if (!require('BiocManager'))
install.packages('BiocManager')
BiocManager::install('glmSparseNet')
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())
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', FALSE, cache = tempdir())
Build the survival data from the clinical columns.
xdata
and ydata
skcm.metastatic <- TCGAutils::splitAssays(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)
rowwise %>%
mutate(time = max(days_to_last_followup, days_to_death, na.rm = TRUE)) %>%
# Keep only survival variables and codes
select(patientID, status = vital_status, time) %>%
# Discard individuals with survival time less or equal to 0
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)
rowwise %>%
mutate(time = max(days_to_last_followup, days_to_death, na.rm = TRUE)) %>%
# Keep only survival variables and codes
select(patientID, status = vital_status, time) %>%
# Discard individuals with survival time less or equal to 0
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 %>% select(time, status)
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))
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)
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(.))$external_gene_name,
coefficient = .,
stringsAsFactors = FALSE)
} %>%
arrange(gene.name) %>%
knitr::kable()
ensembl.id | gene.name | coefficient |
---|---|---|
PCYT2 | AMICA1 | 0.0646641 |
AMICA1 | C4orf49 | -0.2758400 |
C4orf49 | PCYT2 | -0.0059089 |
geneNames(names(coefs.v)) %>% { hallmarks(.$external_gene_name)$heatmap }
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 2829