params <-
list(seed = 29221)

## ----eval=FALSE---------------------------------------------------------------
#  if (!require("BiocManager"))
#    install.packages("BiocManager")
#  BiocManager::install("glmSparseNet")

## ----packages, message=FALSE, warning=FALSE-----------------------------------
library(dplyr)
library(ggplot2)
library(survival)
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 <- glmSparseNet:::show.message(FALSE)
# Setting ggplot2 default theme as minimal
theme_set(ggplot2::theme_minimal())

## ----curated_data, include=TRUE, results="hide", message=FALSE, warning=FALSE----
brca <- tryCatch({
  curatedTCGAData(
    diseaseCode = "BRCA",
    assays = "RNASeq2GeneNorm",
    version = "1.1.38", 
    dry.run = FALSE
  )
}, error = function(err) {
  NULL
})

## ----curated_data_non_eval, eval=FALSE----------------------------------------
#  brca <- curatedTCGAData(diseaseCode = "BRCA", assays = "RNASeq2GeneNorm",
#                          version = "1.1.38", dry.run = FALSE)

## ----data.show, warning=FALSE, error=FALSE, eval=!is.null(brca)---------------
brca <- TCGAutils::TCGAsplitAssays(brca, c('01','11'))
xdata.raw <- t(cbind(assay(brca[[1]]), assay(brca[[2]])))

# Get matches between survival and assay data
class.v        <- TCGAbiospec(rownames(xdata.raw))$sample_definition %>% factor
names(class.v) <- rownames(xdata.raw)

# keep features with standard deviation > 0
xdata.raw <- xdata.raw %>% 
  { (apply(., 2, sd) != 0) } %>% 
  { xdata.raw[, .] } %>%
  scale()

set.seed(params$seed)
small.subset <- c('CD5', 'CSF2RB', 'HSF1', 'IRGC', 'LRRC37A6P', 'NEUROG2', 
                  'NLRC4', 'PDE11A', 'PIK3CB', 'QARS', 'RPGRIP1L', 'SDC1', 
                  'TMEM31', 'YME1L1', 'ZBTB11', 
                  sample(colnames(xdata.raw), 100))

xdata <- xdata.raw[, small.subset[small.subset %in% colnames(xdata.raw)]]
ydata <- class.v

## ----fit.show, eval=!is.null(brca)--------------------------------------------
fitted <- cv.glmHub(xdata, ydata, 
                    family  = 'binomial',
                    network = 'correlation', 
                    nlambda = 1000,
                    network.options = networkOptions(cutoff = .6, 
                                                     min.degree = .2))

## ----results, eval=!is.null(brca)---------------------------------------------
plot(fitted)

## ----show_coefs, eval=!is.null(brca)------------------------------------------
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()

## ----hallmarks, eval=!is.null(brca)-------------------------------------------
geneNames(names(coefs.v)) %>% { hallmarks(.$external_gene_name)$heatmap }

## ----accuracy, echo=FALSE, eval=!is.null(brca)--------------------------------
resp <- predict(fitted, s = 'lambda.min', newx = xdata, type = 'class')
flog.info('Misclassified (%d)', sum(ydata != resp))
flog.info('  * False primary solid tumour: %d', 
          sum(resp != ydata & resp == 'Primary Solid Tumor'))
flog.info('  * False normal              : %d', 
          sum(resp != ydata & resp == 'Solid Tissue Normal'))

## ----predict, echo=FALSE, warning=FALSE, eval=!is.null(brca)------------------
response <- predict(fitted, s = 'lambda.min', newx = xdata, type = 'response')
qplot(response, bins = 100)

## ----roc, echo=FALSE, eval=!is.null(brca)-------------------------------------
roc_obj <- pROC::roc(ydata, as.vector(response))

data.frame(TPR = roc_obj$sensitivities, FPR = 1 - roc_obj$specificities) %>%
  ggplot() +geom_line(aes(FPR,TPR), color = 2, size = 1, alpha = 0.7)+
      labs(title= sprintf("ROC curve (AUC = %f)", pROC::auc(roc_obj)), 
           x = "False Positive Rate (1-Specificity)", 
           y = "True Positive Rate (Sensitivity)")

## ----sessionInfo--------------------------------------------------------------
sessionInfo()