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Knit directory: ATAC_learning/

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    Modified:   analysis/final_four_analysis.Rmd

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library(tidyverse)
library(kableExtra)
library(broom)
library(RColorBrewer)
library("TxDb.Hsapiens.UCSC.hg38.knownGene")
library("org.Hs.eg.db")
library(rtracklayer)
library(ggfortify)
library(readr)
library(BiocGenerics)
library(gridExtra)
library(VennDiagram)
library(scales)
library(ggVennDiagram)
library(BiocParallel)
library(ggpubr)
library(edgeR)
library(genomation)
library(ggsignif)
library(plyranges)
library(ggrepel)
library(ComplexHeatmap)
library(cowplot)
library(smplot2)
library(readxl)
library(devtools)
library(vargen)
library(liftOver)

Loading Atrial Fibrillation and Heart Failure SNPs and I

gwas_HF <- readRDS("data/other_papers/HF_gwas_association_downloaded_2025_01_23_EFO_0003144_withChildTraits.RDS")

gwas_ARR <- readRDS("data/other_papers/AF_gwas_association_downloaded_2025_01_23_EFO_0000275.RDS")

gwas_IHD   <- readRDS("data/other_papers/IHD_IHD_gwas_association_downloaded_2025_06_26_EFO_1001375_withChildTraits")
gwas_CAD <- readRDS( "data/CAD_gwas_dataframe.RDS")
gwas_ACresp <- readRDS("data/gwas_3_dataframe.RDS")
Short_gwas_gr <-
  gwas_ARR %>% 
          distinct(SNPS,.keep_all = TRUE) %>%
          dplyr::select(CHR_ID, CHR_POS,SNPS) %>% 
          mutate(gwas="AF") %>% 
   rbind(gwas_HF %>% 
          distinct(SNPS,.keep_all = TRUE) %>%
          dplyr::select(CHR_ID, CHR_POS,SNPS) %>% 
          mutate(gwas="HF")) %>% 
  rbind(gwas_IHD %>% 
          distinct(SNPS,.keep_all = TRUE) %>%
          dplyr::select(CHR_ID, CHR_POS,SNPS) %>% 
          mutate(gwas="IHD")) %>% 
  rbind(gwas_CAD %>% 
          distinct(SNPS,.keep_all = TRUE) %>%
          dplyr::select(CHR_ID, CHR_POS,SNPS) %>% 
          mutate(gwas="CAD")) %>% 
  
  na.omit() %>% 
 mutate(seqnames=paste0("chr",CHR_ID), CHR_POS=as.numeric(CHR_POS)) %>% 
  na.omit() %>%
   mutate(start=CHR_POS, end=CHR_POS, width=1) %>% 
  GRanges()
# gwas_CAD %>% 
#   distinct(SNPS)

Loading ATAC-seq regions

toptable_results <- readRDS("data/Final_four_data/re_analysis/Toptable_results.RDS")

all_results  <- toptable_results %>%
  imap(~ .x %>% tibble::rownames_to_column(var = "rowname") %>%
         mutate(source = .y)) %>%
  bind_rows()

DOX_3_sig <-all_results %>% 
  dplyr::select(source,genes, logFC,adj.P.Val) %>% 
  mutate("Peakid"=genes) %>% 
  dplyr::filter(source=="DOX_3") %>% 
   dplyr::filter(adj.P.Val<0.05) 

DOX_24_sig <-all_results %>% 
  dplyr::select(source,genes, logFC,adj.P.Val) %>% 
  mutate("Peakid"=genes) %>% 
  dplyr::filter(source=="DOX_24") %>% 
   dplyr::filter(adj.P.Val<0.05) 

EPI_3_sig <-all_results %>% 
  dplyr::select(source,genes, logFC,adj.P.Val) %>% 
  mutate("Peakid"=genes) %>% 
  dplyr::filter(source=="EPI_3") %>% 
   dplyr::filter(adj.P.Val<0.05) 

EPI_24_sig <-all_results %>% 
  dplyr::select(source,genes, logFC,adj.P.Val) %>% 
  mutate("Peakid"=genes) %>% 
  dplyr::filter(source=="EPI_24") %>% 
   dplyr::filter(adj.P.Val<0.05) 

DNR_3_sig <-all_results %>% 
  dplyr::select(source,genes, logFC,adj.P.Val) %>% 
  mutate("Peakid"=genes) %>% 
  dplyr::filter(source=="DNR_3") %>% 
   dplyr::filter(adj.P.Val<0.05) 

DNR_24_sig <-all_results %>% 
  dplyr::select(source,genes, logFC,adj.P.Val) %>% 
  mutate("Peakid"=genes) %>% 
  dplyr::filter(source=="DNR_24") %>% 
   dplyr::filter(adj.P.Val<0.05) 

MTX_3_sig <-all_results %>% 
  dplyr::select(source,genes, logFC,adj.P.Val) %>% 
  mutate("Peakid"=genes) %>% 
  dplyr::filter(source=="MTX_3") %>% 
   dplyr::filter(adj.P.Val<0.05) 

MTX_24_sig <-all_results %>% 
  dplyr::select(source,genes, logFC,adj.P.Val) %>% 
  mutate("Peakid"=genes) %>% 
  dplyr::filter(source=="MTX_24") %>% 
   dplyr::filter(adj.P.Val<0.05) 

all_regions_gr <- all_results %>%
  dplyr::select(source,genes, logFC,adj.P.Val) %>% 
  mutate("Peakid"=genes) %>% 
  dplyr::filter(source=="DOX_3") %>% 
  distinct(Peakid) %>% 
  separate_wider_delim(., cols="Peakid",names = c("seqnames","start","end"), delim= ".", cols_remove = FALSE) %>% 
  makeGRangesFromDataFrame(.,keep.extra.columns=TRUE) 

all_regions_peak <- all_results %>%
  dplyr::select(source,genes, logFC,adj.P.Val) %>% 
  mutate("Peakid"=genes) %>% 
  dplyr::filter(source=="DOX_3") %>% 
  distinct(Peakid) 
MCF7_DARs_hyper <- read_excel("C:/Users/renee/Downloads/MCF7-doxATAC/Table 4.XLSX", 
    sheet = "hyper") %>% GRanges()
MCF7_DARs_hypo <- read_excel("C:/Users/renee/Downloads/MCF7-doxATAC/Table 4.XLSX", 
    sheet = "hypo") %>% GRanges()


  MCF7_DARs_hyper$names <- paste0("hyper_", seq_along(seqnames(MCF7_DARs_hyper)))
 MCF7_DARs_hypo$names <- paste0("hypo_", seq_along(seqnames(MCF7_DARs_hypo)))
 
 MCF7_ARsmcf7_1 <- read_excel("C:/Users/renee/Downloads/MCF7-doxATAC/Table 3.XLSX") %>%
  GRanges()
ch = import.chain("C:/Users/renee/ATAC_folder/liftOver_genome/hg19ToHg38.over.chain")

MCF7_DARs_hyper_LO <- as.data.frame(liftOver(MCF7_DARs_hyper,ch)) %>% 
  GRanges()

MCF7_DARs_hypo_LO <- as.data.frame(liftOver(MCF7_DARs_hypo,ch)) %>% 
  GRanges()

MCF7_DAR_all <- c(MCF7_DARs_hyper_LO,MCF7_DARs_hypo_LO)
MCF7_ARsmcf7_1_LO <- as.data.frame(liftOver(MCF7_ARsmcf7_1,ch)) %>%
  GRanges()

Overlapping ATAC regions and SNPs

AF_ol_peaks <-   join_overlap_inner(all_regions_gr, Short_gwas_gr) %>%
  as.data.frame() %>% 
  dplyr::filter(gwas =="AF") %>% 
  distinct(Peakid)

HF_ol_peaks <-   join_overlap_inner(all_regions_gr, Short_gwas_gr) %>%
  as.data.frame() %>% 
  dplyr::filter(gwas =="HF") %>% 
  distinct(Peakid)

IHD_ol_peaks <-   join_overlap_inner(all_regions_gr, Short_gwas_gr) %>%
  as.data.frame() %>% 
  dplyr::filter(gwas =="IHD") %>% 
  distinct(Peakid)

CAD_ol_peaks <-   join_overlap_inner(all_regions_gr, Short_gwas_gr) %>%
  as.data.frame() %>% 
  dplyr::filter(gwas =="CAD") %>% 
  distinct(Peakid)
HF_AF_ol <- join_overlap_inner(all_regions_gr, Short_gwas_gr) %>%
  as.data.frame() %>% 
  dplyr::filter(gwas =="AF"|gwas=="HF")

SNP_overlaps <- join_overlap_inner(all_regions_gr, Short_gwas_gr) %>%
  as.data.frame() #%>% saveRDS(., 
                  # "data/Final_four_data/re_analysis/GWAS_overlaps_dataframe.RDS")
gwas_annote_df <-all_regions_peak %>%
  mutate(AF_status=case_when(Peakid %in% AF_ol_peaks$Peakid ~"AF_peak",
                              TRUE~ "not_AF_peak"),
         HF_status=case_when(Peakid %in% HF_ol_peaks$Peakid ~"HF_peak",
                              TRUE~ "not_HF_peak"),
          CAD_status=case_when(Peakid %in% CAD_ol_peaks$Peakid ~"CAD_peak",
                              TRUE~ "not_CAD_peak"),
         IHD_status=case_when(Peakid %in% IHD_ol_peaks$Peakid ~"IHD_peak",
                              TRUE~ "not_IHD_peak")) %>% 
  mutate(DOX_3=case_when(Peakid %in% DOX_3_sig$Peakid ~"sig_peak",
                              TRUE~ "not_sig_peak")) %>% 
  mutate(DOX_24=case_when(Peakid %in% DOX_24_sig$Peakid ~"sig_peak",
                              TRUE~ "not_sig_peak")) %>% 
  mutate(EPI_3=case_when(Peakid %in% EPI_3_sig$Peakid ~"sig_peak",
                              TRUE~ "not_sig_peak")) %>% 
  mutate(EPI_24=case_when(Peakid %in% EPI_24_sig$Peakid ~"sig_peak",
                              TRUE~ "not_sig_peak")) %>% 
  mutate(DNR_3=case_when(Peakid %in% DNR_3_sig$Peakid ~"sig_peak",
                              TRUE~ "not_sig_peak")) %>% 
  mutate(DNR_24=case_when(Peakid %in% DNR_24_sig$Peakid ~"sig_peak",
                              TRUE~ "not_sig_peak")) %>% 
  mutate(MTX_3=case_when(Peakid %in% MTX_3_sig$Peakid ~"sig_peak",
                              TRUE~ "not_sig_peak")) %>% 
  mutate(MTX_24=case_when(Peakid %in% MTX_24_sig$Peakid ~"sig_peak",
                              TRUE~ "not_sig_peak")) 
 
# saveRDS(gwas_annote_df,"data/Final_four_data/re_analysis/GWAS_SNP_annotations.RDS")

Testing for enrichment: ### DOX enrichment tests

 gwas_annote_df %>% 
  group_by(DOX_3,AF_status) %>% 
  tally() %>% 
  pivot_wider(., DOX_3, names_from = AF_status, values_from = n) %>% 
  arrange(desc(DOX_3)) %>% 
  print() %>% 
  column_to_rownames("DOX_3") %>% 
  chisq.test(.)
# A tibble: 2 × 3
# Groups:   DOX_3 [2]
  DOX_3        AF_peak not_AF_peak
  <chr>          <int>       <int>
1 sig_peak           5        3468
2 not_sig_peak      71      152013

    Pearson's Chi-squared test with Yates' continuity correction

data:  .
X-squared = 4.7391, df = 1, p-value = 0.02948
DOX_darsnp_3_AF <- gwas_annote_df %>%
  group_by(DOX_3,AF_status) %>% 
  tally() %>% 
  pivot_wider(., DOX_3, names_from = AF_status, values_from = n) %>% 
  arrange(desc(DOX_3)) %>% 
  column_to_rownames("DOX_3") %>% 
  fisher.test(.)
gwas_annote_df %>% 
  group_by(DOX_24,AF_status) %>% 
  tally() %>% 
  pivot_wider(., DOX_24, names_from = AF_status, values_from = n) %>% 
  arrange(desc(DOX_24)) %>% 
  print() %>% 
  column_to_rownames("DOX_24") %>% 
  chisq.test(.)
# A tibble: 2 × 3
# Groups:   DOX_24 [2]
  DOX_24       AF_peak not_AF_peak
  <chr>          <int>       <int>
1 sig_peak          34       64786
2 not_sig_peak      42       90695

    Pearson's Chi-squared test with Yates' continuity correction

data:  .
X-squared = 0.1816, df = 1, p-value = 0.67
DOX_darsnp_24_AF <-  gwas_annote_df %>% 
  group_by(DOX_24,AF_status) %>% 
  tally() %>% 
  pivot_wider(., DOX_24, names_from = AF_status, values_from = n) %>% 
  arrange(desc(DOX_24)) %>% 
  column_to_rownames("DOX_24") %>% 
  fisher.test(.)
gwas_annote_df %>% 
  group_by(DOX_3,HF_status) %>% 
  tally() %>% 
  pivot_wider(., DOX_3, names_from = HF_status, values_from = n) %>% 
  arrange(desc(DOX_3)) %>% 
  print() %>% 
  column_to_rownames("DOX_3") %>% 
  fisher.test(.)
# A tibble: 2 × 3
# Groups:   DOX_3 [2]
  DOX_3        HF_peak not_HF_peak
  <chr>          <int>       <int>
1 sig_peak           1        3472
2 not_sig_peak      28      152056

    Fisher's Exact Test for Count Data

data:  .
p-value = 0.4805
alternative hypothesis: true odds ratio is not equal to 1
95 percent confidence interval:
 0.038240 9.465039
sample estimates:
odds ratio 
  1.564073 
DOX_darsnp_3_HF <- gwas_annote_df %>% 
  group_by(DOX_3,HF_status) %>% 
  tally() %>% 
  pivot_wider(., DOX_3, names_from = HF_status, values_from = n) %>% 
  arrange(desc(DOX_3)) %>% 
  column_to_rownames("DOX_3") %>% 
  fisher.test(.)
gwas_annote_df %>%
  group_by(DOX_24,HF_status) %>%
  tally() %>%
  pivot_wider(., DOX_24, names_from = HF_status, values_from = n) %>%
  arrange(desc(DOX_24)) %>%
  print() %>%
  column_to_rownames("DOX_24") %>%
  chisq.test(.)
# A tibble: 2 × 3
# Groups:   DOX_24 [2]
  DOX_24       HF_peak not_HF_peak
  <chr>          <int>       <int>
1 sig_peak          14       64806
2 not_sig_peak      15       90722

    Pearson's Chi-squared test with Yates' continuity correction

data:  .
X-squared = 0.28443, df = 1, p-value = 0.5938
DOX_darsnp_24_HF <- gwas_annote_df %>%
  group_by(DOX_24,HF_status) %>%
  tally() %>%
  pivot_wider(., DOX_24, names_from = HF_status, values_from = n) %>%
  arrange(desc(DOX_24)) %>%
  column_to_rownames("DOX_24") %>%
  fisher.test(.)
gwas_annote_df %>% 
  group_by(DOX_3,IHD_status) %>% 
  tally() %>% 
  pivot_wider(., DOX_3, names_from = IHD_status, values_from = n, values_fill = 0) %>% 
  arrange(desc(DOX_3))%>% 
  print() %>% 
  column_to_rownames("DOX_3") %>% 
  fisher.test(.)
# A tibble: 2 × 3
# Groups:   DOX_3 [2]
  DOX_3        IHD_peak not_IHD_peak
  <chr>           <int>        <int>
1 sig_peak            0         3473
2 not_sig_peak        7       152077

    Fisher's Exact Test for Count Data

data:  .
p-value = 1
alternative hypothesis: true odds ratio is not equal to 1
95 percent confidence interval:
  0.00000 30.37975
sample estimates:
odds ratio 
         0 
DOX_darsnp_3_IHD <- gwas_annote_df %>% 
  group_by(DOX_3,IHD_status) %>% 
  tally() %>% 
  pivot_wider(., DOX_3, names_from = IHD_status, values_from = n, values_fill = 0) %>% 
  arrange(desc(DOX_3))%>% 
  column_to_rownames("DOX_3") %>% 
  fisher.test(.)
gwas_annote_df %>% 
  group_by(DOX_24,IHD_status) %>% 
  tally() %>% 
  pivot_wider(., DOX_24, names_from = IHD_status, values_from = n, values_fill = 0) %>% 
  arrange(desc(DOX_24)) %>% 
  print() %>% 
  column_to_rownames("DOX_24") %>% 
  fisher.test(.)
# A tibble: 2 × 3
# Groups:   DOX_24 [2]
  DOX_24       IHD_peak not_IHD_peak
  <chr>           <int>        <int>
1 sig_peak            3        64817
2 not_sig_peak        4        90733

    Fisher's Exact Test for Count Data

data:  .
p-value = 1
alternative hypothesis: true odds ratio is not equal to 1
95 percent confidence interval:
 0.1537767 6.2053650
sample estimates:
odds ratio 
  1.049845 
DOX_darsnp_24_IHD <- gwas_annote_df %>% 
  group_by(DOX_24,IHD_status) %>% 
  tally() %>% 
  pivot_wider(., DOX_24, names_from = IHD_status, values_from = n, values_fill = 0) %>% 
  arrange(desc(DOX_24)) %>% 
  column_to_rownames("DOX_24") %>% 
  fisher.test(.)
gwas_annote_df %>% 
  group_by(DOX_3,CAD_status) %>% 
  tally() %>% 
  pivot_wider(., DOX_3, names_from = CAD_status, values_from = n) %>% 
  arrange(desc(DOX_3)) %>% 
  print() %>% 
  column_to_rownames("DOX_3") %>% 
  fisher.test(.)
# A tibble: 2 × 3
# Groups:   DOX_3 [2]
  DOX_3        CAD_peak not_CAD_peak
  <chr>           <int>        <int>
1 sig_peak            2         3471
2 not_sig_peak      136       151948

    Fisher's Exact Test for Count Data

data:  .
p-value = 0.7736
alternative hypothesis: true odds ratio is not equal to 1
95 percent confidence interval:
 0.07714899 2.37238460
sample estimates:
odds ratio 
 0.6437719 
DOX_darsnp_3_CAD <- gwas_annote_df %>% 
  group_by(DOX_3,CAD_status) %>% 
  tally() %>% 
  pivot_wider(., DOX_3, names_from = CAD_status, values_from = n) %>% 
  arrange(desc(DOX_3)) %>% 
  column_to_rownames("DOX_3") %>% 
  fisher.test(.)
gwas_annote_df %>% 
  group_by(DOX_24,CAD_status) %>% 
  tally() %>% 
  pivot_wider(., DOX_24, names_from = CAD_status, values_from = n) %>% 
  arrange(desc(DOX_24)) %>% 
  print() %>% 
  column_to_rownames("DOX_24") %>% 
  chisq.test(.)
# A tibble: 2 × 3
# Groups:   DOX_24 [2]
  DOX_24       CAD_peak not_CAD_peak
  <chr>           <int>        <int>
1 sig_peak           59        64761
2 not_sig_peak       79        90658

    Pearson's Chi-squared test with Yates' continuity correction

data:  .
X-squared = 0.029597, df = 1, p-value = 0.8634
DOX_darsnp_24_CAD <- gwas_annote_df %>% 
  group_by(DOX_24,CAD_status) %>% 
  tally() %>% 
  pivot_wider(., DOX_24, names_from = CAD_status, values_from = n) %>% 
  arrange(desc(DOX_24)) %>% 
  column_to_rownames("DOX_24") %>% 
  fisher.test(.)

EPI enrichment tests

 gwas_annote_df %>% 
  group_by(EPI_3,AF_status) %>% 
  tally() %>% 
  pivot_wider(., EPI_3, names_from = AF_status, values_from = n) %>% 
  arrange(desc(EPI_3)) %>% 
  print() %>% 
  column_to_rownames("EPI_3") %>% 
  chisq.test(.)
# A tibble: 2 × 3
# Groups:   EPI_3 [2]
  EPI_3        AF_peak not_AF_peak
  <chr>          <int>       <int>
1 sig_peak          14       14220
2 not_sig_peak      62      141261

    Pearson's Chi-squared test with Yates' continuity correction

data:  .
X-squared = 6.7851, df = 1, p-value = 0.009192
EPI_darsnp_3_AF <- gwas_annote_df %>%
  group_by(EPI_3,AF_status) %>% 
  tally() %>% 
  pivot_wider(., EPI_3, names_from = AF_status, values_from = n) %>% 
  arrange(desc(EPI_3)) %>% 
  column_to_rownames("EPI_3") %>% 
  fisher.test(.)
gwas_annote_df %>% 
  group_by(EPI_24,AF_status) %>% 
  tally() %>% 
  pivot_wider(., EPI_24, names_from = AF_status, values_from = n) %>% 
  arrange(desc(EPI_24)) %>% 
  print() %>% 
  column_to_rownames("EPI_24") %>% 
 chisq.test(.)
# A tibble: 2 × 3
# Groups:   EPI_24 [2]
  EPI_24       AF_peak not_AF_peak
  <chr>          <int>       <int>
1 sig_peak          39       66462
2 not_sig_peak      37       89019

    Pearson's Chi-squared test with Yates' continuity correction

data:  .
X-squared = 1.9427, df = 1, p-value = 0.1634
EPI_darsnp_24_AF <-  gwas_annote_df %>% 
  group_by(EPI_24,AF_status) %>% 
  tally() %>% 
  pivot_wider(., EPI_24, names_from = AF_status, values_from = n) %>% 
  arrange(desc(EPI_24)) %>% 
  column_to_rownames("EPI_24") %>% 
  fisher.test(.)
gwas_annote_df %>% 
  group_by(EPI_3,HF_status) %>% 
  tally() %>% 
  pivot_wider(., EPI_3, names_from = HF_status, values_from = n) %>% 
  arrange(desc(EPI_3)) %>% 
  print() %>% 
  column_to_rownames("EPI_3") %>% 
  fisher.test(.)
# A tibble: 2 × 3
# Groups:   EPI_3 [2]
  EPI_3        HF_peak not_HF_peak
  <chr>          <int>       <int>
1 sig_peak           3       14231
2 not_sig_peak      26      141297

    Fisher's Exact Test for Count Data

data:  .
p-value = 0.7452
alternative hypothesis: true odds ratio is not equal to 1
95 percent confidence interval:
 0.2219052 3.7390450
sample estimates:
odds ratio 
   1.14563 
EPI_darsnp_3_HF <- gwas_annote_df %>% 
  group_by(EPI_3,HF_status) %>% 
  tally() %>% 
  pivot_wider(., EPI_3, names_from = HF_status, values_from = n) %>% 
  arrange(desc(EPI_3)) %>% 
  column_to_rownames("EPI_3") %>% 
  fisher.test(.)
gwas_annote_df %>%
  group_by(EPI_24,HF_status) %>%
  tally() %>%
  pivot_wider(., EPI_24, names_from = HF_status, values_from = n) %>%
  arrange(desc(EPI_24)) %>%
  print() %>%
  column_to_rownames("EPI_24") %>%
  chisq.test(.)
# A tibble: 2 × 3
# Groups:   EPI_24 [2]
  EPI_24       HF_peak not_HF_peak
  <chr>          <int>       <int>
1 sig_peak          15       66486
2 not_sig_peak      14       89042

    Pearson's Chi-squared test with Yates' continuity correction

data:  .
X-squared = 0.62289, df = 1, p-value = 0.43
EPI_darsnp_24_HF <- gwas_annote_df %>%
  group_by(EPI_24,HF_status) %>%
  tally() %>%
  pivot_wider(., EPI_24, names_from = HF_status, values_from = n) %>%
  arrange(desc(EPI_24)) %>%
  column_to_rownames("EPI_24") %>%
  fisher.test(.)
gwas_annote_df %>% 
  group_by(EPI_3,IHD_status) %>% 
  tally() %>% 
  pivot_wider(., EPI_3, names_from = IHD_status, values_from = n, values_fill = 0) %>% 
  arrange(desc(EPI_3))%>% 
  print() %>% 
  column_to_rownames("EPI_3") %>% 
  fisher.test(.)
# A tibble: 2 × 3
# Groups:   EPI_3 [2]
  EPI_3        IHD_peak not_IHD_peak
  <chr>           <int>        <int>
1 sig_peak            0        14234
2 not_sig_peak        7       141316

    Fisher's Exact Test for Count Data

data:  .
p-value = 1
alternative hypothesis: true odds ratio is not equal to 1
95 percent confidence interval:
 0.000000 6.889309
sample estimates:
odds ratio 
         0 
EPI_darsnp_3_IHD <- gwas_annote_df %>% 
  group_by(EPI_3,IHD_status) %>% 
  tally() %>% 
  pivot_wider(., EPI_3, names_from = IHD_status, values_from = n, values_fill = 0) %>% 
  arrange(desc(EPI_3))%>% 
  column_to_rownames("EPI_3") %>% 
  fisher.test(.)
gwas_annote_df %>% 
  group_by(EPI_24,IHD_status) %>% 
  tally() %>% 
  pivot_wider(., EPI_24, names_from = IHD_status, values_from = n, values_fill = 0) %>% 
  arrange(desc(EPI_24)) %>% 
  print() %>% 
  column_to_rownames("EPI_24") %>% 
  fisher.test(.)
# A tibble: 2 × 3
# Groups:   EPI_24 [2]
  EPI_24       IHD_peak not_IHD_peak
  <chr>           <int>        <int>
1 sig_peak            3        66498
2 not_sig_peak        4        89052

    Fisher's Exact Test for Count Data

data:  .
p-value = 1
alternative hypothesis: true odds ratio is not equal to 1
95 percent confidence interval:
 0.1471093 5.9381589
sample estimates:
odds ratio 
  1.004376 
EPI_darsnp_24_IHD <- gwas_annote_df %>% 
  group_by(EPI_24,IHD_status) %>% 
  tally() %>% 
  pivot_wider(., EPI_24, names_from = IHD_status, values_from = n, values_fill = 0) %>% 
  arrange(desc(EPI_24)) %>% 
  column_to_rownames("EPI_24") %>% 
  fisher.test(.)
gwas_annote_df %>% 
  group_by(EPI_3,CAD_status) %>% 
  tally() %>% 
  pivot_wider(., EPI_3, names_from = CAD_status, values_from = n) %>% 
  arrange(desc(EPI_3)) %>% 
  print() %>% 
  column_to_rownames("EPI_3") %>% 
  chisq.test(.)
# A tibble: 2 × 3
# Groups:   EPI_3 [2]
  EPI_3        CAD_peak not_CAD_peak
  <chr>           <int>        <int>
1 sig_peak           18        14216
2 not_sig_peak      120       141203

    Pearson's Chi-squared test with Yates' continuity correction

data:  .
X-squared = 2.0714, df = 1, p-value = 0.1501
EPI_darsnp_3_CAD <- gwas_annote_df %>% 
  group_by(EPI_3,CAD_status) %>% 
  tally() %>% 
  pivot_wider(., EPI_3, names_from = CAD_status, values_from = n) %>% 
  arrange(desc(EPI_3)) %>% 
  column_to_rownames("EPI_3") %>% 
  fisher.test(.)
gwas_annote_df %>% 
  group_by(EPI_24,CAD_status) %>% 
  tally() %>% 
  pivot_wider(., EPI_24, names_from = CAD_status, values_from = n) %>% 
  arrange(desc(EPI_24)) %>% 
  print() %>% 
  column_to_rownames("EPI_24") %>% 
 chisq.test(.)
# A tibble: 2 × 3
# Groups:   EPI_24 [2]
  EPI_24       CAD_peak not_CAD_peak
  <chr>           <int>        <int>
1 sig_peak           58        66443
2 not_sig_peak       80        88976

    Pearson's Chi-squared test with Yates' continuity correction

data:  .
X-squared = 0.0072711, df = 1, p-value = 0.932
EPI_darsnp_24_CAD <- gwas_annote_df %>% 
  group_by(EPI_24,CAD_status) %>% 
  tally() %>% 
  pivot_wider(., EPI_24, names_from = CAD_status, values_from = n) %>% 
  arrange(desc(EPI_24)) %>% 
  column_to_rownames("EPI_24") %>% 
  fisher.test(.)

DNR enrichment tests

 gwas_annote_df %>% 
  group_by(DNR_3,AF_status) %>% 
  tally() %>% 
  pivot_wider(., DNR_3, names_from = AF_status, values_from = n) %>% 
  arrange(desc(DNR_3)) %>% 
  print() %>% 
  column_to_rownames("DNR_3") %>% 
  chisq.test(.)
# A tibble: 2 × 3
# Groups:   DNR_3 [2]
  DNR_3        AF_peak not_AF_peak
  <chr>          <int>       <int>
1 sig_peak          21       22717
2 not_sig_peak      55      132764

    Pearson's Chi-squared test with Yates' continuity correction

data:  .
X-squared = 9.3022, df = 1, p-value = 0.002289
DNR_darsnp_3_AF <- gwas_annote_df %>%
  group_by(DNR_3,AF_status) %>% 
  tally() %>% 
  pivot_wider(., DNR_3, names_from = AF_status, values_from = n) %>% 
  arrange(desc(DNR_3)) %>% 
  column_to_rownames("DNR_3") %>% 
  fisher.test(.)
gwas_annote_df %>% 
  group_by(DNR_24,AF_status) %>% 
  tally() %>% 
  pivot_wider(., DNR_24, names_from = AF_status, values_from = n) %>% 
  arrange(desc(DNR_24)) %>% 
  print() %>% 
  column_to_rownames("DNR_24") %>% 
  chisq.test(.)
# A tibble: 2 × 3
# Groups:   DNR_24 [2]
  DNR_24       AF_peak not_AF_peak
  <chr>          <int>       <int>
1 sig_peak          41       79954
2 not_sig_peak      35       75527

    Pearson's Chi-squared test with Yates' continuity correction

data:  .
X-squared = 0.10583, df = 1, p-value = 0.7449
DNR_darsnp_24_AF <-  gwas_annote_df %>% 
  group_by(DNR_24,AF_status) %>% 
  tally() %>% 
  pivot_wider(., DNR_24, names_from = AF_status, values_from = n) %>% 
  arrange(desc(DNR_24)) %>% 
  column_to_rownames("DNR_24") %>% 
  fisher.test(.)
gwas_annote_df %>% 
  group_by(DNR_3,HF_status) %>% 
  tally() %>% 
  pivot_wider(., DNR_3, names_from = HF_status, values_from = n) %>% 
  arrange(desc(DNR_3)) %>% 
  print() %>% 
  column_to_rownames("DNR_3") %>% 
  fisher.test(.)
# A tibble: 2 × 3
# Groups:   DNR_3 [2]
  DNR_3        HF_peak not_HF_peak
  <chr>          <int>       <int>
1 sig_peak           6       22732
2 not_sig_peak      23      132796

    Fisher's Exact Test for Count Data

data:  .
p-value = 0.4252
alternative hypothesis: true odds ratio is not equal to 1
95 percent confidence interval:
 0.5075285 3.8506709
sample estimates:
odds ratio 
   1.52394 
DNR_darsnp_3_HF <- gwas_annote_df %>% 
  group_by(DNR_3,HF_status) %>% 
  tally() %>% 
  pivot_wider(., DNR_3, names_from = HF_status, values_from = n) %>% 
  arrange(desc(DNR_3)) %>% 
  column_to_rownames("DNR_3") %>% 
  fisher.test(.)
gwas_annote_df %>%
  group_by(DNR_24,HF_status) %>%
  tally() %>%
  pivot_wider(., DNR_24, names_from = HF_status, values_from = n) %>%
  arrange(desc(DNR_24)) %>%
  print() %>%
  column_to_rownames("DNR_24") %>%
  fisher.test(.)
# A tibble: 2 × 3
# Groups:   DNR_24 [2]
  DNR_24       HF_peak not_HF_peak
  <chr>          <int>       <int>
1 sig_peak          19       79976
2 not_sig_peak      10       75552

    Fisher's Exact Test for Count Data

data:  .
p-value = 0.1406
alternative hypothesis: true odds ratio is not equal to 1
95 percent confidence interval:
 0.7940266 4.3218505
sample estimates:
odds ratio 
  1.794883 
DNR_darsnp_24_HF <- gwas_annote_df %>%
  group_by(DNR_24,HF_status) %>%
  tally() %>%
  pivot_wider(., DNR_24, names_from = HF_status, values_from = n) %>%
  arrange(desc(DNR_24)) %>%
  column_to_rownames("DNR_24") %>%
  fisher.test(.)
gwas_annote_df %>% 
  group_by(DNR_3,IHD_status) %>% 
  tally() %>% 
  pivot_wider(., DNR_3, names_from = IHD_status, values_from = n, values_fill = 0) %>% 
  arrange(desc(DNR_3))%>% 
  print() %>% 
  column_to_rownames("DNR_3") %>% 
  fisher.test(.)
# A tibble: 2 × 3
# Groups:   DNR_3 [2]
  DNR_3        IHD_peak not_IHD_peak
  <chr>           <int>        <int>
1 sig_peak            2        22736
2 not_sig_peak        5       132814

    Fisher's Exact Test for Count Data

data:  .
p-value = 0.2727
alternative hypothesis: true odds ratio is not equal to 1
95 percent confidence interval:
  0.2224883 14.2718586
sample estimates:
odds ratio 
  2.336612 
DNR_darsnp_3_IHD <- gwas_annote_df %>% 
  group_by(DNR_3,IHD_status) %>% 
  tally() %>% 
  pivot_wider(., DNR_3, names_from = IHD_status, values_from = n, values_fill = 0) %>% 
  arrange(desc(DNR_3))%>% 
  column_to_rownames("DNR_3") %>% 
  fisher.test(.)
gwas_annote_df %>% 
  group_by(DNR_24,IHD_status) %>% 
  tally() %>% 
  pivot_wider(., DNR_24, names_from = IHD_status, values_from = n, values_fill = 0) %>% 
  arrange(desc(DNR_24)) %>% 
  print() %>% 
  column_to_rownames("DNR_24") %>% 
  fisher.test(.)
# A tibble: 2 × 3
# Groups:   DNR_24 [2]
  DNR_24       IHD_peak not_IHD_peak
  <chr>           <int>        <int>
1 sig_peak            3        79992
2 not_sig_peak        4        75558

    Fisher's Exact Test for Count Data

data:  .
p-value = 0.7194
alternative hypothesis: true odds ratio is not equal to 1
95 percent confidence interval:
 0.1037956 4.1876739
sample estimates:
odds ratio 
 0.7084326 
DNR_darsnp_24_IHD <- gwas_annote_df %>% 
  group_by(DNR_24,IHD_status) %>% 
  tally() %>% 
  pivot_wider(., DNR_24, names_from = IHD_status, values_from = n, values_fill = 0) %>% 
  arrange(desc(DNR_24)) %>% 
  column_to_rownames("DNR_24") %>% 
  fisher.test(.)
gwas_annote_df %>% 
  group_by(DNR_3,CAD_status) %>% 
  tally() %>% 
  pivot_wider(., DNR_3, names_from = CAD_status, values_from = n) %>% 
  arrange(desc(DNR_3)) %>% 
  print() %>% 
  column_to_rownames("DNR_3") %>% 
  chisq.test(.)
# A tibble: 2 × 3
# Groups:   DNR_3 [2]
  DNR_3        CAD_peak not_CAD_peak
  <chr>           <int>        <int>
1 sig_peak           28        22710
2 not_sig_peak      110       132709

    Pearson's Chi-squared test with Yates' continuity correction

data:  .
X-squared = 3.1209, df = 1, p-value = 0.07729
DNR_darsnp_3_CAD <- gwas_annote_df %>% 
  group_by(DNR_3,CAD_status) %>% 
  tally() %>% 
  pivot_wider(., DNR_3, names_from = CAD_status, values_from = n) %>% 
  arrange(desc(DNR_3)) %>% 
  column_to_rownames("DNR_3") %>% 
  fisher.test(.)
gwas_annote_df %>% 
  group_by(DNR_24,CAD_status) %>% 
  tally() %>% 
  pivot_wider(., DNR_24, names_from = CAD_status, values_from = n) %>% 
  arrange(desc(DNR_24)) %>% 
  print() %>% 
  column_to_rownames("DNR_24") %>% 
  chisq.test(.)
# A tibble: 2 × 3
# Groups:   DNR_24 [2]
  DNR_24       CAD_peak not_CAD_peak
  <chr>           <int>        <int>
1 sig_peak           68        79927
2 not_sig_peak       70        75492

    Pearson's Chi-squared test with Yates' continuity correction

data:  .
X-squared = 0.17661, df = 1, p-value = 0.6743
DNR_darsnp_24_CAD <- gwas_annote_df %>% 
  group_by(DNR_24,CAD_status) %>% 
  tally() %>% 
  pivot_wider(., DNR_24, names_from = CAD_status, values_from = n) %>% 
  arrange(desc(DNR_24)) %>% 
  column_to_rownames("DNR_24") %>% 
  fisher.test(.)

MTX enrichment tests

 gwas_annote_df %>% 
  group_by(MTX_3,AF_status) %>% 
  tally() %>% 
  pivot_wider(., MTX_3, names_from = AF_status, values_from = n,values_fill = 0) %>% 
  arrange(desc(MTX_3)) %>% 
  print() %>% 
  column_to_rownames("MTX_3") %>% 
  fisher.test(.)
# A tibble: 2 × 3
# Groups:   MTX_3 [2]
  MTX_3        AF_peak not_AF_peak
  <chr>          <int>       <int>
1 sig_peak           0         804
2 not_sig_peak      76      154677

    Fisher's Exact Test for Count Data

data:  .
p-value = 1
alternative hypothesis: true odds ratio is not equal to 1
95 percent confidence interval:
 0.000000 9.590161
sample estimates:
odds ratio 
         0 
MTX_darsnp_3_AF <- gwas_annote_df %>%
  group_by(MTX_3,AF_status) %>% 
  tally() %>% 
  pivot_wider(., MTX_3, names_from = AF_status, values_from = n,values_fill = 0) %>% 
  arrange(desc(MTX_3)) %>% 
  column_to_rownames("MTX_3") %>% 
  fisher.test(.)
gwas_annote_df %>% 
  group_by(MTX_24,AF_status) %>% 
  tally() %>% 
  pivot_wider(., MTX_24, names_from = AF_status, values_from = n) %>% 
  arrange(desc(MTX_24)) %>% 
  print() %>% 
  column_to_rownames("MTX_24") %>% 
  chisq.test(.)
# A tibble: 2 × 3
# Groups:   MTX_24 [2]
  MTX_24       AF_peak not_AF_peak
  <chr>          <int>       <int>
1 sig_peak          20       24230
2 not_sig_peak      56      131251

    Pearson's Chi-squared test with Yates' continuity correction

data:  .
X-squared = 5.8581, df = 1, p-value = 0.01551
MTX_darsnp_24_AF <-  gwas_annote_df %>% 
  group_by(MTX_24,AF_status) %>% 
  tally() %>% 
  pivot_wider(., MTX_24, names_from = AF_status, values_from = n) %>% 
  arrange(desc(MTX_24)) %>% 
  column_to_rownames("MTX_24") %>% 
  fisher.test(.)
gwas_annote_df %>% 
  group_by(MTX_3,HF_status) %>% 
  tally() %>% 
  pivot_wider(., MTX_3, names_from = HF_status, values_from = n) %>% 
  arrange(desc(MTX_3)) %>% 
  print() %>% 
  column_to_rownames("MTX_3") %>% 
  fisher.test(.)
# A tibble: 2 × 3
# Groups:   MTX_3 [2]
  MTX_3        HF_peak not_HF_peak
  <chr>          <int>       <int>
1 sig_peak           1         803
2 not_sig_peak      28      154725

    Fisher's Exact Test for Count Data

data:  .
p-value = 0.1395
alternative hypothesis: true odds ratio is not equal to 1
95 percent confidence interval:
  0.1680849 41.7539207
sample estimates:
odds ratio 
  6.880335 
MTX_darsnp_3_HF <- gwas_annote_df %>% 
  group_by(MTX_3,HF_status) %>% 
  tally() %>% 
  pivot_wider(., MTX_3, names_from = HF_status, values_from = n) %>% 
  arrange(desc(MTX_3)) %>% 
  column_to_rownames("MTX_3") %>% 
  fisher.test(.)
gwas_annote_df %>%
  group_by(MTX_24,HF_status) %>%
  tally() %>%
  pivot_wider(., MTX_24, names_from = HF_status, values_from = n) %>%
  arrange(desc(MTX_24)) %>%
  print() %>%
  column_to_rownames("MTX_24") %>%
  fisher.test(.)
# A tibble: 2 × 3
# Groups:   MTX_24 [2]
  MTX_24       HF_peak not_HF_peak
  <chr>          <int>       <int>
1 sig_peak          10       24240
2 not_sig_peak      19      131288

    Fisher's Exact Test for Count Data

data:  .
p-value = 0.009723
alternative hypothesis: true odds ratio is not equal to 1
95 percent confidence interval:
 1.183787 6.443806
sample estimates:
odds ratio 
  2.850689 
MTX_darsnp_24_HF <- gwas_annote_df %>%
  group_by(MTX_24,HF_status) %>%
  tally() %>%
  pivot_wider(., MTX_24, names_from = HF_status, values_from = n) %>%
  arrange(desc(MTX_24)) %>%
  column_to_rownames("MTX_24") %>%
  fisher.test(.)
gwas_annote_df %>% 
  group_by(MTX_3,IHD_status) %>% 
  tally() %>% 
  pivot_wider(., MTX_3, names_from = IHD_status, values_from = n, values_fill = 0) %>% 
  arrange(desc(MTX_3))%>% 
  print() %>% 
  column_to_rownames("MTX_3") %>% 
  fisher.test(.)
# A tibble: 2 × 3
# Groups:   MTX_3 [2]
  MTX_3        IHD_peak not_IHD_peak
  <chr>           <int>        <int>
1 sig_peak            0          804
2 not_sig_peak        7       154746

    Fisher's Exact Test for Count Data

data:  .
p-value = 1
alternative hypothesis: true odds ratio is not equal to 1
95 percent confidence interval:
   0.0000 133.7927
sample estimates:
odds ratio 
         0 
MTX_darsnp_3_IHD <- gwas_annote_df %>% 
  group_by(MTX_3,IHD_status) %>% 
  tally() %>% 
  pivot_wider(., MTX_3, names_from = IHD_status, values_from = n, values_fill = 0) %>% 
  arrange(desc(MTX_3))%>% 
  column_to_rownames("MTX_3") %>% 
  fisher.test(.)
gwas_annote_df %>% 
  group_by(MTX_24,IHD_status) %>% 
  tally() %>% 
  pivot_wider(., MTX_24, names_from = IHD_status, values_from = n, values_fill = 0) %>% 
  arrange(desc(MTX_24)) %>% 
  print() %>% 
  column_to_rownames("MTX_24") %>% 
  fisher.test(.)
# A tibble: 2 × 3
# Groups:   MTX_24 [2]
  MTX_24       IHD_peak not_IHD_peak
  <chr>           <int>        <int>
1 sig_peak            2        24248
2 not_sig_peak        5       131302

    Fisher's Exact Test for Count Data

data:  .
p-value = 0.2999
alternative hypothesis: true odds ratio is not equal to 1
95 percent confidence interval:
  0.2062384 13.2298655
sample estimates:
odds ratio 
  2.165985 
MTX_darsnp_24_IHD <- gwas_annote_df %>% 
  group_by(MTX_24,IHD_status) %>% 
  tally() %>% 
  pivot_wider(., MTX_24, names_from = IHD_status, values_from = n, values_fill = 0) %>% 
  arrange(desc(MTX_24)) %>% 
  column_to_rownames("MTX_24") %>% 
  fisher.test(.)
gwas_annote_df %>% 
  group_by(MTX_3,CAD_status) %>% 
  tally() %>% 
  pivot_wider(., MTX_3, names_from = CAD_status, values_from = n, values_fill = 0) %>% 
  arrange(desc(MTX_3)) %>% 
  print() %>% 
  column_to_rownames("MTX_3") %>% 
  fisher.test(.)
# A tibble: 2 × 3
# Groups:   MTX_3 [2]
  MTX_3        CAD_peak not_CAD_peak
  <chr>           <int>        <int>
1 sig_peak            0          804
2 not_sig_peak      138       154615

    Fisher's Exact Test for Count Data

data:  .
p-value = 1
alternative hypothesis: true odds ratio is not equal to 1
95 percent confidence interval:
 0.000000 5.222361
sample estimates:
odds ratio 
         0 
MTX_darsnp_3_CAD <- gwas_annote_df %>% 
  group_by(MTX_3,CAD_status) %>% 
  tally() %>% 
  pivot_wider(., MTX_3, names_from = CAD_status, values_from = n, values_fill = 0) %>% 
  arrange(desc(MTX_3)) %>% 
  column_to_rownames("MTX_3") %>% 
  fisher.test(.)
gwas_annote_df %>% 
  group_by(MTX_24,CAD_status) %>% 
  tally() %>% 
  pivot_wider(., MTX_24, names_from = CAD_status, values_from = n) %>% 
  arrange(desc(MTX_24)) %>% 
  print() %>% 
  column_to_rownames("MTX_24") %>% 
  chisq.test(.)
# A tibble: 2 × 3
# Groups:   MTX_24 [2]
  MTX_24       CAD_peak not_CAD_peak
  <chr>           <int>        <int>
1 sig_peak           28        24222
2 not_sig_peak      110       131197

    Pearson's Chi-squared test with Yates' continuity correction

data:  .
X-squared = 1.9756, df = 1, p-value = 0.1599
MTX_darsnp_24_CAD <- gwas_annote_df %>% 
  group_by(MTX_24,CAD_status) %>% 
  tally() %>% 
  pivot_wider(., MTX_24, names_from = CAD_status, values_from = n) %>% 
  arrange(desc(MTX_24)) %>% 
  column_to_rownames("MTX_24") %>% 
  fisher.test(.)

Collecting all data to display:

All_24_results <- mget(ls(pattern = "*_darsnp_24*"))
All_3_results <- mget(ls(pattern = "*_darsnp_3*"))
# All_dar_results <- mget(ls(pattern = "*_darsnp_*"))


# convert to data frames with metadata
combined_df_24 <- bind_rows(
  lapply(names(All_24_results), function(name) {
    res <- All_24_results[[name]]
    parts <- strsplit(name, "_")[[1]]
    
    # convert htest to data.frame
    data.frame(
      
      p.value = res$p.value,
      estimate = if (!is.null(res$estimate)) unname(res$estimate) else NA,
      conf.low = if (!is.null(res$conf.int)) res$conf.int[1] else NA,
      conf.high = if (!is.null(res$conf.int)) res$conf.int[2] else NA,
      drug = parts[1],
      time = parts[3],
      population = parts[4],
      stringsAsFactors = FALSE
    )
  })
)

combined_df_3 <- bind_rows(
  lapply(names(All_3_results), function(name) {
    res <- All_3_results[[name]]
    parts <- strsplit(name, "_")[[1]]
    
    # convert htest to data.frame
    data.frame(
      p.value = res$p.value,
      estimate = if (!is.null(res$estimate)) unname(res$estimate) else NA,
      conf.low = if (!is.null(res$conf.int)) res$conf.int[1] else NA,
      conf.high = if (!is.null(res$conf.int)) res$conf.int[2] else NA,
      drug = parts[1],
      time = parts[3],
      population = parts[4],
      stringsAsFactors = FALSE
    )
  })
)
drug_pal <- c("#8B006D","#DF707E","#F1B72B", "#3386DD","#707031","#41B333")
combined_df_3 %>% 
  mutate(drug=factor(drug, levels = c("DOX","EPI","DNR","MTX")),
         time=factor(time, levels = c("3","24")),
         population=factor(population,levels = c("AF","HF","IHD","CAD"))) %>% 
  mutate(log10_pvalue=-log10(p.value)) %>% 
  ggplot(., aes(x=drug, y=log10_pvalue))+
  geom_col(aes(fill=drug))+
  geom_hline(yintercept= -log10(0.05), linetype = "dashed",color="black")+
  theme_classic()+
  facet_wrap(~time+population,nrow=2)+
  xlab("treatment")+
  ylab("log10 pvalue of fisher exact test")+
  scale_fill_manual(values = drug_pal)

Version Author Date
88047ef reneeisnowhere 2025-07-28
combined_df_3 %>% 
  dplyr::filter(population!= "IHD" & population != "CAD") %>%
  mutate(drug=factor(drug, levels = c("DOX","EPI","DNR","MTX")),
         time=factor(time, levels = c("3","24")),
         population=factor(population,levels = c("AF","HF","IHD", "CAD"))) %>%
    group_by(time,drug) %>% 
  mutate(rank_val=rank(p.value, ties.method = "first")) %>%
  mutate(BH_correction= p.adjust(p.value,method= "BH")) %>% 
  mutate(log10_pvalue=-log10(BH_correction)) %>% 
  ggplot(., aes(x=drug, y=log10_pvalue))+
  geom_col(aes(fill=drug))+
  geom_hline(yintercept= -log10(0.05), linetype = "dashed",color="black")+
  theme_classic()+
  facet_wrap(~time+population,nrow=2)+
  xlab("treatment")+
  ylab("log10 pvalue of fisher exact test")+
  scale_fill_manual(values = drug_pal)

Version Author Date
88047ef reneeisnowhere 2025-07-28

OR of results

combined_df_3 %>% 
  mutate(group=paste0(drug,"_",time)) %>% 
  # separate_wider_delim(.,cols="group", names = c("trt","time"), delim = "_",cols_remove = FALSE) %>% 
    mutate(time= factor(time, levels =c("3","24")),
         drug=factor(drug, levels= c("DOX", "EPI", "DNR", "MTX"))) %>%
  mutate(population=factor(population, levels= c("AF","HF","IHD","CAD"))) %>% 
  mutate(
    significant = case_when(
      p.value < 0.001 ~ "***",
      p.value < 0.01 ~ "**",
      p.value < 0.05 ~ "*",
      TRUE ~ ""
    )
  ) %>% 
ggplot(., aes(x = drug, y = estimate)) +
   geom_point(aes(color = drug), size=4)+
   geom_errorbar(aes(ymin = conf.low, ymax = conf.high), width = 0.2) +
  geom_hline(yintercept = 1, linetype = "dashed", color = "gray40") +
  geom_text(
  aes(y = conf.high + 0.1 * estimate, label = significant),
  hjust = 0,  # aligns text to the left of the y point
  size = 4,
  color = "black"
)+
  labs(
    title = "Odds Ratio of SNP enrichment by type",
    y = "Odds Ratio (95% confidence interval)",
    x = "treatment"
  ) +
  # coord_flip()+
  theme_bw() +
  facet_grid(rows = vars(population), cols = vars(time), scales = "free_y")+
  theme(
    text = element_text(size = 12),
    plot.title = element_text(hjust = 0.5)
  )

Version Author Date
651ce34 reneeisnowhere 2025-07-29

MCF7 enrichment tests

library(regioneR)
AF_gr <- Short_gwas_gr %>% 
  dplyr::filter(gwas == "AF")
HF_gr <- Short_gwas_gr %>% 
  dplyr::filter(gwas == "HF")
IHD_gr <- Short_gwas_gr %>% 
  dplyr::filter(gwas == "IHD")
CAD_gr <- Short_gwas_gr %>% 
  dplyr::filter(gwas == "CAD")


# AF_MCF7_ol_peaks <-   join_overlap_inner(MCF7_DAR_all, Short_gwas_gr) %>%
#   dplyr::filter(mcols(gwas =="AF")) %>% 
#   as.data.frame() %>% 
#   dplyr::filter(gwas =="AF") %>% 
#   distinct(names)
# 
# HF_MCF7_ol_peaks <-   join_overlap_inner(MCF7_DAR_all, Short_gwas_gr) %>%
#   as.data.frame() %>% 
#   dplyr::filter(gwas =="HF") %>% 
#   distinct(names)
# 
# IHD_MCF7_ol_peaks <-   join_overlap_inner(MCF7_DAR_all, Short_gwas_gr) %>%
#   as.data.frame() %>% 
#   dplyr::filter(gwas =="IHD") %>% 
#   distinct(names)

# saveRDS(AF,"data/Final_four_data/re_analysis/MCF7_DAR_AF_permtest.RDS")

IHD <-readRDS("data/Final_four_data/re_analysis/MCF7_DAR_IHD_permtest.RDS")

HF <- readRDS("data/Final_four_data/re_analysis/MCF7_DAR_HF_permtest.RDS")
AF <- readRDS("data/Final_four_data/re_analysis/MCF7_DAR_AF_permtest.RDS")
CAD <- readRDS("data/Final_four_data/re_analysis/MCF7_DAR_CAD_permtest.RDS")
# param <- SnowParam(workers = 8)
# AF<- permTest(A= MCF7_DAR_all,
#                           B= AF_gr,
#                           ntimes=1000,
#                           randomize.function=randomizeRegions,
#                           evaluate.function = numOverlaps,
#                           genome="hg38",
#                           count.once= TRUE,
#                           universe=universe,
#                         # universe = union_accessible_regions,
#                           verbose = TRUE,
#                           BPPARAM = param)
AF
$numOverlaps
P-value: 0.64035964035964
Z-score: -0.0163
Number of iterations: 1000
Alternative: less
Evaluation of the original region set: 4
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(AF)

Version Author Date
651ce34 reneeisnowhere 2025-07-29
2baaf88 reneeisnowhere 2025-07-28
88047ef reneeisnowhere 2025-07-28
HF
$numOverlaps
P-value: 0.434565434565435
Z-score: 0.3761
Number of iterations: 1000
Alternative: greater
Evaluation of the original region set: 3
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(HF)

Version Author Date
651ce34 reneeisnowhere 2025-07-29
2baaf88 reneeisnowhere 2025-07-28
88047ef reneeisnowhere 2025-07-28
IHD
$numOverlaps
P-value: 0.614385614385614
Z-score: -0.7021
Number of iterations: 1000
Alternative: less
Evaluation of the original region set: 0
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(IHD)

Version Author Date
651ce34 reneeisnowhere 2025-07-29
2baaf88 reneeisnowhere 2025-07-28
88047ef reneeisnowhere 2025-07-28
CAD
$numOverlaps
P-value: 0.045954045954046
Z-score: 1.8555
Number of iterations: 1000
Alternative: greater
Evaluation of the original region set: 19
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(CAD)

Version Author Date
651ce34 reneeisnowhere 2025-07-29
2baaf88 reneeisnowhere 2025-07-28
88047ef reneeisnowhere 2025-07-28

PT DOX 24hr check

# DOX_24_gr <- DOX_24_sig %>% separate_wider_delim(., cols="genes",names = c("seqnames","start","end"), delim= ".") %>% 
#   GRanges() 
# 
# DOX_3_gr <- DOX_3_sig %>% separate_wider_delim(., cols="genes",names = c("seqnames","start","end"), delim= ".") %>% 
#   GRanges() 
# param <- SnowParam(workers = 1)

DOX_AF <- readRDS("data/Final_four_data/re_analysis/perm_test_1000/DOX_AF_24h.RDS")
DOX_HF <- readRDS("data/Final_four_data/re_analysis/perm_test_1000/DOX_HF_24h.RDS")
DOX_IHD <- readRDS("data/Final_four_data/re_analysis/perm_test_1000/DOX_IHD_24h.RDS")
DOX_CAD <- readRDS("data/Final_four_data/re_analysis/perm_test_1000/DOX_CAD_24h.RDS")

DOX_AF_3 <- readRDS("data/Final_four_data/re_analysis/perm_test_1000/DOX_AF_3h.RDS")
DOX_HF_3 <- readRDS("data/Final_four_data/re_analysis/perm_test_1000/DOX_HF_3h.RDS")
DOX_IHD_3 <- readRDS("data/Final_four_data/re_analysis/perm_test_1000/DOX_IHD_3h.RDS")
DOX_CAD_3 <-  readRDS("data/Final_four_data/re_analysis/perm_test_1000/DOX_CAD_3h.RDS")
# DOX_CAD<- permTest(A= DOX_24_gr,
#                           B= CAD_gr,
#                           ntimes=1000,
#                           randomize.function=randomizeRegions,
#                           evaluate.function = numOverlaps,
#                           genome="hg38",
#                           count.once= TRUE,
#                           universe=universe,
#                         # universe = union_accessible_regions,
#                           verbose = TRUE,
#                           BPPARAM = param)

# DOX_AF<- permTest(A= DOX_24_gr,
#                           B= AF_gr,
#                           ntimes=1000,
#                           randomize.function=randomizeRegions,
#                           evaluate.function = numOverlaps,
#                           genome="hg38",
#                           count.once= TRUE,
#                           universe=universe,
#                         # universe = union_accessible_regions,
#                           verbose = TRUE,
#                           BPPARAM = param)
# 
# DOX_HF<- permTest(A= DOX_24_gr,
#                           B= HF_gr,
#                           ntimes=1000,
#                           randomize.function=randomizeRegions,
#                           evaluate.function = numOverlaps,
#                           genome="hg38",
#                           count.once= TRUE,
#                           universe=universe,
#                         # universe = union_accessible_regions,
#                           verbose = TRUE,
#                           BPPARAM = param)

# DOX_IHD<- permTest(A= DOX_24_gr,
#                           B= IHD_gr,
#                           ntimes=1000,
#                           randomize.function=randomizeRegions,
#                           evaluate.function = numOverlaps,
#                           genome="hg38",
#                           count.once= TRUE,
#                           universe=universe,
#                         # universe = union_accessible_regions,
#                           verbose = TRUE,
#                           BPPARAM = param)
DOX_AF
$numOverlaps
P-value: 0.000999000999000999
Z-score: 9.1355
Number of iterations: 1000
Alternative: greater
Evaluation of the original region set: 34
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(DOX_AF)

Version Author Date
88047ef reneeisnowhere 2025-07-28
DOX_HF
$numOverlaps
P-value: 0.002997002997003
Z-score: 4.1771
Number of iterations: 1000
Alternative: greater
Evaluation of the original region set: 14
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(DOX_HF)

Version Author Date
88047ef reneeisnowhere 2025-07-28
DOX_IHD
$numOverlaps
P-value: 0.0899100899100899
Z-score: 1.9409
Number of iterations: 1000
Alternative: greater
Evaluation of the original region set: 3
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(DOX_IHD)

Version Author Date
88047ef reneeisnowhere 2025-07-28
DOX_CAD
$numOverlaps
P-value: 0.000999000999000999
Z-score: 6.9373
Number of iterations: 1000
Alternative: greater
Evaluation of the original region set: 59
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(DOX_CAD)

Version Author Date
88047ef reneeisnowhere 2025-07-28
# DOX_CAD_3<- permTest(A= DOX_3_gr,
#                           B= CAD_gr,
#                           ntimes=1000,
#                           randomize.function=randomizeRegions,
#                           evaluate.function = numOverlaps,
#                           genome="hg38",
#                           count.once= TRUE,
#                           universe=universe,
#                         # universe = union_accessible_regions,
#                           verbose = TRUE,
#                           BPPARAM = param)

# DOX_AF_3<- permTest(A= DOX_3_gr,
#                           B= AF_gr,
#                           ntimes=1000,
#                           randomize.function=randomizeRegions,
#                           evaluate.function = numOverlaps,
#                           genome="hg38",
#                           count.once= TRUE,
#                           universe=universe,
#                         # universe = union_accessible_regions,
#                           verbose = TRUE,
#                           BPPARAM = param)

# DOX_HF_3<- permTest(A= DOX_3_gr,
#                           B= HF_gr,
#                           ntimes=1000,
#                           randomize.function=randomizeRegions,
#                           evaluate.function = numOverlaps,
#                           genome="hg38",
#                           count.once= TRUE,
#                           universe=universe,
#                         # universe = union_accessible_regions,
#                           verbose = TRUE,
#                           BPPARAM = param)

# DOX_IHD_3<- permTest(A= DOX_3_gr,
#                           B= IHD_gr,
#                           ntimes=1000,
#                           randomize.function=randomizeRegions,
#                           evaluate.function = numOverlaps,
#                           genome="hg38",
#                           count.once= TRUE,
#                           universe=universe,
#                         # universe = union_accessible_regions,
#                           verbose = TRUE,
#                           BPPARAM = param)
DOX_AF_3
$numOverlaps
P-value: 0.000999000999000999
Z-score: 6.3369
Number of iterations: 1000
Alternative: greater
Evaluation of the original region set: 5
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(DOX_AF_3)

Version Author Date
88047ef reneeisnowhere 2025-07-28
DOX_HF_3
$numOverlaps
P-value: 0.236763236763237
Z-score: 1.38
Number of iterations: 1000
Alternative: greater
Evaluation of the original region set: 1
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(DOX_HF_3)

Version Author Date
88047ef reneeisnowhere 2025-07-28
DOX_IHD_3
$numOverlaps
P-value: 0.93006993006993
Z-score: -0.2661
Number of iterations: 1000
Alternative: less
Evaluation of the original region set: 0
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(DOX_IHD_3)

Version Author Date
88047ef reneeisnowhere 2025-07-28
DOX_CAD_3
$numOverlaps
P-value: 0.467532467532468
Z-score: 0.3003
Number of iterations: 1000
Alternative: greater
Evaluation of the original region set: 2
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(DOX_CAD_3)

Version Author Date
88047ef reneeisnowhere 2025-07-28
# saveRDS(DOX_AF,"data/Final_four_data/re_analysis/perm_test_100/DOX_AF_24h.RDS")
# saveRDS(DOX_HF,"data/Final_four_data/re_analysis/perm_test_100/DOX_HF_24h.RDS")
# saveRDS(DOX_IHD,"data/Final_four_data/re_analysis/perm_test_100/DOX_IHD_24h.RDS")
# saveRDS(DOX_CAD,"data/Final_four_data/re_analysis/perm_test_100/DOX_CAD_24h.RDS")

# saveRDS(DOX_AF_3,"data/Final_four_data/re_analysis/perm_test_100/DOX_AF_3h.RDS")
# saveRDS(DOX_HF_3,"data/Final_four_data/re_analysis/perm_test_100/DOX_HF_3h.RDS")
# saveRDS(DOX_IHD_3,"data/Final_four_data/re_analysis/perm_test_100/DOX_IHD_3h.RDS")
# saveRDS(DOX_CAD_3,"data/Final_four_data/re_analysis/perm_test_100/DOX_CAD_3h.RDS")

# saveRDS(DOX_AF,"data/Final_four_data/re_analysis/perm_test_1000/DOX_AF_24h.RDS")
# saveRDS(DOX_HF,"data/Final_four_data/re_analysis/perm_test_1000/DOX_HF_24h.RDS")
# saveRDS(DOX_IHD,"data/Final_four_data/re_analysis/perm_test_1000/DOX_IHD_24h.RDS")
# saveRDS(DOX_CAD,"data/Final_four_data/re_analysis/perm_test_1000/DOX_CAD_24h.RDS")

# saveRDS(DOX_AF_3,"data/Final_four_data/re_analysis/perm_test_1000/DOX_AF_3h.RDS")
# saveRDS(DOX_HF_3,"data/Final_four_data/re_analysis/perm_test_1000/DOX_HF_3h.RDS")
# saveRDS(DOX_IHD_3,"data/Final_four_data/re_analysis/perm_test_1000/DOX_IHD_3h.RDS")
# saveRDS(DOX_CAD_3,"data/Final_four_data/re_analysis/perm_test_1000/DOX_CAD_3h.RDS")

PT EPI 24hr check

EPI_24_gr <- EPI_24_sig %>% separate_wider_delim(., cols="genes",names = c("seqnames","start","end"), delim= ".") %>% 
  GRanges() 

EPI_3_gr <- EPI_3_sig %>% separate_wider_delim(., cols="genes",names = c("seqnames","start","end"), delim= ".") %>% 
  GRanges() 

EPI_AF <- readRDS("data/Final_four_data/re_analysis/perm_test_1000/EPI_AF_24h.RDS")
EPI_HF <- readRDS("data/Final_four_data/re_analysis/perm_test_1000/EPI_HF_24h.RDS")
EPI_IHD <- readRDS("data/Final_four_data/re_analysis/perm_test_1000/EPI_IHD_24h.RDS")
EPI_CAD <- readRDS("data/Final_four_data/re_analysis/perm_test_1000/EPI_CAD_24h.RDS")

EPI_AF_3 <- readRDS("data/Final_four_data/re_analysis/perm_test_1000/EPI_AF_3h.RDS")
EPI_HF_3 <- readRDS("data/Final_four_data/re_analysis/perm_test_1000/EPI_HF_3h.RDS")
EPI_IHD_3 <- readRDS("data/Final_four_data/re_analysis/perm_test_1000/EPI_IHD_3h.RDS")
EPI_CAD_3 <- readRDS("data/Final_four_data/re_analysis/perm_test_1000/EPI_CAD_3h.RDS")



# EPI_AF_3<- permTest(A= EPI_3_gr,
#                           B= AF_gr,
#                           ntimes=1000,
#                           randomize.function=randomizeRegions,
#                           evaluate.function = numOverlaps,
#                           genome="hg38",
#                           count.once= TRUE,
#                           universe=universe,
#                         #
#                           verbose = TRUE,
#                           BPPARAM = param)
# EPI_HF_3<- permTest(A= EPI_3_gr,
#                           B= HF_gr,
#                           ntimes=1000,
#                           randomize.function=randomizeRegions,
#                           evaluate.function = numOverlaps,
#                           genome="hg38",
#                           count.once= TRUE,
#                           universe=universe,
# 
#                           verbose = TRUE,
#                           BPPARAM = param)
# 
# 
# EPI_IHD_3<- permTest(A= EPI_3_gr,
#                           B= IHD_gr,
#                           ntimes=1000,
#                           randomize.function=randomizeRegions,
#                           evaluate.function = numOverlaps,
#                           genome="hg38",
#                           count.once= TRUE,
#                           universe=universe,
# 
#                           verbose = TRUE,
#                           BPPARAM = param)
# 
# EPI_CAD_3<- permTest(A= EPI_3_gr,
#                           B= CAD_gr,
#                           ntimes=1000,
#                           randomize.function=randomizeRegions,
#                           evaluate.function = numOverlaps,
#                           genome="hg38",
#                           count.once= TRUE,
#                           universe=universe,
# 
#                           verbose = TRUE,
#                           BPPARAM = param)






EPI_AF_3
$numOverlaps
P-value: 0.000999000999000999
Z-score: 7.7892
Number of iterations: 1000
Alternative: greater
Evaluation of the original region set: 14
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(EPI_AF_3)

Version Author Date
88047ef reneeisnowhere 2025-07-28
EPI_HF_3
$numOverlaps
P-value: 0.155844155844156
Z-score: 1.4052
Number of iterations: 1000
Alternative: greater
Evaluation of the original region set: 3
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(EPI_HF_3)

Version Author Date
88047ef reneeisnowhere 2025-07-28
EPI_IHD_3
$numOverlaps
P-value: 0.775224775224775
Z-score: -0.4919
Number of iterations: 1000
Alternative: less
Evaluation of the original region set: 0
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(EPI_IHD_3)

Version Author Date
88047ef reneeisnowhere 2025-07-28
EPI_CAD_3
$numOverlaps
P-value: 0.000999000999000999
Z-score: 4.0831
Number of iterations: 1000
Alternative: greater
Evaluation of the original region set: 18
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(EPI_CAD_3)

Version Author Date
88047ef reneeisnowhere 2025-07-28
# EPI_AF<- permTest(A= EPI_24_gr,
#                           B= AF_gr,
#                           ntimes=1000,
#                           randomize.function=randomizeRegions,
#                           evaluate.function = numOverlaps,
#                           genome="hg38",
#                           count.once= TRUE,
#                           universe=universe,
#                           verbose = TRUE,
#                           BPPARAM = param)
# 
# 
# EPI_HF<- permTest(A= EPI_24_gr,
#                           B= HF_gr,
#                           ntimes=1000,
#                           randomize.function=randomizeRegions,
#                           evaluate.function = numOverlaps,
#                           genome="hg38",
#                           count.once= TRUE,
#                           universe=universe,
#                           verbose = TRUE,
#                           BPPARAM = param)
# 
# 
# EPI_IHD<- permTest(A= EPI_24_gr,
#                           B= IHD_gr,
#                           ntimes=1000,
#                           randomize.function=randomizeRegions,
#                           evaluate.function = numOverlaps,
#                           genome="hg38",
#                           count.once= TRUE,
#                           universe=universe,
#                           verbose = TRUE,
#                           BPPARAM = param)
# 
# EPI_CAD <- permTest(A= EPI_24_gr,
#                           B= CAD_gr,
#                           ntimes=1000,
#                           randomize.function=randomizeRegions,
#                           evaluate.function = numOverlaps,
#                           genome="hg38",
#                           count.once= TRUE,
#                           universe=universe,
#                           verbose = TRUE,
#                           BPPARAM = param)


EPI_AF
$numOverlaps
P-value: 0.000999000999000999
Z-score: 10.6464
Number of iterations: 1000
Alternative: greater
Evaluation of the original region set: 39
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(EPI_AF)

Version Author Date
88047ef reneeisnowhere 2025-07-28
EPI_HF
$numOverlaps
P-value: 0.000999000999000999
Z-score: 4.3344
Number of iterations: 1000
Alternative: greater
Evaluation of the original region set: 15
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(EPI_HF)

Version Author Date
88047ef reneeisnowhere 2025-07-28
EPI_IHD
$numOverlaps
P-value: 0.0639360639360639
Z-score: 2.1658
Number of iterations: 1000
Alternative: greater
Evaluation of the original region set: 3
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(EPI_IHD)

Version Author Date
88047ef reneeisnowhere 2025-07-28
EPI_CAD
$numOverlaps
P-value: 0.000999000999000999
Z-score: 6.1142
Number of iterations: 1000
Alternative: greater
Evaluation of the original region set: 58
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(EPI_CAD)

Version Author Date
88047ef reneeisnowhere 2025-07-28
# saveRDS(EPI_AF,"data/Final_four_data/re_analysis/perm_test_100/EPI_AF_24h.RDS")
# saveRDS(EPI_HF,"data/Final_four_data/re_analysis/perm_test_100/EPI_HF_24h.RDS")
# saveRDS(EPI_IHD,"data/Final_four_data/re_analysis/perm_test_100/EPI_IHD_24h.RDS")
# saveRDS(EPI_CAD,"data/Final_four_data/re_analysis/perm_test_100/EPI_CAD_24h.RDS")
# 
# saveRDS(EPI_AF_3,"data/Final_four_data/re_analysis/perm_test_100/EPI_AF_3h.RDS")
# saveRDS(EPI_HF_3,"data/Final_four_data/re_analysis/perm_test_100/EPI_HF_3h.RDS")
# saveRDS(EPI_IHD_3,"data/Final_four_data/re_analysis/perm_test_100/EPI_IHD_3h.RDS")
# saveRDS(EPI_CAD_3,"data/Final_four_data/re_analysis/perm_test_100/EPI_CAD_3h.RDS")

# saveRDS(EPI_AF,"data/Final_four_data/re_analysis/perm_test_1000/EPI_AF_24h.RDS")
# saveRDS(EPI_HF,"data/Final_four_data/re_analysis/perm_test_1000/EPI_HF_24h.RDS")
# saveRDS(EPI_IHD,"data/Final_four_data/re_analysis/perm_test_1000/EPI_IHD_24h.RDS")
# saveRDS(EPI_CAD,"data/Final_four_data/re_analysis/perm_test_1000/EPI_CAD_24h.RDS")
# 
# saveRDS(EPI_AF_3,"data/Final_four_data/re_analysis/perm_test_1000/EPI_AF_3h.RDS")
# saveRDS(EPI_HF_3,"data/Final_four_data/re_analysis/perm_test_1000/EPI_HF_3h.RDS")
# saveRDS(EPI_IHD_3,"data/Final_four_data/re_analysis/perm_test_1000/EPI_IHD_3h.RDS")
# saveRDS(EPI_CAD_3,"data/Final_four_data/re_analysis/perm_test_1000/EPI_CAD_3h.RDS")

PT DNR 24hr check

DNR_24_gr <- DNR_24_sig %>% separate_wider_delim(., cols="genes",names = c("seqnames","start","end"), delim= ".") %>% 
  GRanges() 

DNR_3_gr <- DNR_3_sig %>% separate_wider_delim(., cols="genes",names = c("seqnames","start","end"), delim= ".") %>% 
  GRanges() 

DNR_AF <- readRDS("data/Final_four_data/re_analysis/perm_test_1000/DNR_AF_24h.RDS")
DNR_HF <- readRDS("data/Final_four_data/re_analysis/perm_test_1000/DNR_HF_24h.RDS")
DNR_IHD <- readRDS("data/Final_four_data/re_analysis/perm_test_1000/DNR_IHD_24h.RDS")
DNR_CAD <- readRDS("data/Final_four_data/re_analysis/perm_test_1000/DNR_CAD_24h.RDS")

DNR_AF_3 <- readRDS("data/Final_four_data/re_analysis/perm_test_1000/DNR_AF_3h.RDS")
DNR_HF_3 <- readRDS("data/Final_four_data/re_analysis/perm_test_1000/DNR_HF_3h.RDS")
DNR_IHD_3 <- readRDS("data/Final_four_data/re_analysis/perm_test_1000/DNR_IHD_3h.RDS")
DNR_CAD_3 <- readRDS("data/Final_four_data/re_analysis/perm_test_1000/DNR_CAD_3h.RDS")

# DNR_AF_3<- permTest(A= DNR_3_gr,
#                           B= AF_gr,
#                           ntimes=1000,
#                           randomize.function=randomizeRegions,
#                           evaluate.function = numOverlaps,
#                           genome="hg38",
#                           count.once= TRUE,
#                           universe=universe,
#                         #
#                           verbose = TRUE,
#                           BPPARAM = param)
# DNR_HF_3<- permTest(A= DNR_3_gr,
#                           B= HF_gr,
#                           ntimes=1000,
#                           randomize.function=randomizeRegions,
#                           evaluate.function = numOverlaps,
#                           genome="hg38",
#                           count.once= TRUE,
#                           universe=universe,
# 
#                           verbose = TRUE,
#                           BPPARAM = param)
# 
# 
# DNR_IHD_3<- permTest(A= DNR_3_gr,
#                           B= IHD_gr,
#                           ntimes=1000,
#                           randomize.function=randomizeRegions,
#                           evaluate.function = numOverlaps,
#                           genome="hg38",
#                           count.once= TRUE,
#                           universe=universe,
# 
#                           verbose = TRUE,
#                           BPPARAM = param)
# 
# DNR_CAD_3<- permTest(A= DNR_3_gr,
#                           B= CAD_gr,
#                           ntimes=1000,
#                           randomize.function=randomizeRegions,
#                           evaluate.function = numOverlaps,
#                           genome="hg38",
#                           count.once= TRUE,
#                           universe=universe,
# 
#                           verbose = TRUE,
#                           BPPARAM = param)






DNR_AF_3
$numOverlaps
P-value: 0.000999000999000999
Z-score: 9.0434
Number of iterations: 1000
Alternative: greater
Evaluation of the original region set: 21
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(DNR_AF_3)

Version Author Date
88047ef reneeisnowhere 2025-07-28
DNR_HF_3
$numOverlaps
P-value: 0.035964035964036
Z-score: 2.4989
Number of iterations: 1000
Alternative: greater
Evaluation of the original region set: 6
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(DNR_HF_3)

Version Author Date
88047ef reneeisnowhere 2025-07-28
DNR_IHD_3
$numOverlaps
P-value: 0.0749250749250749
Z-score: 2.36
Number of iterations: 1000
Alternative: greater
Evaluation of the original region set: 2
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(DNR_IHD_3)

Version Author Date
88047ef reneeisnowhere 2025-07-28
DNR_CAD_3
$numOverlaps
P-value: 0.000999000999000999
Z-score: 4.6739
Number of iterations: 1000
Alternative: greater
Evaluation of the original region set: 28
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(DNR_CAD_3)

Version Author Date
88047ef reneeisnowhere 2025-07-28
# DNR_AF<- permTest(A= DNR_24_gr,
#                           B= AF_gr,
#                           ntimes=1000,
#                           randomize.function=randomizeRegions,
#                           evaluate.function = numOverlaps,
#                           genome="hg38",
#                           count.once= TRUE,
#                           universe=universe,
#                           verbose = TRUE,
#                           BPPARAM = param)
# 
# 
# DNR_HF<- permTest(A= DNR_24_gr,
#                           B= HF_gr,
#                           ntimes=1000,
#                           randomize.function=randomizeRegions,
#                           evaluate.function = numOverlaps,
#                           genome="hg38",
#                           count.once= TRUE,
#                           universe=universe,
#                           verbose = TRUE,
#                           BPPARAM = param)
# 
# 
# DNR_IHD<- permTest(A= DNR_24_gr,
#                           B= IHD_gr,
#                           ntimes=1000,
#                           randomize.function=randomizeRegions,
#                           evaluate.function = numOverlaps,
#                           genome="hg38",
#                           count.once= TRUE,
#                           universe=universe,
#                           verbose = TRUE,
#                           BPPARAM = param)
# 
# DNR_CAD <- permTest(A= DNR_24_gr,
#                           B= CAD_gr,
#                           ntimes=1000,
#                           randomize.function=randomizeRegions,
#                           evaluate.function = numOverlaps,
#                           genome="hg38",
#                           count.once= TRUE,
#                           universe=universe,
#                           verbose = TRUE,
#                           BPPARAM = param)
# 

DNR_AF
$numOverlaps
P-value: 0.000999000999000999
Z-score: 9.4608
Number of iterations: 1000
Alternative: greater
Evaluation of the original region set: 41
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(DNR_AF)

Version Author Date
88047ef reneeisnowhere 2025-07-28
DNR_HF
$numOverlaps
P-value: 0.000999000999000999
Z-score: 5.3281
Number of iterations: 1000
Alternative: greater
Evaluation of the original region set: 19
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(DNR_HF)

Version Author Date
88047ef reneeisnowhere 2025-07-28
DNR_IHD
$numOverlaps
P-value: 0.108891108891109
Z-score: 1.6634
Number of iterations: 1000
Alternative: greater
Evaluation of the original region set: 3
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(DNR_IHD)

Version Author Date
88047ef reneeisnowhere 2025-07-28
DNR_CAD
$numOverlaps
P-value: 0.000999000999000999
Z-score: 6.3211
Number of iterations: 1000
Alternative: greater
Evaluation of the original region set: 68
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(DNR_CAD)

Version Author Date
88047ef reneeisnowhere 2025-07-28
# saveRDS(DNR_AF,"data/Final_four_data/re_analysis/perm_test_100/DNR_AF_24h.RDS")
# saveRDS(DNR_HF,"data/Final_four_data/re_analysis/perm_test_100/DNR_HF_24h.RDS")
# saveRDS(DNR_IHD,"data/Final_four_data/re_analysis/perm_test_100/DNR_IHD_24h.RDS")
# saveRDS(DNR_CAD,"data/Final_four_data/re_analysis/perm_test_100/DNR_CAD_24h.RDS")
# 
# saveRDS(DNR_AF_3,"data/Final_four_data/re_analysis/perm_test_100/DNR_AF_3h.RDS")
# saveRDS(DNR_HF_3,"data/Final_four_data/re_analysis/perm_test_100/DNR_HF_3h.RDS")
# saveRDS(DNR_IHD_3,"data/Final_four_data/re_analysis/perm_test_100/DNR_IHD_3h.RDS")
# saveRDS(DNR_CAD_3,"data/Final_four_data/re_analysis/perm_test_100/DNR_CAD_3h.RDS")

# saveRDS(DNR_AF,"data/Final_four_data/re_analysis/perm_test_1000/DNR_AF_24h.RDS")
# saveRDS(DNR_HF,"data/Final_four_data/re_analysis/perm_test_1000/DNR_HF_24h.RDS")
# saveRDS(DNR_IHD,"data/Final_four_data/re_analysis/perm_test_1000/DNR_IHD_24h.RDS")
# saveRDS(DNR_CAD,"data/Final_four_data/re_analysis/perm_test_1000/DNR_CAD_24h.RDS")
# 
# saveRDS(DNR_AF_3,"data/Final_four_data/re_analysis/perm_test_1000/DNR_AF_3h.RDS")
# saveRDS(DNR_HF_3,"data/Final_four_data/re_analysis/perm_test_1000/DNR_HF_3h.RDS")
# saveRDS(DNR_IHD_3,"data/Final_four_data/re_analysis/perm_test_1000/DNR_IHD_3h.RDS")
# saveRDS(DNR_CAD_3,"data/Final_four_data/re_analysis/perm_test_1000/DNR_CAD_3h.RDS")

PT MTX 24hr check

MTX_24_gr <- MTX_24_sig %>% separate_wider_delim(., cols="genes",names = c("seqnames","start","end"), delim= ".") %>% 
  GRanges() 

MTX_3_gr <- MTX_3_sig %>% separate_wider_delim(., cols="genes",names = c("seqnames","start","end"), delim= ".") %>% 
  GRanges() 

MTX_AF <- readRDS("data/Final_four_data/re_analysis/perm_test_1000/MTX_AF_24h.RDS")
MTX_HF <- readRDS("data/Final_four_data/re_analysis/perm_test_1000/MTX_HF_24h.RDS")
MTX_IHD <- readRDS("data/Final_four_data/re_analysis/perm_test_1000/MTX_IHD_24h.RDS")
MTX_CAD <- readRDS("data/Final_four_data/re_analysis/perm_test_1000/MTX_CAD_24h.RDS")

MTX_AF_3 <- readRDS("data/Final_four_data/re_analysis/perm_test_1000/MTX_AF_3h.RDS")
MTX_HF_3 <- readRDS("data/Final_four_data/re_analysis/perm_test_1000/MTX_HF_3h.RDS")
MTX_IHD_3 <- readRDS("data/Final_four_data/re_analysis/perm_test_1000/MTX_IHD_3h.RDS")
MTX_CAD_3 <- readRDS("data/Final_four_data/re_analysis/perm_test_1000/MTX_CAD_3h.RDS")

# MTX_AF_3<- permTest(A= MTX_3_gr,
#                           B= AF_gr,
#                           ntimes=1000,
#                           randomize.function=randomizeRegions,
#                           evaluate.function = numOverlaps,
#                           genome="hg38",
#                           count.once= TRUE,
#                           universe=universe,
#                         #
#                           verbose = TRUE,
#                           BPPARAM = param)
# MTX_HF_3<- permTest(A= MTX_3_gr,
#                           B= HF_gr,
#                           ntimes=1000,
#                           randomize.function=randomizeRegions,
#                           evaluate.function = numOverlaps,
#                           genome="hg38",
#                           count.once= TRUE,
#                           universe=universe,
# 
#                           verbose = TRUE,
#                           BPPARAM = param)
# 
# 
# MTX_IHD_3<- permTest(A= MTX_3_gr,
#                           B= IHD_gr,
#                           ntimes=1000,
#                           randomize.function=randomizeRegions,
#                           evaluate.function = numOverlaps,
#                           genome="hg38",
#                           count.once= TRUE,
#                           universe=universe,
# 
#                           verbose = TRUE,
#                           BPPARAM = param)
# 
# MTX_CAD_3<- permTest(A= MTX_3_gr,
#                           B= CAD_gr,
#                           ntimes=1000,
#                           randomize.function=randomizeRegions,
#                           evaluate.function = numOverlaps,
#                           genome="hg38",
#                           count.once= TRUE,
#                           universe=universe,
# 
#                           verbose = TRUE,
#                           BPPARAM = param)






MTX_AF_3
$numOverlaps
P-value: 0.877122877122877
Z-score: -0.3634
Number of iterations: 1000
Alternative: less
Evaluation of the original region set: 0
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(MTX_AF_3)

Version Author Date
88047ef reneeisnowhere 2025-07-28
MTX_HF_3
$numOverlaps
P-value: 0.0749250749250749
Z-score: 3.3231
Number of iterations: 1000
Alternative: greater
Evaluation of the original region set: 1
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(MTX_HF_3)

Version Author Date
88047ef reneeisnowhere 2025-07-28
MTX_IHD_3
$numOverlaps
P-value: 0.983016983016983
Z-score: -0.1314
Number of iterations: 1000
Alternative: less
Evaluation of the original region set: 0
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(MTX_IHD_3)

Version Author Date
88047ef reneeisnowhere 2025-07-28
MTX_CAD_3
$numOverlaps
P-value: 0.704295704295704
Z-score: -0.5928
Number of iterations: 1000
Alternative: less
Evaluation of the original region set: 0
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(MTX_CAD_3)

Version Author Date
88047ef reneeisnowhere 2025-07-28
# MTX_AF<- permTest(A= MTX_24_gr,
#                           B= AF_gr,
#                           ntimes=1000,
#                           randomize.function=randomizeRegions,
#                           evaluate.function = numOverlaps,
#                           genome="hg38",
#                           count.once= TRUE,
#                           universe=universe,
#                           verbose = TRUE,
#                           BPPARAM = param)
# 
# 
# MTX_HF<- permTest(A= MTX_24_gr,
#                           B= HF_gr,
#                           ntimes=1000,
#                           randomize.function=randomizeRegions,
#                           evaluate.function = numOverlaps,
#                           genome="hg38",
#                           count.once= TRUE,
#                           universe=universe,
#                           verbose = TRUE,
#                           BPPARAM = param)
# 
# 
# MTX_IHD<- permTest(A= MTX_24_gr,
#                           B= IHD_gr,
#                           ntimes=1000,
#                           randomize.function=randomizeRegions,
#                           evaluate.function = numOverlaps,
#                           genome="hg38",
#                           count.once= TRUE,
#                           universe=universe,
#                           verbose = TRUE,
#                           BPPARAM = param)
# 
# MTX_CAD <- permTest(A= MTX_24_gr,
#                           B= CAD_gr,
#                           ntimes=1000,
#                           randomize.function=randomizeRegions,
#                           evaluate.function = numOverlaps,
#                           genome="hg38",
#                           count.once= TRUE,
#                           universe=universe,
#                           verbose = TRUE,
#                           BPPARAM = param)


MTX_AF
$numOverlaps
P-value: 0.000999000999000999
Z-score: 8.8214
Number of iterations: 1000
Alternative: greater
Evaluation of the original region set: 20
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(MTX_AF)

Version Author Date
88047ef reneeisnowhere 2025-07-28
MTX_HF
$numOverlaps
P-value: 0.000999000999000999
Z-score: 5.7248
Number of iterations: 1000
Alternative: greater
Evaluation of the original region set: 10
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(MTX_HF)

Version Author Date
88047ef reneeisnowhere 2025-07-28
MTX_IHD
$numOverlaps
P-value: 0.0549450549450549
Z-score: 2.6148
Number of iterations: 1000
Alternative: greater
Evaluation of the original region set: 2
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(MTX_IHD)

Version Author Date
88047ef reneeisnowhere 2025-07-28
MTX_CAD
$numOverlaps
P-value: 0.000999000999000999
Z-score: 5.5747
Number of iterations: 1000
Alternative: greater
Evaluation of the original region set: 28
Evaluation function: numOverlaps
Randomization function: randomizeRegions

attr(,"class")
[1] "permTestResultsList"
plot(MTX_CAD)

Version Author Date
88047ef reneeisnowhere 2025-07-28
# saveRDS(MTX_AF,"data/Final_four_data/re_analysis/perm_test_100/MTX_AF_24h.RDS")
# saveRDS(MTX_HF,"data/Final_four_data/re_analysis/perm_test_100/MTX_HF_24h.RDS")
# saveRDS(MTX_IHD,"data/Final_four_data/re_analysis/perm_test_100/MTX_IHD_24h.RDS")
# saveRDS(MTX_CAD,"data/Final_four_data/re_analysis/perm_test_100/MTX_CAD_24h.RDS")
# 
# saveRDS(MTX_AF_3,"data/Final_four_data/re_analysis/perm_test_100/MTX_AF_3h.RDS")
# saveRDS(MTX_HF_3,"data/Final_four_data/re_analysis/perm_test_100/MTX_HF_3h.RDS")
# saveRDS(MTX_IHD_3,"data/Final_four_data/re_analysis/perm_test_100/MTX_IHD_3h.RDS")
# saveRDS(MTX_CAD_3,"data/Final_four_data/re_analysis/perm_test_100/MTX_CAD_3h.RDS")

# saveRDS(MTX_AF,"data/Final_four_data/re_analysis/perm_test_1000/MTX_AF_24h.RDS")
# saveRDS(MTX_HF,"data/Final_four_data/re_analysis/perm_test_1000/MTX_HF_24h.RDS")
# saveRDS(MTX_IHD,"data/Final_four_data/re_analysis/perm_test_1000/MTX_IHD_24h.RDS")
# saveRDS(MTX_CAD,"data/Final_four_data/re_analysis/perm_test_1000/MTX_CAD_24h.RDS")
# 
# saveRDS(MTX_AF_3,"data/Final_four_data/re_analysis/perm_test_1000/MTX_AF_3h.RDS")
# saveRDS(MTX_HF_3,"data/Final_four_data/re_analysis/perm_test_1000/MTX_HF_3h.RDS")
# saveRDS(MTX_IHD_3,"data/Final_four_data/re_analysis/perm_test_1000/MTX_IHD_3h.RDS")
# saveRDS(MTX_CAD_3,"data/Final_four_data/re_analysis/perm_test_1000/MTX_CAD_3h.RDS")

Creating heatmaps

all_results_LFC <- all_results %>%  dplyr::select(source,genes,logFC) %>%
    pivot_wider(id_cols=genes, values_from = logFC, names_from = source) %>% 
  dplyr::rename("Peakid"=genes)


ATAC_all_adj.pvals <- readRDS("data/Final_four_data/re_analysis/ATAC_all_adj_pvals.RDS")

AF_heatmap_df <- SNP_overlaps %>% 
  as.data.frame() %>% 
  dplyr::filter(gwas=="AF") %>% 
  group_by(Peakid) %>%
  summarise(SNPS=paste(unique(SNPS),collapse = ";"))

HF_heatmap_df <- SNP_overlaps %>% 
  as.data.frame() %>% 
  dplyr::filter(gwas=="HF") %>% 
  group_by(Peakid) %>%
  summarise(SNPS=paste(unique(SNPS),collapse = ";"))
AF_mat <- AF_heatmap_df %>% 
  left_join(., all_results_LFC, by=c("Peakid"="Peakid")) %>% 
  tidyr::unite(., name,Peakid,SNPS) %>% 
  column_to_rownames("name") %>% 
  as.matrix()

AF_sig_mat <- AF_heatmap_df %>% 
  left_join(., ATAC_all_adj.pvals, by=c("Peakid"="genes")) %>% 
  tidyr::unite(., name,Peakid,SNPS) %>% 
  column_to_rownames("name") %>% 
  as.matrix()


simply_AF_lfc <- ComplexHeatmap::Heatmap(AF_mat,
                                         
                        show_row_names = TRUE,
                       row_names_max_width=
ComplexHeatmap::max_text_width(rownames(AF_mat),                                                        gp=gpar(fontsize=14)),
                        heatmap_legend_param = list(direction = "horizontal"),
column_title = "AF_SNPS",
                       
                        show_column_names = TRUE,
                        cluster_rows = FALSE,
                        cluster_columns = FALSE,
                        cell_fun = function(j, i, x, y, width, height, fill) {
                          if (!is.na(AF_sig_mat[i, j]) && AF_sig_mat[i, j] <0.05) {
                              grid.text("*", x, y, gp = gpar(fontsize = 20))  # Add star if significant
                            } })

ComplexHeatmap::draw(simply_AF_lfc, 
     merge_legend = TRUE, 
     heatmap_legend_side = "left", 
    annotation_legend_side = "left")

Version Author Date
651ce34 reneeisnowhere 2025-07-29
HF_mat <- HF_heatmap_df %>% 
  left_join(., all_results_LFC, by=c("Peakid"="Peakid")) %>% 
  tidyr::unite(., name,Peakid,SNPS) %>% 
  column_to_rownames("name") %>% 
  as.matrix()

HF_sig_mat <- HF_heatmap_df %>% 
  left_join(., ATAC_all_adj.pvals, by=c("Peakid"="genes")) %>% 
  tidyr::unite(., name,Peakid,SNPS) %>% 
  column_to_rownames("name") %>% 
  as.matrix()


simply_HF_lfc <- ComplexHeatmap::Heatmap(HF_mat,
                                         
                        show_row_names = TRUE,
                       row_names_max_width=
ComplexHeatmap::max_text_width(rownames(HF_mat),                                                        gp=gpar(fontsize=14)),
                        heatmap_legend_param = list(direction = "horizontal"),
column_title = "HF_SNPS",
                       
                        show_column_names = TRUE,
                        cluster_rows = FALSE,
                        cluster_columns = FALSE,
                        cell_fun = function(j, i, x, y, width, height, fill) {
                          if (!is.na(HF_sig_mat[i, j]) && HF_sig_mat[i, j] <0.05) {
                              grid.text("*", x, y, gp = gpar(fontsize = 20))  # Add star if significant
                            } })

ComplexHeatmap::draw(simply_HF_lfc, 
     merge_legend = TRUE, 
     heatmap_legend_side = "left", 
    annotation_legend_side = "left")

Version Author Date
651ce34 reneeisnowhere 2025-07-29

sessionInfo()
R version 4.4.2 (2024-10-31 ucrt)
Platform: x86_64-w64-mingw32/x64
Running under: Windows 11 x64 (build 26100)

Matrix products: default


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] regioneR_1.38.0                         
 [2] liftOver_1.30.0                         
 [3] Homo.sapiens_1.3.1                      
 [4] TxDb.Hsapiens.UCSC.hg19.knownGene_3.2.2 
 [5] GO.db_3.20.0                            
 [6] OrganismDbi_1.48.0                      
 [7] gwascat_2.38.0                          
 [8] vargen_0.2.3                            
 [9] devtools_2.4.5                          
[10] usethis_3.1.0                           
[11] readxl_1.4.5                            
[12] smplot2_0.2.5                           
[13] cowplot_1.1.3                           
[14] ComplexHeatmap_2.22.0                   
[15] ggrepel_0.9.6                           
[16] plyranges_1.26.0                        
[17] ggsignif_0.6.4                          
[18] genomation_1.38.0                       
[19] edgeR_4.4.2                             
[20] limma_3.62.2                            
[21] ggpubr_0.6.1                            
[22] BiocParallel_1.40.2                     
[23] ggVennDiagram_1.5.4                     
[24] scales_1.4.0                            
[25] VennDiagram_1.7.3                       
[26] futile.logger_1.4.3                     
[27] gridExtra_2.3                           
[28] ggfortify_0.4.18                        
[29] rtracklayer_1.66.0                      
[30] org.Hs.eg.db_3.20.0                     
[31] TxDb.Hsapiens.UCSC.hg38.knownGene_3.20.0
[32] GenomicFeatures_1.58.0                  
[33] AnnotationDbi_1.68.0                    
[34] Biobase_2.66.0                          
[35] GenomicRanges_1.58.0                    
[36] GenomeInfoDb_1.42.3                     
[37] IRanges_2.40.1                          
[38] S4Vectors_0.44.0                        
[39] BiocGenerics_0.52.0                     
[40] RColorBrewer_1.1-3                      
[41] broom_1.0.8                             
[42] kableExtra_1.4.0                        
[43] lubridate_1.9.4                         
[44] forcats_1.0.0                           
[45] stringr_1.5.1                           
[46] dplyr_1.1.4                             
[47] purrr_1.0.4                             
[48] readr_2.1.5                             
[49] tidyr_1.3.1                             
[50] tibble_3.3.0                            
[51] ggplot2_3.5.2                           
[52] tidyverse_2.0.0                         
[53] workflowr_1.7.1                         

loaded via a namespace (and not attached):
  [1] fs_1.6.6                    matrixStats_1.5.0          
  [3] bitops_1.0-9                httr_1.4.7                 
  [5] doParallel_1.0.17           profvis_0.4.0              
  [7] tools_4.4.2                 backports_1.5.0            
  [9] utf8_1.2.6                  R6_2.6.1                   
 [11] GetoptLong_1.0.5            urlchecker_1.0.1           
 [13] withr_3.0.2                 prettyunits_1.2.0          
 [15] cli_3.6.5                   textshaping_1.0.1          
 [17] formatR_1.14                Cairo_1.6-2                
 [19] labeling_0.4.3              sass_0.4.10                
 [21] Rsamtools_2.22.0            systemfonts_1.2.3          
 [23] txdbmaker_1.2.1             foreign_0.8-90             
 [25] svglite_2.2.1               dichromat_2.0-0.1          
 [27] sessioninfo_1.2.3           plotrix_3.8-4              
 [29] BSgenome_1.74.0             pwr_1.3-0                  
 [31] rstudioapi_0.17.1           impute_1.80.0              
 [33] RSQLite_2.4.1               generics_0.1.4             
 [35] shape_1.4.6.1               BiocIO_1.16.0              
 [37] car_3.1-3                   Matrix_1.7-3               
 [39] abind_1.4-8                 lifecycle_1.0.4            
 [41] whisker_0.4.1               yaml_2.3.10                
 [43] carData_3.0-5               SummarizedExperiment_1.36.0
 [45] SparseArray_1.6.2           BiocFileCache_2.14.0       
 [47] blob_1.2.4                  promises_1.3.3             
 [49] crayon_1.5.3                miniUI_0.1.2               
 [51] lattice_0.22-7              KEGGREST_1.46.0            
 [53] magick_2.8.7                pillar_1.11.0              
 [55] knitr_1.50                  rjson_0.2.23               
 [57] codetools_0.2-20            glue_1.8.0                 
 [59] getPass_0.2-4               data.table_1.17.6          
 [61] remotes_2.5.0               vctrs_0.6.5                
 [63] png_0.1-8                   cellranger_1.1.0           
 [65] gtable_0.3.6                cachem_1.1.0               
 [67] xfun_0.52                   S4Arrays_1.6.0             
 [69] mime_0.13                   survival_3.8-3             
 [71] iterators_1.0.14            statmod_1.5.0              
 [73] ellipsis_0.3.2              bit64_4.6.0-1              
 [75] progress_1.2.3              filelock_1.0.3             
 [77] rprojroot_2.0.4             bslib_0.9.0                
 [79] KernSmooth_2.23-26          rpart_4.1.24               
 [81] colorspace_2.1-1            DBI_1.2.3                  
 [83] Hmisc_5.2-3                 seqPattern_1.38.0          
 [85] nnet_7.3-20                 tidyselect_1.2.1           
 [87] processx_3.8.6              bit_4.6.0                  
 [89] compiler_4.4.2              curl_6.4.0                 
 [91] git2r_0.36.2                graph_1.84.1               
 [93] httr2_1.1.2                 htmlTable_2.4.3            
 [95] xml2_1.3.8                  DelayedArray_0.32.0        
 [97] checkmate_2.3.2             RBGL_1.82.0                
 [99] callr_3.7.6                 rappdirs_0.3.3             
[101] digest_0.6.37               rmarkdown_2.29             
[103] XVector_0.46.0              htmltools_0.5.8.1          
[105] pkgconfig_2.0.3             base64enc_0.1-3            
[107] MatrixGenerics_1.18.1       dbplyr_2.5.0               
[109] fastmap_1.2.0               rlang_1.1.6                
[111] GlobalOptions_0.1.2         htmlwidgets_1.6.4          
[113] UCSC.utils_1.2.0            shiny_1.11.1               
[115] farver_2.1.2                jquerylib_0.1.4            
[117] zoo_1.8-14                  jsonlite_2.0.0             
[119] VariantAnnotation_1.52.0    RCurl_1.98-1.17            
[121] magrittr_2.0.3              Formula_1.2-5              
[123] GenomeInfoDbData_1.2.13     patchwork_1.3.1            
[125] Rcpp_1.1.0                  stringi_1.8.7              
[127] zlibbioc_1.52.0             plyr_1.8.9                 
[129] pkgbuild_1.4.8              parallel_4.4.2             
[131] snpStats_1.56.0             Biostrings_2.74.1          
[133] splines_4.4.2               hms_1.1.3                  
[135] circlize_0.4.16             locfit_1.5-9.12            
[137] ps_1.9.1                    biomaRt_2.62.1             
[139] reshape2_1.4.4              pkgload_1.4.0              
[141] futile.options_1.0.1        XML_3.99-0.18              
[143] evaluate_1.0.4              BiocManager_1.30.26        
[145] lambda.r_1.2.4              tzdb_0.5.0                 
[147] foreach_1.5.2               httpuv_1.6.16              
[149] clue_0.3-66                 gridBase_0.4-7             
[151] xtable_1.8-4                restfulr_0.0.16            
[153] rstatix_0.7.2               later_1.4.2                
[155] viridisLite_0.4.2           memoise_2.0.1              
[157] GenomicAlignments_1.42.0    cluster_2.1.8.1            
[159] timechange_0.3.0