HierFabs: SKCM Data Analysis with Cox-GE model

This vignette introduces the HierFabs workflow for the analysis of the skin cutaneous melanoma (SKCM) dataset downloaded from The Cancer Genome Atlas TCGA, which contains disease outcomes, environmental factors, and high-dimensional gene expressions. The goal of analysis is to identify interactions that are associated with the prognosis of SKCM.

We demonstrate the use of HierFabs to the SKCM data that are here, which can be downloaded to the current working path by the following command:

githubURL <- "https://github.com/XiaoZhangryy/HierFabs/blob/master/vignettes_data/cleaned_menaloma_Data.rda?raw=true"
download.file(githubURL, "cleaned_menaloma_Data.rda", mode = "wb")

The outcome of interest is overall survival. After removing samples with missing survival time and genes with minimal expression variations, we obtain 17,944 gene expressions on 253 patients. For gene expression measurements, the top 2,000 are screened out for downstream analysis (Jiang et al. 2016). Each gene expression is standardized to have mean zero and standard deviation one.

The package can be loaded with the command:

library(HierFabs)
library(Matrix)

Then load datasets to R

load("cleaned_menaloma_Data.rda")

Fit Cox-GE

Fit a Cox model with gene-environment interaction under weak hierarchy constraint.

y = data$y
status = data$status
E = as.matrix(data$E)
G = as.matrix(data$G)
fit <- HierFabs(E, y, G, model = "cox", eps = 0.01, hier = "weak", status = status, diagonal = TRUE,
    max_s = 40, criteria = "BIC")

Then, we can use the print function to show the result.

print(fit)
#> 5 x 20 sparse Matrix of class "dgCMatrix"
#>                             main effect CREG1    ZNF25    NXT2     MDP1   
#> main effect                    .       -0.00814  .        .        .      
#> tumor_status                   0.92192  .       -0.17667 -0.05527 -0.11836
#> breslow_thickness_at_diagnosis 0.00207  .        .        .        .      
#> age_at_diagnosis               0.00500  .        .        .        .      
#> new_tumor_event_dx_indicator   .       -0.03493  .        .        .      
#>                                                                           
#>                                 RPS6KA3  TBC1D19  CSMD1    IFITM1   TBRG1 
#> main effect                     .        .        .        .        .     
#> tumor_status                   -0.01062 -0.05482 -0.01383 -0.10996 -0.0125
#> breslow_thickness_at_diagnosis  .        .        .        .        .     
#> age_at_diagnosis                .        .        .        .        .     
#> new_tumor_event_dx_indicator    .        .        .        .        .     
#>                                                                            
#>                                 CARS     PTGR2    TSG101   CCT6B    VPS26A 
#> main effect                     .        .        .        .        .      
#> tumor_status                   -0.13057 -0.01511 -0.02738 -0.01543 -0.03612
#> breslow_thickness_at_diagnosis  .        .        .        .        .      
#> age_at_diagnosis                .        .        .        .        .      
#> new_tumor_event_dx_indicator    .        .        .        .        .      
#>                                                                          
#>                                 ADAM21   TMEM27   SNX14    TMC2     GNL3L 
#> main effect                     .        .        .        .       .     
#> tumor_status                   -0.01176 -0.01233  .        .       .     
#> breslow_thickness_at_diagnosis  .        .       -0.00461 -0.12921 .     
#> age_at_diagnosis                .        .        .        .        8e-04
#> new_tumor_event_dx_indicator    .        .        .        .       .

Session information

sessionInfo()
#> R version 4.1.3 (2022-03-10)
#> Platform: x86_64-w64-mingw32/x64 (64-bit)
#> Running under: Windows 10 x64 (build 19043)
#> 
#> Matrix products: default
#> 
#> locale:
#> [1] LC_COLLATE=English_United States.1252 
#> [2] LC_CTYPE=English_United States.1252   
#> [3] LC_MONETARY=English_United States.1252
#> [4] LC_NUMERIC=C                          
#> [5] LC_TIME=English_United States.1252    
#> system code page: 936
#> 
#> attached base packages:
#> [1] stats     graphics  grDevices utils     datasets  methods   base     
#> 
#> other attached packages:
#> [1] Matrix_1.5-1   HierFabs_0.1.0
#> 
#> loaded via a namespace (and not attached):
#>  [1] rstudioapi_0.13   knitr_1.38        magrittr_2.0.3    lattice_0.20-45  
#>  [5] R6_2.5.1          ragg_1.2.2        rlang_1.0.6       fastmap_1.1.0    
#>  [9] stringr_1.4.1     tools_4.1.3       grid_4.1.3        xfun_0.30        
#> [13] cli_3.2.0         jquerylib_0.1.4   htmltools_0.5.3   systemfonts_1.0.4
#> [17] yaml_2.3.5        digest_0.6.29     rprojroot_2.0.3   pkgdown_2.0.6    
#> [21] textshaping_0.3.6 purrr_0.3.4       formatR_1.12      sass_0.4.2       
#> [25] fs_1.5.2          memoise_2.0.1     cachem_1.0.6      evaluate_0.15    
#> [29] rmarkdown_2.13    stringi_1.7.8     compiler_4.1.3    bslib_0.4.0      
#> [33] desc_1.4.1        jsonlite_1.8.2

Xiao Zhang

2022-10-22

Fit Cox-GE

Session information