if (!require("BiocManager")) {
    install.packages("BiocManager")
}
BiocManager::install("glmSparseNet")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())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 <- classVFit 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
    )
)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)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 | 
## [INFO] Misclassified (11)## [INFO]   * False primary solid tumour: 7## [INFO]   * False normal              : 4Histogram 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.sessionInfo()## R version 4.4.1 (2024-06-14)
## Platform: x86_64-pc-linux-gnu
## Running under: Ubuntu 24.04.1 LTS
## 
## Matrix products: default
## BLAS:   /home/biocbuild/bbs-3.20-bioc/R/lib/libRblas.so 
## LAPACK: /usr/lib/x86_64-linux-gnu/lapack/liblapack.so.3.12.0
## 
## locale:
##  [1] LC_CTYPE=en_US.UTF-8       LC_NUMERIC=C              
##  [3] LC_TIME=en_GB              LC_COLLATE=C              
##  [5] LC_MONETARY=en_US.UTF-8    LC_MESSAGES=en_US.UTF-8   
##  [7] LC_PAPER=en_US.UTF-8       LC_NAME=C                 
##  [9] LC_ADDRESS=C               LC_TELEPHONE=C            
## [11] LC_MEASUREMENT=en_US.UTF-8 LC_IDENTIFICATION=C       
## 
## time zone: America/New_York
## tzcode source: system (glibc)
## 
## attached base packages:
## [1] stats4    stats     graphics  grDevices utils     datasets  methods  
## [8] base     
## 
## other attached packages:
##  [1] glmSparseNet_1.24.0         TCGAutils_1.26.0           
##  [3] curatedTCGAData_1.27.1      MultiAssayExperiment_1.32.0
##  [5] SummarizedExperiment_1.36.0 Biobase_2.66.0             
##  [7] GenomicRanges_1.58.0        GenomeInfoDb_1.42.0        
##  [9] IRanges_2.40.0              S4Vectors_0.44.0           
## [11] BiocGenerics_0.52.0         MatrixGenerics_1.18.0      
## [13] matrixStats_1.4.1           futile.logger_1.4.3        
## [15] survival_3.7-0              ggplot2_3.5.1              
## [17] dplyr_1.1.4                 BiocStyle_2.34.0           
## 
## loaded via a namespace (and not attached):
##   [1] jsonlite_1.8.9            shape_1.4.6.1            
##   [3] magrittr_2.0.3            magick_2.8.5             
##   [5] GenomicFeatures_1.58.0    farver_2.1.2             
##   [7] rmarkdown_2.28            BiocIO_1.16.0            
##   [9] zlibbioc_1.52.0           vctrs_0.6.5              
##  [11] memoise_2.0.1             Rsamtools_2.22.0         
##  [13] RCurl_1.98-1.16           tinytex_0.53             
##  [15] progress_1.2.3            htmltools_0.5.8.1        
##  [17] S4Arrays_1.6.0            BiocBaseUtils_1.8.0      
##  [19] AnnotationHub_3.14.0      lambda.r_1.2.4           
##  [21] curl_5.2.3                pROC_1.18.5              
##  [23] SparseArray_1.6.0         sass_0.4.9               
##  [25] bslib_0.8.0               plyr_1.8.9               
##  [27] httr2_1.0.5               futile.options_1.0.1     
##  [29] cachem_1.1.0              GenomicAlignments_1.42.0 
##  [31] mime_0.12                 lifecycle_1.0.4          
##  [33] iterators_1.0.14          pkgconfig_2.0.3          
##  [35] Matrix_1.7-1              R6_2.5.1                 
##  [37] fastmap_1.2.0             GenomeInfoDbData_1.2.13  
##  [39] digest_0.6.37             colorspace_2.1-1         
##  [41] AnnotationDbi_1.68.0      ps_1.8.1                 
##  [43] ExperimentHub_2.14.0      RSQLite_2.3.7            
##  [45] labeling_0.4.3            filelock_1.0.3           
##  [47] fansi_1.0.6               httr_1.4.7               
##  [49] abind_1.4-8               compiler_4.4.1           
##  [51] bit64_4.5.2               withr_3.0.2              
##  [53] backports_1.5.0           BiocParallel_1.40.0      
##  [55] DBI_1.2.3                 highr_0.11               
##  [57] biomaRt_2.62.0            rappdirs_0.3.3           
##  [59] DelayedArray_0.32.0       rjson_0.2.23             
##  [61] tools_4.4.1               chromote_0.3.1           
##  [63] glue_1.8.0                restfulr_0.0.15          
##  [65] promises_1.3.0            grid_4.4.1               
##  [67] checkmate_2.3.2           generics_0.1.3           
##  [69] gtable_0.3.6              tzdb_0.4.0               
##  [71] websocket_1.4.2           hms_1.1.3                
##  [73] xml2_1.3.6                utf8_1.2.4               
##  [75] XVector_0.46.0            BiocVersion_3.20.0       
##  [77] foreach_1.5.2             pillar_1.9.0             
##  [79] stringr_1.5.1             later_1.3.2              
##  [81] splines_4.4.1             BiocFileCache_2.14.0     
##  [83] lattice_0.22-6            rtracklayer_1.66.0       
##  [85] bit_4.5.0                 tidyselect_1.2.1         
##  [87] Biostrings_2.74.0         knitr_1.48               
##  [89] bookdown_0.41             xfun_0.48                
##  [91] stringi_1.8.4             UCSC.utils_1.2.0         
##  [93] yaml_2.3.10               evaluate_1.0.1           
##  [95] codetools_0.2-20          tibble_3.2.1             
##  [97] BiocManager_1.30.25       cli_3.6.3                
##  [99] munsell_0.5.1             processx_3.8.4           
## [101] jquerylib_0.1.4           Rcpp_1.0.13              
## [103] GenomicDataCommons_1.30.0 dbplyr_2.5.0             
## [105] png_0.1-8                 XML_3.99-0.17            
## [107] parallel_4.4.1            readr_2.1.5              
## [109] blob_1.2.4                prettyunits_1.2.0        
## [111] bitops_1.0-9              glmnet_4.1-8             
## [113] scales_1.3.0              purrr_1.0.2              
## [115] crayon_1.5.3              rlang_1.1.4              
## [117] KEGGREST_1.46.0           rvest_1.0.4              
## [119] formatR_1.14