params <- list(isSlides = "no") ## ----include=FALSE------------------------------------------------------------ suppressPackageStartupMessages(require(knitr)) knitr::opts_chunk$set(echo = TRUE, tidy = T) ## ----setup, include=FALSE----------------------------------------------------- library(TxDb.Mmusculus.UCSC.mm10.knownGene) library(GenomicAlignments) library(DESeq2) library(tximport) library(org.Mm.eg.db) library(goseq) ## ---- eval=F------------------------------------------------------------------ ## setwd("Path/to/Download/RU_RNAseq-master") ## ## ## ---- results='asis',include=TRUE,echo=FALSE---------------------------------- if(params$isSlides == "yes"){ cat("class: inverse, center, middle # Gene Sets

--- " ) }else{ cat("# Gene Sets --- " ) } ## ----eval=T,echo=T, eval=F, echo=T, warning=FALSE,tidy=T---------------------- ## library(GO.db) ## library(reactome.db) ## library(GSEABase) ## ## ---- results='asis',include=TRUE,echo=FALSE---------------------------------- if(params$isSlides == "yes"){ cat("class: inverse, center, middle # MSigDB and Gene Set Collections

--- " ) }else{ cat("# MSigDB and gmt files --- " ) } ## ----gseabase, warning=F, message=F------------------------------------------- library(GSEABase) hallMarks <- getGmt(con="data/h.all.v7.1.symbols.gmt") hallMarks ## ---- GeneSetCollection------------------------------------------------------- hallMarks[[1]] ## ----------------------------------------------------------------------------- names(hallMarks) ## ---- geneIDs----------------------------------------------------------------- geneIds(hallMarks)[1:3] ## ---- wehiA------------------------------------------------------------------- library(msigdbr) mm_H <- msigdbr(species = "Mus musculus", category = "H") head(mm_H) ## ---- results='asis',include=TRUE,echo=FALSE---------------------------------- if(params$isSlides == "yes"){ cat("class: inverse, center, middle # Testing gene set enrichment

--- " ) }else{ cat("# Testing gene set enrichment --- " ) } ## ---- deres------------------------------------------------------------------- Activated_minus_Resting <- read.delim(file="data/Group_Activated_minus_Resting.csv",sep=",") Activated_minus_Resting[1:3,] ## ---- deresFilter------------------------------------------------------------- Activated_minus_Resting <- Activated_minus_Resting[!is.na(Activated_minus_Resting$padj),] Activated_minus_Resting[1:3,] ## ---- results='asis',include=TRUE,echo=FALSE---------------------------------- if(params$isSlides == "yes"){ cat("class: inverse, center, middle # Functional enrichment

--- " ) }else{ cat("# Functional enrichment --- " ) } ## ----func,eval=TRUE,echo=TRUE,cache=TRUE,dependson="anno2"-------------------- UpInAct <- Activated_minus_Resting$padj < 0.05 & Activated_minus_Resting$log2FoldChange > 0 UpInAct <- as.integer(UpInAct) names(UpInAct) <- Activated_minus_Resting$ENTREZID UpInAct[1:4] table(UpInAct) ## ----include=FALSE------------------------------------------------------------ library(goseq) ## ----eval=T,echo=T, eval=T, echo=T, warning=FALSE,tidy=T---------------------- supGenomes <- supportedGenomes() supGenomes[1:2,] ## ----func1,eval=TRUE,echo=TRUE,cache=TRUE,dependson="func", warning=F, message=F, fig.height=3.75,fig.width=3.75---- library(goseq) pwf <- nullp(UpInAct, "mm10", "knownGene", plot.fit = TRUE) ## ----funca,eval=TRUE,echo=FALSE,cache=TRUE,include=FALSE---------------------- load(file = "data/fit.RData") ## ----func2,eval=TRUE,echo=TRUE,cache=TRUE,dependson="func1",warning=FALSE,message=FALSE---- GO_UpInAct <- goseq(pwf,"mm10","knownGene", test.cats=c("GO:BP")) GO_UpInAct[1:3,] ## ----func3,eval=TRUE,echo=TRUE,cache=TRUE,dependson="funca",warning=FALSE,message=FALSE---- library(org.Mm.eg.db) ImmuneResponseGenes <- AnnotationDbi::select(org.Mm.eg.db, keytype = "GOALL", keys = "GO:0006955", columns = "ENTREZID") ImmuneResponseGenes ## ----func4,eval=TRUE,echo=TRUE,cache=TRUE,dependson="func3",warning=FALSE,message=FALSE---- IRG_Entrez <- unique(ImmuneResponseGenes$ENTREZID) IRG_Res <- Activated_minus_Resting[Activated_minus_Resting$ENTREZID %in% IRG_Entrez,] write.table(IRG_Res, file="data/ImmuneResponseGeneTable.csv",sep=",", row.names = FALSE) IRG_Res[1:3,] ## ---- results='asis',include=TRUE,echo=FALSE---------------------------------- if(params$isSlides == "yes"){ cat("class: inverse, center, middle # ClusterProfiler

--- " ) }else{ cat("# ClusterProfiler --- " ) } ## ---- warning=F, message=F---------------------------------------------------- library(clusterProfiler) ## ---- warning=F, message=F---------------------------------------------------- sig_genes <- Activated_minus_Resting[Activated_minus_Resting$padj<0.05,1] head(sig_genes) ## ---- warning=F, message=F---------------------------------------------------- sig_gene_enr <- enrichGO(sig_genes, OrgDb = org.Mm.eg.db) ## ----------------------------------------------------------------------------- sig_gene_enr ## ---- fig.width=10, fig.height=4, message=FALSE, warning=FALSE---------------- library(ggplot2) clusterProfiler::dotplot(sig_gene_enr, showCategory = 6) + theme( axis.text.y = element_text(size = 7)) ## ----------------------------------------------------------------------------- library(enrichplot) sig_gene_enr <- pairwise_termsim(sig_gene_enr) emapplot(sig_gene_enr, showCategory = 15, cex_label_category=0.6) + theme( text = element_text(size = 7)) ## ---- results='asis',include=TRUE,echo=FALSE---------------------------------- if(params$isSlides == "yes"){ cat("class: inverse, center, middle # GSEA

--- " ) }else{ cat("# GSEA --- " ) } ## ---- myRNK------------------------------------------------------------------- forRNK <- Activated_minus_Resting$stat names(forRNK) <- Activated_minus_Resting$ENTREZID forRNK <- forRNK[order(forRNK, decreasing = T)] forRNK[1:6] ## ----------------------------------------------------------------------------- mm_c7 <- msigdbr(species = "Mus musculus", category = "C7")[,c("gs_name","entrez_gene")] head(mm_c7) ## ---- warning=F, message=F---------------------------------------------------- sig_gene_enr <- GSEA(forRNK, TERM2GENE = mm_c7, eps=1e-100) ## ---- fig.width=10, fig.height=4, message=FALSE, warning=FALSE---------------- clusterProfiler::dotplot(sig_gene_enr, showCategory = 6) + theme( axis.text.y = element_text(size = 7)) ## ----------------------------------------------------------------------------- library(enrichplot) sig_gene_enr <- pairwise_termsim(sig_gene_enr) emapplot(sig_gene_enr, showCategory = 10, cex_label_category=0.6) + theme( text = element_text(size = 7)) ## ----------------------------------------------------------------------------- gseaplot(sig_gene_enr, geneSetID = 1, by = "runningScore", title = "GSE15330_HSC_VS_LYMPHOID_PRIMED_MULTIPOTENT_PROGENITOR_DN") ## ----------------------------------------------------------------------------- write.csv(as.data.frame(sig_gene_enr), "cluster_profiler_GSEA_result.csv")