# HG changeset patch
# User artbio
# Date 1634485865 0
# Node ID 8d9f31389f3324c87a30749747619338f4dc49ae
# Parent 8c6ee1c2248f1760d312b4f522d097f8e3616251
"planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit 1cb9c8fd0c74943a8e6de4c63ac5e4a84ef27430"
diff -r 8c6ee1c2248f -r 8d9f31389f33 mutational_patterns.R
--- 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()
}
diff -r 8c6ee1c2248f -r 8d9f31389f33 mutational_patterns.xml
--- 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>
diff -r 8c6ee1c2248f -r 8d9f31389f33 test-data/cosmic_output1.pdf
Binary file test-data/cosmic_output1.pdf has changed
diff -r 8c6ee1c2248f -r 8d9f31389f33 test-data/cosmic_output_v3.pdf
Binary file test-data/cosmic_output_v3.pdf has changed
diff -r 8c6ee1c2248f -r 8d9f31389f33 test-data/denovo_1.RData
Binary file test-data/denovo_1.RData has changed
diff -r 8c6ee1c2248f -r 8d9f31389f33 test-data/denovo_output1.pdf
Binary file test-data/denovo_output1.pdf has changed
diff -r 8c6ee1c2248f -r 8d9f31389f33 test-data/sig_contrib_table.tsv
--- 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
diff -r 8c6ee1c2248f -r 8d9f31389f33 test-data/sig_contrib_table_user_defined.tsv
--- /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
diff -r 8c6ee1c2248f -r 8d9f31389f33 test-data/sig_contrib_table_v3.tsv
--- 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
diff -r 8c6ee1c2248f -r 8d9f31389f33 test-data/spectrum_output1.pdf
Binary file test-data/spectrum_output1.pdf has changed
diff -r 8c6ee1c2248f -r 8d9f31389f33 test-data/user_defined_signature.tsv
--- /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
+A[C>A]A 0.000876022860356065 5.79005909129116e-07 0.0209197492105927 0.0424507363741909 0.0120520481367051 0.000425145613703031 6.71694562134893e-05 0.0443106405724723 0.000560638966969298 0.00218526226624343 0.000147337461127982 0.00454236809131541 0.00181687918087284 0.00112609260941517 0.000946030090875022 0.0160943727268514 0.00207279918632882 0.0516883199119327 0.00127961346873583 0.000624247512114177 0.000157722171783313 0.00604617162363952 0.000844506730061431 0.0366237270205082 0.00993578471500029 0.000876874614431855 0.000785670933284911 0.0634975968681214 0.00181050219506439
+A[C>A]C 0.0022201195808427 0.000145504532003707 0.0163431921068143 0.0329895820389566 0.00933708706453245 0.000516225985778605 0.000176729831442553 0.0472995640705189 0.00404699056207519 0.00173937218490227 0.000548604298962786 0.00111836131396873 0.000708842466041201 0.0129714099117801 0.000490511447644093 0.00287284286844122 0.000905293428455269 0.015617160603031 0.000636052426566461 0.00138051386891227 0.00233488180943175 9.45179243898909e-05 0.000397419651060091 0.0262583136241544 0.00691870511579565 0.000522296335554948 0.00249692183598218 0.0506605586475702 0.000501229784403264
+A[C>A]G 0.000179727205679816 5.36186073164881e-05 0.00180754877738393 0.0161159612218968 0.00190813974719045 5.34208697464283e-05 7.3305382042244e-05 0.00476727552433761 0.000439559345708089 0.000153712628486902 9.75233896485778e-05 0.000557309553139576 0.000270655854422162 0.000426446913390031 4.74452478520416e-05 0.00105369054278497 4.89499976093771e-05 0.0025046687585242 0.000254547611912212 2.25777938295459e-05 0.000303318754994713 0.000790362401227405 1.02308497833945e-07 0.0152926133494441 0.00149449277081636 0.000117594481949321 0.000363293951337536 0.0198107208240535 9.43096572057688e-05
+A[C>A]T 0.00126505263784183 9.75912243380865e-05 0.0122650656971785 0.0296627698719921 0.00663587169503364 0.000179985776931981 0.000248522446240606 0.0472045874219964 0.00306313282723616 0.0169560731896464 0.000268323600008673 0.00122552063885904 0.000347256843861562 0.0830143252239989 0.00111191821370535 0.0106580277520086 6.18574864123409e-05 0.0214692003868359 0.000575079781725448 0.00124998489684999 0.000623593537179773 0.00172962261411101 5.67148006587459e-18 0.022125889785216 0.00498586225712035 0.000621485230278024 0.00397678433704963 0.0357525578677183 0.000559008293866678
+A[C>G]A 0.00183905476327572 2.22617789199643e-16 0.0198134163196479 0.00693093776346386 0.0101438071817268 0.000471161374245006 6.50641448993352e-05 0.00435068194283005 0.00486288996439319 2.22517573229354e-16 0.00017155731775176 0.00122603740517805 0.00386336397251532 2.23207642223365e-16 0.000113243008759404 0.0017502630340451 0.00101136578656624 0.00173632608636201 0.0032141472167459 0.00884434681945288 1.69777369626624e-05 0.001669990831155 5.80535165335642e-18 0.00336052879803564 0.00805902537994468 0.000428895143599544 0.000154328219038108 0.00315478566718198 0.0010762429715105
+A[C>G]C 0.0011879587230825 0.000130757451057385 0.0115888089484683 0.00281352591563474 0.00563785977413505 0.00028471242345423 2.13260578723975e-05 0.00291911535581654 0.00193938912021207 2.38795164367939e-05 0.000288216026628999 0.000635387578378694 0.0009349641958463 5.72326330458696e-06 0.000265488087356663 0.00199117729847134 0.000561124140295259 0.00256002822543356 0.00177618384329792 0.00149969492234355 0.000711347466517554 0.000193197015262356 4.06384004091522e-05 0.00363652871700555 0.0016209537699864 0.000373916694772293 0.000221071340418976 0.00260229041490448 0.000462597449241747
+A[C>G]G 0.000116771913294796 1.55832281302221e-05 0.000261319908958935 0.00132233527974538 0.00177405425144193 2.28066020840521e-16 5.23021546031742e-05 0.000295117056268519 0.00140328805202582 2.28519441017194e-16 6.17682680452204e-05 7.75073100755226e-05 0.000270655854422162 4.03730612918892e-05 3.15958591986481e-05 0.000874976362489088 0.000156310916735826 0.00197899753759936 0.000637403776170416 0.000485733270920046 2.29036610914376e-16 0.000238658450566707 2.9705817645186e-18 0.00095062191091139 0 7.04535361152515e-05 2.28473816421906e-16 0.000924500305122498 0.000135318347140807
+A[C>G]T 0.00112668750557787 9.10053134931849e-05 0.0174927986172873 0.00356958756086685 0.0101395316368895 0.000253979929670684 9.58013945992012e-05 0.00573485519531064 0.0064376004664209 2.22423783605362e-16 0.000539673406032481 0.00144651616389921 0.00399145797542025 0.000205023272950312 0.000325561639147962 0.0115629546366131 1.96182319366e-05 0.00409319334477992 0.00215529025024949 0.0044555913258685 6.21585184403027e-05 6.23468616714434e-05 5.67148006587459e-18 0.00286630844944844 0.00344094719153376 0.000730922855642006 8.34423514549708e-05 0.00250067048007356 0.000734955148950615
+A[C>T]A 0.0247184780010176 6.09952776686017e-05 0.0142817518649239 0.00875169209610095 0.0327413974380489 0.0641219619726219 0.000122308562060383 0.00684252748976273 0.0081383075850382 0.00103775011730282 0.0260363458705612 0.00553726729715663 0.00716768819706977 0.0124674538899537 0.00506086012597336 0.00177038099995366 0.0012216497619909 0.00923364161533556 0.0282119504918135 0.0497179359405959 0.00217998160999866 0.0017705926884535 0.0228573079034591 0.0118725268912637 0.0210759069712127 0.00267180581258733 0.000778656014237724 0.00511396784903066 0.106618462598236
+A[C>T]C 0.00615401568023061 0.00135673144706159 0.0122821564923938 0.00414103462230746 0.017704857887196 0.022560257775439 0.0174755196454368 0.00279047637403479 0.00536300460793338 0.000819568588818356 0.146095710049872 0.00209816458903868 2.18256626159704e-16 0.0100008580235862 0.00681978692800943 0.00369507031009854 0.00168633089614217 0.0045961896711452 0.0139911688215087 0.0129112807883881 0.00387827825973409 0.000217965863372914 0.0805795733603041 0.0110978533053031 0.012947862430989 0.00251256191725297 0.00333580861882205 0.00426458999552788 0.0895477717590021
+A[C>T]G 0.370623898718264 3.35244447275174e-05 0.00265451449021527 0.00080889728440674 0.00637421818250647 0.123278930184066 2.29594103868264e-16 0.00333296535575984 0.00451941299108317 0.00570786227114695 0.00785576294937534 0.000121782457908277 0.000310639105643618 0.0273628164766001 0.0766739905634947 0.00337800791657534 4.06202711254284e-05 0.0125748801868293 0.00160385690432491 0.013774525593255 0.00763455369714586 0.00140508871329317 0.00905715838692384 0.000531108328487451 0.020304487989712 0.0054980577964025 0.00725558741339839 0.0207393483626811 0.014874688540669
+A[C>T]T 0.00946812833634737 0.0018560294199268 0.0121645323717918 0.00427344989681243 0.0220861085159969 0.021298316936951 0.00743563125445683 0.0125544115484033 0.00651794493402053 0.00298227404923781 0.109952151883253 0.00239076977088896 0.00031732090904591 0.0161807583063727 0.00178307605441038 0.0060328458973634 0.000737685558024193 0.00799577229360196 0.0370629351444772 0.0131046803702014 4.18741553951635e-05 0.000619446238542083 0.0353835654733708 0.00920235870612394 0.00574828787390334 0.00280120160335329 0.00506864703916149 0.00183784216005405 0.0294585305940534
+A[T>A]A 0.00078381163610561 9.48666602243016e-05 0.00547148843052349 0.00938995869583773 0.007344732367776 9.73419994045933e-05 0.0019272531382518 0.0194152976169594 0.0126442421336871 5.01311206493012e-05 0.000417000315032316 0.00514842552285569 2.19607737098627e-16 0.00061074027733891 0.00202583059382285 0.0230253401146335 0.00100218583421313 0.00247642132964036 0.000784761393453593 0.000510654394011762 0.00344436523281768 0.0637010892781995 8.29825885678988e-18 0.00157528175677483 0.0202879024291499 0.0015128882279558 0.000170802047458607 0.000616269766054594 0.000361803844684707
+A[T>A]C 0.00220131415270956 0.000875074368898528 0.00723975465288627 0.00354521785330032 0.00694877566789748 0.000545301711163398 0.000670605757085524 0.0213670461234536 0.0028287439259023 0.000193266520071015 0.000444318463682 0.00271899635623067 6.49826924028379e-05 0.000373417331006569 0.000841442409446559 0.00777303240060496 0.000996729902283197 0.000879782153423284 0.000256513783977942 0.00522551350062126 0.00566678830643069 0.00704075872058155 5.61418702443501e-18 0.00226015965274144 0.0089076713292278 0.00352989154729524 0.000478242276827957 0.00200616039185069 0.000394652216301763
+A[T>A]G 0.00111728056139953 2.52331144101491e-05 0.00961049698369561 0.0123643171487896 0.00907925311827972 2.20129081319081e-16 0.000583325289017739 0.0227080561753272 0.00274874110524235 2.2056672199249e-16 3.93123087970585e-05 0.0031079509606343 0.000583824540399692 0.000352805235694251 0.000536416823365478 0.00878426956449829 0.000198514646019871 0.00258662939629398 0.000950796783927343 0.000302889678081424 0.000246956494006603 0.0604302369049086 0.000354891481800625 0.00199465056462219 0.00620765027619678 0.000622270116230185 0.000150988505169337 0.00246983286782249 0.000636096349610561
+A[T>A]T 0.000179455599598813 2.20792375685429e-16 0.00609478732997757 0.00420028810063082 0.00617583249118727 0.00164695247679033 0.0036888852531921 0.0249134374949811 0.0188336758793869 0.006591099805114 3.40301176189128e-06 0.0028107175465514 0.000600000333259913 0.00184481160044234 0.00948212197839832 0.0109741518257995 0.0014499864598697 0.00780414727584747 0.000653547318318845 0.025605327998176 0.00159417974083247 0.00250440133779996 0.000161497841595752 0.00179621312995545 0.0148312396863771 0.00305834050159412 0.00168965388763028 0.00195308205308782 0.00048881760356036
+A[T>C]A 0.0010679433541939 6.10351713851867e-05 0.0164443641354531 0.00792464667005413 0.0459792188877034 0.00219069061796488 0.000486780431826485 0.00972756193424069 0.0202108752215629 0.000736640727489732 0.00114000086123943 0.0732928662441351 0.00188941791828098 0.0125535521932631 0.00386298088724064 0.241217848819971 9.57533990114523e-05 0.00200898437183676 0.002585918586571 0.0106927632405595 0.0166245373953917 0.0249221789038338 0.000887953785883555 0.00638088812870817 0.0205862539354608 0.0844032379806922 0.000545176302644044 0.00195135499429242 0.000608986636645607
+A[T>C]C 0.00300089462970272 2.14283586917066e-05 0.00779202442529785 0.00071808236971947 0.0134363050432649 0.00112855482347004 0.000227205234117036 0.00502577000368558 0.0105325571709128 0.00360631341575812 0.000945058319577588 0.0404337834524339 0.000141526722717837 0.00632400318640156 0.00196103106125477 0.0129550540010083 0.0126965594373085 0.00209424225587091 0.000597526226207442 0.00458113418647914 0.0100297138166915 0.00090294466330996 0.000179734764451337 0.00218984357465615 0.00951888387262813 0.0261733435751152 0.000441223523182278 0.00229705364866905 0.000459925483629027
+A[T>C]G 0.000103887490796799 1.30618474593714e-05 0.0122623561099021 0.00498561175354419 0.0380293277541979 0.00420426713870676 0.000185829351015873 0.00695185228525369 0.0142416658713643 0.00211664926037636 0.000320100224301749 0.070227738052794 0.000423520175069607 0.0123581494988947 0.000238407477051324 0.0637133740262703 0.000373207534517357 0.00206930351703518 0.0023070804315884 0.0185932277634142 0.00386367418042589 0.00772828937315251 0.00047118360578049 0.00175529249686752 0.0197968334128711 0.0781571265985111 0.000402304898641981 0.00273872596230317 0.000276173493482955
+A[T>C]T 0.00562882591091358 0.000153465552606464 0.0172569264825878 0.00155640129144515 0.0381507071633021 0.000498054303222136 0.000611499846553408 0.0148484087470088 0.0288982328308053 0.00332523954131878 0.00119105411666195 0.0635899927198509 0.000949505477881611 0.00595325689440044 0.000923363869804197 0.135680422573521 0.0077365715906746 0.00422061026142771 0.00173879561754556 0.000103021436867661 0.0255068758533195 0.00075331594025457 0.000261807059978206 0.00243486668727293 0.0144330856008368 0.0370587187815313 0.000591378860670595 0.00114594100053623 0.000543684885592646
+A[T>G]A 0.000168519501762706 0.000235435507126004 0.00393668111121453 0.00104665144698828 0.00384155378585574 2.54754519826685e-05 0.000469892131130464 0.00163287631240069 0.0449019937188417 0.00189845663997353 0.000218000164693154 0.00200161224389554 6.07383561164671e-05 0.000211218497219982 0.000464749371524065 0.0111638012677011 0.000844415985064724 0.0007170681842051 0.0023263283037492 1.0492898507091e-05 0.000390228662215183 0.00232274707383732 8.29825885678988e-18 0.00320041420205519 0.00525098651107407 0.0029063379115993 0.00980125702567707 0.000405204838100516 3.88714874454643e-05
+A[T>G]C 0.000204337233009363 7.43514213209911e-05 0.00261072983321836 0.000159685450049505 0.00260704426212603 0.000203739100874237 0.000247223316418096 0.000670102667158077 0.00695148773280245 0.0012353117777735 4.70514110066879e-05 0.000666204273260946 2.21260087629294e-16 0.00298131578787503 0.000415218311439147 0.0044288207863912 0.000699810362686298 0.000859741557673323 0.00190121981066004 2.14457490487924e-05 0.000438298493789418 5.11233407813982e-05 5.48292006163347e-18 0.00140632156170579 0 0.00253710954961845 0.017308768596493 0.000819516520071009 0.000110462452399985
+A[T>G]G 0.000262658938995679 2.0285444917963e-06 0.00628071898312057 0.00141591373800655 0.00790452519288826 0.000106098250906043 0.000274272197221288 0.00475076438404873 0.00530825727932672 0.000316508300617026 0.000179056062968791 0.000804879607754009 8.16364823440247e-05 0.000706607096348091 0.000183772430227062 0.00460650685448151 0.000713660152441437 0.001979766345625 0.00176776292810021 2.68902057438624e-05 0.000186213162819495 0.00294173595494192 5.69430400177274e-18 0.00205449008156085 0.00710298445064824 0.00227999770586739 0.00762889289276645 0.000418278146969939 0.000408776651003652
+A[T>G]T 0.000109830749481241 3.72277727613099e-06 0.00396011549918346 0.00021550171727702 0.00481117273103783 0.000382966057856065 0.000307241386317078 0.000737437749851441 0.0238161298157326 0.00912461564611879 0.000285252456511475 0.00127578668779638 0.000316831859147149 0.0110688696026541 0.0036079772307742 0.0079412953212149 0.0124142676358707 0.00183158558514788 0.00161887867840448 5.82121128708532e-05 6.92471824924106e-05 4.17067633147563e-05 7.45297492581637e-18 0.00470009102338341 0 0.00590747855845378 0.11430011592793 0.0008071410525516 0.000792084035156992
+C[C>A]A 0.00030502624638518 0.000205314317697578 0.0223756961412788 0.0802688813720344 0.00737852110914031 0.00180020125217332 0.000451034045542104 0.0398395762397846 0.00476860354309263 0.00313752699107907 0.000616665568136236 0.00538572376899194 0.00138192220412928 0.0162048340802795 0.0414200040189608 0.0103439951982173 0.00029208536613245 0.0734374867262265 0.00131507315259792 0.0374934077426348 2.20519484890833e-16 0.00182036294784901 0.000151006097983349 0.0252694488704786 0.0146868815523791 0.00140037150513469 0.00201150705564858 0.0538443819505899 0.000763815855594349
+C[C>A]C 0.00173825872471949 9.34388688604433e-05 0.024991557884713 0.0787427844376687 0.00605658270412868 0.00401838690605083 0.000236313177974284 0.0382896003886823 0.001894654296248 0.000197965946461223 0.000977275273030938 0.00422442231350393 0.000949095003583006 0.0194536895515796 0.00497054492682487 0.00892116335552276 0.00114083948146752 0.0193206141617684 0.000759014573984962 0.0979585012931139 0.00256534697289677 0.0043771294852436 0.000625801872333874 0.0344878603181427 0.0077082075618903 0.00148963500853605 0.000107282970713144 0.0364121435704463 0.000383299228825728
+C[C>A]G 9.19544820464989e-05 2.2214428150603e-16 0.00251908100337676 0.0245931486072583 0.00346761587777843 0.00164705457389517 2.23088490673349e-16 0.00341899991854442 0.00137355141503852 4.62011413966183e-05 9.26453072669708e-06 0.00117328906708923 4.31338108329658e-06 0.00138455574000147 6.62012543170414e-05 0.00174654022727639 2.21827370404397e-16 0.0120182630528982 0.000237280668469444 0.00747704952819194 0.00198487681526093 0.000136527513132735 0.000131200431762527 0.0160641003998816 0.00128189431159794 0.000362833264903189 2.21999946885344e-16 0.014838062597311 0.000408503923719535
+C[C>A]T 2.18022097545941e-16 0.000415576547930377 0.0153153805568239 0.0686334453739113 0.00644522734929124 0.00949585203217325 0.000368768572780014 0.0327866701698049 0.00304007599691614 0.0170694484315435 0.000149680600957248 0.00109307637455717 2.19139954870867e-16 0.258489773751404 0.0284399472029193 0.00247666548725803 0.000135650495389082 0.0360251456145823 3.42726319545804e-05 0.251293146846734 0.0189731917686133 0.000109424007654134 0.000580040830794875 0.0170126198585227 0.0125040717266269 0.00709145576834455 0.000201156742643552 0.0515610201931592 0.000295390778118642
+C[C>G]A 2.35613222368039e-05 2.20120638685384e-16 0.0191933749122969 0.00778817027438698 0.0069117775127344 4.0652896408969e-05 2.2105624649646e-16 0.00496752820944945 0.000887158950829523 4.5089617450413e-05 0.00026043642926142 0.0013315258026659 0.00553755968940376 8.50008168014664e-05 8.28400080379215e-05 0.00353088297631456 0.000547536296512695 0.000608340261664552 0.00176339354552903 7.66819961544843e-05 1.95686209565288e-05 0.00104447054384779 0.000174007026815249 0.00259658510047043 0.00714496940386009 0.000361514346006403 1.42688185228274e-05 0.00326841359072769 0.00126308090703753
+C[C>G]C 7.45800391388028e-05 0.000344145256768264 0.0139281014298204 0.00678748969995965 0.00894677607922593 3.65486535220271e-05 0.000128987609644297 0.00538817572479911 0.00151967063344892 2.18546564657687e-16 0.000175433796477156 0.000879429972273833 0.000635344589175401 7.76172588200078e-05 1.67325274764402e-05 0.00448528035814766 0.000231118343228333 0.00222778510232635 0.00179115564395408 4.33830369730878e-06 0.000269361432154162 0.000775631297046552 0.000253300757849425 0.00515835618512049 0.0045342397422884 0.000317657266720932 7.43106815490126e-05 0.00625617859719863 0.000783392496027841
+C[C>G]G 0.000347295897858022 4.85131233602853e-05 0.00150542689444827 0.00341292674549708 0.00249548079065557 8.41495155026445e-05 7.75307534851325e-05 1.05277123591544e-05 0.000438132823629076 2.0013856510173e-05 1.12785591455442e-05 0.000173486332142254 0.000486127013544741 1.91630540826291e-05 5.02009511588441e-05 0.00146548777691007 0.000231819594296487 0.00358544847744795 4.83610175990688e-05 0.00018919048604308 1.01248766839068e-05 0.000239927026755321 1.87717540829462e-18 0.000948785929868007 0.000825219463091178 4.17959865924393e-05 2.21999946885344e-16 0.00130334333625029 0.000120443417312885
+C[C>G]T 2.18022097545941e-16 6.27806851505273e-05 0.0221774666504659 0.00678376952826196 0.00946425526020733 1.42437780482599e-05 9.47695579509928e-05 0.00545450967370389 0.00301027133027971 2.96988669242462e-05 9.61947328818582e-06 0.00155018104028108 0.0063175482485295 0.000176966075875962 8.37343393256682e-05 0.0095684827258724 3.86158344538264e-05 0.00376130308207347 0.00320807775853922 1.00716697744128e-05 0.00017185142282566 0.000318324385902936 0.000227015980328339 0.0046859321364703 0.000194507782414196 0.000620750680002149 2.19984221019056e-16 0.00664630491507196 0.00101447337939736
+C[C>T]A 0.00195529645118705 0.00426422044448814 0.016011053683315 0.0126321535740376 0.0192655867452654 0.0134520533129435 0.0495641808288027 0.00265266006384601 0.00719264367749804 3.63084884502231e-05 0.00406121175131793 0.00654832465639426 1.90507846712108e-05 0.00271406116804682 0.01070181922021 0.0071313889972325 0.000812888425744885 0.011611062090498 0.118555837241782 0.0105699500551045 0.00134099686757939 0.00120362796005317 0.0622025118845316 0.00535234783162105 0.0141907031215555 0.00167845946360116 0.000289339931157332 0.00756006912627286 0.109400708483566
+C[C>T]C 0.000262195450097354 0.000166680038890613 0.0199537339632887 0.0113618823216209 0.0187418683026783 0.0145408621539247 0.0544504947582412 0.00396711839078616 0.00864436022663152 2.18546564657687e-16 0.124885075458314 0.000250701698044392 0.00132363456078209 0.00136274576554212 0.0109253561757933 0.00280577009188091 0.00169158957596907 0.0066636403945691 0.0910421653280527 0.0128762438504598 0.00509122706928745 0.00315192845551401 0.187740561700162 0.00874548893454336 0.00585508349330285 0.00279183249944173 0.000206691961924406 0.00161831749201984 0.101752114868685
+C[C>T]G 0.193380670398217 0.00275937067162198 0.00224810416237608 0.0033225845669398 0.0175385196130411 0.121782216978916 0.00671266265658373 0.00149393251572762 0.00652687570211735 2.22044278694954e-16 0.000926453072669708 4.10149767897006e-05 0.00198236220687302 0.0116382946260993 0.0248004698952058 0.000693597297154013 0.00189852253949709 0.0168255682740574 0.0157851970125859 0.016604484147398 0.00623532009642577 0.000427652357312832 0.0143311240848299 0.00637543984620301 0.0116171671988564 0.00334768813474214 0.00254999938989923 0.0153393484958688 0.0168620784238039
+C[C>T]T 0.000191624803224234 0.00143132065201674 0.0228736203121397 0.0159150018258346 0.0229406397178162 0.013650287296249 0.0561083366111526 0.0144062641655204 0.0110277266554802 0.000101627351933467 0.0649613808154458 0.00335872558727567 0.00143131952505746 0.00135210035500735 0.0154586472601234 0.0191966441381848 0.00172286030640148 0.00659964788807086 0.257044739659354 0.0116671818178841 0.000322842268314101 0.00159162192951468 0.156010982075863 0.00426807831538378 0.0134964583715973 0.00163878179520568 0.00328985411614084 0.00066860436589588 0.0459496765962332
+C[T>A]A 4.22647255611115e-05 0.000241151049401394 0.00793855615880444 0.0144000217946099 0.00353435975793 6.62294093591927e-05 0.000176399835642859 0.0189780208752371 0.00478423467624768 2.21203602212548e-16 0.000184589090212015 0.000545461889317742 0.00020740958700283 0.000154922916359623 0.000346689014328885 0.00320986660695816 0.000432020637731996 0.000540769705046038 9.61555142479685e-05 0.000144363214349458 6.18175267245055e-06 0.128009985516857 0.000464500830790235 0.00132027064102051 0.0262392010262764 0.000942590651391115 0.000139469916011327 0.00194761316927034 0.000213977546760926
+C[T>A]C 0.000387448809235948 0.000242876161926022 0.0178506158388513 0.0122369354851455 0.00519741064896797 0.000549592040065498 0.00026090211488275 0.029254477978796 0.00313569259960173 2.21872960040954e-16 0.000213322296117674 0.00561140970729071 0.000340424516303349 0.00295745512795048 0.000243816360966088 0.00571701050702001 0.0404372832153514 0.00306229253692668 0.00040487428153939 0.00651600245916603 0.000689162435091889 0.0552710429959024 4.50779570121621e-18 0.00187604315218444 0.0158111743498565 0.00145221633805444 0.00134895808237884 0.00141253554812439 0.000779269416160331
+C[T>A]G 0.000318465389581822 0.000147868880093755 0.0131978316093994 0.0325006203827893 0.00500210553477132 0.000114362101132749 0.000111622196726545 0.0275685569425765 0.00530370200736314 2.21207489901257e-16 0.00030598185864358 0.00140863513006559 0.000224284165027034 0.000316847920077617 8.16925253172157e-05 0.00102997529953389 0.0123436637303954 0.00320276985498905 0.00029448143785184 0.000123312412787463 0.000124835648581241 0.168016058848099 0.000132716855561906 0.00503111972749332 0.0627556939696148 0.00113831803817037 0.00080296234269458 0.00197761120502015 0.000586948726511565
+C[T>A]T 0.000257226113285384 2.22751099017644e-16 0.0127807650071292 0.0118772192765515 0.00432123671222928 0.000179168556045325 0.00037216105934257 0.042024805362163 0.00446366960350049 0.000375411253189398 0.000163581931065117 0.00150832572663273 0.000522415843319051 0.0013883378435206 0.00105288816782393 0.00657244928191707 0.0724411225100271 0.00226962243655234 0.000219781718705371 0.000102926293333388 2.23154711469131e-16 0.0606992466203346 0.000379496606827927 0.00483239450668407 0.0367542913423926 0.000645235526824811 0.00103281333887838 0.00199051470923485 0.000615939367466022
+C[T>C]A 2.19186832561114e-16 0.000299702127239593 0.00882839431766289 0.00518000784000551 0.0132788092600195 0.0016507630561 0.000449470767654969 0.00238723525746402 0.0136835104518984 0.00012101721735395 0.000329050117334461 0.0453552559982152 4.70393034637998e-05 0.00315842848836393 0.000747174599846735 0.0106995553565272 0.0110493757576617 0.000385123812080757 0.000452732212917518 0.0117295111658935 0.0114846778244235 0.00674052579987197 6.89713354809744e-18 0.00227046542054284 0.00900912491510553 0.0519223663901885 0.00131500206524966 0.00117855566140462 0.00126986674946905
+C[T>C]C 0.00246468708165361 2.83687320282444e-05 0.0145412320035586 0.00236714489712651 0.0104148498553501 0.00102736806037652 0.000258902864960277 0.0070130597894374 0.0153278264453376 4.09917755770732e-05 0.000717447156282554 0.0498012611522051 0.000121437985347978 0.00535349504517138 0.0021483818691684 0.0031794602293427 0.172732098672983 0.00246184301988223 8.17785769660207e-05 0.00485683516632283 0.00282476463220803 0.00134415966632503 4.50779570121621e-18 0.00224723885609259 0.0108076381631931 0.0312476894808956 0.00261797790802411 0.00184330880038928 0.00138403062329635
+C[T>C]G 0.000353850432868692 2.21307115845015e-16 0.0100983408526466 0.00550010498785665 0.0207672245754977 0.00529049024370626 0.000103649182674649 0.00125856455607414 0.0153817346352905 0.00104155993002835 0.00013142171633544 0.0373637970669879 2.20314533787618e-16 0.00446785552917019 0.00138478792915768 0.00960976954225309 0.0869033744889939 0.00161635114177017 0.000498815496769445 0.0261662924695347 0.0143810667165589 0.00203019404441453 0.000391112551618042 0.00422093941352323 0.0133692575388368 0.0785838856175511 0.00248061567408127 0.00390528273314585 0.00126988906758039
+C[T>C]T 4.21455093306053e-05 0.000185792396490052 0.015900479300208 0.0025767526566078 0.0149735876772596 0.00127119590043331 0.00182569576281261 0.00649474264687974 0.0330753896295419 2.43617940899503e-06 8.53251430555703e-05 0.0461547672349615 0.000111874903349396 0.00207244634612496 0.00175481361303988 0.0156007601638154 0.426831510225056 0.00257089975113894 0.00039419565143945 0.00696266101961155 0.021812870445406 0.000539548858847419 4.76647738175876e-05 0.00365449834567983 0.00899777186961305 0.0557797067582196 0.000368002422687735 0.00178945261739294 0.00412639118727237
+C[T>G]A 3.48929711027782e-05 0.000151835845919396 0.00436920534181051 0.000870001316757682 0.00258587338221432 4.92245610102108e-05 8.3914498085473e-05 0.00121858870883101 0.0259687059671064 0.000153751382703789 2.22710750147104e-16 0.000892119903224805 4.10849612531922e-05 4.84758802802692e-05 0.000205223956757903 0.0039598354403596 0.000308586169808569 0.000110748039225296 0.000715156637219265 0.000965428995962005 4.34420422054279e-06 0.00491038303818566 6.88707941756085e-18 0.00143029319443888 0 0.00141788000527054 0.0145447198126098 0.00078004404369238 0.000197979225507772
+C[T>G]C 0.000209005464524226 0.0001542860864694 0.00706001884862431 0.000442335126963047 0.00461658248395806 0.000781996659548731 0.000171935493332694 0.00195363808420042 0.00742347672940856 2.21872960040954e-16 2.23384668576054e-16 0.00114232269041275 2.80700916951883e-06 0.00121305786604071 0.000156881838818343 0.00108322304343537 0.00103838949491272 0.00199149089819741 0.00209972021939783 0.00160888949609038 5.44919134723819e-05 0.000882731721168677 0.000149251401293064 0.000882843836322089 0.00289204391589148 0.00494755083447512 0.0220829434226461 5.70023210555164e-06 0.000215627959426604
+C[T>G]G 0.000125813487242202 0.000120081439539223 0.0106982422894375 0.00379007234617759 0.00612034070422119 0.000918874621275298 2.22247766696603e-16 0.00469464556630831 0.0141831579104627 5.30699583395393e-05 2.22714664324179e-16 0.000592425980233258 2.20314533787618e-16 0.00043479130988569 0.000270980083979057 0.00223994628248147 1.93118609975542e-06 0.00292340052184359 0.00133217793313928 0.00271688324108962 2.00735722918635e-05 0.00803076757470381 6.55540832017901e-05 0.00304067673391247 0.0117729282804683 0.00555179674756778 0.0154415835133573 0.000331599454579136 7.8493143153591e-05
+C[T>G]T 0.000169175636045387 0.000202773421975702 0.00707470692914318 0.0012078528077849 0.00733605302308692 0.00130122415004985 2.65829328101836e-05 0.000577087040140707 0.0568012010355355 0.00129796443921866 0.000134298745874448 0.000345909366641107 5.54380101418879e-05 0.000967812322802043 0.00249684908369673 0.00255651166555426 0.00532036459928414 0.00415762694129501 0.0022179806474854 0.0051564054797413 0.000185962259557609 0.0011978789963217 0.000249961765030661 0.00474178710968374 0.00858604346932942 0.00783931013899303 0.1012758710939 0.000771073122213703 0.000266705771860287
+G[C>A]A 0.00155626959896502 8.57251586418347e-05 0.00714379030371472 0.0316669246757628 0.0102053008592886 0.000425522645095338 4.05479677564356e-05 0.0242231620266631 0.00772702665785464 0.00120279288768101 0.000165878576436296 0.00198223485826488 0.000943771595094771 0.00208336541185369 0.0022862013018325 0.00862786324756968 0.00177563180537408 0.108982737880842 0.000817044133069938 0.0108501553378358 0.00214167170363847 0.00223489380127447 0.00033954127061467 0.0623444170648387 0.0134972961152905 0.000496307638601642 0.000155738235960387 0.0971863943910265 0.000944896570124019
+G[C>A]C 0.000329319171160487 2.18723508330305e-16 0.0107709803774159 0.0343943906004591 0.00754877784507113 0.000897336117074769 0.000135928872319561 0.0258646334571483 0.00659418521599397 0.000432348184052405 0.000401560463896683 0.000411732872756684 0.000442350782909231 0.0221278746071123 0.00245170324081858 0.00420028345986967 0.0012593094186941 0.0170595231665851 0.000269264800137913 0.00559822329227382 0.0069782754446415 0.0017099668838652 0.000537587921460353 0.126533849939756 0.00637979695169204 0.000657253762226891 0.00100429290192421 0.0891381382659674 0.000488190245322219
+G[C>A]G 0.000582768122955382 1.39330364080141e-05 0.00144412619456053 0.0154539740009943 0.00235977957739148 0.000358585693129542 4.278208329961e-05 0.00276436872588365 0.000172512735058905 1.0520217535087e-05 1.40848133350125e-05 0.000451052798812981 0.000164389652646842 0.00112061139310283 0.000406527838174309 0.00137362741467688 0.000106578282799433 0.00761873647016609 0.000207398166174927 0.00158979743821415 0.00170473065168831 0.000520222578057959 0.000120848028584184 0.0665767419655722 0.000663084446466065 0.000130103486010139 3.97463898948079e-05 0.0232029933881708 2.24210266196506e-16
+G[C>A]T 2.18542738645068e-16 5.06611173221181e-05 0.00996880129206236 0.0211377344953292 0.00678912471479853 0.00121956144041388 2.21590783544867e-16 0.026789926332534 0.0085245732337014 0.0109782276190141 2.22056300983659e-16 2.73921665662364e-05 6.0852661370642e-05 0.125567263886908 0.0180781566196098 0.00578271603175148 4.6648162619811e-05 0.0619759273756968 0.000272638716882124 0.00248894510826296 0.00886202361956813 0.000549423711009974 3.09759703041576e-05 0.054251263186867 0.0104449430818803 0.000813383036365003 0.000156939227648042 0.0842481502845766 0.000859376783552309
+G[C>G]A 9.44596547726241e-06 6.5039737531044e-05 0.0127245633740781 0.0053012035295818 0.00468243215896773 1.93328789574931e-05 1.95748809858655e-05 0.00258246934003268 0.00136123785682413 1.49106556324092e-05 4.6948663755e-05 0.000564636595990604 0.00149173592480733 2.22359192995922e-16 0.000992351132760484 0.00105217844482557 0.000875845351190133 0.000634899436278302 0.00131489903479314 0.00067210684453816 0.000388303093930714 0.00140307234160729 4.35257652538687e-18 0.00272631534431449 0.0041691648000564 0.000395244994450905 0.00018269293064584 0.00227201972469238 0.000516035772655217
+G[C>G]C 0.000159316649174985 0.000255994778808114 0.00852784960156868 0.00568298120553562 0.00501278319646553 0.000673247798681508 3.27017287029667e-05 0.00235940740315207 0.0027936443355184 8.14696918248409e-05 0.00011303183428203 0.000285349640831371 0.000469813802690735 4.27739718967841e-05 0.00059864882346092 0.00305385315082289 0.000821502628601225 0.00132137347070659 0.00127702791241878 0.00283379090546958 0.00140157724630706 0.000919230752598057 0.000126199012986071 0.00572367961836865 0.00235667924490633 0.000571396288782838 2.18581396301151e-16 0.00161889863517372 0.000252989276928114
+G[C>G]G 0.000164803251125372 2.23530008560227e-16 0.00244390586771782 0.00333321007864583 0.0015227637443851 2.22986061273833e-16 4.53993401602921e-05 0.000492340123442051 0.000525608976407541 2.23429381935655e-16 3.2830787917583e-06 9.62649597466631e-05 0.000241572599316397 2.24122278620565e-16 1.01631959543577e-05 8.2114638833258e-05 2.38292953051562e-05 0.00064396463021642 0.000603983927836252 0.000700726004614135 0.000118019814347652 0.000213139735864523 1.85841926310133e-18 0.00317224536831406 0.000421229937116741 7.44312966476612e-05 2.23384773586008e-16 6.94072150046153e-06 0.000118164870022483
+G[C>G]T 2.18542738645068e-16 0.000132589642991481 0.0146541378993316 0.00303107136159437 0.00668957743159035 0.000318275790547037 4.1734587035356e-05 0.00484011308461396 0.00853453184729216 3.50116448390178e-05 0.000186047171094417 0.000502023707250297 0.00267158025529648 8.00242165882437e-05 0.000447980694255164 0.00322037461768229 0.00078110859535726 0.00122360177643832 0.000319576517957068 0.00301872057307395 0.000206116729129281 0.000453698345752338 4.04993268701608e-18 0.00337075863183108 0.00197956540313731 0.000303649725937975 2.20509547708008e-16 0.00319664967391833 0.00039778577336122
+G[C>T]A 0.00437331456924348 2.21771582101267e-16 0.0164317196326678 0.00409866208619841 0.0194100820264901 0.0932761582691419 8.47911936581621e-05 0.000276264161956984 0.00698635311811209 4.19486445125112e-05 0.019804896701788 0.00448505664900337 0.00714044262674442 0.0171276675686049 0.0735777449541727 0.00651348561082496 0.00163597537124353 0.00967846699712435 0.0612281229941845 0.0423959773385805 0.00932728050369656 0.00238522298073239 0.0541049443086285 0.0299694223511041 0.00999799712243741 0.00275170565756959 0.00324454658250808 0.0104092533642294 0.049799957089251
+G[C>T]C 9.01499088014548e-05 1.26526155043091e-07 0.0132413887208598 0.00440801672638068 0.0213141962684361 0.109095628691456 0.0115244043923105 0.000241863938816845 0.00644611219467675 0.0122547671216668 0.114023341600293 0.00179701157893804 0.000903337186384482 0.00806086860687663 0.12701595103036 0.00522811753004954 2.18411477304757e-16 0.00805643377289017 0.0393007814907174 0.0527124741856579 0.0193457141039566 0.00184834570683695 0.153028724408308 0.0431994472059948 0.00685310491719624 0.00537842793413898 0.000185104966237011 0.0078575811804773 0.0602826011430271
+G[C>T]G 0.21642836593573 2.23530008560227e-16 0.000533215825683888 0.000486850684214331 0.0124039695734681 0.178790625706046 5.55663764267877e-06 0.00192698695855393 0.00480210888234146 0.0149286896450281 0.0018036667436203 7.52763731352313e-05 0.00017842291567767 1.9383548421238e-05 0.27873319597595 0.00118172358468526 0.00161878335195365 0.0149149867405367 0.00324755177278789 0.0207585015817771 4.37782901084454e-05 2.24251286075469e-16 0.0124910147192056 0.0256608383296743 0.0105811347840329 0.00673714175618397 0.000216341109554017 0.0184615121305881 0.00529217024716077
+G[C>T]T 3.76324715873121e-05 4.986953736396e-05 0.0112647454600304 0.00379880983147189 0.0185157946767232 0.0737685944445469 0.0159982583635531 0.00459113607408855 0.0106557165421268 0.0133518984555576 0.0696176511192015 0.0026595303538855 0.00125663219415797 0.0104639386572423 0.0766831698370259 0.00669997443678791 6.55059304873942e-05 0.00665519990599377 0.108855751429126 0.0330859771419695 0.00801565057724982 0.00175496502972333 0.107263068690772 0.0202444971083345 0.00976850867276805 0.00495795290220039 0.000101315197595571 0.00509870602195074 0.0176461358107609
+G[T>A]A 7.9349463735341e-05 2.20022003325224e-16 0.00701785012530352 0.00916663518164201 0.00364293921658587 5.04225955894216e-05 0.000397326609637921 0.0127111738260776 0.00263148684988798 3.26432728266e-06 1.53598613764735e-06 0.000820408565705625 6.61052135246548e-06 5.73374200868884e-05 0.000506127698697752 0.00093451908476587 6.39330835286649e-05 0.00158712604586607 0.000188210190833585 5.54175359798683e-05 0.00116167650831745 0.0533932717325025 6.25744760438378e-18 0.00156123060494486 0.0359072212665768 0.000777304648532239 0.000114891754612327 0.00340596813240751 0.000327060952879306
+G[T>A]C 0.000126346023404813 0.000129543744927479 0.00745220659822295 0.00358728125037528 0.00289509453936029 0.000484560246366744 0.000222451427826069 0.0134367227794364 0.00210996422391121 2.20421759369717e-16 0.000374870912666693 0.00180182502377761 0.00012855476015994 0.0027189979628774 0.000584707144634046 0.000605825851122446 0.00337253100285632 0.00193869704329636 7.76506022348499e-05 0.00255738601617242 0.00324414939740277 0.0101647410678499 0.000140260319791196 0.00234217405872419 0.00581584728253081 0.00114422450292515 0.000117137723770792 0.000785248949096863 0.000181337693809127
+G[T>A]G 0.000242932687993135 6.36128439391058e-05 0.0116525307841752 0.0131617368574235 0.00412278383242369 0.000194828512577401 0.000290378300035954 0.0156553639414538 0.000790759520378531 7.27530898697516e-05 0.000119943417377965 0.00251933976702705 4.68620895156323e-05 0.000120505387176107 0.000187173212165083 0.00557591553253315 0.000695089646217959 0.00183444800825451 0.00048908065122771 0.00214543274809031 0.000744502451702263 0.0376796098478996 4.72750093431439e-18 0.00250224386182608 0.0382912436554116 0.000609952427170116 7.17650365039881e-05 0.00367274204917463 9.90541319368099e-05
+G[T>A]T 0.000257267500406029 6.32263555982741e-05 0.0124761834984729 0.00560009453413295 0.00326151204421666 0.000250198070942701 0.000309386927499133 0.0284747068870532 0.00259401539779767 0.000428699082788376 0.000166912044798336 0.000927360272458488 0.000360430214687028 0.000869001269360813 0.000848976649800963 0.000979974335224901 0.00484743087611687 0.00350223101019034 0.000287570955616168 0.0043733892200774 0.000949327781446514 0.00945595538417047 5.89559960696741e-18 0.00132927841802348 0.0204456937354964 0.00084483677046417 0.000327456139280693 0.00108419522957727 0.000193750762896379
+G[T>C]A 0.0010260706517501 2.20022003325224e-16 0.00992041703265284 0.00288321497036462 0.0139960335024143 0.00254090334636889 0.000100074781978629 0.00258195718342201 0.00945349238148439 0.00216964351113353 0.0008068914190628 0.0706187034160653 0.000283167108680238 0.010930877312925 0.0127770006129178 0.00204798863257202 0.000121730174520523 0.000702303275295736 0.000950013344207623 0.00275094243353302 0.221413556713498 0.000716881730337696 0.000217911114657455 0.00367933327279999 0.0173584633194777 0.0828926413185722 0.00048630906478149 0.00107243311457729 0.00092948933417067
+G[T>C]C 0.00186091042224142 2.70954092443735e-05 0.00561904347780447 0.0011758310765119 0.00789933011770473 0.00109992203163003 7.35877267942486e-05 0.00260771953200914 0.00973370288200549 0.00620739304413374 0.000859703959715617 0.0302626965319554 0.000179976664223916 0.0065136434715085 0.0115154548009422 0.00118574467571663 0.0147796211595762 0.00224690016299988 0.000370287576209888 0.00225769234240221 0.0659776395852161 0.00123571362001313 0.000418777240519429 0.00363784481461417 0.00402635581098287 0.024675450150038 0.000582710541130975 0.00357293248068154 0.00055298033002234
+G[T>C]G 0.0011554115648454 0.000106686117578124 0.0109493608230612 0.00238116918718272 0.0150466563227142 0.002447845414434 7.25945750089884e-05 0.00281997260740288 0.00633209717460473 2.2224574028705e-16 0.00056544753906755 0.0416544224428775 0.000194427818203156 0.0110463271578099 0.00595551129616173 0.00429998531157511 0.00357046048488937 0.00398967381030214 0.000959040865473267 0.0040894164118529 0.117394591440922 0.000583782755243459 4.72750093431439e-18 0.00268312896027134 0.013432006936715 0.071428639497553 0.000731663063938847 0.00300040948826014 0.000503307506088659
+G[T>C]T 7.10975689106584e-05 1.25848637735419e-05 0.0103461033889776 0.000765954958925793 0.0138766195670087 0.000914030049492286 0.000819976464711755 0.00637387566973541 0.00999101243058008 0.00532351677922656 0.00024120825986101 0.046925443294894 2.23507004638325e-16 0.0113568427267691 0.00592262281884958 0.00243471884527925 0.00529177870642758 0.0031884473069652 0.00239811821644578 0.000943838417728331 0.134749834506282 0.000846165964634997 0.000814979945669026 0.00404871823504863 0.0143727153982202 0.0559172538724487 0.000860077699160089 0.00157056318303249 0.000451408845491563
+G[T>G]A 2.17917862228831e-16 0.000206208962757721 0.00439361155153563 0.00059453881113036 0.00250141875362299 4.3007508002742e-05 8.97700519531063e-05 0.00130090919626263 0.0082420154166303 0.000201185125577837 9.54505671252287e-05 0.000409211052143725 8.65287645688391e-05 7.74104856978961e-05 0.000201064428249792 0.00089674065367959 0.000489889726728934 0.000862999787439676 0.000633342229471749 2.21271456610266e-16 0.000283965368699823 0.00158091810157688 6.25744760438378e-18 0.00106402340591783 0.00550511265274866 0.00136003495337058 0.00114891754612327 4.45854137449264e-05 0.000186891973073888
+G[T>G]C 2.18412117978862e-16 0.000131521512025609 0.00233130527270611 0.000252106154540262 0.00170124112106739 0.00021106611958306 0.000120163494495332 0.000652925195800761 0.00582230693862292 0.000823369172892262 2.21923580298682e-16 0.000212037972411398 2.19531975042359e-16 0.00209153689452107 0.000575772740047108 0.00089777811161402 0.000202351860171379 3.67855336420335e-05 0.000701650043330328 6.64320976857288e-05 0.000530408475096834 0.000235184205099273 8.70615842132499e-05 0.00152490481270129 0 0.00120392317264299 0.00191589666845449 9.1264041358913e-05 0.000351715417113308
+G[T>G]G 0.000343660875697606 3.69911678705458e-05 0.0109493608230612 0.0024414519514152 0.00531648523402569 0.00027375903818568 0.000325423956936844 0.00398408941330585 0.00398390265977509 2.2224574028705e-16 0.000131030624026348 0.00049784562726909 0.000424750002843816 0.000784289228204497 0.000347321415087079 0.00067815188909187 0.000835107704448914 0.00584417043066872 0.000513232782152536 8.76303516825622e-05 0.000213718358777064 0.000452155318174796 0.000158593514249436 0.00314539087852033 0.00871075673731746 0.00235754638791081 0.00313283911098302 0.000772680704334551 0.00138635600479511
+G[T>G]T 1.45585484725892e-05 2.24513969719987e-16 0.00591350811350385 0.000255656489601722 0.00238029605711464 0.000793975329967362 0.000844242106084236 0.00130720184641632 0.0196577729364354 0.00222400228394909 0.00015673448109112 0.000167228901590875 2.90961821353495e-06 0.00228150858350272 0.00140485421812302 0.00242457418342393 0.00731154157147627 0.00216611975774778 0.000346507759240682 0.0036207594473199 0.00262407572459602 1.988591475641e-05 5.89559960696741e-18 0.00271943981702514 0.00280369166570916 0.00612861206391874 0.0208197421888341 0.00116525655515314 0.000162304303996966
+T[C>A]A 6.506497550281e-05 0.000637963041647135 0.00845919028028641 0.040040132747806 0.0078948124438419 0.000356154495115312 0.000391022093072092 0.0299450720527654 0.0170819584732253 0.0938052110346799 0.000181665513453229 0.00349754082855578 0.0788717380408331 0.000348919482513261 0.0172385630822092 0.0108646936994442 0.000190274305032279 0.0740766285648105 0.00139057311147815 0.00172465384483994 0.001466849682889 0.000788790589583101 0.00215444743386719 0.0299858992926758 0.00696572152109804 0.000942249143754519 0.0143317861882612 0.0454169855156073 0.000700124780608385
+T[C>A]C 0.00249718027421162 0.000169414891007159 0.016867475091287 0.0470970035386436 0.00919383285851163 0.00049730837414768 0.000636504974589714 0.0251762369482197 0.00246735616605835 0.00993121232576557 0.000944954334462 0.00288924276387019 0.0292987874938127 0.0243898997939911 0.00581241674741198 0.00589440306962073 2.5890134404874e-05 0.0436836916732799 0.00113658306834887 0.00339268648640506 0.000236675201748481 0.00174744253930744 0.000670397483955859 0.0521286129615447 0.0102191507752106 0.000631700848231911 0.000452179339655883 0.0412220598749574 0.000243994749606079
+T[C>A]G 2.23914876101514e-16 8.64769572871816e-05 0.00144015295005676 0.0111351389815758 0.00234586931440499 0.000203177276829163 3.5022878628519e-05 0.00193873926790096 0.000454051859720809 0.00117547611223964 2.27514807541004e-16 0.000515384833945259 0.012266944423306 7.22912459698431e-06 7.82628506836997e-05 0.00152207729457011 2.2575440092516e-16 0.0129444998484509 0.000291619330489473 2.2736076008153e-16 6.96803248449787e-05 2.26806418126163e-16 9.36715797567612e-05 0.0100032290512064 0 0.000125465618537268 0.000131283667559097 0.0177535752847651 8.43728976999751e-05
+T[C>A]T 5.83920556565815e-06 0.000441166370976711 0.0100712416848926 0.04172703727096 0.012810853164459 0.000750523154758313 0.000617237388477755 0.0321925102694674 0.0275490386880618 0.67147365110273 4.79420044428837e-05 0.00237195514914897 0.0355940769058342 0.152485221068715 0.00810258428624253 0.00934524143409597 0.000289650373401285 0.122981486612632 0.00139652556062946 0.00091564962639986 2.23996272572608e-16 0.000400125201180533 0.000243793769296718 0.023040437561744 0.0247968666317603 0.00141236195465111 0.000560627684109871 0.041474079305438 0.000671804512708742
+T[C>G]A 2.20508959530801e-16 2.22638119385464e-16 0.0133777920009285 0.00360159988033029 0.0078445909906368 4.97215685596377e-05 2.23584427577119e-16 0.00147715623884447 0.00270296872311623 5.53849916215398e-05 1.57443444992799e-05 0.00097388421346855 0.316485328594229 1.98089735029142e-05 0.000214479796487952 0.00252503529496343 0.00375541391511077 0.0021480214787086 0.00176340793122229 0.000130105465487925 0.000657068282609183 0.00358175318739266 0.000213421788049755 0.00377339336736691 0.00983632145630559 0.00131593430524351 0.000115255623192311 0.000107513660401991 0.000127752653932852
+T[C>G]C 0.000200366638602751 9.83602926023915e-05 0.0203815324019718 0.00597499298624583 0.00761975242363014 0.000112843064816642 5.09404138468812e-05 0.0013440700203432 0.00200598062281167 2.22132432161055e-16 0.00022566073658794 0.00155497440416625 0.0632813947570443 0.000150554936999945 6.12254569606907e-05 0.00525174242829923 0.000722724601340692 0.00464890663678942 0.00313817625951194 2.83898394411343e-05 0.000632805306369882 0.0015265015285904 0.000268562847488341 0.00560457919702156 0.00327613951322927 0.000747011320528213 0.000136053960604425 0.00685028391596007 0.000990036309101209
+T[C>G]G 6.96847192889911e-05 4.17684717494946e-05 0.000531120236900364 0.00186947746204437 0.0017441028381011 1.98097844908434e-06 6.46497904915974e-06 7.97944267104501e-05 0.000412217868151026 2.25975149163311e-16 2.27514807541004e-16 0.000218400701909476 0.0139903994249275 1.86854491701713e-05 5.94349867350853e-05 0.000448450961286094 0.000386426452034058 0.00091630750895727 0.00045124254296792 0.000126994298423918 6.39671503335311e-05 0.000389248852730038 2.62937767738276e-18 0.00137940339316942 0.00209957099953792 9.59862984094057e-05 2.5035490092665e-05 0.000915227415542201 0.00010827514716946
+T[C>G]T 0.00154917698680726 0.00118312799489209 0.023738633861081 0.00341494881297445 0.0126091074453337 0.000128603699878265 0.000282942424408236 0.000251283230630012 0.00568135852797758 5.46198716195504e-05 0.000187511011034534 0.00307849498081038 0.369977869809939 0.000324157324258659 0.000175136604447975 0.0287934465807281 0.000284621721085291 0.00320558301170631 0.00162927982073437 0.00113443316545115 0.00069317765431253 0.000392041863782947 0.000473366235384462 0.00411292021387271 0.0165312444211735 0.00222951422841352 0.000143931344394454 0.000339058166584603 0.000110115326143237
+T[C>T]A 0.00109760065057932 0.535130188298692 0.00579369037032696 0.00376256523811042 0.020389910001271 0.0120052077005162 0.238623738849123 0.00506453567603817 0.00429058604003952 0.000365241566369073 0.00987049289762546 0.00554782338322641 0.00691874866611359 0.0035595820406252 0.0265594140510781 0.00639809740078382 0.000532768054090381 0.0114427312417187 0.0442363475318049 0.00813915586424462 0.00361688962904137 0.00159971560897593 0.0154756083277784 0.00241497175511482 0.0111411396086727 0.00330490371316884 0.00485075840218073 0.0064206756071843 0.098580788074169
+T[C>T]C 3.68161360585349e-05 0.0969651111470385 0.0133534177806022 0.00701936150821149 0.0230597770715122 0.0104854175272101 0.331262809102509 0.000252765406810811 0.00735191898260476 0.00274926238907853 0.159171412414708 0.00264847253354768 0.00446457714191431 0.00013750684245995 0.0095639766101994 0.00369529868759868 9.05654894626094e-05 0.0114218826852154 0.0251456431050637 0.00925186611574555 8.09308846656884e-05 0.0013256460643022 0.0440200757537281 0.012253739463022 0.00646211004903022 0.00253683039051862 0.00413163865659026 3.62072107417509e-18 0.134548545050266
+T[C>T]G 0.110451284175635 0.0448098653234869 0.00101014983518165 0.000287061839800255 0.0162170965647997 0.0528260919755823 0.0754417240224782 4.25502249849842e-05 0.0033263125004266 0.00282722271823155 3.01303393770519e-07 9.03199164438721e-05 0.00120641850113505 0.00543205407570007 0.0215757143627365 0.00308501572456493 0.0001799933737106 0.012027173087537 0.00442033511478779 0.00270374957934791 0.000323406485737309 3.85162250601639e-05 0.00294777888050334 0.00274858898342648 0.0143708500453809 0.00268272013620337 0.00177080295777387 0.0146926140287711 0.0150155156923684
+T[C>T]T 2.21452864139757e-16 0.300795252938667 0.00825296334659709 0.00729465397327677 0.0211833005081606 0.00702296767303963 0.107739642034453 0.00531832379686813 0.00550980773761236 0.022850148127078 0.120615190881674 0.00617717681395393 0.00142376307623337 0.000362531088501118 0.00175136604447975 0.022327549804705 0.000349994201193219 0.00378016864588009 0.0636532302634731 5.06443377433551e-05 7.37573311939531e-05 2.24312612783026e-16 0.0267157338854321 0.00475966933841289 0.0124992335867409 0.00214880783100489 0.00200296066674801 0.00431895521720863 0.0530371983717428
+T[T>A]A 0.0065253612191273 0.000413733817388 0.00643024757567479 0.00877282184314081 0.00622389901853831 0.000446023963298285 0.000350510146653627 0.0113480396930534 0.0256552349256455 0.00199913989547118 0.000184343079106361 0.00370108214431743 0.00029020169081303 0.000197487516363174 0.00107278581156196 0.01215102041542 0.000117027361175677 0.0106454128609929 0.000488827463385557 0.0118850492057889 0.000253559441412713 0.0709388281187948 7.71775921775898e-18 0.00407110156831556 0.0214870620857536 0.00111469297487924 0.000185027397259894 0.000753853814099974 0.000278566716929665
+T[T>A]C 2.23458694616433e-16 0.000194252630197133 0.0107026941471358 0.00439400679420254 0.00421396214023788 0.000115575106095981 0.000395236739337946 0.0198570498946921 0.00188378565808845 0.000364059718848336 0.000206596220576125 0.00656922717834412 0.000234721743345091 0.0017628398742663 0.000159456888467747 0.00476081855088227 0.00578458778890884 0.00277688893997694 0.000485042024679598 0.000325015421350811 0.000809414353469721 0.024061831345353 5.40179292099938e-18 0.0033344144860323 0.00346842281204361 0.00128263910220536 0.00126953685575951 0.00196520652192813 0.000245671212859929
+T[T>A]G 2.77413168349881e-05 5.01164213447466e-05 0.00676243311328127 0.00961631044803802 0.00482061500777009 2.95704621589026e-05 2.24021250029031e-16 0.0129881253907799 0.0168132966507811 0.000692915075108917 0.000203256155633775 0.00278940119221799 0.000188061472942725 0.000359676136997044 0.000149625821581235 0.00522120993197726 0.00183622246876959 0.00180021983072328 0.000376592127501802 0.000177855034227178 9.91554637678174e-05 0.0737911711696773 0.000187488956244335 0.00200632624642849 0.0102578058167269 0.000279804937026675 0.000322342061830407 0.000930249629541836 0.000191499425344798
+T[T>A]T 0.00222100529801663 0.000204312163335997 0.0130533460040592 0.00564409677378196 0.0087735028880773 0.00042544530033313 0.000798702934054665 0.0380184150597998 0.0170523155725394 0.00526987704693399 0.000679055985310023 0.00526730603298707 6.17919226981037e-05 0.00182689182455662 0.000475238837186997 0.0071903901086876 0.00197941762563075 0.00711424626391767 0.000676979479671814 0.00675575747023961 7.66252339497848e-05 0.0302313717024711 7.39116809280727e-18 0.00219983763776419 0.0145284853310333 0.00131365071990518 0.00572276630184896 0.00120366828009243 0.00070393073433441
+T[T>C]A 0.000247614153404384 2.18631851368541e-16 0.0150137885023436 0.00238091223445601 0.017754387057637 0.00145399882308692 0.00211684498681263 0.00205251500535226 0.0138143572676553 0.000715378492006843 0.00011199337601623 0.0849768460335281 2.16670856992161e-05 0.00619123363798551 0.00336598850967147 0.0128425419024765 0.00205535449459803 0.00177423547683216 0.00122701630485444 0.0136678065866573 0.0830727819725698 0.00457446760710334 7.71775921775898e-18 0.00144267191498561 0.0142918532221755 0.041727002510966 0.00128928665111947 0.00255560389858499 0.000537376929112546
+T[T>C]C 0.00339697298094039 4.40103615290382e-05 0.00916354479835724 0.000512804041179555 0.00988347158978499 0.0011050602249528 0.000605555518368679 0.00268833906266601 0.0138483702432448 0.00522830207346082 0.00047762591588639 0.0471558478073384 2.51921181435033e-05 0.00293466984848956 0.0060126419091023 0.00374137132371262 0.0155270514333869 0.00628614419379396 0.00056469103083751 0.0169662138189417 0.0557935931699882 2.26344345706286e-16 0.000194751547436411 0.00305909585874523 0.00753695396986603 0.0319641808009909 0.00208204044344561 0.00152736258180943 0.000291543431028795
+T[T>C]G 0.000412156707262679 0.000117038349248211 0.00698415223174951 0.00175391825781825 0.0127811713149645 0.00213508760672754 0.000320460891297134 2.23516576492492e-16 0.00937316118675277 0.000362955515533242 0.000156739821508632 0.0402801616204763 9.98326329770421e-05 0.00434230854469821 0.00132554419118947 0.00728751888189104 0.00235799060197187 0.00327861265260217 0.00109040079812854 0.0121264796063986 0.0277836629440787 0.00122985285282796 0.000306063052896157 0.00204665441218585 0.00491771278860734 0.0304967251507491 0.00141589503794665 0.000381563430299087 0.000204602017605231
+T[T>C]T 0.00427420130684977 3.56798802313596e-05 0.0139570391889557 0.000638726965858598 0.0185496918205062 0.00173773432530434 0.000812715266231062 0.00458427854415 0.0385181716462065 0.00323763712713336 0.000106795154959736 0.0598967943179672 0.000529217918591825 0.00293105721302489 0.00135067880042621 0.00842561075585042 0.0209938233021443 0.00337676195907078 0.0014786921769949 0.0194316123957711 0.0408199871957622 2.22968920862079e-16 7.39116809280727e-18 0.00368648590438109 0.0170333965950045 0.0575599628416469 0.00206099625556099 0.000824512771863318 0.000446860451895595
+T[T>G]A 2.16541004741874e-16 1.63728785554019e-05 0.00716118201592046 0.000372449756178388 0.00514877224671474 0.000103155321908193 0.000126026120145124 2.19066505378943e-16 0.0648288051774966 0.00263612074451836 8.43419141502759e-05 0.00160873703872998 0.000180395645640532 9.79538081161343e-05 0.00022735185547781 0.00966154306201693 2.18319951100843e-16 0.000686037717708436 0.00164261860165997 2.19873410307095e-16 0.000458774864812886 0.00499931017104599 0.000184749448456007 0.000121540168180294 0.00205014170359484 0.00141062916290027 0.041631164383476 0.000460798077466869 0.00011656337800603
+T[T>G]C 5.52133366518629e-05 7.12259644056158e-05 0.00640123040419171 0.000177391457584975 0.00667719604829963 0.000290965398680233 0.000117859798877126 0.00116087368615123 0.00877742290417431 2.25514770286608e-16 6.88313150731349e-05 0.00115088786225254 2.24604426821595e-16 0.00122277910353731 0.000298600797512851 0.00561715422170478 0.00011772143570411 0.00213606841536688 0.00206270503126902 2.2689755830151e-16 0.000385871748383677 0.000766715981851926 5.40179292099938e-18 0.00269200435569581 0.000588919885094795 0.00175090417126447 0.0362579726004918 0.000101111402915784 9.82684851439715e-05
+T[T>G]G 0.000577613846957072 9.54312693870027e-05 0.00811290410758782 0.00233855767709101 0.00698435660833494 0.00032477388947405 2.24021250029031e-16 0.00311110910523333 0.0109739481133841 2.15973529904078e-05 0.000102133690144334 0.00088112853544792 3.67120003031808e-05 0.000114854564755359 0.000148621621436395 0.00528168726709669 0.000923128235665583 0.00145827863382612 0.00208993486307971 0.00281940650848766 0.000131871733538925 0.00561498392643583 0.000184448594791724 0.00306494059755911 0.00948344204428778 0.00285843892502071 0.0140585322916688 0.000181217460300358 0.000819415962133265
+T[T>G]T 2.20126302870092e-16 2.22251767921597e-16 0.0105430871571248 0.000570435403471201 0.0135362615987478 0.001008684866987 8.29730241016687e-05 0.000999111910278643 0.0640966450050156 0.0188281051393293 5.5916331134579e-05 0.00221728501579075 1.88365699837768e-05 0.000607290963657555 0.00599301186263181 0.0158670619716849 0.00457865289161051 0.00517035362279086 0.00425501218278124 0.00152029713562769 2.22654475613249e-16 0.000597596882490708 7.39116809280727e-18 0.00397778860527223 0.00788546065898152 0.0094763353458809 0.47923165359889 0.000930836803271484 0.00892716723000414
diff -r 8c6ee1c2248f -r 8d9f31389f33 test-data/user_output.pdf
Binary file test-data/user_output.pdf has changed