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Knit directory: multigroup_ctwas_analysis/

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library(dplyr)
library(scales)
library(tidyr)
library(ggplot2)
library(eulerr)
library(patchwork)
library(ctwas)
library(EnsDb.Hsapiens.v86)

ens_db <- EnsDb.Hsapiens.v86

source("/project/xinhe/xsun/multi_group_ctwas/14.comparing_diff_settings/0.functions.R")

traits_silver <- c("T2D","LDL","BMI","RBC","IBD","SCZ","aFib")
names(traits_silver) <- c("T2D-panukb","LDL-ukb-d-30780_irnt","BMI-panukb","RBC-panukb","IBD-ebi-a-GCST004131","SCZ-ieu-b-5102","aFib-ebi-a-GCST006414")

traits <- c("LDL-ukb-d-30780_irnt","IBD-ebi-a-GCST004131","BMI-panukb","RBC-panukb","SCZ-ieu-b-5102","aFib-ebi-a-GCST006414","T2D-panukb")
db <- "GO_Biological_Process_2023"

mapping_predictdb <- readRDS("/project2/xinhe/shared_data/multigroup_ctwas/weights/mapping_files/PredictDB_mapping.RDS")
mapping_munro <- readRDS("/project2/xinhe/shared_data/multigroup_ctwas/weights/mapping_files/Munro_mapping.RDS")
mapping_two <- rbind(mapping_predictdb,mapping_munro)

snp_map <- readRDS("/project2/xinhe/shared_data/multigroup_ctwas/LD_region_info/snp_map.RDS")

folder_results <- "/project/xinhe/xsun/multi_group_ctwas/15.susie_weights/snakemake_outputs/"

create_summary_plot_withTP <- function(df, columns_to_plot, x_var = "setting", x_order = NULL, title = NULL) {

  # Reshape data
  df_long <- df %>%
    pivot_longer(
      cols = all_of(columns_to_plot),
      names_to = "variable",
      values_to = "value"
    )
  
  # Convert to factor with specified order if x_order is provided
  if (!is.null(x_order)) {
    df_long <- df_long %>%
      mutate(across(all_of(x_var), ~factor(., levels = x_order)))
  }
  
  # Identify the max value for scaling
  max_main <- max(df_long$value[df_long$variable != "TP_rate"], na.rm = TRUE)
  max_tp_rate <- max(df_long$value[df_long$variable == "TP_rate"], na.rm = TRUE)
  
  if(max_tp_rate ==0) {
    max_tp_rate <- 1
  }
  
  # Rescale TP_rate
  df_long <- df_long %>%
    mutate(scaled_value = ifelse(variable == "TP_rate", 
                                 value * (max_main / max_tp_rate), value))
  
  # Create plot
  ggplot(df_long, aes(x = .data[[x_var]], y = scaled_value, color = variable, shape = variable)) +
    #geom_point(size = 3, position = position_jitter(width = 0.2)) +
    geom_point(size = 3) + 
    scale_y_continuous(
      name = "Count",
      sec.axis = sec_axis(~ . * (max_tp_rate / max_main), name = "TP Rate")
    ) +
    labs(x = "Settings", title = title) +
    theme_minimal() +
    theme(
      axis.text.x = element_text(angle = 45, hjust = 1, size = 10),
      legend.position = "right",
      legend.title = element_blank()
    ) +
    scale_color_brewer(palette = "Set1")
}

DT::datatable(matrix())
thin <- 1
var_struc <- "shared_all"
L <- 5
st <- "with_susieST"

The number of genes at PIP > 0.8

setting_names <- c()
num_gene_pip08_all <- c()
num_silver_pip08_all <- c()
num_bystander_pip08_all <- c()
go_num_fdr005 <- c()
for (trait in traits) {
  for (cs in c("CS_filtered","CS_NOT_filtered")){

    if(cs == "CS_filtered"){
      cs_setting <- NULL
    }else{
      cs_setting <- "_csF"
    }

    setting_names <- c(setting_names, paste0(traits_silver[trait],"-",cs))

    # num_gene_pip08 -- cs filtered
    combined_pip_by_group <- readRDS(paste0(folder_results,"/",trait,"/",trait,".",st,".thin",thin,".",var_struc,".L",L, ".combined_pip_bygroup_final",cs_setting,".RDS"))
    combined_pip_sig <- combined_pip_by_group[combined_pip_by_group$combined_pip > 0.8,]

    num_gene_pip08_all <- c(num_gene_pip08_all, nrow(combined_pip_sig))

    # silver_standard genes
    known <- readRDS(paste0("/project/xinhe/xsun/multi_group_ctwas/data/silverstandard/known_annotations_",traits_silver[trait],".RDS"))
    bystander <- readRDS(paste0("/project/xinhe/xsun/multi_group_ctwas/data/silverstandard/bystanders_",traits_silver[trait],".RDS"))

    num_silver_pip08_all <- c(num_silver_pip08_all,sum(combined_pip_sig$gene_name %in% known))
    num_bystander_pip08_all <- c(num_bystander_pip08_all,sum(combined_pip_sig$gene_name %in% bystander))

    file_go <- paste0(folder_results,trait,"/",trait,".",st,".thin",thin,".",var_struc,".L",L, ".enrichr_",db,"_",cs,".RDS")
    if(!file.exists(file_go)){
      go_num_fdr005 <- c(go_num_fdr005,0)
    }else{
      go <- readRDS(paste0(folder_results,trait,"/",trait,".",st,".thin",thin,".",var_struc,".L",L, ".enrichr_",db,"_",cs,".RDS"))
      go_num_fdr005 <- c(go_num_fdr005,nrow(go))
    }


  }
}

df <- data.frame(setting = setting_names,
                 num_gene_pip08 = num_gene_pip08_all,
                 num_silver_pip08 = num_silver_pip08_all,
                 num_bystander_pip08 = num_bystander_pip08_all,
                 TP_rate = num_silver_pip08_all/(num_silver_pip08_all+num_bystander_pip08_all),
                 go_num_fdr005 = go_num_fdr005)

create_summary_plot_withTP(df,x_order = setting_names,
                    columns_to_plot = c("num_gene_pip08","num_silver_pip08","TP_rate"))

Version Author Date
fdbf208 XSun 2025-05-01
3b4edbe XSun 2025-04-28
create_summary_plot_withTP(df,x_order = setting_names,
                    columns_to_plot = c("go_num_fdr005"), title = "Number of GO terms at p.adjust < 0.05")

Version Author Date
fdbf208 XSun 2025-05-01
a742ef4 XSun 2025-04-30
DT::datatable(df,caption = htmltools::tags$caption( style = 'caption-side: left; text-align: left; color:black;  font-size:150% ;',''),options = list(pageLength = 10) )

Number of GO terms at adjusted.p < 0.05

traits <- c("LDL-ukb-d-30780_irnt","IBD-ebi-a-GCST004131")

for (trait in traits) {

  file_go_filtered <- paste0(folder_results,trait,"/",trait,".",st,".thin",thin,".",var_struc,".L",L, ".enrichr_",db,"_CS_filtered.RDS")
  if(!file.exists(file_go_filtered)){
    go_filtered <- NULL
  }else{
    go_filtered <- readRDS(file_go_filtered)
  }



  file_go_nofiltered <- paste0(folder_results,trait,"/",trait,".",st,".thin",thin,".",var_struc,".L",L, ".enrichr_",db,"_CS_NOT_filtered.RDS")
  if(!file.exists(file_go_nofiltered)){
    go_nofiltered <- NULL
  }else{
    go_nofiltered <- readRDS(file_go_nofiltered)
  }

  set1 <- unique(go_filtered$Term)
  set2 <- unique(go_nofiltered$Term)

  venn_input <- list(
    Filtered = set1,
    NoFiltered = set2
  )

  fit <- euler(venn_input)

  print(plot(fit,
       fills = c("skyblue", "orange"),
       labels = TRUE,
       quantities = TRUE,
       main = trait))


}

Version Author Date
a742ef4 XSun 2025-04-30

Version Author Date
fdbf208 XSun 2025-05-01
a742ef4 XSun 2025-04-30
traits <- c("LDL-ukb-d-30780_irnt","IBD-ebi-a-GCST004131")

for (trait in traits) {

  file_go_filtered <- paste0(folder_results,trait,"/",trait,".",st,".thin",thin,".",var_struc,".L",L, ".enrichr_",db,"_CS_filtered.RDS")
  if(!file.exists(file_go_filtered)){
    go_filtered <- NULL
  }else{
    go_filtered <- readRDS(file_go_filtered)
  }



  file_go_nofiltered <- paste0(folder_results,trait,"/",trait,".",st,".thin",thin,".",var_struc,".L",L, ".enrichr_",db,"_CS_NOT_filtered.RDS")
  if(!file.exists(file_go_nofiltered)){
    go_nofiltered <- NULL
  }else{
    go_nofiltered <- readRDS(file_go_nofiltered)
  }


  cat("\n\n")
  cat(knitr::knit_print(DT::datatable(go_filtered[!go_filtered$Term %in% go_nofiltered$Term,], caption = htmltools::tags$caption( style = 'font-size: 150%; caption-side: topleft; text-align = left; color:black;',paste0("Unique GO terms at p.adjust < 0.05 -- ",trait, "--CS_filtered")),options = list(pageLength = 5))))
  cat("\n\n")

  cat("\n\n")
  cat(knitr::knit_print(DT::datatable(go_nofiltered[!go_nofiltered$Term %in% go_filtered$Term,], caption = htmltools::tags$caption( style = 'font-size: 150%; caption-side: topleft; text-align = left; color:black;',paste0("Unique GO terms at p.adjust < 0.05 -- ",trait, "--CS_NOT_filtered")),options = list(pageLength = 5))))
  cat("\n\n")



}

Comparing PIPs at gene-level

LDL-ukb-d-30780_irnt

trait <- "LDL-ukb-d-30780_irnt"

combined_pip_filtered <- readRDS(paste0(folder_results,"/",trait,"/",trait,".",st,".thin",thin,".",var_struc,".L",L, ".combined_pip_bygroup_final_csincluded.RDS"))
combined_pip_filtered_plot <- combined_pip_filtered[,c("gene_name","combined_pip")]
colnames(combined_pip_filtered_plot) <- c("gene_name","combined_pip_csfiltered")

combined_pip_NOTfiltered <- readRDS(paste0(folder_results,"/",trait,"/",trait,".",st,".thin",thin,".",var_struc,".L",L, ".combined_pip_bygroup_final_csF.RDS"))
combined_pip_NOTfiltered_plot <- combined_pip_NOTfiltered[,c("gene_name","combined_pip")]
colnames(combined_pip_NOTfiltered_plot) <- c("gene_name","combined_pip_csNOTfiltered")

combined_pip_filtered_sig <- combined_pip_filtered[combined_pip_filtered$combined_pip > 0.8,]
combined_pip_NOTfiltered_sig <- combined_pip_NOTfiltered[combined_pip_NOTfiltered$combined_pip > 0.8,]
combined_pip_NOTfiltered_sig_plot <- combined_pip_NOTfiltered_plot[combined_pip_NOTfiltered_plot$combined_pip > 0.8,]

df_merge <- merge(combined_pip_NOTfiltered_sig_plot, combined_pip_filtered_plot, by = "gene_name", all.x = T)
df_merge$combined_pip_csfiltered[is.na(df_merge$combined_pip_csfiltered)] <- 1.1

p <-ggplot(data = df_merge,aes(x = combined_pip_csfiltered, y = combined_pip_csNOTfiltered)) +
  #p[[trait]] <-ggplot(data = df_merge,aes(x = combined_pip_csfiltered, y = combined_pip_csNOTfiltered)) +
  geom_point() + 
  labs(x = "Combined PIP -- CS filtered", y = "Combined PIP -- CS NOT filtered") +
  geom_abline(slope = 1, intercept = 0, col = "Red") +
  ggtitle(trait) +
  theme_minimal()

print("PIP = 1.1 means PIP = NA when filtering CS")

[1] “PIP = 1.1 means PIP = NA when filtering CS”

print(p)

Version Author Date
fdbf208 XSun 2025-05-01
# Merge the two data frames by 'gene_name' with suffixes to distinguish columns
merged_df <- merge(combined_pip_NOTfiltered_sig, combined_pip_filtered, 
                   by = "gene_name", suffixes = c("_NOTfiltered", "_filtered"),all.x=T)

# List of columns to process (excluding 'gene_name')
original_cols <- setdiff(names(combined_pip_NOTfiltered_sig), "gene_name")

# Iterate over each column and concatenate values from both data frames
for (col in original_cols) {
  notfiltered_col <- paste0(col, "_NOTfiltered")
  filtered_col <- paste0(col, "_filtered")
  merged_df[[col]] <- paste(round(merged_df[[notfiltered_col]],digits = 5), round(merged_df[[filtered_col]],digits = 5), sep = "-")
}

# Select the relevant columns to match the original structure
df <- merged_df[, c("gene_name", original_cols)]

DT::datatable(df, caption = htmltools::tags$caption( style = 'font-size: 150%; caption-side: topleft; text-align = left; color:black;', trait),options = list(pageLength = 5))
Gene Involvement in LDL/Lipid Metabolism Evidence Level
KIF13B Enhances LDL uptake via LRP1 Strong
TTC39B Regulates cholesterol homeostasis via LXR degradation Strong
USP53 Modulates SR-A ubiquitination affecting LDL clearance Moderate
ACVR1C Influences adipose lipid metabolism Moderate
LRRK2 Affects lipid storage and lysosomal function Moderate
ACP6 Involved in LPA metabolism; indirect link to LDL Limited
CD163L1 Scavenger receptor; unclear role in LDL metabolism Limited
KDSR Sphingolipid biosynthesis; indirect association with LDL Limited
ZNF518A Function not well-characterized; no direct link to LDL Limited
file_ctwas_result <- get_ctwas_file(trait, tissue = NULL, folder_results,st,thin, var_struc, L)
ctwas_res <- readRDS(file_ctwas_result)
weights <- readRDS(paste0(folder_results,"/",trait,"/",trait,".",st,".preprocessed.weights.RDS"))

finemap_res <- ctwas_res$finemap_res
finemap_res$molecular_id <- get_molecular_ids(finemap_res)
finemap_res <- anno_finemap_res(finemap_res,
                                snp_map = snp_map,
                                mapping_table = mapping_two,
                                add_gene_annot = TRUE,
                                map_by = "molecular_id",
                                drop_unmapped = TRUE,
                                add_position = TRUE,
                                use_gene_pos = "mid")

2025-05-01 15:47:22 INFO::Annotating fine-mapping result … 2025-05-01 15:47:27 INFO::Map molecular traits to genes 2025-05-01 15:47:27 INFO::Split PIPs for molecular traits mapped to multiple genes 2025-05-01 15:48:04 INFO::Add gene positions 2025-05-01 15:48:05 INFO::Add SNP positions

finemap_res <- finemap_res[complete.cases(finemap_res$id),]

make_locusplot(finemap_res,
               region_id = "8_28304875_29470379",
               ens_db = ens_db,
               weights = weights,
               highlight_pip = 0.8,
               filter_protein_coding_genes = TRUE,
               filter_cs = F,
               focal_gene = "KIF13B",
               color_pval_by = "cs",
               color_pip_by = "cs",
               label.text.size = 6,
               axis.text.size = 16,
               axis.title.size = 16,
               legend.text.size = 16,
               point.sizes = c(3,5,5,5))

2025-05-01 15:48:30 INFO::Limit to protein coding genes 2025-05-01 15:48:30 INFO::focal id: intron_8_29092878_29099133|Whole_Blood_sQTL 2025-05-01 15:48:30 INFO::focal molecular trait: KIF13B Whole_Blood sQTL 2025-05-01 15:48:30 INFO::Range of locus: chr8:28306293-29470014 2025-05-01 15:48:32 INFO::focal molecular trait QTL positions: 29092792

make_locusplot(finemap_res,
               region_id = "9_14836365_16659657",
               ens_db = ens_db,
               weights = weights,
               highlight_pip = 0.8,
               filter_protein_coding_genes = TRUE,
               filter_cs = F,
               focal_gene = "TTC39B",
               color_pval_by = "cs",
               color_pip_by = "cs",
               label.text.size = 6,
               axis.text.size = 16,
               axis.title.size = 16,
               legend.text.size = 16,
               point.sizes = c(3,5,5,5))

2025-05-01 15:48:34 INFO::Limit to protein coding genes 2025-05-01 15:48:34 INFO::focal id: ENSG00000155158.20|Liver_eQTL 2025-05-01 15:48:34 INFO::focal molecular trait: TTC39B Liver eQTL 2025-05-01 15:48:34 INFO::Range of locus: chr9:14822730-16659361 2025-05-01 15:48:35 INFO::focal molecular trait QTL positions: 15280189,15303585,15306294

make_locusplot(finemap_res,
               region_id = "4_119012357_119471529",
               ens_db = ens_db,
               weights = weights,
               highlight_pip = 0.8,
               filter_protein_coding_genes = TRUE,
               filter_cs = F,
               focal_gene = "USP53",
               color_pval_by = "cs",
               color_pip_by = "cs",
               label.text.size = 6,
               axis.text.size = 16,
               axis.title.size = 16,
               legend.text.size = 16,
               point.sizes = c(3,5,5,5))

2025-05-01 15:48:37 INFO::Limit to protein coding genes 2025-05-01 15:48:37 INFO::focal id: ENSG00000145390.11|Liver_eQTL 2025-05-01 15:48:37 INFO::focal molecular trait: USP53 Liver eQTL 2025-05-01 15:48:37 INFO::Range of locus: chr4:118955868-119561793 2025-05-01 15:48:38 INFO::focal molecular trait QTL positions: 119212999,119214746

make_locusplot(finemap_res,
               region_id = "2_156704123_157676706",
               ens_db = ens_db,
               weights = weights,
               highlight_pip = 0.8,
               filter_protein_coding_genes = TRUE,
               filter_cs = F,
               focal_gene = "ACVR1C",
               color_pval_by = "cs",
               color_pip_by = "cs",
               label.text.size = 6,
               axis.text.size = 16,
               axis.title.size = 16,
               legend.text.size = 16,
               point.sizes = c(3,5,5,5))

2025-05-01 15:48:39 INFO::Limit to protein coding genes 2025-05-01 15:48:39 INFO::focal id: ENSG00000123612.15|Liver_eQTL 2025-05-01 15:48:39 INFO::focal molecular trait: ACVR1C Liver eQTL 2025-05-01 15:48:39 INFO::Range of locus: chr2:156704023-157675796 2025-05-01 15:48:41 INFO::focal molecular trait QTL positions: 157625480,157628563

IBD-ebi-a-GCST004131

trait <- "IBD-ebi-a-GCST004131"

combined_pip_filtered <- readRDS(paste0(folder_results,"/",trait,"/",trait,".",st,".thin",thin,".",var_struc,".L",L, ".combined_pip_bygroup_final_csincluded.RDS"))
combined_pip_filtered_plot <- combined_pip_filtered[,c("gene_name","combined_pip")]
colnames(combined_pip_filtered_plot) <- c("gene_name","combined_pip_csfiltered")

combined_pip_NOTfiltered <- readRDS(paste0(folder_results,"/",trait,"/",trait,".",st,".thin",thin,".",var_struc,".L",L, ".combined_pip_bygroup_final_csF.RDS"))
combined_pip_NOTfiltered_plot <- combined_pip_NOTfiltered[,c("gene_name","combined_pip")]
colnames(combined_pip_NOTfiltered_plot) <- c("gene_name","combined_pip_csNOTfiltered")

combined_pip_filtered_sig <- combined_pip_filtered[combined_pip_filtered$combined_pip > 0.8,]
combined_pip_NOTfiltered_sig <- combined_pip_NOTfiltered[combined_pip_NOTfiltered$combined_pip > 0.8,]
combined_pip_NOTfiltered_sig_plot <- combined_pip_NOTfiltered_plot[combined_pip_NOTfiltered_plot$combined_pip > 0.8,]

df_merge <- merge(combined_pip_NOTfiltered_sig_plot, combined_pip_filtered_plot, by = "gene_name", all.x = T)
df_merge$combined_pip_csfiltered[is.na(df_merge$combined_pip_csfiltered)] <- 1.1

p <-ggplot(data = df_merge,aes(x = combined_pip_csfiltered, y = combined_pip_csNOTfiltered)) +
  #p[[trait]] <-ggplot(data = df_merge,aes(x = combined_pip_csfiltered, y = combined_pip_csNOTfiltered)) +
  geom_point() + 
  labs(x = "Combined PIP -- CS filtered", y = "Combined PIP -- CS NOT filtered") +
  geom_abline(slope = 1, intercept = 0, col = "Red") +
  ggtitle(trait) +
  theme_minimal()

print("PIP = 1.1 means PIP = NA when filtering CS")

[1] “PIP = 1.1 means PIP = NA when filtering CS”

print(p)

# Merge the two data frames by 'gene_name' with suffixes to distinguish columns
merged_df <- merge(combined_pip_NOTfiltered_sig, combined_pip_filtered, 
                   by = "gene_name", suffixes = c("_NOTfiltered", "_filtered"),all.x=T)

# List of columns to process (excluding 'gene_name')
original_cols <- setdiff(names(combined_pip_NOTfiltered_sig), "gene_name")

# Iterate over each column and concatenate values from both data frames
for (col in original_cols) {
  notfiltered_col <- paste0(col, "_NOTfiltered")
  filtered_col <- paste0(col, "_filtered")
  merged_df[[col]] <- paste(round(merged_df[[notfiltered_col]],digits = 5), round(merged_df[[filtered_col]],digits = 5), sep = "-")
}

# Select the relevant columns to match the original structure
df <- merged_df[, c("gene_name", original_cols)]

DT::datatable(df, caption = htmltools::tags$caption( style = 'font-size: 150%; caption-side: topleft; text-align = left; color:black;', trait),options = list(pageLength = 5))
Gene Evidence of Association with IBD Evidence Level
SLC26A3 Identified as an IBD susceptibility gene; downregulation impairs epithelial barrier and increases inflammation. Strong
MAST2 Regulates NF-κB signaling; involved in inflammatory response modulation. Moderate
DOCK8 Deficiency leads to immune dysregulation with IBD-like enteropathy and colitis. Moderate
FOXN2 Regulates REG Iβ, which is upregulated in IBD mucosa. Limited
ACBD3 No direct link to IBD; studied more in cancer and viral replication contexts. Limited
TMEM151B No known evidence linking it to IBD. None

BMI-panukb

trait <- "BMI-panukb"

combined_pip_filtered <- readRDS(paste0(folder_results,"/",trait,"/",trait,".",st,".thin",thin,".",var_struc,".L",L, ".combined_pip_bygroup_final_csincluded.RDS"))
combined_pip_filtered_plot <- combined_pip_filtered[,c("gene_name","combined_pip")]
colnames(combined_pip_filtered_plot) <- c("gene_name","combined_pip_csfiltered")

combined_pip_NOTfiltered <- readRDS(paste0(folder_results,"/",trait,"/",trait,".",st,".thin",thin,".",var_struc,".L",L, ".combined_pip_bygroup_final_csF.RDS"))
combined_pip_NOTfiltered_plot <- combined_pip_NOTfiltered[,c("gene_name","combined_pip")]
colnames(combined_pip_NOTfiltered_plot) <- c("gene_name","combined_pip_csNOTfiltered")

combined_pip_filtered_sig <- combined_pip_filtered[combined_pip_filtered$combined_pip > 0.8,]
combined_pip_NOTfiltered_sig <- combined_pip_NOTfiltered[combined_pip_NOTfiltered$combined_pip > 0.8,]
combined_pip_NOTfiltered_sig_plot <- combined_pip_NOTfiltered_plot[combined_pip_NOTfiltered_plot$combined_pip > 0.8,]

df_merge <- merge(combined_pip_NOTfiltered_sig_plot, combined_pip_filtered_plot, by = "gene_name", all.x = T)
df_merge$combined_pip_csfiltered[is.na(df_merge$combined_pip_csfiltered)] <- 1.1

p <-ggplot(data = df_merge,aes(x = combined_pip_csfiltered, y = combined_pip_csNOTfiltered)) +
  #p[[trait]] <-ggplot(data = df_merge,aes(x = combined_pip_csfiltered, y = combined_pip_csNOTfiltered)) +
  geom_point() + 
  labs(x = "Combined PIP -- CS filtered", y = "Combined PIP -- CS NOT filtered") +
  geom_abline(slope = 1, intercept = 0, col = "Red") +
  ggtitle(trait) +
  theme_minimal()

print("PIP = 1.1 means PIP = NA when filtering CS")

[1] “PIP = 1.1 means PIP = NA when filtering CS”

print(p)

# Merge the two data frames by 'gene_name' with suffixes to distinguish columns
merged_df <- merge(combined_pip_NOTfiltered_sig, combined_pip_filtered, 
                   by = "gene_name", suffixes = c("_NOTfiltered", "_filtered"),all.x=T)

# List of columns to process (excluding 'gene_name')
original_cols <- setdiff(names(combined_pip_NOTfiltered_sig), "gene_name")

# Iterate over each column and concatenate values from both data frames
for (col in original_cols) {
  notfiltered_col <- paste0(col, "_NOTfiltered")
  filtered_col <- paste0(col, "_filtered")
  merged_df[[col]] <- paste(round(merged_df[[notfiltered_col]],digits = 5), round(merged_df[[filtered_col]],digits = 5), sep = "-")
}

# Select the relevant columns to match the original structure
df <- merged_df[, c("gene_name", original_cols)]

DT::datatable(df, caption = htmltools::tags$caption( style = 'font-size: 150%; caption-side: topleft; text-align = left; color:black;', trait),options = list(pageLength = 5))

RBC-panukb

trait <- "RBC-panukb"

combined_pip_filtered <- readRDS(paste0(folder_results,"/",trait,"/",trait,".",st,".thin",thin,".",var_struc,".L",L, ".combined_pip_bygroup_final_csincluded.RDS"))
combined_pip_filtered_plot <- combined_pip_filtered[,c("gene_name","combined_pip")]
colnames(combined_pip_filtered_plot) <- c("gene_name","combined_pip_csfiltered")

combined_pip_NOTfiltered <- readRDS(paste0(folder_results,"/",trait,"/",trait,".",st,".thin",thin,".",var_struc,".L",L, ".combined_pip_bygroup_final_csF.RDS"))
combined_pip_NOTfiltered_plot <- combined_pip_NOTfiltered[,c("gene_name","combined_pip")]
colnames(combined_pip_NOTfiltered_plot) <- c("gene_name","combined_pip_csNOTfiltered")

combined_pip_filtered_sig <- combined_pip_filtered[combined_pip_filtered$combined_pip > 0.8,]
combined_pip_NOTfiltered_sig <- combined_pip_NOTfiltered[combined_pip_NOTfiltered$combined_pip > 0.8,]
combined_pip_NOTfiltered_sig_plot <- combined_pip_NOTfiltered_plot[combined_pip_NOTfiltered_plot$combined_pip > 0.8,]

df_merge <- merge(combined_pip_NOTfiltered_sig_plot, combined_pip_filtered_plot, by = "gene_name", all.x = T)
df_merge$combined_pip_csfiltered[is.na(df_merge$combined_pip_csfiltered)] <- 1.1

p <-ggplot(data = df_merge,aes(x = combined_pip_csfiltered, y = combined_pip_csNOTfiltered)) +
  #p[[trait]] <-ggplot(data = df_merge,aes(x = combined_pip_csfiltered, y = combined_pip_csNOTfiltered)) +
  geom_point() + 
  labs(x = "Combined PIP -- CS filtered", y = "Combined PIP -- CS NOT filtered") +
  geom_abline(slope = 1, intercept = 0, col = "Red") +
  ggtitle(trait) +
  theme_minimal()

print("PIP = 1.1 means PIP = NA when filtering CS")

[1] “PIP = 1.1 means PIP = NA when filtering CS”

print(p)

# Merge the two data frames by 'gene_name' with suffixes to distinguish columns
merged_df <- merge(combined_pip_NOTfiltered_sig, combined_pip_filtered, 
                   by = "gene_name", suffixes = c("_NOTfiltered", "_filtered"),all.x=T)

# List of columns to process (excluding 'gene_name')
original_cols <- setdiff(names(combined_pip_NOTfiltered_sig), "gene_name")

# Iterate over each column and concatenate values from both data frames
for (col in original_cols) {
  notfiltered_col <- paste0(col, "_NOTfiltered")
  filtered_col <- paste0(col, "_filtered")
  merged_df[[col]] <- paste(round(merged_df[[notfiltered_col]],digits = 5), round(merged_df[[filtered_col]],digits = 5), sep = "-")
}

# Select the relevant columns to match the original structure
df <- merged_df[, c("gene_name", original_cols)]

DT::datatable(df, caption = htmltools::tags$caption( style = 'font-size: 150%; caption-side: topleft; text-align = left; color:black;', trait),options = list(pageLength = 5))

SCZ-ieu-b-5102

trait <- "SCZ-ieu-b-5102"

combined_pip_filtered <- readRDS(paste0(folder_results,"/",trait,"/",trait,".",st,".thin",thin,".",var_struc,".L",L, ".combined_pip_bygroup_final_csincluded.RDS"))
combined_pip_filtered_plot <- combined_pip_filtered[,c("gene_name","combined_pip")]
colnames(combined_pip_filtered_plot) <- c("gene_name","combined_pip_csfiltered")

combined_pip_NOTfiltered <- readRDS(paste0(folder_results,"/",trait,"/",trait,".",st,".thin",thin,".",var_struc,".L",L, ".combined_pip_bygroup_final_csF.RDS"))
combined_pip_NOTfiltered_plot <- combined_pip_NOTfiltered[,c("gene_name","combined_pip")]
colnames(combined_pip_NOTfiltered_plot) <- c("gene_name","combined_pip_csNOTfiltered")

combined_pip_filtered_sig <- combined_pip_filtered[combined_pip_filtered$combined_pip > 0.8,]
combined_pip_NOTfiltered_sig <- combined_pip_NOTfiltered[combined_pip_NOTfiltered$combined_pip > 0.8,]
combined_pip_NOTfiltered_sig_plot <- combined_pip_NOTfiltered_plot[combined_pip_NOTfiltered_plot$combined_pip > 0.8,]

df_merge <- merge(combined_pip_NOTfiltered_sig_plot, combined_pip_filtered_plot, by = "gene_name", all.x = T)
df_merge$combined_pip_csfiltered[is.na(df_merge$combined_pip_csfiltered)] <- 1.1

p <-ggplot(data = df_merge,aes(x = combined_pip_csfiltered, y = combined_pip_csNOTfiltered)) +
  #p[[trait]] <-ggplot(data = df_merge,aes(x = combined_pip_csfiltered, y = combined_pip_csNOTfiltered)) +
  geom_point() + 
  labs(x = "Combined PIP -- CS filtered", y = "Combined PIP -- CS NOT filtered") +
  geom_abline(slope = 1, intercept = 0, col = "Red") +
  ggtitle(trait) +
  theme_minimal()

print("PIP = 1.1 means PIP = NA when filtering CS")

[1] “PIP = 1.1 means PIP = NA when filtering CS”

print(p)

# Merge the two data frames by 'gene_name' with suffixes to distinguish columns
merged_df <- merge(combined_pip_NOTfiltered_sig, combined_pip_filtered, 
                   by = "gene_name", suffixes = c("_NOTfiltered", "_filtered"),all.x=T)

# List of columns to process (excluding 'gene_name')
original_cols <- setdiff(names(combined_pip_NOTfiltered_sig), "gene_name")

# Iterate over each column and concatenate values from both data frames
for (col in original_cols) {
  notfiltered_col <- paste0(col, "_NOTfiltered")
  filtered_col <- paste0(col, "_filtered")
  merged_df[[col]] <- paste(round(merged_df[[notfiltered_col]],digits = 5), round(merged_df[[filtered_col]],digits = 5), sep = "-")
}

# Select the relevant columns to match the original structure
df <- merged_df[, c("gene_name", original_cols)]

DT::datatable(df, caption = htmltools::tags$caption( style = 'font-size: 150%; caption-side: topleft; text-align = left; color:black;', trait),options = list(pageLength = 5))

aFib-ebi-a-GCST006414

trait <- "aFib-ebi-a-GCST006414"

combined_pip_filtered <- readRDS(paste0(folder_results,"/",trait,"/",trait,".",st,".thin",thin,".",var_struc,".L",L, ".combined_pip_bygroup_final_csincluded.RDS"))
combined_pip_filtered_plot <- combined_pip_filtered[,c("gene_name","combined_pip")]
colnames(combined_pip_filtered_plot) <- c("gene_name","combined_pip_csfiltered")

combined_pip_NOTfiltered <- readRDS(paste0(folder_results,"/",trait,"/",trait,".",st,".thin",thin,".",var_struc,".L",L, ".combined_pip_bygroup_final_csF.RDS"))
combined_pip_NOTfiltered_plot <- combined_pip_NOTfiltered[,c("gene_name","combined_pip")]
colnames(combined_pip_NOTfiltered_plot) <- c("gene_name","combined_pip_csNOTfiltered")

combined_pip_filtered_sig <- combined_pip_filtered[combined_pip_filtered$combined_pip > 0.8,]
combined_pip_NOTfiltered_sig <- combined_pip_NOTfiltered[combined_pip_NOTfiltered$combined_pip > 0.8,]
combined_pip_NOTfiltered_sig_plot <- combined_pip_NOTfiltered_plot[combined_pip_NOTfiltered_plot$combined_pip > 0.8,]

df_merge <- merge(combined_pip_NOTfiltered_sig_plot, combined_pip_filtered_plot, by = "gene_name", all.x = T)
df_merge$combined_pip_csfiltered[is.na(df_merge$combined_pip_csfiltered)] <- 1.1

p <-ggplot(data = df_merge,aes(x = combined_pip_csfiltered, y = combined_pip_csNOTfiltered)) +
  #p[[trait]] <-ggplot(data = df_merge,aes(x = combined_pip_csfiltered, y = combined_pip_csNOTfiltered)) +
  geom_point() + 
  labs(x = "Combined PIP -- CS filtered", y = "Combined PIP -- CS NOT filtered") +
  geom_abline(slope = 1, intercept = 0, col = "Red") +
  ggtitle(trait) +
  theme_minimal()

print("PIP = 1.1 means PIP = NA when filtering CS")

[1] “PIP = 1.1 means PIP = NA when filtering CS”

print(p)

# Merge the two data frames by 'gene_name' with suffixes to distinguish columns
merged_df <- merge(combined_pip_NOTfiltered_sig, combined_pip_filtered, 
                   by = "gene_name", suffixes = c("_NOTfiltered", "_filtered"),all.x=T)

# List of columns to process (excluding 'gene_name')
original_cols <- setdiff(names(combined_pip_NOTfiltered_sig), "gene_name")

# Iterate over each column and concatenate values from both data frames
for (col in original_cols) {
  notfiltered_col <- paste0(col, "_NOTfiltered")
  filtered_col <- paste0(col, "_filtered")
  merged_df[[col]] <- paste(round(merged_df[[notfiltered_col]],digits = 5), round(merged_df[[filtered_col]],digits = 5), sep = "-")
}

# Select the relevant columns to match the original structure
df <- merged_df[, c("gene_name", original_cols)]

DT::datatable(df, caption = htmltools::tags$caption( style = 'font-size: 150%; caption-side: topleft; text-align = left; color:black;', trait),options = list(pageLength = 5))
traits <- c("LDL-ukb-d-30780_irnt","IBD-ebi-a-GCST004131","BMI-panukb","RBC-panukb","SCZ-ieu-b-5102","aFib-ebi-a-GCST006414","T2D-panukb")

p <- list()
for (trait in traits) {
  
  combined_pip_filtered <- readRDS(paste0(folder_results,"/",trait,"/",trait,".",st,".thin",thin,".",var_struc,".L",L, ".combined_pip_bygroup_final_csincluded.RDS"))
  combined_pip_filtered_plot <- combined_pip_filtered[,c("gene_name","combined_pip")]
  colnames(combined_pip_filtered_plot) <- c("gene_name","combined_pip_csfiltered")
  
  combined_pip_NOTfiltered <- readRDS(paste0(folder_results,"/",trait,"/",trait,".",st,".thin",thin,".",var_struc,".L",L, ".combined_pip_bygroup_final_csF.RDS"))
  combined_pip_NOTfiltered_plot <- combined_pip_NOTfiltered[,c("gene_name","combined_pip")]
  colnames(combined_pip_NOTfiltered_plot) <- c("gene_name","combined_pip_csNOTfiltered")

  combined_pip_filtered_sig <- combined_pip_filtered[combined_pip_filtered$combined_pip > 0.8,]
  combined_pip_NOTfiltered_sig <- combined_pip_NOTfiltered[combined_pip_NOTfiltered$combined_pip > 0.8,]
  combined_pip_NOTfiltered_sig_plot <- combined_pip_NOTfiltered_plot[combined_pip_NOTfiltered_plot$combined_pip > 0.8,]
  
  df_merge <- merge(combined_pip_NOTfiltered_sig_plot, combined_pip_filtered_plot, by = "gene_name", all.x = T)
  df_merge$combined_pip_csfiltered[is.na(df_merge$combined_pip_csfiltered)] <- 1.1
  
  p <-ggplot(data = df_merge,aes(x = combined_pip_csfiltered, y = combined_pip_csNOTfiltered)) +
  #p[[trait]] <-ggplot(data = df_merge,aes(x = combined_pip_csfiltered, y = combined_pip_csNOTfiltered)) +
    geom_point() + 
    labs(x = "Combined PIP -- CS filtered", y = "Combined PIP -- CS NOT filtered") +
    geom_abline(slope = 1, intercept = 0, col = "Red") +
    ggtitle(trait) +
    theme_minimal()
  
  print("PIP = 1.1 means PIP = NA when filtering CS")
  print(p)
  
  # Merge the two data frames by 'gene_name' with suffixes to distinguish columns
  merged_df <- merge(combined_pip_NOTfiltered_sig, combined_pip_filtered, 
                     by = "gene_name", suffixes = c("_NOTfiltered", "_filtered"),all.x=T)
  
  # List of columns to process (excluding 'gene_name')
  original_cols <- setdiff(names(combined_pip_NOTfiltered_sig), "gene_name")
  
  # Iterate over each column and concatenate values from both data frames
  for (col in original_cols) {
    notfiltered_col <- paste0(col, "_NOTfiltered")
    filtered_col <- paste0(col, "_filtered")
    merged_df[[col]] <- paste(round(merged_df[[notfiltered_col]],digits = 5), round(merged_df[[filtered_col]],digits = 5), sep = "-")
  }
  
  # Select the relevant columns to match the original structure
  df <- merged_df[, c("gene_name", original_cols)]
  
  cat("\n\n")
  cat(knitr::knit_print(DT::datatable(df, caption = htmltools::tags$caption( style = 'font-size: 150%; caption-side: topleft; text-align = left; color:black;', trait),options = list(pageLength = 5))))
  cat("\n\n")

  
}

[1] “PIP = 1.1 means PIP = NA when filtering CS”

[1] “PIP = 1.1 means PIP = NA when filtering CS”

[1] “PIP = 1.1 means PIP = NA when filtering CS”

[1] “PIP = 1.1 means PIP = NA when filtering CS”

[1] “PIP = 1.1 means PIP = NA when filtering CS”

[1] “PIP = 1.1 means PIP = NA when filtering CS”

[1] “PIP = 1.1 means PIP = NA when filtering CS”

#wrap_plots(lapply(p, wrap_elements), ncol = 4)

LDL:

Gene Involvement in LDL/Lipid Metabolism Evidence Level
KIF13B Enhances LDL uptake via LRP1 Strong
TTC39B Regulates cholesterol homeostasis via LXR degradation Strong
USP53 Modulates SR-A ubiquitination affecting LDL clearance Moderate
ACVR1C Influences adipose lipid metabolism Moderate
LRRK2 Affects lipid storage and lysosomal function Moderate
ACP6 Involved in LPA metabolism; indirect link to LDL Limited
CD163L1 Scavenger receptor; unclear role in LDL metabolism Limited
KDSR Sphingolipid biosynthesis; indirect association with LDL Limited
ZNF518A Function not well-characterized; no direct link to LDL Limited

T2D-panukb

trait <- "T2D-panukb"

combined_pip_filtered <- readRDS(paste0(folder_results,"/",trait,"/",trait,".",st,".thin",thin,".",var_struc,".L",L, ".combined_pip_bygroup_final_csincluded.RDS"))
combined_pip_filtered_plot <- combined_pip_filtered[,c("gene_name","combined_pip")]
colnames(combined_pip_filtered_plot) <- c("gene_name","combined_pip_csfiltered")

combined_pip_NOTfiltered <- readRDS(paste0(folder_results,"/",trait,"/",trait,".",st,".thin",thin,".",var_struc,".L",L, ".combined_pip_bygroup_final_csF.RDS"))
combined_pip_NOTfiltered_plot <- combined_pip_NOTfiltered[,c("gene_name","combined_pip")]
colnames(combined_pip_NOTfiltered_plot) <- c("gene_name","combined_pip_csNOTfiltered")

combined_pip_filtered_sig <- combined_pip_filtered[combined_pip_filtered$combined_pip > 0.8,]
combined_pip_NOTfiltered_sig <- combined_pip_NOTfiltered[combined_pip_NOTfiltered$combined_pip > 0.8,]
combined_pip_NOTfiltered_sig_plot <- combined_pip_NOTfiltered_plot[combined_pip_NOTfiltered_plot$combined_pip > 0.8,]

df_merge <- merge(combined_pip_NOTfiltered_sig_plot, combined_pip_filtered_plot, by = "gene_name", all.x = T)
df_merge$combined_pip_csfiltered[is.na(df_merge$combined_pip_csfiltered)] <- 1.1

p <-ggplot(data = df_merge,aes(x = combined_pip_csfiltered, y = combined_pip_csNOTfiltered)) +
  #p[[trait]] <-ggplot(data = df_merge,aes(x = combined_pip_csfiltered, y = combined_pip_csNOTfiltered)) +
  geom_point() + 
  labs(x = "Combined PIP -- CS filtered", y = "Combined PIP -- CS NOT filtered") +
  geom_abline(slope = 1, intercept = 0, col = "Red") +
  ggtitle(trait) +
  theme_minimal()

print("PIP = 1.1 means PIP = NA when filtering CS")

[1] “PIP = 1.1 means PIP = NA when filtering CS”

print(p)

# Merge the two data frames by 'gene_name' with suffixes to distinguish columns
merged_df <- merge(combined_pip_NOTfiltered_sig, combined_pip_filtered, 
                   by = "gene_name", suffixes = c("_NOTfiltered", "_filtered"),all.x=T)

# List of columns to process (excluding 'gene_name')
original_cols <- setdiff(names(combined_pip_NOTfiltered_sig), "gene_name")

# Iterate over each column and concatenate values from both data frames
for (col in original_cols) {
  notfiltered_col <- paste0(col, "_NOTfiltered")
  filtered_col <- paste0(col, "_filtered")
  merged_df[[col]] <- paste(round(merged_df[[notfiltered_col]],digits = 5), round(merged_df[[filtered_col]],digits = 5), sep = "-")
}

# Select the relevant columns to match the original structure
df <- merged_df[, c("gene_name", original_cols)]

DT::datatable(df, caption = htmltools::tags$caption( style = 'font-size: 150%; caption-side: topleft; text-align = left; color:black;', trait),options = list(pageLength = 5))

sessionInfo()
R version 4.2.0 (2022-04-22)
Platform: x86_64-pc-linux-gnu (64-bit)
Running under: Red Hat Enterprise Linux 8.4 (Ootpa)

Matrix products: default
BLAS/LAPACK: /software/openblas-0.3.13-el8-x86_64/lib/libopenblas_skylakexp-r0.3.13.so

locale:
 [1] LC_CTYPE=en_US.UTF-8       LC_NUMERIC=C              
 [3] LC_TIME=en_US.UTF-8        LC_COLLATE=en_US.UTF-8    
 [5] LC_MONETARY=en_US.UTF-8    LC_MESSAGES=en_US.UTF-8   
 [7] LC_PAPER=en_US.UTF-8       LC_NAME=C                 
 [9] LC_ADDRESS=C               LC_TELEPHONE=C            
[11] LC_MEASUREMENT=en_US.UTF-8 LC_IDENTIFICATION=C       

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

other attached packages:
 [1] EnsDb.Hsapiens.v86_2.99.0 ensembldb_2.22.0         
 [3] AnnotationFilter_1.22.0   GenomicFeatures_1.50.4   
 [5] AnnotationDbi_1.60.2      Biobase_2.58.0           
 [7] GenomicRanges_1.50.2      GenomeInfoDb_1.34.9      
 [9] IRanges_2.32.0            S4Vectors_0.36.2         
[11] BiocGenerics_0.44.0       ctwas_0.5.13             
[13] patchwork_1.1.1           eulerr_7.0.2             
[15] ggplot2_3.4.2             tidyr_1.3.0              
[17] scales_1.2.0              dplyr_1.1.2              

loaded via a namespace (and not attached):
  [1] colorspace_2.0-3            rjson_0.2.21               
  [3] ellipsis_0.3.2              rprojroot_2.0.3            
  [5] XVector_0.38.0              locuszoomr_0.1.5           
  [7] base64enc_0.1-3             fs_1.5.2                   
  [9] rstudioapi_0.14             farver_2.1.0               
 [11] DT_0.22                     ggrepel_0.9.3              
 [13] bit64_4.0.5                 fansi_1.0.3                
 [15] xml2_1.3.3                  codetools_0.2-18           
 [17] logging_0.10-108            cachem_1.0.6               
 [19] knitr_1.42                  polyclip_1.10-0            
 [21] jsonlite_1.8.9              workflowr_1.7.1            
 [23] Rsamtools_2.14.0            dbplyr_2.3.2               
 [25] png_0.1-7                   readr_2.1.4                
 [27] compiler_4.2.0              httr_1.4.7                 
 [29] Matrix_1.6-1.1              fastmap_1.1.0              
 [31] lazyeval_0.2.2              cli_3.6.2                  
 [33] later_1.3.0                 htmltools_0.5.7            
 [35] prettyunits_1.1.1           tools_4.2.0                
 [37] gtable_0.3.0                glue_1.6.2                 
 [39] GenomeInfoDbData_1.2.9      rappdirs_0.3.3             
 [41] Rcpp_1.0.14                 jquerylib_0.1.4            
 [43] vctrs_0.6.1                 Biostrings_2.66.0          
 [45] rtracklayer_1.58.0          crosstalk_1.2.0            
 [47] polylabelr_0.3.0            xfun_0.38                  
 [49] stringr_1.5.0               irlba_2.3.5                
 [51] lifecycle_1.0.4             restfulr_0.0.15            
 [53] XML_3.99-0.9                zlibbioc_1.44.0            
 [55] gggrid_0.2-0                hms_1.1.3                  
 [57] promises_1.2.0.1            MatrixGenerics_1.10.0      
 [59] ProtGenerics_1.30.0         parallel_4.2.0             
 [61] SummarizedExperiment_1.28.0 RColorBrewer_1.1-3         
 [63] LDlinkR_1.3.0               yaml_2.3.5                 
 [65] curl_4.3.2                  memoise_2.0.1              
 [67] sass_0.4.1                  biomaRt_2.54.1             
 [69] stringi_1.7.6               RSQLite_2.3.1              
 [71] highr_0.9                   BiocIO_1.8.0               
 [73] filelock_1.0.2              BiocParallel_1.32.6        
 [75] repr_1.1.4                  rlang_1.1.2                
 [77] pkgconfig_2.0.3             matrixStats_1.2.0          
 [79] bitops_1.0-7                evaluate_0.15              
 [81] lattice_0.20-45             purrr_1.0.1                
 [83] labeling_0.4.2              GenomicAlignments_1.34.1   
 [85] htmlwidgets_1.6.2           cowplot_1.1.1              
 [87] bit_4.0.4                   tidyselect_1.2.0           
 [89] magrittr_2.0.3              AMR_2.1.1                  
 [91] R6_2.5.1                    generics_0.1.3             
 [93] DelayedArray_0.24.0         DBI_1.1.2                  
 [95] pgenlibr_0.3.6              pillar_1.9.0               
 [97] whisker_0.4                 withr_2.5.0                
 [99] KEGGREST_1.38.0             RCurl_1.98-1.12            
[101] mixsqp_0.3-48               tibble_3.2.1               
[103] crayon_1.5.1                utf8_1.2.2                 
[105] BiocFileCache_2.6.1         plotly_4.10.0              
[107] tzdb_0.3.0                  rmarkdown_2.21             
[109] progress_1.2.2              grid_4.2.0                 
[111] data.table_1.14.4           blob_1.2.3                 
[113] git2r_0.30.1                digest_0.6.29              
[115] httpuv_1.6.5                munsell_0.5.0              
[117] viridisLite_0.4.0           skimr_2.1.4                
[119] bslib_0.3.1