.80E-04	1.32E-03	2.67E-02	1.96E-02	2.24E-03	1.09E-03	0.000538464673	0.023324448028
+T>C	TTG	T[T>C]G	4.16E-04	1.17E-04	6.93E-03	1.74E-03	1.27E-02	2.13E-03	3.19E-04	3.81E-03	1.29E-02	2.28E-02	2.22E-16	9.31E-03	3.63E-04	6.68E-04	1.55E-04	4.00E-02	9.98E-05	4.31E-03	1.32E-03	7.23E-03	2.35E-03	1.21E-03	3.26E-03	1.08E-03	1.20E-02	2.76E-02	1.22E-03	3.02E-04	2.03E-03	4.89E-03	3.03E-02	1.15E-03	1.41E-03	3.79E-04	2.03E-04	4.01E-03	1.69E-03	3.20E-01	1.10E-03	4.38E-04	1.38E-03	1.00E-02	1.92E-03	4.98E-03	6.01E-03	2.05E-02	3.41E-03	2.78E-05	1.91E-02	1.24E-03	2.37E-02	1.58E-03	2.97E-04	6.31E-05	1.02E-03	2.47E-03	1.07E-03	4.72E-03	8.84E-02	4.16E-03	1.85E-03	2.96E-03	2.16E-03	1.35E-03	1.09E-04	0.000022365153	0.003823534542
+T>C	TTT	T[T>C]T	4.33E-03	3.58E-05	1.39E-02	6.36E-04	1.85E-02	1.74E-03	8.12E-04	2.97E-03	8.81E-02	4.31E-02	4.57E-03	3.84E-02	3.25E-03	2.51E-05	1.06E-04	5.97E-02	5.31E-04	2.92E-03	1.35E-03	8.39E-03	2.10E-02	1.00E-03	3.37E-03	1.47E-03	1.93E-02	4.07E-02	2.22E-16	7.32E-18	3.67E-03	1.70E-02	5.74E-02	1.53E-03	2.06E-03	8.22E-04	4.45E-04	1.21E-02	6.84E-04	9.12E-03	7.08E-03	1.06E-03	2.80E-03	6.14E-02	3.06E-03	9.48E-03	1.02E-02	4.61E-02	2.36E-03	1.84E-03	3.71E-02	5.45E-04	3.65E-02	1.15E-02	5.32E-04	2.08E-04	5.11E-03	2.13E-02	2.00E-03	2.19E-03	1.25E-02	8.87E-04	2.85E-04	1.95E-01	3.20E-02	2.61E-03	1.32E-03	0.009820763708	0.094054377313
+T>G	ATA	A[T>G]A	1.72E-04	2.38E-04	3.95E-03	1.05E-03	3.86E-03	2.57E-05	4.73E-04	8.44E-05	1.19E-02	3.70E-03	1.64E-03	4.51E-02	1.92E-03	3.47E-05	2.18E-04	2.01E-03	6.14E-05	2.12E-04	4.68E-04	1.12E-02	8.51E-04	1.41E-03	7.21E-04	2.33E-03	1.05E-05	3.92E-04	2.33E-03	8.28E-18	3.21E-03	5.28E-03	2.92E-03	1.14E-03	9.87E-03	4.07E-04	3.90E-05	3.68E-03	3.86E-04	9.79E-04	2.82E-03	3.05E-03	1.09E-03	2.17E-02	1.15E-03	3.88E-03	7.23E-03	7.53E-03	1.20E-03	2.63E-03	2.40E-08	1.17E-04	1.00E-04	1.71E-04	5.17E-04	1.96E-04	7.43E-04	7.23E-04	1.73E-03	4.59E-03	3.87E-05	2.62E-04	1.21E-04	7.06E-03	1.35E-02	1.79E-03	2.50E-02	0.000127137772	0.023838221813
+T>G	ATC	A[T>G]C	2.07E-04	7.46E-05	2.60E-03	1.59E-04	2.60E-03	2.04E-04	2.47E-04	9.32E-04	1.05E-03	2.66E-03	6.68E-04	6.93E-03	1.24E-03	5.33E-05	4.67E-05	6.64E-04	2.22E-16	2.97E-03	4.15E-04	4.41E-03	7.00E-04	4.48E-03	8.58E-04	1.89E-03	2.13E-05	4.37E-04	5.09E-05	5.43E-18	1.40E-03	0.00E+00	2.53E-03	9.59E-04	1.73E-02	8.17E-04	1.10E-04	2.48E-03	4.29E-04	3.02E-04	4.62E-04	9.66E-04	6.23E-04	1.06E-02	1.07E-03	2.97E-03	7.05E-03	1.64E-03	4.05E-04	4.07E-03	3.26E-05	5.84E-04	8.00E-04	1.72E-03	4.10E-05	8.28E-05	6.07E-04	4.09E-03	5.29E-04	2.90E-03	1.58E-03	9.20E-04	7.99E-18	7.89E-04	7.88E-04	1.56E-03	1.05E-02	0.001270955861	0.003434920439
+T>G	ATG	A[T>G]G	2.68E-04	2.05E-06	6.30E-03	1.42E-03	7.94E-03	1.07E-04	2.76E-04	1.47E-03	6.04E-04	1.06E-02	4.77E-03	5.33E-03	3.20E-04	5.23E-04	1.79E-04	8.08E-04	8.25E-05	7.09E-04	1.85E-04	4.62E-03	7.19E-04	9.90E-04	1.99E-03	1.77E-03	2.69E-05	1.87E-04	2.95E-03	5.68E-18	2.06E-03	7.14E-03	2.29E-03	6.77E-05	7.68E-03	4.20E-04	4.10E-04	4.02E-03	1.27E-03	4.75E-04	1.97E-04	4.48E-03	9.36E-04	1.68E-02	2.07E-03	7.66E-03	8.06E-03	2.70E-03	6.37E-04	3.49E-02	7.47E-06	9.84E-04	1.60E-03	3.68E-03	3.51E-04	1.26E-04	3.94E-03	2.78E-02	1.19E-03	5.06E-03	1.15E-03	1.45E-01	1.27E-05	1.23E-03	2.71E-03	1.70E-03	2.61E-02	0.000952698782	0.004485500819
+T>G	ATT	A[T>G]T	1.12E-04	3.76E-06	3.97E-03	2.16E-04	4.83E-03	3.86E-04	3.09E-04	7.33E-04	2.22E-16	1.43E-02	7.40E-04	2.39E-02	9.22E-03	2.22E-16	2.85E-04	1.28E-03	3.20E-04	1.11E-02	3.63E-03	7.96E-03	1.25E-02	6.91E-02	1.84E-03	1.62E-03	5.82E-05	6.95E-05	4.18E-05	7.43E-18	4.71E-03	0.00E+00	5.93E-03	2.56E-04	1.15E-01	8.10E-04	7.94E-04	7.83E-04	6.45E-18	7.58E-04	1.15E-03	2.63E-03	9.84E-04	2.47E-02	2.86E-03	6.42E-03	1.80E-02	7.61E-03	9.11E-04	5.64E-03	1.42E-03	1.66E-04	6.00E-04	8.08E-03	1.99E-04	1.26E-04	1.03E-04	2.13E-03	1.86E-03	2.06E-03	3.40E-04	2.28E-03	5.75E-03	5.97E-03	2.08E-03	3.44E-03	1.64E-02	0.001764975843	0.003178596391
+T>G	CTA	C[T>G]A	3.55E-05	1.53E-04	4.37E-03	8.70E-04	2.59E-03	4.95E-05	8.42E-05	3.59E-04	3.28E-03	1.48E-03	1.22E-03	2.60E-02	1.55E-04	2.27E-04	2.22E-16	8.93E-04	4.14E-05	4.85E-05	2.06E-04	3.96E-03	3.10E-04	2.05E-03	1.11E-04	7.14E-04	9.63E-04	4.35E-06	4.91E-03	6.85E-18	1.43E-03	0.00E+00	1.42E-03	0.00E+00	1.46E-02	7.81E-04	1.98E-04	1.97E-03	5.81E-05	7.28E-04	1.06E-03	3.71E-03	4.78E-04	2.60E-03	9.83E-04	5.30E-03	3.35E-03	3.47E-03	8.70E-04	2.73E-03	2.34E-04	1.02E-04	0.00E+00	1.37E-04	1.34E-04	1.06E-04	8.94E-04	2.78E-03	8.03E-04	1.49E-03	4.36E-03	1.65E-03	5.82E-03	1.40E-04	5.03E-04	1.01E-03	3.23E-03	0.000897193499	0.003736474707
+T>G	CTC	C[T>G]C	2.12E-04	1.55E-04	7.04E-03	4.41E-04	4.61E-03	7.84E-04	1.72E-04	7.92E-04	5.58E-03	4.98E-05	1.95E-03	7.41E-03	2.23E-16	1.15E-03	2.22E-16	1.14E-03	2.82E-06	1.21E-03	1.57E-04	1.08E-03	1.04E-03	3.14E-02	1.99E-03	2.09E-03	1.60E-03	5.44E-05	8.80E-04	1.48E-04	8.80E-04	2.89E-03	4.94E-03	3.81E-04	2.21E-02	5.69E-06	2.15E-04	1.43E-03	4.50E-04	9.49E-04	2.22E-16	5.18E-04	5.66E-04	2.38E-03	1.41E-03	7.39E-03	5.67E-03	2.41E-03	7.53E-04	7.26E-03	2.53E-03	2.81E-04	1.80E-03	5.15E-05	9.28E-05	2.67E-05	6.18E-05	2.56E-03	7.75E-04	4.24E-03	1.89E-02	4.66E-04	3.93E-07	8.47E-04	1.04E-03	2.62E-03	4.16E-03	0.002148873221	0.002478170057
+T>G	CTG	C[T>G]G	1.28E-04	1.21E-04	1.07E-02	3.79E-03	6.13E-03	9.24E-04	2.23E-16	1.29E-03	1.19E-03	2.58E-05	4.70E-03	1.42E-02	5.35E-05	4.79E-04	2.22E-16	5.93E-04	2.22E-16	4.35E-04	2.72E-04	2.24E-03	1.94E-06	1.37E-02	2.93E-03	1.33E-03	2.71E-03	2.01E-05	8.03E-03	6.52E-05	3.04E-03	1.18E-02	5.56E-03	4.03E-04	1.55E-02	3.32E-04	7.85E-05	1.50E-03	1.09E-03	1.07E-03	4.36E-04	6.36E-03	8.87E-04	3.77E-03	1.59E-03	9.83E-03	5.59E-03	3.04E-03	5.68E-03	4.65E-02	3.47E-03	6.49E-04	1.60E-03	3.67E-03	1.04E-04	1.12E-04	3.66E-03	5.93E-03	7.96E-04	2.98E-03	2.21E-02	1.13E-01	4.45E-03	2.19E-03	6.99E-04	2.02E-03	7.11E-03	0.000788671403	0.001120299176
+T>G	CTT	C[T>G]T	1.71E-04	2.03E-04	7.03E-03	1.20E-03	7.30E-03	1.30E-03	2.65E-05	3.68E-06	3.40E-03	1.56E-04	5.74E-04	5.65E-02	1.30E-03	5.23E-03	1.33E-04	3.44E-04	5.55E-05	9.62E-04	2.49E-03	2.54E-03	5.31E-03	5.50E-01	4.14E-03	2.20E-03	5.11E-03	1.85E-04	1.19E-03	2.47E-04	4.71E-03	8.55E-03	7.80E-03	1.44E-03	1.01E-01	7.67E-04	2.65E-04	9.49E-04	6.76E-04	1.92E-04	6.55E-07	2.71E-03	1.07E-03	4.11E-03	6.88E-03	4.94E-03	1.31E-02	1.05E-02	3.48E-03	6.26E-18	3.84E-04	7.28E-04	2.00E-03	1.07E-04	6.57E-05	9.29E-05	4.71E-04	2.30E-03	8.63E-04	2.72E-03	8.86E-04	1.18E-03	6.78E-18	5.16E-03	4.73E-04	2.12E-02	1.80E-05	0.000000000000	0.001756870383
+T>G	GTA	G[T>G]A	2.23E-16	2.09E-04	4.42E-03	5.98E-04	2.52E-03	4.35E-05	9.06E-05	3.23E-04	2.48E-03	7.48E-05	1.31E-03	8.30E-03	2.04E-04	4.81E-04	9.57E-05	4.12E-04	8.77E-05	7.79E-05	2.03E-04	9.02E-04	4.95E-04	2.81E-04	8.70E-04	6.36E-04	2.22E-16	2.86E-04	1.59E-03	6.26E-18	1.07E-03	5.55E-03	1.37E-03	0.00E+00	1.16E-03	4.49E-05	1.88E-04	3.04E-04	1.15E-03	5.81E-04	3.65E-04	1.76E-03	1.85E-04	1.18E-02	5.04E-04	3.33E-03	2.49E-03	1.80E-03	1.14E-03	6.11E-02	7.68E-18	4.40E-04	0.00E+00	2.20E-02	7.64E-06	6.61E-05	8.67E-03	2.19E-03	1.13E-03	4.38E-03	1.70E-04	5.67E-03	6.72E-18	1.40E-03	8.07E-03	1.23E-03	2.82E-02	0.000018879250	0.007699623603
+T>G	GTC	G[T>G]C	2.23E-16	1.33E-04	2.34E-03	2.53E-04	1.71E-03	2.13E-04	1.21E-04	3.21E-04	1.66E-03	2.23E-05	6.56E-04	5.85E-03	8.33E-04	9.42E-04	2.22E-16	2.13E-04	2.22E-16	2.10E-03	5.80E-04	9.01E-04	2.04E-04	6.25E-03	3.70E-05	7.03E-04	6.65E-05	5.33E-04	2.36E-04	8.69E-05	1.53E-03	0.00E+00	1.21E-03	5.08E-05	1.93E-03	9.17E-05	3.53E-04	8.72E-04	7.40E-04	6.37E-04	2.22E-16	5.07E-03	3.13E-04	6.86E-03	9.39E-04	5.80E-03	2.24E-03	9.50E-04	7.05E-05	7.56E-02	1.83E-05	5.20E-04	1.00E-04	1.04E-02	1.35E-04	4.37E-05	9.59E-03	5.30E-03	5.61E-04	1.74E-03	1.53E-03	3.20E-03	9.19E-07	1.71E-04	2.69E-03	1.65E-03	2.88E-02	0.001229435537	0.000800067973
+T>G	GTG	G[T>G]G	3.48E-04	3.71E-05	1.09E-02	2.43E-03	5.30E-03	2.74E-04	3.25E-04	2.41E-03	6.03E-03	3.80E-03	3.97E-03	3.97E-03	2.23E-16	1.73E-03	1.30E-04	4.96E-04	4.26E-04	7.81E-04	3.47E-04	6.75E-04	8.35E-04	1.48E-03	5.83E-03	5.10E-04	8.70E-05	2.13E-04	4.50E-04	1.57E-04	3.13E-03	8.69E-03	2.35E-03	4.74E-03	3.13E-03	7.70E-04	1.38E-03	2.55E-03	3.01E-03	5.42E-03	5.65E-05	4.04E-03	1.53E-03	9.83E-03	2.16E-03	7.72E-03	4.45E-03	1.20E-03	4.10E-04	2.41E-01	1.03E-04	1.79E-04	1.20E-03	2.72E-02	6.63E-05	1.47E-04	3.51E-02	7.62E-02	1.37E-03	4.73E-03	7.45E-18	2.99E-01	6.72E-18	8.61E-04	2.34E-02	2.29E-03	6.62E-01	0.000212751233	0.001946513805
+T>G	GTT	G[T>G]T	1.46E-05	2.23E-16	5.83E-03	2.52E-04	2.35E-03	7.87E-04	8.35E-04	1.83E-03	6.75E-03	6.84E-03	1.29E-03	1.94E-02	2.21E-03	5.16E-03	1.54E-04	1.65E-04	2.89E-06	2.25E-03	1.39E-03	2.39E-03	7.24E-03	1.14E-01	2.14E-03	3.41E-04	3.56E-03	2.59E-03	1.96E-05	5.78E-18	2.68E-03	2.77E-03	6.05E-03	2.30E-03	2.06E-02	1.15E-03	1.60E-04	2.81E-03	7.85E-04	4.51E-04	4.17E-04	3.35E-03	4.89E-04	1.71E-02	3.34E-03	5.94E-03	5.48E-03	3.47E-03	9.20E-04	7.46E-02	2.80E-03	4.96E-04	6.00E-04	8.84E-02	1.15E-05	1.02E-04	3.65E-02	2.09E-03	8.64E-04	2.03E-03	1.21E-05	1.44E-03	1.14E-04	2.83E-03	1.69E-02	7.45E-03	4.74E-02	0.001340078646	0.002927905616
+T>G	TTA	T[T>G]A	2.23E-16	1.67E-05	7.25E-03	3.77E-04	5.22E-03	1.05E-04	1.28E-04	9.55E-04	1.93E-02	2.11E-04	2.22E-16	6.57E-02	2.69E-03	1.13E-02	8.51E-05	1.63E-03	1.84E-04	9.92E-05	2.31E-04	9.78E-03	2.22E-16	1.22E-05	6.96E-04	1.66E-03	2.22E-16	4.65E-04	5.06E-03	1.86E-04	1.23E-04	2.08E-03	1.43E-03	1.19E-03	4.23E-02	4.67E-04	1.18E-04	2.25E-03	2.26E-05	4.68E-04	2.22E-16	4.29E-03	7.88E-04	1.83E-02	1.17E-03	8.39E-03	8.46E-03	4.19E-02	1.15E-03	2.04E-04	7.68E-18	2.85E-04	7.00E-04	2.41E-03	2.50E-04	1.50E-04	3.27E-04	2.55E-03	1.43E-03	1.30E-03	3.24E-05	6.06E-03	9.46E-03	3.22E-03	7.98E-04	1.60E-03	1.61E-03	0.001875698241	0.007106411217
+T>G	TTC	T[T>G]C	5.51E-05	7.04E-05	6.28E-03	1.74E-04	6.56E-03	2.87E-04	1.16E-04	1.55E-03	1.74E-02	1.15E-04	1.14E-03	8.62E-03	2.23E-16	5.55E-03	6.73E-05	1.13E-03	2.22E-16	1.20E-03	2.94E-04	5.51E-03	1.16E-04	8.75E-03	2.10E-03	2.02E-03	2.22E-16	3.79E-04	7.52E-04	5.27E-18	2.64E-03	5.79E-04	1.72E-03	2.80E-04	3.57E-02	9.93E-05	9.64E-05	2.38E-03	2.24E-04	1.64E-04	2.22E-16	1.94E-03	7.44E-04	1.95E-02	9.03E-04	5.08E-03	1.14E-02	1.55E-02	2.74E-04	8.25E-03	7.68E-18	1.35E-04	1.00E-03	2.25E-05	2.22E-04	1.38E-04	6.55E-04	3.47E-03	1.12E-03	4.36E-03	7.06E-04	5.65E-03	1.00E-06	3.96E-03	1.59E-03	2.33E-03	1.06E-02	0.000737916543	0.006404453857
+T>G	TTG	T[T>G]G	5.83E-04	9.54E-05	8.05E-03	2.32E-03	6.94E-03	3.24E-04	2.23E-16	1.35E-03	7.64E-03	1.25E-04	3.09E-03	1.09E-02	2.16E-05	2.76E-03	1.01E-04	8.75E-04	3.67E-05	1.14E-04	1.48E-04	5.24E-03	9.20E-04	4.78E-03	1.45E-03	2.07E-03	2.79E-03	1.31E-04	5.57E-03	1.82E-04	3.04E-03	9.43E-03	2.84E-03	2.35E-03	1.40E-02	1.80E-04	8.13E-04	5.35E-03	8.18E-04	9.59E-04	1.52E-03	4.82E-03	9.02E-04	3.02E-02	1.90E-03	7.28E-03	8.66E-03	1.94E-02	2.93E-03	2.28E-02	9.17E-04	7.08E-04	9.00E-04	1.54E-03	3.50E-04	1.12E-04	8.72E-03	2.76E-03	1.48E-03	6.15E-03	7.69E-03	7.95E-02	1.01E-04	5.40E-03	6.74E-03	1.96E-03	2.39E-02	0.000000000000	0.003409999931
+T>G	TTT	T[T>G]T	2.23E-16	2.23E-16	1.05E-02	5.68E-04	1.35E-02	1.01E-03	8.29E-05	1.77E-03	2.17E-02	1.66E-04	9.96E-04	6.39E-02	1.89E-02	9.09E-02	5.55E-05	2.21E-03	1.89E-05	6.05E-04	5.99E-03	1.58E-02	4.58E-03	1.22E-01	5.16E-03	4.23E-03	1.51E-03	2.22E-16	5.95E-04	7.32E-18	3.96E-03	7.87E-03	9.45E-03	1.40E-04	4.79E-01	9.28E-04	8.89E-03	7.30E-03	6.35E-04	2.25E-03	2.32E-04	3.62E-03	1.81E-03	2.91E-02	5.29E-03	1.09E-02	2.50E-02	8.79E-02	1.74E-03	1.32E-03	9.00E-03	7.24E-04	1.00E-03	3.62E-03	3.20E-07	3.64E-04	1.60E-03	2.91E-03	2.53E-03	7.05E-03	4.99E-04	4.12E-02	2.90E-02	1.19E-01	2.17E-02	1.30E-17	3.18E-02	0.006603134330	0.012708761755
Binary file test-data/cosmic_output1.pdf has changed
Binary file test-data/denovo_1.RData has changed
Binary file test-data/denovo_output1.pdf has changed
--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/test-data/sigmatrix.tab	Thu Sep 24 01:32:52 2020 +0000
@@ -0,0 +1,97 @@
+substitution	context	NewSig_1	NewSig_2	NewSig_3	NewSig_4
+C>A	A.A	2.012349e-02	2.099063e-02	1.788529e-02	2.529973e-02
+C>A	A.C	1.232623e-02	5.099845e-05	2.019020e-02	8.344265e-03
+C>A	A.G	2.056317e-03	5.061512e-03	5.110667e-03	5.598599e-04
+C>A	A.T	4.276274e-03	7.030586e-03	1.433976e-02	9.044799e-03
+C>A	C.A	9.858499e-03	6.774294e-03	1.254817e-02	1.109854e-02
+C>A	C.C	7.182083e-03	5.137412e-03	1.754580e-02	7.871756e-03
+C>A	C.G	3.071657e-03	7.744685e-04	3.478215e-03	3.033573e-03
+C>A	C.T	9.805120e-04	1.022892e-02	8.612445e-03	1.089991e-02
+C>A	G.A	1.295094e-02	5.191677e-03	2.838657e-03	1.229298e-02
+C>A	G.C	4.262714e-03	5.183579e-03	8.941540e-03	5.390685e-03
+C>A	G.G	3.769228e-03	1.557726e-03	1.699600e-03	3.945304e-03
+C>A	G.T	6.573060e-03	1.031818e-04	1.059791e-02	7.185424e-03
+C>A	T.A	3.862713e-03	1.624881e-02	5.519485e-03	1.246359e-02
+C>A	T.C	8.824563e-03	6.792814e-03	4.042968e-03	1.212436e-02
+C>A	T.G	1.024188e-03	9.815808e-04	2.029646e-03	1.087012e-03
+C>A	T.T	1.181704e-02	9.618044e-03	1.665114e-02	1.307952e-02
+C>G	A.A	1.983228e-02	1.270519e-02	1.655687e-02	1.398506e-02
+C>G	A.C	4.742892e-11	1.043116e-02	9.102239e-03	2.314023e-20
+C>G	A.G	2.906055e-03	1.687383e-03	5.265593e-03	2.218107e-03
+C>G	A.T	6.407465e-03	8.581278e-03	1.079483e-02	9.668306e-03
+C>G	C.A	3.411641e-03	6.888991e-03	7.212837e-03	7.949635e-03
+C>G	C.C	1.962245e-04	9.715947e-03	1.158418e-12	7.156965e-03
+C>G	C.G	3.300401e-20	1.855024e-03	4.346525e-03	6.200559e-03
+C>G	C.T	9.865314e-03	1.922285e-03	6.273441e-03	6.226190e-03
+C>G	G.A	1.351834e-19	2.119713e-03	1.072168e-02	8.229779e-03
+C>G	G.C	2.379848e-03	4.610717e-03	8.965747e-04	6.505033e-03
+C>G	G.G	6.979718e-04	1.181697e-03	4.111756e-03	2.523959e-03
+C>G	G.T	2.220903e-03	5.934769e-03	8.611327e-03	6.739344e-03
+C>G	T.A	3.709345e-03	8.786940e-03	7.620791e-03	8.983741e-03
+C>G	T.C	3.827093e-03	8.865683e-03	6.057793e-03	6.240498e-03
+C>G	T.G	1.899263e-04	4.938065e-03	3.040335e-03	1.626378e-03
+C>G	T.T	3.860261e-03	2.446381e-02	2.353559e-02	1.511199e-02
+C>T	A.A	3.499419e-02	3.714546e-02	4.085734e-02	3.151538e-02
+C>T	A.C	1.719840e-02	1.389005e-02	5.154001e-03	1.603745e-02
+C>T	A.G	7.482535e-02	1.348050e-02	3.052063e-02	1.592390e-02
+C>T	A.T	1.607143e-02	1.438585e-02	1.967215e-02	1.741898e-02
+C>T	C.A	1.606874e-02	1.435234e-02	1.105389e-02	1.125796e-02
+C>T	C.C	1.700219e-02	9.214402e-03	1.282668e-02	1.377429e-02
+C>T	C.G	4.356691e-02	1.624586e-02	1.169686e-02	1.963077e-02
+C>T	C.T	2.301602e-02	3.266347e-02	1.574218e-02	2.039183e-02
+C>T	G.A	1.970589e-02	7.742080e-03	1.178227e-02	1.297792e-02
+C>T	G.C	1.466426e-02	1.914382e-02	6.909098e-03	1.355502e-02
+C>T	G.G	3.701827e-02	2.542796e-02	1.262381e-02	3.190790e-02
+C>T	G.T	1.382222e-02	2.392818e-02	6.174897e-03	1.508942e-02
+C>T	T.A	1.143013e-02	1.914536e-02	1.002998e-02	7.458921e-03
+C>T	T.C	1.879514e-02	2.009898e-02	1.421423e-02	1.556176e-02
+C>T	T.G	3.061491e-02	4.743450e-03	1.167740e-02	7.144683e-03
+C>T	T.T	3.133938e-02	2.219653e-02	3.807693e-02	3.192865e-02
+T>A	A.A	1.841481e-02	8.914346e-03	1.741295e-02	1.361688e-02
+T>A	A.C	3.425691e-03	8.698638e-03	3.992626e-03	5.443164e-03
+T>A	A.G	9.072656e-03	1.149533e-02	1.354019e-03	8.223373e-03
+T>A	A.T	9.659453e-03	1.830189e-02	1.174139e-02	1.710128e-02
+T>A	C.A	2.727069e-03	7.915424e-03	5.772823e-03	4.530720e-03
+T>A	C.C	1.215316e-02	3.470147e-03	7.886743e-03	1.369393e-02
+T>A	C.G	3.791221e-03	6.605963e-03	3.294232e-03	8.818173e-03
+T>A	C.T	6.289729e-03	1.435186e-02	3.597548e-03	1.211551e-02
+T>A	G.A	6.615841e-04	4.146662e-03	4.933783e-03	4.863214e-03
+T>A	G.C	1.515807e-03	4.210462e-03	3.382936e-03	9.183128e-04
+T>A	G.G	1.070023e-02	1.089710e-02	5.492536e-03	8.802992e-03
+T>A	G.T	8.128051e-03	4.233917e-03	9.103699e-03	1.259684e-02
+T>A	T.A	1.476324e-02	6.549494e-03	1.579044e-02	7.620545e-03
+T>A	T.C	6.738527e-03	8.767946e-04	7.353978e-03	5.436410e-03
+T>A	T.G	2.186518e-03	5.445354e-03	2.568144e-03	7.932364e-03
+T>A	T.T	1.942541e-02	1.590353e-02	2.306069e-02	3.009347e-02
+T>C	A.A	3.011297e-02	3.375076e-02	4.906885e-02	3.383597e-02
+T>C	A.C	9.041893e-03	8.933211e-03	8.243474e-03	6.303632e-03
+T>C	A.G	2.247578e-02	9.001629e-03	1.950973e-02	8.972544e-03
+T>C	A.T	1.210116e-02	1.578255e-02	1.360358e-02	9.528566e-03
+T>C	C.A	6.835997e-03	6.652934e-03	1.036887e-02	7.994706e-03
+T>C	C.C	9.462334e-03	6.392714e-03	8.437885e-03	1.653238e-02
+T>C	C.G	7.156018e-03	1.612832e-02	1.225799e-02	9.579249e-03
+T>C	C.T	1.040136e-02	2.530647e-02	1.208573e-02	1.371705e-02
+T>C	G.A	8.743261e-03	1.074754e-02	5.087249e-03	1.090594e-02
+T>C	G.C	6.111817e-03	6.456267e-03	3.668932e-20	6.346677e-03
+T>C	G.G	1.768834e-02	1.377477e-02	1.512171e-02	1.240640e-02
+T>C	G.T	3.605052e-03	1.397132e-02	1.282818e-02	1.036663e-02
+T>C	T.A	5.577357e-03	1.122841e-02	7.516272e-03	9.852123e-03
+T>C	T.C	2.142753e-02	1.003311e-02	1.311934e-02	1.883301e-02
+T>C	T.G	3.231084e-03	7.639140e-03	1.374439e-02	6.010940e-03
+T>C	T.T	1.771125e-02	5.247659e-02	2.430165e-02	3.016747e-02
+T>G	A.A	1.331124e-02	1.426333e-02	7.805243e-05	7.473665e-03
+T>G	A.C	3.887921e-03	1.684454e-03	1.435130e-04	6.445063e-04
+T>G	A.G	2.394241e-03	5.040173e-03	6.853239e-03	6.994037e-03
+T>G	A.T	6.066623e-03	7.374853e-03	2.079215e-10	5.136694e-03
+T>G	C.A	5.000218e-10	8.218020e-03	3.668932e-20	2.314023e-20
+T>G	C.C	3.300401e-20	1.904378e-03	4.043369e-03	4.672135e-03
+T>G	C.G	4.310666e-03	2.256883e-03	8.181657e-03	1.928646e-03
+T>G	C.T	2.128603e-03	9.425709e-04	8.787753e-03	6.815812e-04
+T>G	G.A	2.012235e-03	4.628783e-04	4.459546e-03	1.814827e-03
+T>G	G.C	3.997247e-03	1.335924e-03	1.270853e-03	3.568581e-03
+T>G	G.G	7.790802e-03	1.175435e-02	8.700500e-03	8.985015e-03
+T>G	G.T	6.538479e-03	1.329525e-02	4.903674e-03	1.074729e-02
+T>G	T.A	2.781217e-03	4.774228e-03	2.965653e-03	7.301491e-03
+T>G	T.C	5.182071e-03	5.200467e-03	5.617300e-03	2.629881e-03
+T>G	T.G	5.245736e-03	1.345072e-02	1.698469e-02	9.832179e-03
+T>G	T.T	2.041928e-02	1.752970e-02	3.978473e-02	1.976735e-02
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