Author: Sean Davis

# Working with simple somatic mutations

Sean Davis

#### Friday, November 07, 2025

# 1 Background

# 2 Workflow

    library(GenomicDataCommons)
    library(tibble)

## 2.1 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()

## 2.2 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] 1388

    ssms() |>
        GenomicDataCommons::filter(
          consequence.transcript.gene.symbol %in% c('TP53')) |>
        GenomicDataCommons::count()

    ## [1] 1385

## 2.3 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] 5645

    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
    ##                                          27
    ##                Acute Lymphoblastic Leukemia
    ##                                          22
    ##                Adenomas and Adenocarcinomas
    ##                                        1803
    ##        Adnexal and Skin Appendage Neoplasms
    ##                                           1
    ##                        Basal Cell Neoplasms
    ##                                           1
    ##                Complex Epithelial Neoplasms
    ##                                          16
    ##         Complex Mixed and Stromal Neoplasms
    ##                                          72
    ##       Cystic, Mucinous and Serous Neoplasms
    ##                                         624
    ##                Ductal and Lobular Neoplasms
    ##                                         666
    ##                   Epithelial Neoplasms, NOS
    ##                                          22
    ##                       Fibromatous Neoplasms
    ##                                          12
    ##                         Germ Cell Neoplasms
    ##                                           1
    ##                                     Gliomas
    ##                                         543
    ##                        Lipomatous Neoplasms
    ##                                           7
    ##                          Lymphoid Leukemias
    ##                                          23
    ##                     Mature B-Cell Lymphomas
    ##                                          26
    ##                       Mesothelial Neoplasms
    ##                                          11
    ##                   Miscellaneous Bone Tumors
    ##                                           1
    ##                   Myelodysplastic Syndromes
    ##                                           3
    ##                           Myeloid Leukemias
    ##                                          32
    ##                         Myomatous Neoplasms
    ##                                          59
    ##                              Neoplasms, NOS
    ##                                           9
    ##                         Nerve Sheath Tumors
    ##                                           1
    ##                          Nevi and Melanomas
    ##                                          98
    ##                                Not Reported
    ##                                           6
    ##         Osseous and Chondromatous Neoplasms
    ##                                          21
    ##                          Plasma Cell Tumors
    ##                                          53
    ##        Soft Tissue Tumors and Sarcomas, NOS
    ##                                          33
    ##                     Squamous Cell Neoplasms
    ##                                        1217
    ##                 Thymic Epithelial Neoplasms
    ##                                           4
    ## Transitional Cell Papillomas and Carcinomas
    ##                                         231

## 2.4 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: 36
    ## -Summarizing
    ## -Processing clinical data
    ## --Missing clinical data
    ## -Finished in 1.382s elapsed (1.160s 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