## ----setup, include = FALSE---------------------------------------------------
LOCAL <- identical(Sys.getenv("LOCAL"), "TRUE")
#LOCAL=FALSE
knitr::opts_chunk$set(purl = LOCAL)
knitr::opts_chunk$set(
  collapse = TRUE,
  comment = "#>"
)

## ----loadPatterns, echo=FALSE, cache=FALSE, eval = LOCAL----------------------
require(Patterns)

## ----retcll, warning=FALSE, cache=TRUE, eval = LOCAL--------------------------
require(Patterns)
CLLfile <- "https://github.com/fbertran/Patterns/raw/master/add_data/CLL.RData"
repmis::source_data(CLLfile)

CLL[1:10,1:5]

## ----spltcll, warning=FALSE, cache=TRUE, eval = LOCAL-------------------------
hea_US<-CLL[,which((1:48)%%8<5&(1:48)%%8>0)+2]
hea_S<-CLL[,which(!((1:48)%%8<5&(1:48)%%8>0))+2]

agg_US<-CLL[,which((1:40)%%8<5&(1:40)%%8>0)+98]
agg_S<-CLL[,which(!((1:40)%%8<5&(1:40)%%8>0))+98]

m_hea_US<-as.omics_array(hea_US,c(60,90,210,390),6,name=CLL[,1],gene_ID=CLL[,2])
m_hea_S<- as.omics_array(hea_S,c(60,90,210,390),6,name=CLL[,1],gene_ID=CLL[,2])
  
m_agg_US<-as.omics_array((agg_US),c(60,90,210,390),5,name=CLL[,1],gene_ID=CLL[,2])
m_agg_S<- as.omics_array((agg_S),c(60,90,210,390),5,name=CLL[,1],gene_ID=CLL[,2])

## ----focusEGR1, warning=FALSE, cache=TRUE, fig.keep="none", eval = LOCAL------
matplot(t(log(agg_S[which(CLL[,2] %in% "EGR1"),])),type="l",lty=1)

## ----selection1, message=FALSE, warning=FALSE, cache=TRUE, eval = LOCAL-------
selection1<-geneSelection(list(m_agg_US,m_agg_S),list("condition&time",c(1,2),c(1,1)),-1,alpha=0.1)

## ----selection2, message=FALSE, warning=FALSE, cache=TRUE, eval = LOCAL-------
selection2<-geneSelection(list(m_agg_US,m_agg_S),list("condition&time",c(1,2),c(1,1)+1),-1,alpha=0.1)

## ----selection3, message=FALSE, warning=FALSE, cache=TRUE, eval = LOCAL-------
selection3<-geneSelection(list(m_agg_US,m_agg_S),list("condition&time",c(1,2),c(1,1)+2),50,alpha=0.005)

## ----selection4, message=FALSE, warning=FALSE, cache=TRUE, eval = LOCAL-------
selection4<-geneSelection(list(m_agg_US,m_agg_S),list("condition&time",c(1,2),c(1,1)+3),50,alpha=0.005)

## ----mergeselection, warning=FALSE, fig.keep='first', eval = LOCAL------------
selection<-Patterns::unionOmics(list(selection1,selection2,selection3,selection4))
summary(selection)

## ----sizemergeselection, warning=FALSE, cache=TRUE, eval = LOCAL--------------
length(selection@gene_ID)

## ----translatecll, warning=FALSE, cache=TRUE, eval = LOCAL--------------------
require(biomaRt)

affyids=c("202763_at","209310_s_at","207500_at")
ensembl = useMart("ensembl",dataset="hsapiens_gene_ensembl")
infos<-getBM(attributes=c("affy_hg_u133_plus_2","ensembl_gene_id","hgnc_symbol","chromosome_name","start_position","end_position","band"), filters = "affy_hg_u133_plus_2", values = CLL[CLL[,1] %in% selection@name,1] , mart = ensembl,uniqueRows=TRUE, checkFilters = TRUE)

## ----addgeneid, warning=FALSE, cache=TRUE, eval = LOCAL-----------------------
selection@gene_ID <- lapply(selection@name,function(x) {unique(infos[infos$affy_hg_u133_plus_2==x,"hgnc_symbol"])})

## ----addgroupselection, warning=FALSE, fig.keep='last', eval = LOCAL----------
selection@group <- rep(NA, length(selection@name))
names(selection@group) <- selection@name
selection@group[selection@name %in% selection4@name] <- 4
selection@group[selection@name %in% selection3@name] <- 3
selection@group[selection@name %in% selection2@name] <- 2
selection@group[selection@name %in% selection1@name] <- 1
plot(selection)

## ----checkgroup, warning=FALSE, cache=TRUE, eval = LOCAL----------------------
length(selection@group)

## ----inference, warning=FALSE, cache=TRUE, fig.keep='none', eval = LOCAL------
network<-inference(selection,fitfun="LASSO2",Finit=CascadeFinit(4,4),Fshape=CascadeFshape(4,4))
str(network)

## ----plotF, eval = LOCAL------------------------------------------------------
plotF(network@F, choice='F')

## ----saveinference, eval=FALSE------------------------------------------------
#  save(list=c("selection"),file="selection.RData")
#  save(list=c("infos"),file="infos.RData")

## ----HumanTFDBfailsafe, warning=FALSE, cache=TRUE, include=FALSE, eval = LOCAL----
getTF <- FALSE
try({doc <- read.delim("http://bioinfo.life.hust.edu.cn/static/AnimalTFDB3/download/Homo_sapiens_TF",encoding = "UTF-8", header=TRUE); getTF <- TRUE}, silent = TRUE)
if(!getTF){data(doc)}
TF<-as.character(doc[,"Symbol"])
TF<-TF[order(TF)]

## ----HumanTFDB, warning=FALSE, cache=TRUE, eval = FALSE-----------------------
#  doc <- read.delim("http://bioinfo.life.hust.edu.cn/static/AnimalTFDB3/download/Homo_sapiens_TF",encoding = "UTF-8", header=TRUE)
#  TF<-as.character(doc[,"Symbol"])
#  TF<-TF[order(TF)]

## ----TFinsel, warning=FALSE, cache=TRUE, eval = LOCAL-------------------------
infos_selection <- infos[infos$affy_hg_u133_plus_2 %in% selection@name,]
tfs<-which(infos_selection[,"hgnc_symbol"] %in% TF)

## ----plotTFinsel, warning=FALSE, eval = LOCAL---------------------------------
matplot(t(selection@omicsarray[tfs,]),type="l",lty=1)

## ----plotTFinsel2, warning=FALSE, eval = LOCAL--------------------------------
kk<-kmeans((selection@omicsarray[tfs,]),10)
matplot(t(kk$centers),type="l",lty=1)

## ----TODO, warning=FALSE, echo=FALSE, eval=FALSE------------------------------
#  #TO DO
#  #Focus on TF that were not selected.
#  
#  indice<-which(CLL[,2] %in% TF[tfs<-which(! TF %in% selection@gene_ID)])
#  a<-1:200
#  matplot(log(t(agg_S[indice[a],]/agg_US[indice[a],])),lty=1,type="l")
#  kkk<-kmeans(log((agg_S[indice,]/agg_US[indice,])),10)
#  matplot(t(kkk$centers),type="l",lty=1)
#  
#  poi<-indice[which(kkk$cluster==2 )]
#  matmat<-log((agg_S[poi,]/agg_US[poi,]))
#  
#  addna<-function(mat,t,p){
#  
#  
#    mat2<-mat[,1:t]
#    for(i in 2:p){
#      print(1:t+(i-1)*t)
#      mat2<-cbind(mat2,rep(NA,nrow(mat2)),mat[,1:t+(i-1)*t])
#    }
#    return(mat2)
#  }
#  
#  pdf("forgotten_TF.pdf",width=15,height=5)
#  for(i in 1:15){
#  poi<-indice[which(kkk$cluster==i )]
#  if(length(poi)>2){
#  matmat<-log((agg_S[poi,]/agg_US[poi,]))
#  #matplot(t(matmat),lty=1,type="l")
#  matplot(t(addna(matmat,4,5)),lty=1,type="l")}
#  }
#  dev.off()
#  abline(v=c(2,6,10,14,18))
#  
#  
#  poi<-indice[which(kkk$cluster==1 )]
#  matplot(log(t(agg_S[poi,]/agg_US[poi,])),lty=1,type="l")
#  TFi<-function(x) length(which(TF %in% x))
#  
#  
#  
#  n<-40
#  kre<-kmeans(selection@omicsarray,n)
#  kre
#  lll<-split(selection@gene_ID,kre$cluster)
#  
#  require(DCGL)
#  require("clusterProfiler")
#  require("AnnotationFuncs")
#  require(org.Hs.eg.db)
#  
#  pp<-list()
#  
#  for(k in 1:2){
#    print(k)
#  pp[[k]]<-translate(lll[[k]],from=org.Hs.egSYMBOL2EG,simplify=TRUE)
#  # GOs[[k]]<-enrichGO(pp, organism = "human", ont = "MF", pvalueCutoff = 0.05,
#  #          pAdjustMethod = "BH", qvalueCutoff = 0.2, minGSSize = 5,
#  #          readable = FALSE)
#  
#  }
#  
#  names(pp)<-paste("X",1:2,sep="")
#  test<-compareCluster(pp,fun="enrichGO", organism="human", pvalueCutoff=0.05)
#  
#  
#  plot(test)
#  
#  translate(lll[[k]],from=org.Hs.egSYMBOL2EG,simplify=TRUE)
#  
#  
#  TFu<-(unlist(lapply(pp,TFi)))
#  TFy<-unlist(lapply(pp,length))
#  
#  plot(TFu/TFy)
#  plot(TFu)
#  sum(TFu)
#  
#  entrez<-translate(selection@gene_ID,from=org.Hs.egSYMBOL2EG,simplify=TRUE)
#  
#  geneName<-translate(entrez[which(TF %in% entrez)],from=org.Hs.egSYMBOL,simplify=TRUE)
#  
#  which(selection@gene_ID %in% "EGR1")