load("../1.align/txi.rsem.RData")
metadata <- read.csv("metadata.csv", stringsAsFactors = TRUE)
metadata$Trt <- factor(metadata$Trt, levels=c("SAL","LPS"))
rownames(metadata) <- metadata$ID
all.equal(colnames(txi.rsem$counts), rownames(metadata))
## [1] TRUE

Differential gene expression for design: Group + Drug + Trt

dds <- DESeqDataSetFromTximport(txi.rsem, colData = metadata, design = ~ Group + Drug + Trt)

# filter low expressed genes
keep <- rowSums(counts(dds)) >= 50
table(keep)
## keep
## FALSE  TRUE 
## 38866 16621
dds <- dds[keep,]

dds <- DESeq(dds)
resultsNames(dds)
## [1] "Intercept"        "Group_MIA_vs_CON" "Drug_PLX_vs_CON"  "Trt_LPS_vs_SAL"

PCA

vsd <- vst(dds, blind=FALSE)
m <- plotPCA(vsd, intgroup=c("Group", "Drug"), returnData = TRUE)
ggplot(m, aes(PC1, PC2, color = group)) + geom_point(size = 3) + theme_cowplot() + xlab("PC1: 71% variance") + ylab("PC2: 7% variance") + geom_text_repel(aes(label = name)) + scale_color_manual(values = c("black", "turquoise3", "red", "purple2"))

Cluster

tree = hclust(dist(t(assay(vsd))), method = "average")
plot(tree, main = "hclust, average VST", sub="", xlab="", cex.lab = 1, cex.axis = 1, cex.main = 1)

sessionInfo()
## R version 4.0.3 (2020-10-10)
## Platform: x86_64-apple-darwin17.0 (64-bit)
## Running under: macOS Big Sur 10.16
## 
## Matrix products: default
## BLAS:   /Library/Frameworks/R.framework/Versions/4.0/Resources/lib/libRblas.dylib
## LAPACK: /Library/Frameworks/R.framework/Versions/4.0/Resources/lib/libRlapack.dylib
## 
## locale:
## [1] en_US.UTF-8/en_US.UTF-8/en_US.UTF-8/C/en_US.UTF-8/en_US.UTF-8
## 
## attached base packages:
## [1] parallel  stats4    stats     graphics  grDevices utils     datasets 
## [8] methods   base     
## 
## other attached packages:
##  [1] ggfortify_0.4.12            ggrepel_0.9.1              
##  [3] AnnotationHub_2.22.1        BiocFileCache_1.14.0       
##  [5] dbplyr_2.1.1                org.Mm.eg.db_3.12.0        
##  [7] AnnotationDbi_1.52.0        DESeq2_1.30.1              
##  [9] SummarizedExperiment_1.20.0 Biobase_2.50.0             
## [11] MatrixGenerics_1.2.1        matrixStats_0.59.0         
## [13] GenomicRanges_1.42.0        GenomeInfoDb_1.26.7        
## [15] IRanges_2.24.1              S4Vectors_0.28.1           
## [17] BiocGenerics_0.36.1         cowplot_1.1.1              
## [19] forcats_0.5.1               stringr_1.4.0              
## [21] dplyr_1.0.7                 purrr_0.3.4                
## [23] readr_1.4.0                 tidyr_1.1.3                
## [25] tibble_3.1.2                ggplot2_3.3.5              
## [27] tidyverse_1.3.1            
## 
## loaded via a namespace (and not attached):
##  [1] colorspace_2.0-2              ellipsis_0.3.2               
##  [3] XVector_0.30.0                fs_1.5.0                     
##  [5] rstudioapi_0.13               farver_2.1.0                 
##  [7] bit64_4.0.5                   interactiveDisplayBase_1.28.0
##  [9] fansi_0.5.0                   lubridate_1.7.10             
## [11] xml2_1.3.2                    splines_4.0.3                
## [13] cachem_1.0.5                  geneplotter_1.68.0           
## [15] knitr_1.33                    jsonlite_1.7.2               
## [17] broom_0.7.8                   annotate_1.68.0              
## [19] shiny_1.6.0                   BiocManager_1.30.16          
## [21] compiler_4.0.3                httr_1.4.2                   
## [23] backports_1.2.1               assertthat_0.2.1             
## [25] Matrix_1.3-4                  fastmap_1.1.0                
## [27] cli_3.0.0                     later_1.2.0                  
## [29] htmltools_0.5.1.1             tools_4.0.3                  
## [31] gtable_0.3.0                  glue_1.4.2                   
## [33] GenomeInfoDbData_1.2.4        rappdirs_0.3.3               
## [35] Rcpp_1.0.7                    cellranger_1.1.0             
## [37] jquerylib_0.1.4               vctrs_0.3.8                  
## [39] xfun_0.24                     rvest_1.0.0                  
## [41] mime_0.11                     lifecycle_1.0.0              
## [43] XML_3.99-0.6                  zlibbioc_1.36.0              
## [45] scales_1.1.1                  hms_1.1.0                    
## [47] promises_1.2.0.1              RColorBrewer_1.1-2           
## [49] yaml_2.2.1                    curl_4.3.2                   
## [51] gridExtra_2.3                 memoise_2.0.0                
## [53] sass_0.4.0                    stringi_1.6.2                
## [55] RSQLite_2.2.7                 highr_0.9                    
## [57] BiocVersion_3.12.0            genefilter_1.72.1            
## [59] BiocParallel_1.24.1           rlang_0.4.11                 
## [61] pkgconfig_2.0.3               bitops_1.0-7                 
## [63] evaluate_0.14                 lattice_0.20-44              
## [65] labeling_0.4.2                bit_4.0.4                    
## [67] tidyselect_1.1.1              magrittr_2.0.1               
## [69] R6_2.5.0                      generics_0.1.0               
## [71] DelayedArray_0.16.3           DBI_1.1.1                    
## [73] pillar_1.6.1                  haven_2.4.1                  
## [75] withr_2.4.2                   survival_3.2-11              
## [77] RCurl_1.98-1.3                modelr_0.1.8                 
## [79] crayon_1.4.1                  utf8_1.2.1                   
## [81] rmarkdown_2.9                 locfit_1.5-9.4               
## [83] grid_4.0.3                    readxl_1.3.1                 
## [85] blob_1.2.1                    reprex_2.0.0                 
## [87] digest_0.6.27                 xtable_1.8-4                 
## [89] httpuv_1.6.1                  munsell_0.5.0                
## [91] bslib_0.2.5.1