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 Under development (unstable) (2024-01-16 r85808)
## Platform: x86_64-pc-linux-gnu
## Running under: Ubuntu 22.04.3 LTS
## 
## Matrix products: default
## BLAS:   /home/biocbuild/bbs-3.19-bioc/R/lib/libRblas.so 
## LAPACK: /usr/lib/x86_64-linux-gnu/lapack/liblapack.so.3.10.0
## 
## 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_1.21.2         TCGAutils_1.23.3           
##  [3] curatedTCGAData_1.25.4      MultiAssayExperiment_1.29.1
##  [5] SummarizedExperiment_1.33.3 Biobase_2.63.0             
##  [7] GenomicRanges_1.55.3        GenomeInfoDb_1.39.6        
##  [9] IRanges_2.37.1              S4Vectors_0.41.3           
## [11] BiocGenerics_0.49.1         MatrixGenerics_1.15.0      
## [13] matrixStats_1.2.0           futile.logger_1.4.3        
## [15] survival_3.5-8              ggplot2_3.4.4              
## [17] dplyr_1.1.4                 BiocStyle_2.31.0           
## 
## loaded via a namespace (and not attached):
##   [1] jsonlite_1.8.8            shape_1.4.6              
##   [3] magrittr_2.0.3            magick_2.8.2             
##   [5] GenomicFeatures_1.55.3    farver_2.1.1             
##   [7] rmarkdown_2.25            BiocIO_1.13.0            
##   [9] zlibbioc_1.49.0           vctrs_0.6.5              
##  [11] memoise_2.0.1             Rsamtools_2.19.3         
##  [13] RCurl_1.98-1.14           htmltools_0.5.7          
##  [15] S4Arrays_1.3.3            BiocBaseUtils_1.5.0      
##  [17] progress_1.2.3            AnnotationHub_3.11.1     
##  [19] lambda.r_1.2.4            curl_5.2.0               
##  [21] pROC_1.18.5               SparseArray_1.3.4        
##  [23] sass_0.4.8                bslib_0.6.1              
##  [25] plyr_1.8.9                httr2_1.0.0              
##  [27] futile.options_1.0.1      cachem_1.0.8             
##  [29] GenomicAlignments_1.39.4  mime_0.12                
##  [31] lifecycle_1.0.4           iterators_1.0.14         
##  [33] pkgconfig_2.0.3           Matrix_1.6-5             
##  [35] R6_2.5.1                  fastmap_1.1.1            
##  [37] GenomeInfoDbData_1.2.11   digest_0.6.34            
##  [39] colorspace_2.1-0          AnnotationDbi_1.65.2     
##  [41] ps_1.7.6                  ExperimentHub_2.11.1     
##  [43] RSQLite_2.3.5             labeling_0.4.3           
##  [45] filelock_1.0.3            fansi_1.0.6              
##  [47] httr_1.4.7                abind_1.4-5              
##  [49] compiler_4.4.0            bit64_4.0.5              
##  [51] withr_3.0.0               backports_1.4.1          
##  [53] BiocParallel_1.37.0       DBI_1.2.1                
##  [55] highr_0.10                biomaRt_2.59.1           
##  [57] rappdirs_0.3.3            DelayedArray_0.29.2      
##  [59] rjson_0.2.21              tools_4.4.0              
##  [61] chromote_0.2.0            glue_1.7.0               
##  [63] restfulr_0.0.15           promises_1.2.1           
##  [65] grid_4.4.0                checkmate_2.3.1          
##  [67] generics_0.1.3            gtable_0.3.4             
##  [69] tzdb_0.4.0                websocket_1.4.1          
##  [71] hms_1.1.3                 xml2_1.3.6               
##  [73] utf8_1.2.4                XVector_0.43.1           
##  [75] BiocVersion_3.19.1        foreach_1.5.2            
##  [77] pillar_1.9.0              stringr_1.5.1            
##  [79] later_1.3.2               splines_4.4.0            
##  [81] BiocFileCache_2.11.1      lattice_0.22-5           
##  [83] rtracklayer_1.63.0        bit_4.0.5                
##  [85] tidyselect_1.2.0          Biostrings_2.71.2        
##  [87] knitr_1.45                bookdown_0.37            
##  [89] xfun_0.42                 stringi_1.8.3            
##  [91] yaml_2.3.8                evaluate_0.23            
##  [93] codetools_0.2-19          tibble_3.2.1             
##  [95] BiocManager_1.30.22       cli_3.6.2                
##  [97] munsell_0.5.0             processx_3.8.3           
##  [99] jquerylib_0.1.4           Rcpp_1.0.12              
## [101] GenomicDataCommons_1.27.1 dbplyr_2.4.0             
## [103] png_0.1-8                 XML_3.99-0.16.1          
## [105] parallel_4.4.0            readr_2.1.5              
## [107] blob_1.2.4                prettyunits_1.2.0        
## [109] bitops_1.0-7              glmnet_4.1-8             
## [111] scales_1.3.0              purrr_1.0.2              
## [113] crayon_1.5.2              rlang_1.1.3              
## [115] KEGGREST_1.43.0           rvest_1.0.4              
## [117] formatR_1.14