# Data Processing with SelectSim

#### Arvind Iyer

#### 2026-07-12

- The goal of SelectSim package is to implement the SelectSim methodology to infer inter-dependencies between functional alterations in cancer.
- `SelectSim` package provides functions to generate the background model and other utility functions.

### Installation

- You can install the development version of SelectSim from GitHub with:

    devtools::install_github("CSOgroup/SelectSim",dependencies = TRUE, build_vignettes = TRUE)

- For more details on installation refer to INSTALLATION

### Example

- We will process LUAD MAF dataset from TCGA provided with the package.

- We will also use oncokb v3.9 cancer genes and mutations to filter the maf to create the gam provided with the package.

- NOTE: This is an example to process the MAF file. To know more about how we processed the MAF file to run_data object, please refer to SelectSim_analysis repository.

    library(SelectSim)
    library(dplyr)
    #>
    #> Attaching package: 'dplyr'
    #> The following objects are masked from 'package:stats':
    #>
    #>     filter, lag
    #> The following objects are masked from 'package:base':
    #>
    #>     intersect, setdiff, setequal, union
    if (requireNamespace("tictoc", quietly = TRUE)) library(tictoc)
    ## Load the data provided with the package
    data(luad_maf, package = "SelectSim")
    data(oncokb_genes, package = "SelectSim")
    data(oncokb_truncating_genes, package = "SelectSim")
    data(variant_catalogue, package = "SelectSim")

    # Check the MAF
    dim(luad_maf)
    #> [1] 220734      8

- Let print number of lines and number of samples

    input_maf <- luad_maf
    print(paste('##### Number of lines ####',nrow(input_maf),sep="->"))
    #> [1] "##### Number of lines ####->220734"
    genes_to_consider =  oncokb_genes
    print(paste('##### Number of genes ####',length(genes_to_consider),sep="->"))
    #> [1] "##### Number of genes ####->396"

- Let create a table schema of mutations to consider and columns defined in maf file

    mutation_type = list(
          'ignore' = c("Silent","Intron","RNA","3'UTR","5'UTR","5'Flank","3'Flank","IGR"),
          'truncating'= c('Frame_Shift_Del','Frame_Shift_Ins','In_Frame_Del','In_Frame_Ins','Nonsense_Mutation','Nonstop_Mutation','Splice_Region','Splice_Site','Translation_Start_Site'),
          'missense' = c('Missense_Mutation')
    )
    custom_maf_schema = list(
        'name' = 'custom_maf',
        'column' = list(
              'gene' = 'Hugo_Symbol'
            , 'gene.name' = 'Hugo_Symbol'
            , 'sample' = 'sample'
            , 'sample.name' = 'sample'
            , 'mutation.type' = 'Variant_Classification'
            , 'mutation' = 'HGVSp_Short'
            ),
            'mutation.type' = mutation_type
    )

- Number of samples in the maf file

    mut_samples = unique(input_maf[, custom_maf_schema$column$sample])
    print(paste('##### Number of samples ####',length(mut_samples),sep="->"))
    #> [1] "##### Number of samples ####->502"

- Filter the maf file to include oncokb cancer genes

    maf_genes = filter_maf_gene.name(input_maf, genes = genes_to_consider, gene.col = custom_maf_schema$column$gene)
    print(paste('##### Number of lines ####',nrow(maf_genes),sep="->"))
    #> [1] "##### Number of lines ####->6708"

#### Generating the GAMs

- Let generate the truncating data
  - We generate the GAM consider the genes to consider truncating mutations.
  - We also create a TMB dataframe which takes all truncating mutation of all genes in consideration.

    # Creating Truncating GAM
    if (requireNamespace("tictoc", quietly = TRUE)) tictoc::tic('##### Creating Truncating GAM ####')
        maf_trunc = filter_maf_truncating(maf_genes,genes=oncokb_truncating_genes, custom_maf_schema)
        input_maf_trunc<-filter_maf_truncating(input_maf, custom_maf_schema)
        truncating_tmb <- data.frame('sample'=mut_samples,'mutation'=rep(0,length(mut_samples)))
        rownames(truncating_tmb)<-mut_samples
        temp <- input_maf_trunc %>% count(sample)
        rownames(temp)<-temp$sample
        truncating_tmb[intersect(truncating_tmb$sample,temp$sample),]$mutation <-temp[intersect(truncating_tmb$sample,temp$sample),'n']
        tcga_truc_gam = maf2gam(maf_trunc,
                         sample.col = custom_maf_schema$column$sample,
                         gene.col = custom_maf_schema$column$gene,
                         value.var = 'Variant_Classification',
                         samples = mut_samples,
                         genes = genes_to_consider,
                         fun.aggregate = length,
                         binarize=TRUE,
                         fill=0)
        truncating_data <- list('gam'=tcga_truc_gam,
                                'tmb'=truncating_tmb)
    if (requireNamespace("tictoc", quietly = TRUE)) tictoc::toc()
    #> ##### Creating Truncating GAM ####: 0.069 sec elapsed

- Let generate the Missense data
  - We generate the GAM with genes and hotspot mutations from oncokb v3.9.
  - We also create a TMB dataframe which takes all Missense mutation of all genes in consideration.

    # Creating Missense GAM
    if (requireNamespace("tictoc", quietly = TRUE)) tictoc::tic('##### Creating Missense GAM ####')
        maf_valid = filter_maf_schema(input_maf,
                                 schema = custom_maf_schema,
                                 column = 'mutation.type',
                                 values = custom_maf_schema[['mutation.type']][['ignore']],
                                 inclusive = FALSE)
        missense_maf<-filter_maf_mutation.type(input_maf,
                                          variants = 'Missense_Mutation',
                                          variant.col = custom_maf_schema$column$mutation.type)
        missense_tmb <- data.frame('sample'=mut_samples,'mutation'=rep(0,length(mut_samples)))
        rownames(missense_tmb)<-mut_samples
        temp <- missense_maf %>% count(sample)
        rownames(temp)<-temp$sample
        missense_tmb[intersect(missense_tmb$sample,temp$sample),]$mutation <-temp[intersect(missense_tmb$sample,temp$sample),'n']
        t_m = substr(maf_valid[[custom_maf_schema$column$mutation]],3,1000)
        t_m1 =  gsub('[A-Z]*$', '', t_m)
        maf_valid$HGVSp_Short_fixed = t_m1
        maf_hotspot = filter_maf_mutations(maf_valid,
                                      variant_catalogue,
                                      maf.col = c(custom_maf_schema$column$gene, 'HGVSp_Short_fixed'),
                                      values.col = c('gene', 'mut'))

        missense_tcga_gam = maf2gam(maf_hotspot,
                         sample.col = custom_maf_schema$column$sample,
                         gene.col = custom_maf_schema$column$gene,
                         value.var = 'Variant_Classification',
                         samples = mut_samples,
                         genes = genes_to_consider,
                         fun.aggregate = length,
                         binarize=TRUE,
                         fill=0)
        missesne_data <- list('gam'=missense_tcga_gam,
                              'tmb'=missense_tmb)

    if (requireNamespace("tictoc", quietly = TRUE)) tictoc::toc()
    #> ##### Creating Missense GAM ####: 0.578 sec elapsed

#### Generating the run_object to run SelectSim

- We create a run_object data which is list object which consists of
  - M: a list object of GAMs which is presence absence matrix of alterations
  - tmb: a list object of tumor mutation burden as data frame with column names (should be) as sample and mutation
  - sample.class a named vector of sample annotations
  - alteration.class a named vector of alteration annotations

    gene_to_take <- colnames(missesne_data$gam)
    order <- rownames(missesne_data$gam)

    data <-list('M'=list('missense'=t(missesne_data$gam[order,gene_to_take]),
                         'truncating'=t(truncating_data$gam[rownames(missesne_data$gam[order,]),gene_to_take])),
                'tmb'=list('missense'=missesne_data$tmb[order,],
                           'truncating'=truncating_data$tmb[order,]))

    alteration_covariates <- rep('MUT',ncol(missesne_data$gam[order,gene_to_take]))
    names(alteration_covariates)<-colnames(missesne_data$gam[order,gene_to_take])
    sample_covariates<-rep('LUAD',length(order))
    names(sample_covariates)<-order
    run_data <- list('M'=data,'sample.class' = sample_covariates,'alteration.class' = alteration_covariates)
    str(run_data)
    #> List of 3
    #>  $ M               :List of 2
    #>   ..$ M  :List of 2
    #>   .. ..$ missense  : num [1:396, 1:502] NA NA NA NA NA NA NA NA NA NA ...
    #>   .. .. ..- attr(*, "dimnames")=List of 2
    #>   .. .. .. ..$ : chr [1:396] "AKT1" "ATM" "BRAF" "CDKN2A" ...
    #>   .. .. .. ..$ : chr [1:502] "TCGA-05-4244-01" "TCGA-05-4249-01" "TCGA-05-4250-01" "TCGA-05-4382-01" ...
    #>   .. ..$ truncating: num [1:396, 1:502] 0 NA NA NA NA NA NA NA NA 0 ...
    #>   .. .. ..- attr(*, "dimnames")=List of 2
    #>   .. .. .. ..$ : chr [1:396] "AKT1" "ATM" "BRAF" "CDKN2A" ...
    #>   .. .. .. ..$ : chr [1:502] "TCGA-05-4244-01" "TCGA-05-4249-01" "TCGA-05-4250-01" "TCGA-05-4382-01" ...
    #>   ..$ tmb:List of 2
    #>   .. ..$ missense  :'data.frame':    502 obs. of  2 variables:
    #>   .. .. ..$ sample  : chr [1:502] "TCGA-05-4244-01" "TCGA-05-4249-01" "TCGA-05-4250-01" "TCGA-05-4382-01" ...
    #>   .. .. ..$ mutation: num [1:502] 163 253 270 1328 100 ...
    #>   .. ..$ truncating:'data.frame':    502 obs. of  2 variables:
    #>   .. .. ..$ sample  : chr [1:502] "TCGA-05-4244-01" "TCGA-05-4249-01" "TCGA-05-4250-01" "TCGA-05-4382-01" ...
    #>   .. .. ..$ mutation: num [1:502] 24 45 40 206 17 18 73 31 176 108 ...
    #>  $ sample.class    : Named chr [1:502] "LUAD" "LUAD" "LUAD" "LUAD" ...
    #>   ..- attr(*, "names")= chr [1:502] "TCGA-05-4244-01" "TCGA-05-4249-01" "TCGA-05-4250-01" "TCGA-05-4382-01" ...
    #>  $ alteration.class: Named chr [1:396] "MUT" "MUT" "MUT" "MUT" ...
    #>   ..- attr(*, "names")= chr [1:396] "AKT1" "ATM" "BRAF" "CDKN2A" ...

- Save the `run_data` and check the introduction vignette to see how to run selectX to discover EDs.

### Session information

    # Print the sessionInfo
    sessionInfo()
    #> R version 4.5.3 (2026-03-11)
    #> Platform: aarch64-apple-darwin20.0.0
    #> Running under: macOS Sequoia 15.7.3
    #>
    #> Matrix products: default
    #> BLAS/LAPACK: /Users/arvindiyer/micromamba/envs/r_env/lib/libopenblas.0.dylib;  LAPACK version 3.12.0
    #>
    #> locale:
    #> [1] C/en_IN.UTF-8/en_IN.UTF-8/C/en_IN.UTF-8/en_IN.UTF-8
    #>
    #> time zone: America/Toronto
    #> tzcode source: system (macOS)
    #>
    #> attached base packages:
    #> [1] stats     graphics  grDevices utils     datasets  methods   base
    #>
    #> other attached packages:
    #> [1] tictoc_1.2.1    dplyr_1.2.1     SelectSim_0.1.6
    #>
    #> loaded via a namespace (and not attached):
    #>  [1] sass_0.4.10           generics_0.1.4        tidyr_1.3.2
    #>  [4] rstatix_1.0.0         lattice_0.22-9        digest_0.6.39
    #>  [7] magrittr_2.0.5        evaluate_1.0.5        grid_4.5.3
    #> [10] RColorBrewer_1.1-3    iterators_1.0.14      fastmap_1.2.0
    #> [13] foreach_1.5.2         doParallel_1.0.17     jsonlite_2.0.0
    #> [16] Matrix_1.7-5          backports_1.5.1       Formula_1.2-5
    #> [19] purrr_1.2.2           doRNG_1.8.6.3         scales_1.4.0
    #> [22] codetools_0.2-20      jquerylib_0.1.4       abind_1.4-8
    #> [25] cli_3.6.6             zigg_0.0.2            rlang_1.3.0
    #> [28] cachem_1.1.0          yaml_2.3.12           otel_0.2.0
    #> [31] tools_4.5.3           parallel_4.5.3        ggsignif_0.6.4
    #> [34] ggplot2_4.0.3         ggpubr_1.0.0          rngtools_1.5.2
    #> [37] Rfast_2.1.5.2         broom_1.0.13          vctrs_0.7.3
    #> [40] R6_2.6.1              ggridges_0.5.7        lifecycle_1.0.5
    #> [43] car_3.1-5             pkgconfig_2.0.3       RcppParallel_5.1.11-2
    #> [46] pillar_1.11.1         bslib_0.11.0          gtable_0.3.6
    #> [49] Rcpp_1.1.2            glue_1.8.1            xfun_0.59
    #> [52] tibble_3.3.1          tidyselect_1.2.1      knitr_1.51
    #> [55] farver_2.1.2          htmltools_0.5.9       rmarkdown_2.31
    #> [58] carData_3.0-6         compiler_4.5.3        S7_0.2.2