Contents

0.1 Instalation

if (!require("BiocManager")) {
    install.packages("BiocManager")
}
BiocManager::install("glmSparseNet")

1 Required Packages

library(dplyr)
library(ggplot2)
library(survival)
library(futile.logger)
library(curatedTCGAData)
library(MultiAssayExperiment)
library(TCGAutils)
#
library(glmSparseNet)
#
# Some general options for futile.logger the debugging package
flog.layout(layout.format("[~l] ~m"))
options(
    "glmSparseNet.show_message" = FALSE,
    "glmSparseNet.base_dir" = withr::local_tempdir()
)
# Setting ggplot2 default theme as minimal
theme_set(ggplot2::theme_minimal())

2 Load data

The data is loaded from an online curated dataset downloaded from TCGA using curatedTCGAData bioconductor package and processed.

To accelerate the process we use a very reduced dataset down to 107 variables only (genes), which is stored as a data object in this package. However, the procedure to obtain the data manually is described in the following chunk.

brca <- curatedTCGAData(
    diseaseCode = "BRCA", assays = "RNASeq2GeneNorm",
    version = "1.1.38", dry.run = FALSE
)
brca <- TCGAutils::TCGAsplitAssays(brca, c("01", "11"))
xdataRaw <- t(cbind(assay(brca[[1]]), assay(brca[[2]])))

# Get matches between survival and assay data
classV <- TCGAbiospec(rownames(xdataRaw))$sample_definition |> factor()
names(classV) <- rownames(xdataRaw)

# keep features with standard deviation > 0
xdataRaw <- xdataRaw[, apply(xdataRaw, 2, sd) != 0] |>
    scale()

set.seed(params$seed)
smallSubset <- c(
    "CD5", "CSF2RB", "HSF1", "IRGC", "LRRC37A6P", "NEUROG2",
    "NLRC4", "PDE11A", "PIK3CB", "QARS", "RPGRIP1L", "SDC1",
    "TMEM31", "YME1L1", "ZBTB11",
    sample(colnames(xdataRaw), 100)
)

xdata <- xdataRaw[, smallSubset[smallSubset %in% colnames(xdataRaw)]]
ydata <- classV

3 Fit models

Fit model model penalizing by the hubs using the cross-validation function by cv.glmHub.

fitted <- cv.glmHub(xdata, ydata,
    family = "binomial",
    network = "correlation",
    nlambda = 1000,
    options = networkOptions(
        cutoff = .6,
        minDegree = .2
    )
)

4 Results of Cross Validation

Shows the results of 1000 different parameters used to find the optimal value in 10-fold cross-validation. The two vertical dotted lines represent the best model and a model with less variables selected (genes), but within a standard error distance from the best.

plot(fitted)

4.1 Coefficients of selected model from Cross-Validation

Taking the best model described by lambda.min

coefsCV <- Filter(function(.x) .x != 0, coef(fitted, s = "lambda.min")[, 1])
data.frame(
    ensembl.id = names(coefsCV),
    gene.name = geneNames(names(coefsCV))$external_gene_name,
    coefficient = coefsCV,
    stringsAsFactors = FALSE
) |>
    arrange(gene.name) |>
    knitr::kable()
ensembl.id gene.name coefficient
(Intercept) (Intercept) (Intercept) -6.8189813
AMOTL1 AMOTL1 AMOTL1 0.4430643
ATR ATR ATR 1.2498304
B3GALT2 B3GALT2 B3GALT2 -0.0867011
BAG2 BAG2 BAG2 -0.1841676
C16orf82 C16orf82 C16orf82 0.0396368
CD5 CD5 CD5 -1.1200445
CIITA CIITA CIITA 0.4256103
DCP1A DCP1A DCP1A 0.2994599
FAM86B1 FAM86B1 FAM86B1 0.2025463
FNIP2 FNIP2 FNIP2 0.6101759
GDF11 GDF11 GDF11 -0.2676642
GNG11 GNG11 GNG11 3.0659066
GREM2 GREM2 GREM2 -0.2014884
GZMB GZMB GZMB -2.7663574
HAX1 HAX1 HAX1 -0.1516837
IL2 IL2 IL2 0.6327083
MMP28 MMP28 MMP28 -0.8438024
MS4A4A MS4A4A MS4A4A 1.1614779
NDRG2 NDRG2 NDRG2 1.1142519
NLRC4 NLRC4 NLRC4 -1.4434578
PIK3CB PIK3CB PIK3CB -0.3880002
ZBTB11 ZBTB11 ZBTB11 -0.3325729

4.2 Accuracy

## [INFO] Misclassified (11)
## [INFO]   * False primary solid tumour: 7
## [INFO]   * False normal              : 4

Histogram of predicted response

ROC curve

## Setting levels: control = Primary Solid Tumor, case = Solid Tissue Normal
## Setting direction: controls < cases
## Warning: Using `size` aesthetic for lines was deprecated in ggplot2 3.4.0.
## ℹ Please use `linewidth` instead.
## This warning is displayed once every 8 hours.
## Call `lifecycle::last_lifecycle_warnings()` to see where this warning was
## generated.

5 Session Info

sessionInfo()
## R version 4.5.0 Patched (2025-04-21 r88169)
## Platform: aarch64-apple-darwin20
## Running under: macOS Ventura 13.7.1
## 
## Matrix products: default
## BLAS:   /Library/Frameworks/R.framework/Versions/4.5-arm64/Resources/lib/libRblas.0.dylib 
## LAPACK: /Library/Frameworks/R.framework/Versions/4.5-arm64/Resources/lib/libRlapack.dylib;  LAPACK version 3.12.1
## 
## locale:
## [1] C/en_US.UTF-8/en_US.UTF-8/C/en_US.UTF-8/en_US.UTF-8
## 
## time zone: America/New_York
## tzcode source: internal
## 
## attached base packages:
## [1] stats4    stats     graphics  grDevices utils     datasets  methods  
## [8] base     
## 
## other attached packages:
##  [1] glmSparseNet_1.27.0         TCGAutils_1.29.0           
##  [3] curatedTCGAData_1.31.0      MultiAssayExperiment_1.35.1
##  [5] SummarizedExperiment_1.39.0 Biobase_2.69.0             
##  [7] GenomicRanges_1.61.0        GenomeInfoDb_1.45.0        
##  [9] IRanges_2.43.0              S4Vectors_0.47.0           
## [11] BiocGenerics_0.55.0         generics_0.1.3             
## [13] MatrixGenerics_1.21.0       matrixStats_1.5.0          
## [15] futile.logger_1.4.3         survival_3.8-3             
## [17] ggplot2_3.5.2               dplyr_1.1.4                
## [19] BiocStyle_2.37.0           
## 
## loaded via a namespace (and not attached):
##   [1] RColorBrewer_1.1-3        jsonlite_2.0.0           
##   [3] shape_1.4.6.1             magrittr_2.0.3           
##   [5] magick_2.8.6              GenomicFeatures_1.61.0   
##   [7] farver_2.1.2              rmarkdown_2.29           
##   [9] BiocIO_1.19.0             vctrs_0.6.5              
##  [11] memoise_2.0.1             Rsamtools_2.25.0         
##  [13] RCurl_1.98-1.17           tinytex_0.57             
##  [15] htmltools_0.5.8.1         S4Arrays_1.9.0           
##  [17] BiocBaseUtils_1.11.0      progress_1.2.3           
##  [19] AnnotationHub_3.99.0      lambda.r_1.2.4           
##  [21] curl_6.2.2                pROC_1.18.5              
##  [23] SparseArray_1.9.0         sass_0.4.10              
##  [25] bslib_0.9.0               plyr_1.8.9               
##  [27] httr2_1.1.2               futile.options_1.0.1     
##  [29] cachem_1.1.0              GenomicAlignments_1.45.0 
##  [31] lifecycle_1.0.4           iterators_1.0.14         
##  [33] pkgconfig_2.0.3           Matrix_1.7-3             
##  [35] R6_2.6.1                  fastmap_1.2.0            
##  [37] GenomeInfoDbData_1.2.14   digest_0.6.37            
##  [39] AnnotationDbi_1.71.0      ps_1.9.1                 
##  [41] ExperimentHub_2.99.0      RSQLite_2.3.9            
##  [43] labeling_0.4.3            filelock_1.0.3           
##  [45] httr_1.4.7                abind_1.4-8              
##  [47] compiler_4.5.0            bit64_4.6.0-1            
##  [49] withr_3.0.2               backports_1.5.0          
##  [51] BiocParallel_1.43.0       DBI_1.2.3                
##  [53] biomaRt_2.65.0            rappdirs_0.3.3           
##  [55] DelayedArray_0.35.1       rjson_0.2.23             
##  [57] tools_4.5.0               chromote_0.5.1           
##  [59] glue_1.8.0                restfulr_0.0.15          
##  [61] promises_1.3.2            grid_4.5.0               
##  [63] checkmate_2.3.2           gtable_0.3.6             
##  [65] tzdb_0.5.0                websocket_1.4.4          
##  [67] hms_1.1.3                 xml2_1.3.8               
##  [69] XVector_0.49.0            BiocVersion_3.22.0       
##  [71] foreach_1.5.2             pillar_1.10.2            
##  [73] stringr_1.5.1             later_1.4.2              
##  [75] splines_4.5.0             BiocFileCache_2.99.0     
##  [77] lattice_0.22-7            rtracklayer_1.69.0       
##  [79] bit_4.6.0                 tidyselect_1.2.1         
##  [81] Biostrings_2.77.0         knitr_1.50               
##  [83] bookdown_0.43             xfun_0.52                
##  [85] stringi_1.8.7             UCSC.utils_1.5.0         
##  [87] yaml_2.3.10               evaluate_1.0.3           
##  [89] codetools_0.2-20          tibble_3.2.1             
##  [91] BiocManager_1.30.25       cli_3.6.5                
##  [93] processx_3.8.6            jquerylib_0.1.4          
##  [95] dichromat_2.0-0.1         Rcpp_1.0.14              
##  [97] GenomicDataCommons_1.33.0 dbplyr_2.5.0             
##  [99] png_0.1-8                 XML_3.99-0.18            
## [101] parallel_4.5.0            readr_2.1.5              
## [103] blob_1.2.4                prettyunits_1.2.0        
## [105] bitops_1.0-9              glmnet_4.1-8             
## [107] scales_1.4.0              purrr_1.0.4              
## [109] crayon_1.5.3              rlang_1.1.6              
## [111] KEGGREST_1.49.0           rvest_1.0.4              
## [113] formatR_1.14