Example for Survival Data – Skin Melanoma
2021-10-26
Contents
0.1 Instalation
if (!require('BiocManager'))
install.packages('BiocManager')
BiocManager::install('glmSparseNet')1 Required Packages
library(dplyr)
library(ggplot2)
library(survival)
library(loose.rock)
library(futile.logger)
library(curatedTCGAData)
library(TCGAutils)
#
library(glmSparseNet)
#
# Some general options for futile.logger the debugging package
.Last.value <- flog.layout(layout.format('[~l] ~m'))
.Last.value <- loose.rock::show.message(FALSE)
# 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.
skcm <- curatedTCGAData(diseaseCode = 'SKCM', assays = 'RNASeq2GeneNorm',
version = '1.1.38', dry.run = FALSE)Build the survival data from the clinical columns.
- Merge survival times for patients, which have different columns in case they are alive or dead.
- Build two matrix objects that fit the data
xdataandydata
skcm.metastatic <- TCGAutils::TCGAsplitAssays(skcm, '06')
xdata.raw <- t(assay(skcm.metastatic[[1]]))
# Get survival information
ydata.raw <- colData(skcm.metastatic) %>% as.data.frame %>%
# Find max time between all days (ignoring missings)
dplyr::rowwise() %>%
dplyr::mutate(
time = max(days_to_last_followup,
days_to_death,
na.rm = TRUE)
) %>%
# Keep only survival variables and codes
dplyr::select(patientID, status = vital_status, time) %>%
# Discard individuals with survival time less or equal to 0
dplyr::filter(!is.na(time) & time > 0) %>%
as.data.frame()
# Get survival information
ydata.raw <- colData(skcm) %>% as.data.frame %>%
# Find max time between all days (ignoring missings)
dplyr::rowwise() %>%
dplyr::mutate(
time = max(days_to_last_followup, days_to_death, na.rm = TRUE)
) %>%
# Keep only survival variables and codes
dplyr::select(patientID, status = vital_status, time) %>%
# Discard individuals with survival time less or equal to 0
dplyr::filter(!is.na(time) & time > 0) %>% as.data.frame
# Set index as the patientID
rownames(ydata.raw) <- ydata.raw$patientID
# keep only features that have standard deviation > 0
xdata.raw <- xdata.raw[TCGAbarcode(rownames(xdata.raw)) %in%
rownames(ydata.raw),]
xdata.raw <- xdata.raw %>%
{ (apply(., 2, sd) != 0) } %>%
{ xdata.raw[, .] } %>%
scale
# Order ydata the same as assay
ydata.raw <- ydata.raw[TCGAbarcode(rownames(xdata.raw)), ]
set.seed(params$seed)
small.subset <- c('FOXL2', 'KLHL5', 'PCYT2', 'SLC6A10P', 'STRAP', 'TMEM33',
'WT1-AS', sample(colnames(xdata.raw), 100))
xdata <- xdata.raw[, small.subset[small.subset %in% colnames(xdata.raw)]]
ydata <- ydata.raw %>% dplyr::select(time, status)3 Fit models
Fit model model penalizing by the hubs using the cross-validation function by
cv.glmHub.
fitted <- cv.glmHub(xdata,
Surv(ydata$time, ydata$status),
family = 'cox',
foldid = balanced.cv.folds(!!ydata$status)$output,
network = 'correlation',
network.options = networkOptions(min.degree = .2,
cutoff = .6))4 Results of Cross Validation
Shows the results of 100 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
coefs.v <- coef(fitted, s = 'lambda.min')[,1] %>% { .[. != 0]}
coefs.v %>% {
data.frame(ensembl.id = names(.),
gene.name = geneNames(names(.))$external_gene_name,
coefficient = .,
stringsAsFactors = FALSE)
} %>%
arrange(gene.name) %>%
knitr::kable()| ensembl.id | gene.name | coefficient | |
|---|---|---|---|
| PCYT2 | PCYT2 | AMICA1 | 0.0646641 |
| AMICA1 | AMICA1 | C4orf49 | -0.2758400 |
| C4orf49 | C4orf49 | PCYT2 | -0.0059089 |
4.2 Hallmarks of Cancer
geneNames(names(coefs.v)) %>% { hallmarks(.$external_gene_name)$heatmap }
4.3 Survival curves and Log rank test
separate2GroupsCox(as.vector(coefs.v),
xdata[, names(coefs.v)],
ydata,
plot.title = 'Full dataset', legend.outside = FALSE)## $pvalue
## [1] 0.0001269853
##
## $plot
##
## $km
## Call: survfit(formula = survival::Surv(time, status) ~ group, data = prognostic.index.df)
##
## n events median 0.95LCL 0.95UCL
## Low risk 180 79 4000 2927 6164
## High risk 179 114 2005 1524 28295 Session Info
sessionInfo()## R version 4.1.1 (2021-08-10)
## Platform: x86_64-pc-linux-gnu (64-bit)
## Running under: Ubuntu 20.04.3 LTS
##
## Matrix products: default
## BLAS: /home/biocbuild/bbs-3.14-bioc/R/lib/libRblas.so
## LAPACK: /home/biocbuild/bbs-3.14-bioc/R/lib/libRlapack.so
##
## 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
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## [11] LC_MEASUREMENT=en_US.UTF-8 LC_IDENTIFICATION=C
##
## attached base packages:
## [1] grid parallel stats4 stats graphics grDevices utils
## [8] datasets methods base
##
## other attached packages:
## [1] VennDiagram_1.6.20 reshape2_1.4.4
## [3] forcats_0.5.1 glmSparseNet_1.12.0
## [5] glmnet_4.1-2 Matrix_1.3-4
## [7] TCGAutils_1.14.0 curatedTCGAData_1.15.1
## [9] MultiAssayExperiment_1.20.0 SummarizedExperiment_1.24.0
## [11] Biobase_2.54.0 GenomicRanges_1.46.0
## [13] GenomeInfoDb_1.30.0 IRanges_2.28.0
## [15] S4Vectors_0.32.0 BiocGenerics_0.40.0
## [17] MatrixGenerics_1.6.0 matrixStats_0.61.0
## [19] futile.logger_1.4.3 loose.rock_1.2.0
## [21] survival_3.2-13 ggplot2_3.3.5
## [23] dplyr_1.0.7 BiocStyle_2.22.0
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## loaded via a namespace (and not attached):
## [1] readxl_1.3.1 backports_1.2.1
## [3] AnnotationHub_3.2.0 BiocFileCache_2.2.0
## [5] plyr_1.8.6 splines_4.1.1
## [7] sparsebn_0.1.2 BiocParallel_1.28.0
## [9] digest_0.6.28 foreach_1.5.1
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## [29] jsonlite_1.7.2 zoo_1.8-9
## [31] iterators_1.0.13 glue_1.4.2
## [33] survminer_0.4.9 GenomicDataCommons_1.18.0
## [35] gtable_0.3.0 zlibbioc_1.40.0
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