Workflow
library(GenomicDataCommons)
library(tibble)
Genes and gene details
grep_fields('genes', 'symbol')
## [1] "symbol"
head(available_values('genes','symbol'))
## [1] "y_rna" "actl10" "matr3" "a1bg" "a1cf" "a2m"
tp53 = genes() %>%
GenomicDataCommons::filter(symbol=='TP53') %>%
results(size=10000) %>%
as_tibble()
ssms
ssms() %>%
GenomicDataCommons::filter(
chromosome==paste0('chr',tp53$gene_chromosome[1]) &
start_position > tp53$gene_start[1] &
end_position < tp53$gene_end[1]) %>%
GenomicDataCommons::count()
## [1] 1327
ssms() %>%
GenomicDataCommons::filter(
consequence.transcript.gene.symbol %in% c('TP53')) %>%
GenomicDataCommons::count()
## [1] 1325
convert to VRanges
library(VariantAnnotation)
vars = ssms() %>%
GenomicDataCommons::filter(
consequence.transcript.gene.symbol %in% c('TP53')) %>%
GenomicDataCommons::results_all() %>%
as_tibble()
vr = VRanges(seqnames = vars$chromosome,
ranges = IRanges(start=vars$start_position, width=1),
ref = vars$reference_allele,
alt = vars$tumor_allele)
ssm_occurrences() %>%
GenomicDataCommons::filter(
ssm.consequence.transcript.gene.symbol %in% c('TP53')) %>%
GenomicDataCommons::count()
## [1] 5288
var_samples = ssm_occurrences() %>%
GenomicDataCommons::filter(
ssm.consequence.transcript.gene.symbol %in% c('TP53')) %>%
GenomicDataCommons::expand(c('case', 'ssm', 'case.project')) %>%
GenomicDataCommons::results_all() %>%
as_tibble()
table(var_samples$case$disease_type)
##
## Acinar Cell Neoplasms
## 7
## Adenomas and Adenocarcinomas
## 1636
## Adnexal and Skin Appendage Neoplasms
## 1
## Complex Epithelial Neoplasms
## 16
## Complex Mixed and Stromal Neoplasms
## 70
## Cystic, Mucinous and Serous Neoplasms
## 618
## Ductal and Lobular Neoplasms
## 644
## Epithelial Neoplasms, NOS
## 14
## Fibromatous Neoplasms
## 12
## Germ Cell Neoplasms
## 1
## Gliomas
## 493
## Lipomatous Neoplasms
## 6
## Lymphoid Leukemias
## 16
## Mature B-Cell Lymphomas
## 5
## Mesothelial Neoplasms
## 11
## Miscellaneous Bone Tumors
## 1
## Myelodysplastic Syndromes
## 3
## Myeloid Leukemias
## 30
## Myomatous Neoplasms
## 59
## Neoplasms, NOS
## 9
## Nerve Sheath Tumors
## 1
## Nevi and Melanomas
## 90
## Not Reported
## 6
## Osseous and Chondromatous Neoplasms
## 21
## Plasma Cell Tumors
## 53
## Soft Tissue Tumors and Sarcomas, NOS
## 32
## Squamous Cell Neoplasms
## 1203
## Thymic Epithelial Neoplasms
## 4
## Transitional Cell Papillomas and Carcinomas
## 226
OncoPrint
fnames <- files() %>%
GenomicDataCommons::filter(
cases.project.project_id=='TCGA-SKCM' &
data_format=='maf' &
data_type=='Masked Somatic Mutation' &
analysis.workflow_type ==
'Aliquot Ensemble Somatic Variant Merging and Masking'
) %>%
results(size = 1) %>%
ids() %>%
gdcdata()
library(maftools)
melanoma = read.maf(maf = fnames)
## -Reading
## -Validating
## -Silent variants: 252
## -Summarizing
## -Processing clinical data
## --Missing clinical data
## -Finished in 0.262s elapsed (0.236s cpu)
maftools::oncoplot(melanoma)
## Warning in min(x): no non-missing arguments to min; returning Inf
## Warning in max(x): no non-missing arguments to max; returning -Inf
![](data:image/png;base64,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