annotate mutational_patterns.R @ 4:7ba08c826888 draft

"planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e2d6ed12516e1bd24071962a0dfe0220cc348f3c"
author artbio
date Mon, 05 Oct 2020 19:29:42 +0000
parents e332cf9dfa06
children fe31d059a482
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924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
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1 # load packages that are provided in the conda env
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
artbio
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2 options( show.error.messages=F,
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
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3 error = function () { cat( geterrmessage(), file=stderr() ); q( "no", 1, F ) } )
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
artbio
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4 loc <- Sys.setlocale("LC_MESSAGES", "en_US.UTF-8")
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
artbio
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5 warnings()
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
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6 library(optparse)
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
artbio
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7 library(rjson)
2
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
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8 library(grid)
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
artbio
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9 library(gridExtra)
4
7ba08c826888 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e2d6ed12516e1bd24071962a0dfe0220cc348f3c"
artbio
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10 library(scales)
7ba08c826888 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e2d6ed12516e1bd24071962a0dfe0220cc348f3c"
artbio
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11 library(RColorBrewer)
0
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
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12
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
artbio
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13 # Arguments
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
artbio
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14 option_list = list(
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
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15 make_option(
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
artbio
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16 "--inputs",
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
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17 default = NA,
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
artbio
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18 type = 'character',
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
artbio
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19 help = "json formatted dictionary of datasets and their paths"
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
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20 ),
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
artbio
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21 make_option(
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
artbio
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22 "--genome",
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
artbio
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23 default = NA,
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
artbio
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24 type = 'character',
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
artbio
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25 help = "genome name in the BSgenome bioconductor package"
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
artbio
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26 ),
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
artbio
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27 make_option(
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
artbio
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28 "--levels",
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
artbio
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29 default = NA,
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
artbio
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30 type = 'character',
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
artbio
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31 help = "path to the tab separated file describing the levels in function of datasets"
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
artbio
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32 ),
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
artbio
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33 make_option(
3
e332cf9dfa06 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit 0f7593f703ba0dfd12aea1c0460e371f08b57d2f"
artbio
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34 "--cosmic_version",
e332cf9dfa06 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit 0f7593f703ba0dfd12aea1c0460e371f08b57d2f"
artbio
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35 default = "v2",
e332cf9dfa06 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit 0f7593f703ba0dfd12aea1c0460e371f08b57d2f"
artbio
parents: 2
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36 type = 'character',
e332cf9dfa06 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit 0f7593f703ba0dfd12aea1c0460e371f08b57d2f"
artbio
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37 help = "Version of the Cosmic Signature set to be used to express mutational patterns"
e332cf9dfa06 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit 0f7593f703ba0dfd12aea1c0460e371f08b57d2f"
artbio
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38 ),
e332cf9dfa06 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit 0f7593f703ba0dfd12aea1c0460e371f08b57d2f"
artbio
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39 make_option(
0
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
artbio
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40 "--signum",
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
artbio
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41 default = 2,
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
artbio
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42 type = 'integer',
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
artbio
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43 help = "selects the N most significant signatures in samples to express mutational patterns"
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
artbio
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44 ),
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
artbio
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45 make_option(
2
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
artbio
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46 "--nrun",
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
artbio
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47 default = 2,
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
artbio
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48 type = 'integer',
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
artbio
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49 help = "Number of runs to fit signatures"
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
artbio
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50 ),
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
artbio
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51 make_option(
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
artbio
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52 "--rank",
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
artbio
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53 default = 2,
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
artbio
parents: 0
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54 type = 'integer',
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
artbio
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55 help = "number of ranks to display for parameter optimization"
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
artbio
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56 ),
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
artbio
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57 make_option(
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
artbio
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58 "--newsignum",
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
artbio
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59 default = 2,
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
artbio
parents: 0
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60 type = 'integer',
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
artbio
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61 help = "Number of new signatures to be captured"
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
artbio
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62 ),
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
artbio
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63 make_option(
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
artbio
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64 "--output_spectrum",
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
artbio
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65 default = NA,
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
artbio
parents: 0
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66 type = 'character',
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
artbio
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67 help = "path to output dataset"
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
artbio
parents: 0
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68 ),
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
artbio
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69 make_option(
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
artbio
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70 "--output_denovo",
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
artbio
parents: 0
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71 default = NA,
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
artbio
parents: 0
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72 type = 'character',
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
artbio
parents: 0
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73 help = "path to output dataset"
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
artbio
parents: 0
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74 ),
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
artbio
parents: 0
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75 make_option(
3
e332cf9dfa06 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit 0f7593f703ba0dfd12aea1c0460e371f08b57d2f"
artbio
parents: 2
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76 "--sigmatrix",
e332cf9dfa06 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit 0f7593f703ba0dfd12aea1c0460e371f08b57d2f"
artbio
parents: 2
diff changeset
77 default = NA,
e332cf9dfa06 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit 0f7593f703ba0dfd12aea1c0460e371f08b57d2f"
artbio
parents: 2
diff changeset
78 type = 'character',
e332cf9dfa06 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit 0f7593f703ba0dfd12aea1c0460e371f08b57d2f"
artbio
parents: 2
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79 help = "path to signature matrix"
e332cf9dfa06 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit 0f7593f703ba0dfd12aea1c0460e371f08b57d2f"
artbio
parents: 2
diff changeset
80 ),
e332cf9dfa06 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit 0f7593f703ba0dfd12aea1c0460e371f08b57d2f"
artbio
parents: 2
diff changeset
81 make_option(
2
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
artbio
parents: 0
diff changeset
82 "--output_cosmic",
0
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
artbio
parents:
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83 default = NA,
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
artbio
parents:
diff changeset
84 type = 'character',
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
artbio
parents:
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85 help = "path to output dataset"
3
e332cf9dfa06 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit 0f7593f703ba0dfd12aea1c0460e371f08b57d2f"
artbio
parents: 2
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86 ),
e332cf9dfa06 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit 0f7593f703ba0dfd12aea1c0460e371f08b57d2f"
artbio
parents: 2
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87 make_option(
e332cf9dfa06 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit 0f7593f703ba0dfd12aea1c0460e371f08b57d2f"
artbio
parents: 2
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88 c("-r", "--rdata"),
e332cf9dfa06 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit 0f7593f703ba0dfd12aea1c0460e371f08b57d2f"
artbio
parents: 2
diff changeset
89 type="character",
e332cf9dfa06 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit 0f7593f703ba0dfd12aea1c0460e371f08b57d2f"
artbio
parents: 2
diff changeset
90 default=NULL,
e332cf9dfa06 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit 0f7593f703ba0dfd12aea1c0460e371f08b57d2f"
artbio
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diff changeset
91 help="Path to RData output file")
0
924c527fb379 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit e1f3ca871f13569401f41a5af9d0e281bf372540"
artbio
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92 )
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93
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94 opt = parse_args(OptionParser(option_list = option_list),
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95 args = commandArgs(trailingOnly = TRUE))
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96
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97 ################ Manage input data ####################
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98 json_dict <- opt$inputs
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99 parser <- newJSONParser()
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100 parser$addData(json_dict)
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101 fileslist <- parser$getObject()
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102 vcf_paths <- attr(fileslist, "names")
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103 element_identifiers <- unname(unlist(fileslist))
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104 ref_genome <- opt$genome
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105 vcf_table <- data.frame(element_identifier=element_identifiers, path=vcf_paths)
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106
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107 library(MutationalPatterns)
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108 library(ref_genome, character.only = TRUE)
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109 library(ggplot2)
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110
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111 # Load the VCF files into a GRangesList:
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112 vcfs <- read_vcfs_as_granges(vcf_paths, element_identifiers, ref_genome)
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113 if (!is.na(opt$levels)[1]) { # manage levels if there are
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114 levels_table <- read.delim(opt$levels, header=FALSE, col.names=c("element_identifier","level"))
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115 library(plyr)
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116 metadata_table <- join(vcf_table, levels_table, by = "element_identifier")
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117 tissue <- as.vector(metadata_table$level)
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118 }
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119
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120 ##### This is done for any section ######
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121 mut_mat <- mut_matrix(vcf_list = vcfs, ref_genome = ref_genome)
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122 qual_col_pals = brewer.pal.info[brewer.pal.info$category == 'qual',]
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123 col_vector = unique(unlist(mapply(brewer.pal, qual_col_pals$maxcolors, rownames(qual_col_pals))))
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124 col_vector <- col_vector[c(-32, -34, -39)] # 67-color palette
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125
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126 ###### Section 1 Mutation characteristics and spectrums #############
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127 if (!is.na(opt$output_spectrum)[1]) {
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128 pdf(opt$output_spectrum, paper = "special", width = 11.69, height = 11.69)
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129 type_occurrences <- mut_type_occurrences(vcfs, ref_genome)
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130
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131 # mutation spectrum, total or by sample
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132
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133 if (is.na(opt$levels)[1]) {
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134 p1 <- plot_spectrum(type_occurrences, CT = TRUE, legend=TRUE)
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135 plot(p1)
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136 } else {
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137 p2 <- plot_spectrum(type_occurrences, by = tissue, CT=TRUE) # by levels
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138 p3 <- plot_spectrum(type_occurrences, CT=TRUE, legend=TRUE) # total
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139 grid.arrange(p2, p3, ncol=2, widths=c(4,2.3), heights=c(4,1))
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140 }
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141 plot_96_profile(mut_mat, condensed = TRUE)
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142 dev.off()
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143 }
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144
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145 ###### Section 2: De novo mutational signature extraction using NMF #######
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146 if (!is.na(opt$output_denovo)[1]) {
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147 # opt$rank cannot be higher than the number of samples
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148 if (opt$rank > length(element_identifiers)) {opt$rank <-length(element_identifiers)}
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149 # likewise, opt$signum cannot be higher thant the number of samples
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150 if (opt$signum > length(element_identifiers)) {opt$signum <-length(element_identifiers)}
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151 pseudo_mut_mat <- mut_mat + 0.0001 # First add a small pseudocount to the mutation count matrix
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152 # Use the NMF package to generate an estimate rank plot
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153 library("NMF")
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154 estimate <- nmf(pseudo_mut_mat, rank=1:opt$rank, method="brunet", nrun=opt$nrun, seed=123456)
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155 # And plot it
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156 pdf(opt$output_denovo, paper = "special", width = 11.69, height = 11.69)
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157 p4 <- plot(estimate)
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158 grid.arrange(p4)
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159 # Extract 4 (PARAMETIZE) mutational signatures from the mutation count matrix with extract_signatures
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160 # (For larger datasets it is wise to perform more iterations by changing the nrun parameter
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161 # to achieve stability and avoid local minima)
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162 nmf_res <- extract_signatures(pseudo_mut_mat, rank=opt$newsignum, nrun=opt$nrun)
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163 # Assign signature names
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164 colnames(nmf_res$signatures) <- paste0("NewSig_", 1:opt$newsignum)
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165 rownames(nmf_res$contribution) <- paste0("NewSig_", 1:opt$newsignum)
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166 # Plot the 96-profile of the signatures:
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167 p5 <- plot_96_profile(nmf_res$signatures, condensed = TRUE)
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168 new_sig_matrix <- reshape2::dcast(p5$data, substitution + context ~ variable, value.var = "value")
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169 new_sig_matrix = format(new_sig_matrix, scientific=TRUE)
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170 write.table(new_sig_matrix, file=opt$sigmatrix, quote = FALSE, row.names = FALSE, sep="\t")
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171 grid.arrange(p5)
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172 # Visualize the contribution of the signatures in a barplot
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173 pc1 <- plot_contribution(nmf_res$contribution, nmf_res$signature, mode="relative", coord_flip = TRUE)
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174 # Visualize the contribution of the signatures in absolute number of mutations
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175 pc2 <- plot_contribution(nmf_res$contribution, nmf_res$signature, mode="absolute", coord_flip = TRUE)
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176 # Combine the two plots:
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177 grid.arrange(pc1, pc2)
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178
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179 # The relative contribution of each signature for each sample can also be plotted as a heatmap with
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180 # plot_contribution_heatmap, which might be easier to interpret and compare than stacked barplots.
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181 # The samples can be hierarchically clustered based on their euclidean dis- tance. The signatures
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182 # can be plotted in a user-specified order.
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183 # Plot signature contribution as a heatmap with sample clustering dendrogram and a specified signature order:
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184 pch1 <- plot_contribution_heatmap(nmf_res$contribution,
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185 sig_order = paste0("NewSig_", 1:opt$newsignum))
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186 # Plot signature contribution as a heatmap without sample clustering:
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187 pch2 <- plot_contribution_heatmap(nmf_res$contribution, cluster_samples=FALSE)
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188 #Combine the plots into one figure:
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189 grid.arrange(pch1, pch2, ncol = 2, widths = c(2,1.6))
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190
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191 # Compare the reconstructed mutational profile with the original mutational profile:
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192 plot_compare_profiles(pseudo_mut_mat[,1],
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193 nmf_res$reconstructed[,1],
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194 profile_names = c("Original", "Reconstructed"),
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195 condensed = TRUE)
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196 dev.off()
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197 }
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198 ##### Section 3: Find optimal contribution of known signatures: COSMIC mutational signatures ####
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199
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200 if (!is.na(opt$output_cosmic)[1]) {
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201 pdf(opt$output_cosmic, paper = "special", width = 11.69, height = 11.69)
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202 pseudo_mut_mat <- mut_mat + 0.0001 # First add a small psuedocount to the mutation count matrix
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203 if (opt$cosmic_version == "v2") {
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204 sp_url <- paste("https://cancer.sanger.ac.uk/cancergenome/assets/", "signatures_probabilities.txt", sep = "")
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205 cancer_signatures = read.table(sp_url, sep = "\t", header = TRUE)
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206 new_order = match(row.names(pseudo_mut_mat), cancer_signatures$Somatic.Mutation.Type)
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207 cancer_signatures = cancer_signatures[as.vector(new_order),]
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208 row.names(cancer_signatures) = cancer_signatures$Somatic.Mutation.Type
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209 cancer_signatures = as.matrix(cancer_signatures[,4:33])
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210 colnames(cancer_signatures) <- gsub("Signature.", "", colnames(cancer_signatures)) # shorten signature labels
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211 cosmic_tag <- "Signatures (Cosmic v2, March 2015)"
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212 cosmic_colors <- col_vector[1:30]
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213 } else {
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214 sp_url <- "https://raw.githubusercontent.com/ARTbio/startbio/master/sigProfiler_SBS_signatures_2019_05_22.tsv"
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215 cancer_signatures = read.table(sp_url, sep = "\t", header = TRUE)
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216 new_order = match(row.names(pseudo_mut_mat), cancer_signatures$Somatic.Mutation.Type)
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217 cancer_signatures = cancer_signatures[as.vector(new_order),]
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218 row.names(cancer_signatures) = cancer_signatures$Somatic.Mutation.Type
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219 cancer_signatures = as.matrix(cancer_signatures[,4:70])
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220 colnames(cancer_signatures) <- gsub("SBS", "", colnames(cancer_signatures)) # shorten signature labels
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221 cosmic_tag <- "Signatures (Cosmic v3, May 2019)"
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222 cosmic_colors <- col_vector[1:67]
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223 }
2
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224
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225 # Plot mutational profiles of the COSMIC signatures
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226 if (opt$cosmic_version == "v2") {
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227 p6 <- plot_96_profile(cancer_signatures, condensed = TRUE, ymax = 0.3)
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228 grid.arrange(p6, top = textGrob("COSMIC signature profiles",gp=gpar(fontsize=12,font=3)))
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229 } else {
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230 p6 <- plot_96_profile(cancer_signatures[,1:33], condensed = TRUE, ymax = 0.3)
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231 p6bis <- plot_96_profile(cancer_signatures[,34:67], condensed = TRUE, ymax = 0.3)
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232 grid.arrange(p6, top = textGrob("COSMIC signature profiles (on two pages)",gp=gpar(fontsize=12,font=3)))
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233 grid.arrange(p6bis, top = textGrob("COSMIC signature profiles (continued)",gp=gpar(fontsize=12,font=3)))
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234 }
2
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235
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236
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237 # Find optimal contribution of COSMIC signatures to reconstruct 96 mutational profiles
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238 fit_res <- fit_to_signatures(pseudo_mut_mat, cancer_signatures)
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239
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240 # Plot contribution barplots
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241 pc3 <- plot_contribution(fit_res$contribution, cancer_signatures, coord_flip = T, mode = "absolute")
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242 pc4 <- plot_contribution(fit_res$contribution, cancer_signatures, coord_flip = T, mode = "relative")
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243 pc3_data <- pc3$data
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244 pc3 <- ggplot(pc3_data, aes(x=Sample, y=Contribution, fill=as.factor(Signature))) +
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245 geom_bar(stat="identity", position='stack') +
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246 coord_flip() +
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247 scale_fill_manual(name = "Cosmic\nSignatures", values = cosmic_colors) +
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248 labs(x = "Samples", y = "Absolute contribution") + theme_bw() +
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249 theme(panel.grid.minor.x = element_blank(), panel.grid.major.x = element_blank(), legend.position="right")
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250 pc4_data <- pc4$data
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251 pc4 <- ggplot(pc4_data, aes(x=Sample, y=Contribution, fill=as.factor(Signature))) +
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252 geom_bar(stat="identity", position='fill') +
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253 coord_flip() +
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254 scale_fill_manual(name = "Cosmic\nSignatures", values = cosmic_colors) +
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255 scale_y_continuous(labels = scales::percent_format(accuracy = 1)) +
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256 labs(x = "Samples", y = "Relative contribution") + theme_bw() +
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257 theme(panel.grid.minor.x = element_blank(), panel.grid.major.x = element_blank(), legend.position="right")
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258 #####
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259 # ggplot2 alternative
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260 if (!is.na(opt$levels)[1]) { # if there are levels to display in graphs
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261 pc3_data <- pc3$data
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262 pc3_data <- merge (pc3_data, metadata_table[,c(1,3)], by.x="Sample", by.y="element_identifier")
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263 pc3 <- ggplot(pc3_data, aes(x=Sample, y=Contribution, fill=as.factor(Signature))) +
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264 geom_bar(stat="identity", position='stack') +
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265 scale_fill_manual(name = "Cosmic\nSignatures", values = cosmic_colors) +
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266 labs(x = "Samples", y = "Absolute contribution") + theme_bw() +
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267 theme(panel.grid.minor.x = element_blank(), panel.grid.major.x = element_blank(), legend.position="right") +
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268 facet_grid(~level, scales = "free_x")
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269 pc4_data <- pc4$data
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270 pc4_data <- merge (pc4_data, metadata_table[,c(1,3)], by.x="Sample", by.y="element_identifier")
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271 pc4 <- ggplot(pc4_data, aes(x=Sample, y=Contribution, fill=as.factor(Signature))) +
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272 geom_bar(stat="identity", position='fill') +
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273 scale_fill_manual(name = "Cosmic\nSignatures", values = cosmic_colors) +
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274 scale_y_continuous(labels = scales::percent_format(accuracy = 1)) +
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275 labs(x = "Samples", y = "Relative contribution") + theme_bw() +
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276 theme(panel.grid.minor.x = element_blank(), panel.grid.major.x = element_blank(), legend.position="right") +
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277 facet_grid(~level, scales = "free_x")
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278 }
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279 # Combine the two plots:
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280 grid.arrange(pc3, pc4, top = textGrob("Absolute and Relative Contributions of Cosmic signatures to mutational patterns",gp=gpar(fontsize=12,font=3)))
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281
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282 # Select signatures with some contribution (above a threshold)
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283 threshold <- tail(sort(unlist(rowSums(fit_res$contribution), use.names = FALSE)), opt$signum)[1]
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284 select <- which(rowSums(fit_res$contribution) >= threshold) # ensure opt$signum best signatures in samples are retained, the others discarded
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285
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286 ## pie charts of comic signatures contributions in samples
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287 sig_data_pie <- as.data.frame(t(head(fit_res$contribution[select,])))
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288 colnames(sig_data_pie) <- gsub("nature", "", colnames(sig_data_pie))
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289 sig_data_pie_percents <- sig_data_pie / (apply(sig_data_pie,1,sum)) * 100
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290 sig_data_pie_percents$sample <- rownames(sig_data_pie_percents)
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291 library(reshape2)
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292 melted_sig_data_pie_percents <-melt(data=sig_data_pie_percents)
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293 melted_sig_data_pie_percents$label <- sub("Sig.", "", melted_sig_data_pie_percents$variable)
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294 melted_sig_data_pie_percents$pos <- cumsum(melted_sig_data_pie_percents$value) - melted_sig_data_pie_percents$value/2
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295 p7 <- ggplot(melted_sig_data_pie_percents, aes(x="", y=value, group=variable, fill=variable)) +
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296 geom_bar(width = 1, stat = "identity") +
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297 geom_text(aes(label = label), position = position_stack(vjust = 0.5), color="black", size=3) +
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298 coord_polar("y", start=0) + facet_wrap(~ sample) +
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299 labs(x="", y="Samples", fill = cosmic_tag) +
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300 scale_fill_manual(name = paste0(length(select), " most contributing\nSignatures"), values = cosmic_colors[select])
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301 theme(axis.text = element_blank(),
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302 axis.ticks = element_blank(),
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303 panel.grid = element_blank())
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304 grid.arrange(p7)
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305
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306 # Plot relative contribution of the cancer signatures in each sample as a heatmap with sample clustering
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307 if (length(vcf_paths) > 1) {
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308 p8 <- plot_contribution_heatmap(fit_res$contribution, cluster_samples = TRUE, method = "complete")
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309 grid.arrange(p8)
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310 }
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311
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312 # calculate all pairwise cosine similarities
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313 cos_sim_ori_rec <- cos_sim_matrix(pseudo_mut_mat, fit_res$reconstructed)
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314 # extract cosine similarities per sample between original and reconstructed
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315 cos_sim_ori_rec <- as.data.frame(diag(cos_sim_ori_rec))
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316
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317 # We can use ggplot to make a barplot of the cosine similarities between the original and
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318 # reconstructed mutational profile of each sample. This clearly shows how well each mutational
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319 # profile can be reconstructed with the COSMIC mutational signatures. Two identical profiles
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320 # have a cosine similarity of 1. The lower the cosine similarity between original and
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321 # reconstructed, the less well the original mutational profile can be reconstructed with
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322 # the COSMIC signatures. You could use, for example, cosine similarity of 0.95 as a cutoff.
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323
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324 # Adjust data frame for plotting with gpplot
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325 colnames(cos_sim_ori_rec) = "cos_sim"
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326 cos_sim_ori_rec$sample = row.names(cos_sim_ori_rec)
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327 # Make barplot
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328 p9 <- ggplot(cos_sim_ori_rec, aes(y=cos_sim, x=sample)) +
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329 geom_bar(stat="identity", fill = "skyblue4") +
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330 coord_cartesian(ylim=c(0.8, 1)) +
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331 # coord_flip(ylim=c(0.8,1)) +
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332 ylab("Cosine similarity\n original VS reconstructed") +
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333 xlab("") +
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334 # Reverse order of the samples such that first is up
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335 # xlim(rev(levels(factor(cos_sim_ori_rec$sample)))) +
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336 theme_bw() +
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337 theme(panel.grid.minor.y=element_blank(),
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
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338 panel.grid.major.y=element_blank()) +
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
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339 # Add cut.off line
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
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340 geom_hline(aes(yintercept=.95))
3
e332cf9dfa06 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit 0f7593f703ba0dfd12aea1c0460e371f08b57d2f"
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341 grid.arrange(p9, top = textGrob("Similarity between true and reconstructed profiles (with all Cosmic sig.)",gp=gpar(fontsize=12,font=3)))
2
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
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342 dev.off()
aea952be68cb "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit cd8f633245d53cf47eaf860a4e0ae8d806c34419"
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343 }
3
e332cf9dfa06 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit 0f7593f703ba0dfd12aea1c0460e371f08b57d2f"
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344
e332cf9dfa06 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit 0f7593f703ba0dfd12aea1c0460e371f08b57d2f"
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345
e332cf9dfa06 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit 0f7593f703ba0dfd12aea1c0460e371f08b57d2f"
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346 # Output RData file
e332cf9dfa06 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit 0f7593f703ba0dfd12aea1c0460e371f08b57d2f"
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347 if (!is.null(opt$rdata)) {
e332cf9dfa06 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit 0f7593f703ba0dfd12aea1c0460e371f08b57d2f"
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348 save.image(file=opt$rdata)
e332cf9dfa06 "planemo upload for repository https://github.com/ARTbio/tools-artbio/tree/master/tools/mutational_patterns commit 0f7593f703ba0dfd12aea1c0460e371f08b57d2f"
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349 }