## ----'installDer', eval = FALSE--------------------------------------------
#  install.packages("BiocManager")
#  BiocManager::install("derfinderPlot")
#  
#  ## Check that you have a valid Bioconductor installation
#  BiocManager::valid()

## ----'citation'------------------------------------------------------------
## Citation info
citation('derfinderPlot')

## ----vignetteSetup, echo=FALSE, message=FALSE, warning = FALSE-------------
## Track time spent on making the vignette
startTime <- Sys.time()

## Bib setup
library('knitcitations')

## Load knitcitations with a clean bibliography
cleanbib()
cite_options(hyperlink = 'to.doc', citation_format = 'text', style = 'html')
# Note links won't show for now due to the following issue
# https://github.com/cboettig/knitcitations/issues/63

## Write bibliography information
bib <- c(knitcitations = citation('knitcitations'),
    derfinderPlot = citation('derfinderPlot')[1], 
    BiocStyle = citation('BiocStyle'),
    knitr = citation('knitr')[3],
    rmarkdown = citation('rmarkdown'),
    derfinder = citation('derfinder')[1],
    ggbio = citation('ggbio'),
    brainspan = RefManageR::BibEntry(bibtype = 'Unpublished',
        key = 'brainspan',
        title = 'Atlas of the Developing Human Brain [Internet]. Funded by ARRA Awards 1RC2MH089921-01, 1RC2MH090047-01, and 1RC2MH089929-01.',
        author = 'BrainSpan', year = 2011, url = 'http://www.brainspan.org/'),
    R = citation(),
    IRanges = citation('IRanges'),
    sessioninfo = citation('sessioninfo'),
    testthat = citation('testthat'),
    GenomeInfoDb = RefManageR::BibEntry(bibtype = 'manual',
        key = 'GenomeInfoDb',
        author = 'Sonali Arora and Martin Morgan and Marc Carlson and H. Pagès',
        title = "GenomeInfoDb: Utilities for manipulating chromosome and other 'seqname' identifiers",
        year = 2017, doi = '10.18129/B9.bioc.GenomeInfoDb'),
    GenomicRanges = citation('GenomicRanges'),
    ggplot2 = citation('ggplot2'),
    plyr = citation('plyr'),
    RColorBrewer = citation('RColorBrewer'),
    reshape2 = citation('reshape2'),
    scales = citation('scales'),
    biovizBase = citation('biovizBase'),
    bumphunter = citation('bumphunter')[1],
    TxDb.Hsapiens.UCSC.hg19.knownGene = citation('TxDb.Hsapiens.UCSC.hg19.knownGene'),
    bumphunterPaper = RefManageR::BibEntry(bibtype = 'article',
        key = 'bumphunterPaper',
        title = 'Bump hunting to identify differentially methylated regions in epigenetic epidemiology studies',
        author = 'Jaffe, Andrew E and Murakami, Peter and Lee, Hwajin and Leek, Jeffrey T and Fallin, M Daniele and Feinberg, Andrew P and Irizarry, Rafael A',
        year = 2012, journal = 'International Journal of Epidemiology'),
    derfinderData = citation('derfinderData')
)
write.bibtex(bib, file = 'derfinderPlotRef.bib')

## Working on Windows?
windowsFlag <- .Platform$OS.type == 'windows'

## ----'start'---------------------------------------------------------------
## Load libraries
suppressPackageStartupMessages(library('derfinder'))
library('derfinderData')
library('derfinderPlot')

## ----'phenoData', results = 'asis'-----------------------------------------
library('knitr')
## Get pheno table
pheno <- subset(brainspanPheno, structure_acronym == 'A1C')

## Display the main information
p <- pheno[, -which(colnames(pheno) %in% c('structure_acronym',
    'structure_name', 'file'))]
rownames(p) <- NULL
kable(p, format = 'html', row.names = TRUE)

## ----'getData', eval = !windowsFlag----------------------------------------
## Determine the files to use and fix the names
files <- rawFiles(system.file('extdata', 'A1C', package = 'derfinderData'),
    samplepatt = 'bw', fileterm = NULL)
names(files) <- gsub('.bw', '', names(files))

## Load the data from disk
system.time(fullCov <- fullCoverage(files = files, chrs = 'chr21'))

## ----'getDataWindows', eval = windowsFlag, echo = FALSE--------------------
#  ## Load data in Windows case
#  foo <- function() {
#      load(system.file('extdata', 'fullCov', 'fullCovA1C.RData',
#          package = 'derfinderData'))
#      return(fullCovA1C)
#  }
#  fullCov <- foo()

## ----'webData', eval = FALSE-----------------------------------------------
#  ## Determine the files to use and fix the names
#  files <- pheno$file
#  names(files) <- gsub('.A1C', '', pheno$lab)
#  
#  ## Load the data from the web
#  system.time(fullCov <- fullCoverage(files = files, chrs = 'chr21'))

## ----'models'--------------------------------------------------------------
## Get some idea of the library sizes
sampleDepths <- sampleDepth(collapseFullCoverage(fullCov), 1)

## Define models
models <- makeModels(sampleDepths, testvars = pheno$group,
    adjustvars = pheno[, c('gender')])

## ----'analyze'-------------------------------------------------------------
## Filter coverage
filteredCov <- lapply(fullCov, filterData, cutoff = 3)

## Perform differential expression analysis
suppressPackageStartupMessages(library('bumphunter'))
system.time(results <- analyzeChr(chr = 'chr21', filteredCov$chr21,
    models, groupInfo = pheno$group, writeOutput = FALSE,
    cutoffFstat = 5e-02, nPermute = 20, seeds = 20140923 + seq_len(20)))

## Quick access to the results
regions <- results$regions$regions

## Annotation database to use
suppressPackageStartupMessages(library('TxDb.Hsapiens.UCSC.hg19.knownGene'))
txdb <- TxDb.Hsapiens.UCSC.hg19.knownGene

## ----'plotOverview', bootstrap.show.warning=FALSE, fig.cap = "Location of the DERs in the genome. This plot is was designed for many chromosomes but only one is shown here for simplicity."----
## Q-values overview
plotOverview(regions = regions, annotation = results$annotation, type = 'qval')

## ----'plotOverview2', bootstrap.show.warning=FALSE, fig.cap = "Location of the DERs in the genome and colored by annotation class. This plot is was designed for many chromosomes but only one is shown here for simplicity."----
## Annotation overview
plotOverview(regions = regions, annotation = results$annotation,
    type = 'annotation')

## ----'regionData'----------------------------------------------------------
## Get required information for the plots
annoRegs <- annotateRegions(regions, genomicState$fullGenome)
regionCov <- getRegionCoverage(fullCov, regions)

## ----'plotRegCov', fig.cap = paste0("Base-pair resolution plot of differentially expressed region ", 1:10, ".")----
## Plot top 10 regions
plotRegionCoverage(regions = regions, regionCoverage = regionCov, 
    groupInfo = pheno$group, nearestAnnotation = results$annotation, 
    annotatedRegions = annoRegs, whichRegions=1:10, txdb = txdb, scalefac = 1,
    ask = FALSE, verbose = FALSE)

## ----'plotCluster', warning=FALSE, fig.cap = "Cluster plot for cluster 1 using ggbio."----
## First cluster
plotCluster(idx = 1, regions = regions, annotation = results$annotation,
    coverageInfo = fullCov$chr21, txdb = txdb, groupInfo = pheno$group,
    titleUse = 'pval')

## ----'plotCluster2', bootstrap.show.warning=FALSE, fig.cap = "Cluster plot for cluster 2 using ggbio."----
## Second cluster
plotCluster(idx = 2, regions = regions, annotation = results$annotation,
    coverageInfo = fullCov$chr21, txdb = txdb, groupInfo = pheno$group,
    titleUse = 'pval')

## ----'vennRegions', fig.cap = "Venn diagram of regions by annotation class."----
## Make venn diagram
venn <- vennRegions(annoRegs)

## It returns the actual venn counts information
venn

## ----createVignette, eval=FALSE--------------------------------------------
#  ## Create the vignette
#  library('rmarkdown')
#  system.time(render('derfinderPlot.Rmd', 'BiocStyle::html_document'))
#  
#  ## Extract the R code
#  library('knitr')
#  knit('derfinderPlot.Rmd', tangle = TRUE)

## ----createVignette2-------------------------------------------------------
## Clean up
unlink('chr21', recursive = TRUE)
file.remove('derfinderPlotRef.bib')

## ----reproducibility1, echo=FALSE------------------------------------------
## Date the vignette was generated
Sys.time()

## ----reproducibility2, echo=FALSE------------------------------------------
## Processing time in seconds
totalTime <- diff(c(startTime, Sys.time()))
round(totalTime, digits=3)

## ----reproducibility3, echo=FALSE-------------------------------------------------------------------------------------
## Session info
library('sessioninfo')
options(width = 120)
session_info()

## ----vignetteBiblio, results = 'asis', echo = FALSE, warning = FALSE, message = FALSE---------------------------------
## Print bibliography
bibliography()

