Class 18 - maryagarcia.files.wordpress.com · Title: Class 18 Created Date: 6/7/2019 4:17:42 PM

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Class18MaryGarcia5/30/2019##Exploring the Cancer genome Atlas

#Install the packages

#library(BiocManager)

#BiocManager::install(c("GenomicDataCommons", "TCGAbiolinks", "maftools"))

library(GenomicDataCommons)

## Loading required package: magrittr

## ## Attaching package: 'GenomicDataCommons'

## The following object is masked from 'package:stats': ## ## filter

library(TCGAbiolinks)

## Registered S3 methods overwritten by 'ggplot2': ## method from ## [.quosures rlang ## c.quosures rlang ## print.quosures rlang

## Registered S3 method overwritten by 'R.oo': ## method from ## throw.default R.methodsS3

library(maftools)

Can we talk with the NCI-GDC?

GenomicDataCommons::status()

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## $commit ## [1] "3e22a4257d5079ae9f7193950b51ed9dfc561ed1" ## ## $data_release ## [1] "Data Release 17.0 - June 05, 2019" ## ## $status ## [1] "OK" ## ## $tag ## [1] "1.21.0" ## ## $version ## [1] 1

Q9

cases_by_project % facet("project.project_id") %>% aggregations() head(cases_by_project)

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## $project.project_id ## key doc_count ## 1 FM-AD 18004 ## 2 TARGET-NBL 1120 ## 3 TCGA-BRCA 1098 ## 4 TARGET-AML 988 ## 5 TARGET-WT 652 ## 6 TCGA-GBM 617 ## 7 TCGA-OV 608 ## 8 TCGA-LUAD 585 ## 9 TCGA-UCEC 560 ## 10 TCGA-KIRC 537 ## 11 TCGA-HNSC 528 ## 12 TCGA-LGG 516 ## 13 TCGA-THCA 507 ## 14 TCGA-LUSC 504 ## 15 TCGA-PRAD 500 ## 16 NCICCR-DLBCL 489 ## 17 TCGA-SKCM 470 ## 18 TCGA-COAD 461 ## 19 TCGA-STAD 443 ## 20 TCGA-BLCA 412 ## 21 TARGET-OS 381 ## 22 TCGA-LIHC 377 ## 23 CPTAC-3 322 ## 24 TCGA-CESC 307 ## 25 TCGA-KIRP 291 ## 26 TCGA-SARC 261 ## 27 TCGA-LAML 200 ## 28 TCGA-ESCA 185 ## 29 TCGA-PAAD 185 ## 30 TCGA-PCPG 179 ## 31 TCGA-READ 172 ## 32 TCGA-TGCT 150 ## 33 TARGET-ALL-P3 131 ## 34 TCGA-THYM 124 ## 35 TCGA-KICH 113 ## 36 TCGA-ACC 92 ## 37 TCGA-MESO 87 ## 38 TCGA-UVM 80 ## 39 TARGET-RT 75 ## 40 TCGA-DLBC 58 ## 41 TCGA-UCS 57 ## 42 BEATAML1.0-CRENOLANIB 56 ## 43 TCGA-CHOL 51 ## 44 CTSP-DLBCL1 45 ## 45 TARGET-CCSK 13

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## 46 HCMI-CMDC 7 ## 47 VAREPOP-APOLLO 7

Make a summary plot for this data

x

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## For more information about MAF data please read the following GDC manual and web pages:

## GDC manual: https://gdc-docs.nci.nih.gov/Data/PDF/Data_UG.pdf

## https://gdc-docs.nci.nih.gov/Data/Bioinformatics_Pipelines/DNA_Seq_Variant_Calling_Pipeline/

## https://gdc.cancer.gov/about-gdc/variant-calling-gdc

## ============================================================================

## --------------------------------------

## o GDCquery: Searching in GDC database

## --------------------------------------

## Genome of reference: hg38

## --------------------------------------------

## oo Accessing GDC. This might take a while...

## --------------------------------------------

## ooo Project: TCGA-PAAD

## --------------------

## oo Filtering results

## --------------------

## ooo By access

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## ooo By data.type

## ooo By workflow.type

## ----------------

## oo Checking data

## ----------------

## ooo Check if there are duplicated cases

## ooo Check if there results for the query

## -------------------

## o Preparing output

## -------------------

## Downloading data for project TCGA-PAAD

## Of the 1 files for download 1 already exist.

## All samples have been already downloaded

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##PT 2

Lecture18 Investigating cancer genomics datasets (Part 2)

Identifing sites of mutation We start by 1. reading the provided sequences (lecture18_sequences.fa) intoR, then 2. aligning, 3. looking for sites of cancer specific mutation (i.e. differences between the twosequences), and finally 4. outputing all 9-mer contaning subsequences encompasing these mutant sites.

Which positions are different -> run alignment and identify non-identical sites Get the 9-mer around thesesites…

library(bio3d) seqs

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## 1 . . . . . 60 ## P53_wt MEEPQSDPSVEPPLSQETFSDLWKLLPENNVLSPLPSQAMDDLMLSPDDIEQWFTEDPGP ## P53_mutant MEEPQSDPSVEPPLSQETFSDLWKLLPENNVLSPLPSQAMLDLMLSPDDIEQWFTEDPGP ## **************************************** ******************* ## 1 . . . . . 60 ## ## 61 . . . . . 120 ## P53_wt DEAPRMPEAAPPVAPAPAAPTPAAPAPAPSWPLSSSVPSQKTYQGSYGFRLGFLHSGTAK ## P53_mutant DEAPWMPEAAPPVAPAPAAPTPAAPAPAPSWPLSSSVPSQKTYQGSYGFRLGFLHSGTAK ## **** ******************************************************* ## 61 . . . . . 120 ## ## 121 . . . . . 180 ## P53_wt SVTCTYSPALNKMFCQLAKTCPVQLWVDSTPPPGTRVRAMAIYKQSQHMTEVVRRCPHHE ## P53_mutant SVTCTYSPALNKMFCQLAKTCPVQLWVDSTPPPGTRVRAMAIYKQSQHMTEVVRRCPHHE ## ************************************************************ ## 121 . . . . . 180 ## ## 181 . . . . . 240 ## P53_wt RCSDSDGLAPPQHLIRVEGNLRVEYLDDRNTFRHSVVVPYEPPEVGSDCTTIHYNYMCNS ## P53_mutant RCSDSDGLAPPQHLIRVEGNLRVEYLDDRNTFVHSVVVPYEPPEVGSDCTTIHYNYMCNS ## ******************************** *************************** ## 181 . . . . . 240 ## ## 241 . . . . . 300 ## P53_wt SCMGGMNRRPILTIITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENLRKKGEPHHELP ## P53_mutant SCMGGMNRRPILTIITLEV----------------------------------------- ## ****************** ## 241 . . . . . 300 ## ## 301 . . . . . 360 ## P53_wt PGSTKRALPNNTSSSPQPKKKPLDGEYFTLQIRGRERFEMFRELNEALELKDAQAGKEPG ## P53_mutant ------------------------------------------------------------ ## ## 301 . . . . . 360 ## ## 361 . . . 393 ## P53_wt GSRAHSSHLKSKKGQSTSRHKKLMFKTEGPDSD ## P53_mutant --------------------------------- ## ## 361 . . . 393 ## ## Call: ## read.fasta(file = "lecture18_sequences.fa") ## ## Class: ## fasta ##

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## Alignment dimensions: ## 2 sequence rows; 393 position columns (259 non-gap, 134 gap) ## ## + attr: id, ali, call

seqs

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## $id ## [1] "P53_wt" "P53_mutant" ## ## $ali ## [,1] [,2] [,3] [,4] [,5] [,6] [,7] [,8] [,9] [,10] [,11] [,12] ## P53_wt "M" "E" "E" "P" "Q" "S" "D" "P" "S" "V" "E" "P" ## P53_mutant "M" "E" "E" "P" "Q" "S" "D" "P" "S" "V" "E" "P" ## [,13] [,14] [,15] [,16] [,17] [,18] [,19] [,20] [,21] [,22] ## P53_wt "P" "L" "S" "Q" "E" "T" "F" "S" "D" "L" ## P53_mutant "P" "L" "S" "Q" "E" "T" "F" "S" "D" "L" ## [,23] [,24] [,25] [,26] [,27] [,28] [,29] [,30] [,31] [,32] ## P53_wt "W" "K" "L" "L" "P" "E" "N" "N" "V" "L" ## P53_mutant "W" "K" "L" "L" "P" "E" "N" "N" "V" "L" ## [,33] [,34] [,35] [,36] [,37] [,38] [,39] [,40] [,41] [,42] ## P53_wt "S" "P" "L" "P" "S" "Q" "A" "M" "D" "D" ## P53_mutant "S" "P" "L" "P" "S" "Q" "A" "M" "L" "D" ## [,43] [,44] [,45] [,46] [,47] [,48] [,49] [,50] [,51] [,52] ## P53_wt "L" "M" "L" "S" "P" "D" "D" "I" "E" "Q" ## P53_mutant "L" "M" "L" "S" "P" "D" "D" "I" "E" "Q" ## [,53] [,54] [,55] [,56] [,57] [,58] [,59] [,60] [,61] [,62] ## P53_wt "W" "F" "T" "E" "D" "P" "G" "P" "D" "E" ## P53_mutant "W" "F" "T" "E" "D" "P" "G" "P" "D" "E" ## [,63] [,64] [,65] [,66] [,67] [,68] [,69] [,70] [,71] [,72] ## P53_wt "A" "P" "R" "M" "P" "E" "A" "A" "P" "P" ## P53_mutant "A" "P" "W" "M" "P" "E" "A" "A" "P" "P" ## [,73] [,74] [,75] [,76] [,77] [,78] [,79] [,80] [,81] [,82] ## P53_wt "V" "A" "P" "A" "P" "A" "A" "P" "T" "P" ## P53_mutant "V" "A" "P" "A" "P" "A" "A" "P" "T" "P" ## [,83] [,84] [,85] [,86] [,87] [,88] [,89] [,90] [,91] [,92] ## P53_wt "A" "A" "P" "A" "P" "A" "P" "S" "W" "P" ## P53_mutant "A" "A" "P" "A" "P" "A" "P" "S" "W" "P" ## [,93] [,94] [,95] [,96] [,97] [,98] [,99] [,100] [,101] [,102] ## P53_wt "L" "S" "S" "S" "V" "P" "S" "Q" "K" "T" ## P53_mutant "L" "S" "S" "S" "V" "P" "S" "Q" "K" "T" ## [,103] [,104] [,105] [,106] [,107] [,108] [,109] [,110] [,111] ## P53_wt "Y" "Q" "G" "S" "Y" "G" "F" "R" "L" ## P53_mutant "Y" "Q" "G" "S" "Y" "G" "F" "R" "L" ## [,112] [,113] [,114] [,115] [,116] [,117] [,118] [,119] [,120] ## P53_wt "G" "F" "L" "H" "S" "G" "T" "A" "K" ## P53_mutant "G" "F" "L" "H" "S" "G" "T" "A" "K" ## [,121] [,122] [,123] [,124] [,125] [,126] [,127] [,128] [,129] ## P53_wt "S" "V" "T" "C" "T" "Y" "S" "P" "A" ## P53_mutant "S" "V" "T" "C" "T" "Y" "S" "P" "A" ## [,130] [,131] [,132] [,133] [,134] [,135] [,136] [,137] [,138] ## P53_wt "L" "N" "K" "M" "F" "C" "Q" "L" "A" ## P53_mutant "L" "N" "K" "M" "F" "C" "Q" "L" "A" ## [,139] [,140] [,141] [,142] [,143] [,144] [,145] [,146] [,147] ## P53_wt "K" "T" "C" "P" "V" "Q" "L" "W" "V"

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## P53_mutant "K" "T" "C" "P" "V" "Q" "L" "W" "V" ## [,148] [,149] [,150] [,151] [,152] [,153] [,154] [,155] [,156] ## P53_wt "D" "S" "T" "P" "P" "P" "G" "T" "R" ## P53_mutant "D" "S" "T" "P" "P" "P" "G" "T" "R" ## [,157] [,158] [,159] [,160] [,161] [,162] [,163] [,164] [,165] ## P53_wt "V" "R" "A" "M" "A" "I" "Y" "K" "Q" ## P53_mutant "V" "R" "A" "M" "A" "I" "Y" "K" "Q" ## [,166] [,167] [,168] [,169] [,170] [,171] [,172] [,173] [,174] ## P53_wt "S" "Q" "H" "M" "T" "E" "V" "V" "R" ## P53_mutant "S" "Q" "H" "M" "T" "E" "V" "V" "R" ## [,175] [,176] [,177] [,178] [,179] [,180] [,181] [,182] [,183] ## P53_wt "R" "C" "P" "H" "H" "E" "R" "C" "S" ## P53_mutant "R" "C" "P" "H" "H" "E" "R" "C" "S" ## [,184] [,185] [,186] [,187] [,188] [,189] [,190] [,191] [,192] ## P53_wt "D" "S" "D" "G" "L" "A" "P" "P" "Q" ## P53_mutant "D" "S" "D" "G" "L" "A" "P" "P" "Q" ## [,193] [,194] [,195] [,196] [,197] [,198] [,199] [,200] [,201] ## P53_wt "H" "L" "I" "R" "V" "E" "G" "N" "L" ## P53_mutant "H" "L" "I" "R" "V" "E" "G" "N" "L" ## [,202] [,203] [,204] [,205] [,206] [,207] [,208] [,209] [,210] ## P53_wt "R" "V" "E" "Y" "L" "D" "D" "R" "N" ## P53_mutant "R" "V" "E" "Y" "L" "D" "D" "R" "N" ## [,211] [,212] [,213] [,214] [,215] [,216] [,217] [,218] [,219] ## P53_wt "T" "F" "R" "H" "S" "V" "V" "V" "P" ## P53_mutant "T" "F" "V" "H" "S" "V" "V" "V" "P" ## [,220] [,221] [,222] [,223] [,224] [,225] [,226] [,227] [,228] ## P53_wt "Y" "E" "P" "P" "E" "V" "G" "S" "D" ## P53_mutant "Y" "E" "P" "P" "E" "V" "G" "S" "D" ## [,229] [,230] [,231] [,232] [,233] [,234] [,235] [,236] [,237] ## P53_wt "C" "T" "T" "I" "H" "Y" "N" "Y" "M" ## P53_mutant "C" "T" "T" "I" "H" "Y" "N" "Y" "M" ## [,238] [,239] [,240] [,241] [,242] [,243] [,244] [,245] [,246] ## P53_wt "C" "N" "S" "S" "C" "M" "G" "G" "M" ## P53_mutant "C" "N" "S" "S" "C" "M" "G" "G" "M" ## [,247] [,248] [,249] [,250] [,251] [,252] [,253] [,254] [,255] ## P53_wt "N" "R" "R" "P" "I" "L" "T" "I" "I" ## P53_mutant "N" "R" "R" "P" "I" "L" "T" "I" "I" ## [,256] [,257] [,258] [,259] [,260] [,261] [,262] [,263] [,264] ## P53_wt "T" "L" "E" "D" "S" "S" "G" "N" "L" ## P53_mutant "T" "L" "E" "V" "-" "-" "-" "-" "-" ## [,265] [,266] [,267] [,268] [,269] [,270] [,271] [,272] [,273] ## P53_wt "L" "G" "R" "N" "S" "F" "E" "V" "R" ## P53_mutant "-" "-" "-" "-" "-" "-" "-" "-" "-" ## [,274] [,275] [,276] [,277] [,278] [,279] [,280] [,281] [,282] ## P53_wt "V" "C" "A" "C" "P" "G" "R" "D" "R" ## P53_mutant "-" "-" "-" "-" "-" "-" "-" "-" "-" ## [,283] [,284] [,285] [,286] [,287] [,288] [,289] [,290] [,291] ## P53_wt "R" "T" "E" "E" "E" "N" "L" "R" "K" ## P53_mutant "-" "-" "-" "-" "-" "-" "-" "-" "-"

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## [,292] [,293] [,294] [,295] [,296] [,297] [,298] [,299] [,300] ## P53_wt "K" "G" "E" "P" "H" "H" "E" "L" "P" ## P53_mutant "-" "-" "-" "-" "-" "-" "-" "-" "-" ## [,301] [,302] [,303] [,304] [,305] [,306] [,307] [,308] [,309] ## P53_wt "P" "G" "S" "T" "K" "R" "A" "L" "P" ## P53_mutant "-" "-" "-" "-" "-" "-" "-" "-" "-" ## [,310] [,311] [,312] [,313] [,314] [,315] [,316] [,317] [,318] ## P53_wt "N" "N" "T" "S" "S" "S" "P" "Q" "P" ## P53_mutant "-" "-" "-" "-" "-" "-" "-" "-" "-" ## [,319] [,320] [,321] [,322] [,323] [,324] [,325] [,326] [,327] ## P53_wt "K" "K" "K" "P" "L" "D" "G" "E" "Y" ## P53_mutant "-" "-" "-" "-" "-" "-" "-" "-" "-" ## [,328] [,329] [,330] [,331] [,332] [,333] [,334] [,335] [,336] ## P53_wt "F" "T" "L" "Q" "I" "R" "G" "R" "E" ## P53_mutant "-" "-" "-" "-" "-" "-" "-" "-" "-" ## [,337] [,338] [,339] [,340] [,341] [,342] [,343] [,344] [,345] ## P53_wt "R" "F" "E" "M" "F" "R" "E" "L" "N" ## P53_mutant "-" "-" "-" "-" "-" "-" "-" "-" "-" ## [,346] [,347] [,348] [,349] [,350] [,351] [,352] [,353] [,354] ## P53_wt "E" "A" "L" "E" "L" "K" "D" "A" "Q" ## P53_mutant "-" "-" "-" "-" "-" "-" "-" "-" "-" ## [,355] [,356] [,357] [,358] [,359] [,360] [,361] [,362] [,363] ## P53_wt "A" "G" "K" "E" "P" "G" "G" "S" "R" ## P53_mutant "-" "-" "-" "-" "-" "-" "-" "-" "-" ## [,364] [,365] [,366] [,367] [,368] [,369] [,370] [,371] [,372] ## P53_wt "A" "H" "S" "S" "H" "L" "K" "S" "K" ## P53_mutant "-" "-" "-" "-" "-" "-" "-" "-" "-" ## [,373] [,374] [,375] [,376] [,377] [,378] [,379] [,380] [,381] ## P53_wt "K" "G" "Q" "S" "T" "S" "R" "H" "K" ## P53_mutant "-" "-" "-" "-" "-" "-" "-" "-" "-" ## [,382] [,383] [,384] [,385] [,386] [,387] [,388] [,389] [,390] ## P53_wt "K" "L" "M" "F" "K" "T" "E" "G" "P" ## P53_mutant "-" "-" "-" "-" "-" "-" "-" "-" "-" ## [,391] [,392] [,393] ## P53_wt "D" "S" "D" ## P53_mutant "-" "-" "-" ## ## $call ## seqaln(aln = seqs)

Next we calculate identity per equivalent (i.e. aligned) position and then use this information to find nonidentical sites that do not contain gaps (i.e. indels).

## Calculate positional identity scores ide

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## [1] 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 ## [18] 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 ## [35] 1.0 1.0 1.0 1.0 1.0 1.0 0.5 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 ## [52] 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 0.5 1.0 1.0 1.0 ## [69] 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 ## [86] 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 ## [103] 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 ## [120] 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 ## [137] 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 ## [154] 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 ## [171] 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 ## [188] 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 ## [205] 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 0.5 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 ## [222] 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 ## [239] 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 ## [256] 1.0 1.0 1.0 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 ## [273] 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 ## [290] 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 ## [307] 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 ## [324] 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 ## [341] 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 ## [358] 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 ## [375] 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 ## [392] 0.5 0.5

## Exclude gap possitions from analysis mis.match.sites

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## Sequence positions surounding each mutant site start.position

Documents

Class 18 - maryagarcia.files.wordpress.com · Title: Class 18 Created Date: 6/7/2019 4:17:42 PM