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Knit directory: CrossSpecies_CM_Diff_RNA/

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Rmd 0fcf7c3 John D. Hurley 2026-01-28 HeatMap knit update
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Rmd 085c1db John D. Hurley 2026-01-28 Finalizing CorHeatMap

####Library Loading####
library("edgeR")
library("ggplot2")
library("tibble")
library("dplyr")
library("ggrepel")
library("readr")
library("org.Hs.eg.db")
library("AnnotationDbi")
library("pheatmap")
library("Cormotif")
library("tidyverse")
library("workflowr")
library("RUVSeq")
library("SummarizedExperiment")
library("readxl")
library("ggfortify")
library("ComplexHeatmap")

# BiocManager::install("SummarizedExperiment")

RNA_fc_df <- readRDS("data/Raw_Data/RNA_fc_df.RDS")
RNA_Metadata <- readRDS("data/Raw_Data/RNA_Metadata.RDS")

RNA_fc <- readRDS("data/QC/RNA_fc.RDS")
RNA_log2cpm <- ("data/QC/RNA_log2cpm.RDS")

Filt_RMG0_RNA_fc <- readRDS("data/QC/Filt_RMG0_RNA_fc.RDS")
Filt_RMG0_RNA_log2cpm <-("data/QC/RNA_log2cpm_RMG0.RDS")

Cor_Filt_RMG0_RNA_log2cpm <- readRDS("data/QC/Cor_Filt_RMG0_RNA_log2cpm.RDS")
Cor_metadata <- readRDS("data/QC/Cor_RNA_metadata.RDS")
ann_colors <- readRDS("data/QC/ann_colors.RDS")

RNA_Metadata_No4 <- readRDS("data/QC/RNA_Metatdata_No4.RDS")
Filt_RMG0_RNA_fc_NoD4 <- readRDS("data/QC/Filt_RMG0_RNA_fc_NoD4.RDS")
Filt_RMG0_RNA_log2cpm_NoD4 <- readRDS("data/QC/Filt_RMG0_RNA_log2cpm_NoD4.RDS")

Cor_metadata_No4 <- readRDS("data/QC/Cor_metadata_No4.RDS")
Cor_Filt_RMG0_RNA_log2cpm_NoD4 <- readRDS("data/QC/Cor_Filt_RMG0_RNA_log2cpm_NoD4.RDS")
ann_colors_No4 <- readRDS("data/QC/ann_colors_no4.RDS")
# #To keep only OrthoGenes and sample columns
# RNA_fc <- RNA_joined_fc[ , !(names(RNA_joined_fc) %in% c("gene","Chr.x","Start.x","End.x","Strand.x","Length.x","Geneid.x","Chr.y","Start.y","End.y","Strand.y","Length.y","Geneid.y"))]
# # 89 columns; 7 x 6 = 42 Human Exp, 7 x 6 = 42 Chimp Exp, 4 Human Replicate
# rownames(RNA_fc) <- RNA_joined_fc$gene
# 
# #Rename column Names to More Useful Info
col_names <- c("H28126_D0",
              "H28126_D2",
              "H28126_D4",
              "H28126_D5",
              "H28126_D15",
              "H28126_D30",
              "H17_D0",
              "H17_D2",
              "H17_D4",
              "H17_D5",
              "H17_D15",
              "H17_D30",
              "H78_D0",
              "H78_D2",
              "H78_D4",
              "H78_D5",
              "H78_D15",
              "H78_D30",
              "H20682_D0",
              "H20682_D2",
              "H20682_D4",
              "H20682_D5",
              "H20682_D15",
              "H20682_D30",
              "H22422_D0",
              "H22422_D2",
              "H22422_D4",
              "H22422_D5",
              "H22422_D15",
              "H22422_D30",
              "H21792_D0",
              "H21792_D2",
              "H21792_D4",
              "H21792_D5",
              "H21792_D15",
              "H21792_D30",
              "H24280_D0",
              "H24280_D2",
              "H24280_D4",
              "H24280_D5",
              "H24280_D15",
              "H24280_D30",
              "H20682R_D0",
              "H20682R_D2",
              "H20682R_D5",
              "H20682R_D30",
              "C3649_D0",
              "C3649_D2",
              "C3649_D4",
              "C3649_D5",
              "C3649_D15",
              "C3649_D30",
              "C4955_D0",
              "C4955_D2",
              "C4955_D4",
              "C4955_D5",
              "C4955_D15",
              "C4955_D30",
              "C3651_D0",
              "C3651_D2",
              "C3651_D4",
              "C3651_D5",
              "C3651_D15",
              "C3651_D30",
              "C40210_D0",
              "C40210_D2",
              "C40210_D4",
              "C40210_D5",
              "C40210_D15",
              "C40210_D30",
              "C8861_D0",
              "C8861_D2",
              "C8861_D4",
              "C8861_D5",
              "C8861_D15",
              "C8861_D30",
              "C40280_D0",
              "C40280_D2",
              "C40280_D4",
              "C40280_D5",
              "C40280_D15",
              "C40280_D30",
              "C3647_D0",
              "C3647_D2",
              "C3647_D4",
              "C3647_D5",
              "C3647_D15",
              "C3647_D30"
)
# colnames(RNA_fc) <- col_names 
# dim(RNA_fc)
# 
# sum(duplicated(rownames(RNA_fc)))
# ensembl_ids_unfilt <- rownames(RNA_fc)
# entrez_ids_unfilt <- mapIds(org.Hs.eg.db,
#                             keys = ensembl_ids_unfilt,
#                             column = "ENTREZID",
#                             keytype = "ENSEMBL",
#                             multiVals = "first")
# symbol_ids_unfilt <- mapIds(org.Hs.eg.db,
#                             keys = ensembl_ids_unfilt,
#                             column = "SYMBOL",
#                             keytype = "ENSEMBL",
#                             multiVals = "first")
# 
# RNA_fc_df <- as.data.frame(RNA_fc)
# RNA_fc_df <- RNA_fc_df %>%
#   rownames_to_column(var = "Ensemble") %>%
#   dplyr::mutate(
#     Entrez_ID = entrez_ids_unfilt,
#     Symbol    = symbol_ids_unfilt
#   ) %>%
#   dplyr::select(
#     Ensemble,        # 1st column
#     Entrez_ID,       # 2nd column
#     Symbol,          # 3rd column
#     everything()     # rest unchanged
#   )
# 
# # saveRDS(RNA_fc_df,"data/Data_Frames/RNA_fc_df.RDS")
# 
# RNA_Metadata <- read_excel("~/diff_timeline_tes/RNA/RNA_Metadata.xlsx")
# 
# # saveRDS(RNA_Metadata,"data/Data_Frames/RNA_Metadata.RDS")
#####Unfiltered####
RNA_fc <- RNA_fc_df %>% 
  dplyr::select(c(-"Entrez_ID", -"Symbol")) %>% 
  column_to_rownames("Ensemble")

# saveRDS(RNA_fc,"data/QC/RNA_fc.RDS")

RNA_log2cpm <- cpm(RNA_fc,log=TRUE)
print(hist(RNA_log2cpm,  main = "Histogram of all counts (unfiltered)",
     xlab =expression("Log"[2]*" counts-per-million"), col =4 ))

Version Author Date
d9f15a6 John D. Hurley 2026-01-28
$breaks
 [1] -3 -2 -1  0  1  2  3  4  5  6  7  8  9 10 11 12 13 14 15 16

$counts
 [1] 2026734  332340  206543  159084  134510  130097  148151  195453  219757
[10]  174507   94391   39658   15034    5070    1267     310      70      21
[19]       3

$density
 [1] 5.219506e-01 8.558846e-02 5.319160e-02 4.096935e-02 3.464074e-02
 [6] 3.350425e-02 3.815375e-02 5.033557e-02 5.659464e-02 4.494128e-02
[11] 2.430878e-02 1.021324e-02 3.871749e-03 1.305691e-03 3.262941e-04
[16] 7.983518e-05 1.802730e-05 5.408190e-06 7.725985e-07

$mids
 [1] -2.5 -1.5 -0.5  0.5  1.5  2.5  3.5  4.5  5.5  6.5  7.5  8.5  9.5 10.5 11.5
[16] 12.5 13.5 14.5 15.5

$xname
[1] "RNA_log2cpm"

$equidist
[1] TRUE

attr(,"class")
[1] "histogram"
boxplot(RNA_log2cpm, main = "Boxplots of log cpm per sample
          (unfiltered)", xaxt = "n", xlab= "")
axis(1,
     at = 1:length(col_names),  # positions (one per sample)
     labels = col_names,        # your labels vector
     las = 2,               # rotate text vertically (like srt=90)
     cex.axis = 0.3)        # shrink label size

Version Author Date
d9f15a6 John D. Hurley 2026-01-28
# saveRDS(RNA_log2cpm,"data/QC/RNA_log2cpm.RDS")
#####RowMu>0####
row_means <- rowMeans(RNA_log2cpm)
Filt_RMG0_RNA_fc <- RNA_fc[row_means >0,]

# saveRDS(Filt_RMG0_RNA_fc,"data/QC/Filt_RMG0_RNA_fc.RDS")

Filt_RMG0_RNA_log2cpm <- cpm(Filt_RMG0_RNA_fc,log=TRUE)

# saveRDS(Filt_RMG0_RNA_log2cpm,"data/QC/RNA_log2cpm_RMG0.RDS")

hist(Filt_RMG0_RNA_log2cpm, main = "Histogram of filtered counts using rowMeans > 0 method",
     xlab =expression("Log"[2]*" counts-per-million"), col =5 )

Version Author Date
d9f15a6 John D. Hurley 2026-01-28
boxplot(Filt_RMG0_RNA_log2cpm, main = "Boxplots of log cpm per sample (RowMeans>0)",xaxt = "n", xlab= "")
axis(1,
     at = 1:length(col_names),  # positions (one per sample)
     labels = col_names,        # your labels vector
     las = 2,               # rotate text vertically (like srt=90)
     cex.axis = 0.3)        # shrink label size

Version Author Date
d9f15a6 John D. Hurley 2026-01-28
######Cor_HeatMap####
Cor_Filt_RMG0_RNA_log2cpm <- cor(Filt_RMG0_RNA_log2cpm, method = "spearman")
individual <- RNA_Metadata$Individual
species <- RNA_Metadata$Species
timepoint <- RNA_Metadata$Timepoint
timepoint <- factor(timepoint,levels = c("Day0","Day2","Day4","Day5","Day15","Day30"))
Cor_metadata <- data.frame(
  sample_cor = colnames(Filt_RMG0_RNA_log2cpm),
  species_cor = species,
  timepoint_cor = timepoint,
  individual_cor = individual
)


ann_colors <- list(
  timepoint_cor = c(
    "Day0" = "#883268",   # Purple
    "Day2" = "#3E7274",  # blue
    "Day4" = "#5AAA464D",  # light green
    "Day5" = "#94C47D",  # Green
    "Day15" = "#C03830",  # red
    "Day30" = "#830C05"  # dark red
  ),
  species_cor = c(
    "H" = "#171717",  # black
    "C" = "#17171717"   # light grey
  ),
  individual_cor = c(
    H1 = "#091638", #Blue-Green Darkest
    H2 = "#11185B",
    H3 = "#0F2C71",
    H4 = "#0D568F",
    H4R = "#0D568F",
    H5 = "#1D8296",
    H6 = "#46A389",
    H7 = "#9DD484", #Blue-Green Lightest
    C1 = "#340702", #Brown-Orange darkest
    C2 = "#5D0B02",
    C3 = "#951302",
    C4 = "#D32804",
    C5 = "#F74019",
    C6 = "#FA7A38",
    C7 = "#FCC598"
    
  )
)
rownames(Cor_metadata) <- Cor_metadata$sample_cor

# saveRDS(Cor_Filt_RMG0_RNA_log2cpm, "data/QC/Cor_Filt_RMG0_RNA_log2cpm.RDS")
# saveRDS(Cor_metadata, "data/QC/Cor_RNA_metadata.RDS")
# saveRDS(ann_colors,"data/QC/ann_colors.RDS")
print(
  pheatmap(Cor_Filt_RMG0_RNA_log2cpm,
         fontsize_row = 5,
         fontsize_col = 5,
         annotation_col = Cor_metadata[, c("species_cor", "timepoint_cor","individual_cor")],
         annotation_colors = ann_colors,
         clustering_distance_rows = "correlation",
         clustering_distance_cols = "correlation",
         main = "Sample-Sample Correlation \n(Spearman-log2CPM-RowMeans>0)")
)

Version Author Date
d9f15a6 John D. Hurley 2026-01-28
####Subset####
RNA_Metadata_No4 <- RNA_Metadata %>% 
 filter(timepoint != "Day4")

RNA_fc_NoD4 <- RNA_fc %>% 
  dplyr::select(-ends_with("_D4"))

RNA_log2cpm_NoD4 <- cpm(RNA_fc_NoD4,log=TRUE)
dim(RNA_log2cpm_NoD4)
[1] 44125    74
dim(RNA_fc)
[1] 44125    88
row_means_NoD4 <- rowMeans(RNA_log2cpm_NoD4)
Filt_RMG0_RNA_fc_NoD4 <- RNA_fc_NoD4[row_means_NoD4 >0,]
dim(Filt_RMG0_RNA_fc_NoD4)
[1] 14838    74
Filt_RMG0_RNA_log2cpm_NoD4 <- cpm(Filt_RMG0_RNA_fc_NoD4,log=TRUE)

# saveRDS(RNA_Metadata_No4,"data/QC/RNA_Metatdata_No4.RDS")
# saveRDS(Filt_RMG0_RNA_fc_NoD4,"data/QC/Filt_RMG0_RNA_fc_NoD4.RDS")
# saveRDS(Filt_RMG0_RNA_log2cpm_NoD4, "data/QC/Filt_RMG0_RNA_log2cpm_NoD4.RDS")
######Cor_HeatMap####
Cor_Filt_RMG0_RNA_log2cpm_NoD4 <- cor(Filt_RMG0_RNA_log2cpm_NoD4, method = "spearman")

Cor_metadata_No4 <- Cor_metadata %>% 
  dplyr::filter(timepoint_cor !="Day4")

ann_colors_No4 <- ann_colors
ann_colors_No4$timepoint_cor <- ann_colors$timepoint_cor[
  names(ann_colors$timepoint_cor) != "Day4"
]

# saveRDS(Cor_metadata_No4, "data/QC/Cor_metadata_No4.RDS")
# saveRDS(Cor_Filt_RMG0_RNA_log2cpm_NoD4, "data/QC/Cor_Filt_RMG0_RNA_log2cpm_NoD4.RDS")
# saveRDS(ann_colors_No4,"data/QC/ann_colors_no4.RDS")
print(
  pheatmap(Cor_Filt_RMG0_RNA_log2cpm_NoD4,
         fontsize_row = 5,
         fontsize_col = 5,
         annotation_col = Cor_metadata_No4[, c("species_cor", "timepoint_cor","individual_cor")],
         annotation_colors = ann_colors_No4,
         clustering_distance_rows = "correlation",
         clustering_distance_cols = "correlation",
         main = "Sample-Sample Correlation (Spearman) \n (log2CPM-RowMeans>0-NoDay4)")
)

Version Author Date
d9f15a6 John D. Hurley 2026-01-28
filt_gene_list <- rownames(Filt_RMG0_RNA_log2cpm_NoD4)
#14838
length(filt_gene_list)
[1] 14838
# # in order to make this match with annot later down the line, change the col names for counts_raw_matrix to match final_sample_names in annot
# 
# # i'll also want to make sure I keep the replicate for this set
# 
# Ind_RUV <- c(rep("H1",5),
#              rep("H2",5),
#              rep("H3",5),
#              rep("H4",5),
#              rep("H5",5),
#              rep("H6",5),
#              rep("H7",5),
#              rep("H4R",4),
#              rep("C1",5),
#              rep("C2",5),
#              rep("C3",5),
#              rep("C4",5),
#              rep("C5",5),
#              rep("C6",5),
#              rep("C7",5)
#              )
# RNA_Metadata_No4$Ind_RUV <- Ind_RUV
# RNA_Metadata_No4_RUV <- RNA_Metadata_No4 %>%
#    mutate(
#     Ind_RUV = factor(Ind_RUV,
#                         levels = c("H1","H2","H3","H4","H5","H6","H7","H4R","C1","C2","C3","C4","C5","C6","C7"),ordered=TRUE),
#     Timepoint = factor(Timepoint,
#                        levels = c("Day0","Day2","Day5","Day15","Day30"),ordered=TRUE),
#     Species = factor(Species,
#                      levels = c("H","C"),ordered=TRUE),
#     Condition = factor(
#       Condition,
#       levels = expand.grid(
#         Ind_RUV = levels(Ind_RUV),
#         Timepoint = levels(Timepoint),
#         Species = levels(Species)
#       ) %>%
#         transmute(Condition=paste(Species,Timepoint,Ind_RUV,sep="_")) %>%
#         pull(Condition),
#       ordered=TRUE
#     )
#   )
# 
# # saveRDS(RNA_Metadata_No4_RUV,"data/QC/RNA_MetaData_NoD4_RUV.RDS")
# RNA_Metadata_No4_RUV <- readRDS("data/QC/RNA_MetaData_NoD4_RUV.RDS")
# 
# RNA_fc_NoD4_RUV <- RNA_fc_NoD4
# colnames(RNA_fc_NoD4_RUV) <- RNA_Metadata_No4_RUV$Condition
# 
# RUV_filt_counts <- RNA_fc_NoD4_RUV %>% 
#   as.data.frame() %>% 
#   dplyr::filter(., row.names(.)%in% filt_gene_list)
# # saveRDS(RUV_filt_counts, "data/DGE/RUV_filt_counts.RDS")
# dim(RUV_filt_counts)
# 
# #add in the annotation files
# ind_num <- RNA_Metadata_No4_RUV$Ind_RUV
# type(ind_num)
# length(ind_num)
# 
# annot <- as.data.frame(RNA_Metadata_No4_RUV)
# type(annot)
# is.data.frame(annot)
# #same as Metadata
# 
# 
# #  counts need to be integer values and in a numeric matrix
# # note: the log transformation needs to be accounted for in the isLog argument in RUVs function.
# counts <- as.matrix(RUV_filt_counts)
#   
# # saveRDS(counts, "data/QC/filt_counts_matrix.RDS")
# 
# # Create a DataFrame for the phenoData
# phenoData <- DataFrame(annot)
# 
# set <- SummarizedExperiment(assays = counts, metadata = phenoData)
# 
# scIdx <- RUVSeq::makeGroups(phenoData$Cond)
# 
# # # Generate a background matrix
# # # The column "Cond" holds the comparisons that you actually want to make. DOX_24, DMSO_24,5FU_24, DOX_3,etc.
# # Day0 <- c(16,36)
# # Day2 <- c(17,37)
# # Day5 <- c(18,38)
# # Day30 <- c(20,39)
# # scIdx <- rbind(Day0,Day2,Day5,Day30)
# # rownames(scIdx) <- c("[1,]","[2,]","[3,]","[4,]")
# # colnames(scIdx) <- c("[,1]","[,2]")
# ```
# 
# 
# 
# ```{r}
# #now I've made all of the data I need for this - they are located in each section for k values
# 
# #DO NOT USE THESE COUNTS FOR LINEAR MODELING
# 
# #colors for all of the plots
# # txtime_col
# # ind_col
# # time_col
# # tx_col
# log2cpm <- cpm(counts,log=TRUE)
# # before ruv (counts PCA)
# prcomp_res_log2 <- prcomp(t(Filt_RMG0_RNA_log2cpm_NoD4), scale=FALSE, center = TRUE)
# annot_prcomp_res <- prcomp_res_log2$x %>% cbind(., annot)
# # 
# # group_2 <- annot$dgelist
# # dgelist_col <- annot$dgelist
# # individual_list <- annot$Individual
# 
# #now plot my PCA for filtered counts
# ####PC1/PC2####
# individual_list <- RNA_Metadata_No4_RUV$Individual
# 
# suppressWarnings(
#   ggplot2::autoplot(prcomp_res_log2,
#                     data = annot,
#                     colour = "Timepoint",
#                     shape = "Species",
#                     size = 4,
#                     x = 1,
#                     y = 2) +
#     scale_color_manual(values = ann_colors_No4$timepoint_cor) +
#     ggrepel::geom_text_repel(
#       label = individual_list,
#       vjust = -0.5,
#       max.overlaps = 50
#     ) +
#     ggtitle("RNA log2cpm RMG0")
# )
# set1 <- RUVSeq::RUVs(x = counts, k =1, scIdx = scIdx, isLog = FALSE)
# 
# # Get the RUV factors (weights) for modeling
# RUV_df1 <- set1$W %>% as.data.frame()
# RUV_df1$Condition <- rownames(RUV_df1)
# 
# RUV_df_rm1 <- RUV_df1[RUV_df1$Condition %in% annot$Condition, ]
# View(RUV_df_rm1)
# RUV_1 <- RUV_df_rm1$W_1
# 
# saveRDS(RUV_df_rm1, "data/QC/RUV_df_rm1.RDS")
# saveRDS(RUV_1, "data/QC/RUV_1.RDS")
# 
# 
# log2cpm_k1 <- cpm(set1$normalizedCounts, log = TRUE)
# 
# prcomp_res_log2_k1 <- prcomp(t(log2cpm_k1), scale=FALSE, center = TRUE)
# annot_prcomp_res_k1 <- prcomp_res_log2_k1$x %>% cbind(., RNA_Metadata_No4)
# #PCA checks
# #k=1
# 
# ggplot2::autoplot(prcomp_res_log2_k1,
#                   data = annot_prcomp_res_k1,
#                   colour = "Timepoint",
#                   shape = "Species",
#                   size = 4,
#                   x=1,
#                   y=2) +
#   scale_color_manual(values=ann_colors_No4$timepoint_cor)+
#   ggrepel::geom_text_repel(label = individual_list,
#                             vjust = -0.5,
#                             max.overlaps = 50)+
#   ggtitle("RUV Correction k=1 log2cpm")
# git -> commit all changes
# git -> push
# wflow_publish("analysis/RNA_CorrelationHeatMap_Ensemble.Rmd")

sessionInfo()
R version 4.5.1 (2025-06-13 ucrt)
Platform: x86_64-w64-mingw32/x64
Running under: Windows 11 x64 (build 26100)

Matrix products: default
  LAPACK version 3.12.1

locale:
[1] LC_COLLATE=English_United States.utf8 
[2] LC_CTYPE=English_United States.utf8   
[3] LC_MONETARY=English_United States.utf8
[4] LC_NUMERIC=C                          
[5] LC_TIME=English_United States.utf8    

time zone: America/Chicago
tzcode source: internal

attached base packages:
[1] grid      stats4    stats     graphics  grDevices utils     datasets 
[8] methods   base     

other attached packages:
 [1] ComplexHeatmap_2.24.1       ggfortify_0.4.19           
 [3] readxl_1.4.5                RUVSeq_1.42.0              
 [5] EDASeq_2.42.0               ShortRead_1.66.0           
 [7] GenomicAlignments_1.44.0    SummarizedExperiment_1.38.1
 [9] MatrixGenerics_1.20.0       matrixStats_1.5.0          
[11] Rsamtools_2.24.0            GenomicRanges_1.60.0       
[13] Biostrings_2.76.0           GenomeInfoDb_1.44.3        
[15] XVector_0.48.0              BiocParallel_1.42.1        
[17] lubridate_1.9.4             forcats_1.0.1              
[19] stringr_1.5.2               purrr_1.1.0                
[21] tidyr_1.3.1                 tidyverse_2.0.0            
[23] Cormotif_1.54.0             affy_1.86.0                
[25] pheatmap_1.0.13             org.Hs.eg.db_3.21.0        
[27] AnnotationDbi_1.70.0        IRanges_2.42.0             
[29] S4Vectors_0.46.0            Biobase_2.68.0             
[31] BiocGenerics_0.54.0         generics_0.1.4             
[33] readr_2.1.5                 ggrepel_0.9.6              
[35] dplyr_1.1.4                 tibble_3.3.0               
[37] ggplot2_4.0.0               edgeR_4.6.3                
[39] limma_3.64.3                workflowr_1.7.2            

loaded via a namespace (and not attached):
  [1] later_1.4.4             BiocIO_1.18.0           bitops_1.0-9           
  [4] filelock_1.0.3          R.oo_1.27.1             cellranger_1.1.0       
  [7] preprocessCore_1.70.0   XML_3.99-0.20           lifecycle_1.0.5        
 [10] httr2_1.2.2             pwalign_1.4.0           doParallel_1.0.17      
 [13] rprojroot_2.1.1         processx_3.8.6          lattice_0.22-7         
 [16] MASS_7.3-65             magrittr_2.0.3          sass_0.4.10            
 [19] rmarkdown_2.30          jquerylib_0.1.4         yaml_2.3.10            
 [22] httpuv_1.6.16           otel_0.2.0              DBI_1.2.3              
 [25] RColorBrewer_1.1-3      abind_1.4-8             R.utils_2.13.0         
 [28] RCurl_1.98-1.17         rappdirs_0.3.4          git2r_0.36.2           
 [31] circlize_0.4.17         GenomeInfoDbData_1.2.14 codetools_0.2-20       
 [34] DelayedArray_0.34.1     xml2_1.5.1              tidyselect_1.2.1       
 [37] shape_1.4.6.1           UCSC.utils_1.4.0        farver_2.1.2           
 [40] BiocFileCache_2.16.2    jsonlite_2.0.0          GetoptLong_1.1.0       
 [43] iterators_1.0.14        foreach_1.5.2           tools_4.5.1            
 [46] progress_1.2.3          Rcpp_1.1.0              glue_1.8.0             
 [49] gridExtra_2.3           SparseArray_1.8.1       xfun_0.53              
 [52] withr_3.0.2             BiocManager_1.30.27     fastmap_1.2.0          
 [55] latticeExtra_0.6-31     callr_3.7.6             digest_0.6.37          
 [58] timechange_0.3.0        R6_2.6.1                colorspace_2.1-2       
 [61] Cairo_1.7-0             jpeg_0.1-11             biomaRt_2.64.0         
 [64] RSQLite_2.4.3           R.methodsS3_1.8.2       rtracklayer_1.68.0     
 [67] prettyunits_1.2.0       httr_1.4.7              S4Arrays_1.8.1         
 [70] whisker_0.4.1           pkgconfig_2.0.3         gtable_0.3.6           
 [73] blob_1.3.0              S7_0.2.0                hwriter_1.3.2.1        
 [76] htmltools_0.5.8.1       clue_0.3-66             scales_1.4.0           
 [79] png_0.1-8               knitr_1.51              rstudioapi_0.18.0      
 [82] tzdb_0.5.0              rjson_0.2.23            curl_7.0.0             
 [85] cachem_1.1.0            GlobalOptions_0.1.3     parallel_4.5.1         
 [88] restfulr_0.0.16         pillar_1.11.1           vctrs_0.6.5            
 [91] promises_1.3.3          dbplyr_2.5.1            cluster_2.1.8.1        
 [94] evaluate_1.0.5          GenomicFeatures_1.60.0  cli_3.6.5              
 [97] locfit_1.5-9.12         compiler_4.5.1          rlang_1.1.6            
[100] crayon_1.5.3            interp_1.1-6            aroma.light_3.38.0     
[103] ps_1.9.1                getPass_0.2-4           fs_1.6.6               
[106] stringi_1.8.7           deldir_2.0-4            Matrix_1.7-3           
[109] hms_1.1.4               bit64_4.6.0-1           KEGGREST_1.48.1        
[112] statmod_1.5.0           memoise_2.0.1           affyio_1.78.0          
[115] bslib_0.9.0             bit_4.6.0