Last updated: 2023-10-11

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810 Regions of 4 lipid traits

Note: all the code and analysis reproduced here can be found in Repository

This analysis is done by relaxing the P-value threshold when constructing candidate regions.

Feature of 95% credible set

a. Set size and eQTL enrichment of 95% credible set

library(ggpubr)
library(data.table)
library(dplyr)
library(tidyr)
library(ggplot2)
library(patchwork)
library(ggpmisc)
library(VennDiagram)
library(gridExtra)
library(ggbreak)
library(DescTools)
library(coin)
library(susieR)
library(ggrepel)
library(stringr)


load("/net/fantasia/home/borang/Susie_Mult/Revision_Round_1/01_07_Real_Data/summary_res/res.RData")

#####################################################################
#
#     Plot directory and theme
#
####################################################################
plot_dir<-"/net/fantasia/home/borang/Susie_Mult/Revision_Round_1/Real_Data/Lipid_810/Figure/"
system(paste0("mkdir -p ",plot_dir))
custom_theme <- function() {
  theme(
    axis.text.x = element_text(size = 5),
    axis.text.y = element_text(size = 5),  
    axis.title.x = element_text(size = 7, face="bold"),
    axis.title.y = element_text(size = 7, face="bold"),
    strip.text.x = element_text(size = 5),
    strip.text.y = element_text(size = 5),
    strip.background = element_blank(),
    legend.text = element_text(size=7),
    legend.title = element_text(size=7, face="bold"),
    plot.title = element_text(size=7, hjust = 0.5),
    panel.grid.major = element_blank(),
    panel.grid.minor = element_blank(),
    panel.border = element_blank(), 
    axis.line = element_line(color = "black")
  )
}
################################################
#
#       Set Size/Z-score/eQTL 
#
#
###############################################
################################################
#
#       Set SiZe Part
#
###############################################     
###Median set size by Trait
all_sets_info<-data.frame(res_all%>%group_by(Trait,Region) %>% summarise(across(c("MESuSiE_cs", "SuSiE_cs","Paintor_cs"), ~ sum(.x, na.rm = TRUE))))%>%filter(MESuSiE_cs!=0, SuSiE_cs!=0, Paintor_cs!=0) ###Median Set Size across all locus
all_sets_info_long<-all_sets_info%>%pivot_longer(!(Trait|Region), names_to = "Method", values_to = "Count")
all_sets_info_long$Method<-factor(all_sets_info_long$Method,levels=c("MESuSiE_cs","SuSiE_cs","Paintor_cs"))
levels(all_sets_info_long$Method)<-c("MESuSiE","SuSiE","Paintor")

p_set = ggplot(data =all_sets_info_long,aes(x = Trait, y=Count,fill=Method))+geom_boxplot(aes(x = Trait,fill=Method),outlier.size = 0.1,fatten = 0.5,color = "darkgray")+scale_fill_manual(values=c("MESuSiE"="#023e8a","SuSiE"="#2a9d8f","Paintor"="#f4a261"),guide=FALSE)
p_set =p_set + theme_bw() + xlab("") +ylab("Set Size")+coord_cartesian(ylim=c(0,175))
p_set= p_set+custom_theme()

################################################
#
#       Z-score Part
#
###############################################     
MESuSiE_cs_Z<-res_all%>%group_by(Trait) %>%filter(MESuSiE_cs==1)%>%summarise(zmax = median(pmax(abs(zscore_WB),abs(zscore_BB))))
SuSiE_cs_Z<-res_all%>%group_by(Trait) %>%filter(SuSiE_cs==1)%>%summarise(zmax =median(pmax(abs(zscore_WB),abs(zscore_BB))))%>%pull(zmax)
Paintor_cs_Z<-res_all%>%group_by(Trait) %>%filter(Paintor_cs==1)%>%summarise(zmax = median(pmax(abs(zscore_WB),abs(zscore_BB))))%>%pull(zmax)
set_size_z_info<-data.frame(cbind(MESuSiE_cs_Z,SuSiE_cs_Z,Paintor_cs_Z))
colnames(set_size_z_info)<-c("Trait",c("MESuSiE","SuSiE","Paintor"))
set_size_z_info_long<-set_size_z_info %>%pivot_longer(!(Trait), names_to = "Method", values_to = "Z")%>%mutate(Method = factor(Method, levels=c("MESuSiE","SuSiE","Paintor")))

p_z = ggplot(data = set_size_z_info_long,aes(x = Trait, y=Z,fill=Method))+geom_bar( stat = "identity",position="dodge")+scale_fill_manual(values=c("MESuSiE"="#023e8a","SuSiE"="#2a9d8f","Paintor"="#f4a261"))
p_z = p_z + geom_text(label = round(set_size_z_info_long$Z,2),position = position_dodge(width = 1),vjust=-0.5,size = 5*5/14)
p_z = p_z + theme_bw() + xlab("") +ylab("Median |Z|")+ ylim(0,max(round(set_size_z_info_long$Z,2)+1))
p_z = p_z +custom_theme()
################################################
#
#       eQTL enrichment 
#
#
############################################### 
  ann_col_name<-c("missense", "synonymous", "utr_comb", "promotor", "CRE","liver_ind_eQTL")
  # Functions for calculating fold enrichment
  calc_fold_enrichment <- function(df, cs_col, ann_col_name) {
    df %>%
      group_by(Region) %>%
      filter(sum(!!sym(cs_col)) != 0) %>%
      group_by(Trait, !!sym(cs_col)) %>%
      summarise(across(ann_col_name, ~ sum(.x, na.rm = TRUE) / n())) %>%
      group_by(Trait) %>%
      summarise(across(ann_col_name, ~ .x[!!sym(cs_col) == 1] / .x[!!sym(cs_col) == 0]))
  }
  res_all<-res_all%>%mutate(utr_comb = ifelse((utr_5+utr_3)!=0,1,0))
  MESuSiE_PIP_ann <- calc_fold_enrichment(res_all, "MESuSiE_cs", ann_col_name)
  SuSiE_PIP_ann <- calc_fold_enrichment(res_all, "SuSiE_cs", ann_col_name)
  Paintor_PIP_ann <- calc_fold_enrichment(res_all, "Paintor_cs", ann_col_name)
  # Combine results
  Trait_CS_enrichment <- bind_rows(
    MESuSiE_PIP_ann %>% mutate(Method = "MESuSiE"),
    SuSiE_PIP_ann %>% mutate(Method = "SuSiE"),
    Paintor_PIP_ann %>% mutate(Method = "Paintor")
  ) %>% mutate(Method = factor(Method, levels = c("MESuSiE", "SuSiE", "Paintor")))%>%
    dplyr::select(Trait,liver_ind_eQTL ,Method )%>%dplyr::rename(eQTL = liver_ind_eQTL)
  # Pivot to long format
  Trait_CS_enrichment_long <- Trait_CS_enrichment %>%
    pivot_longer(cols = -c(Method, Trait), names_to = "Cat", values_to = "Prop") %>%
    mutate(Method = factor(Method, levels = c("MESuSiE", "SuSiE", "Paintor")))


  
p_eQTL <- ggplot(Trait_CS_enrichment_long, aes(x = Trait, y = Prop, fill = Method)) +
  geom_bar(stat = "identity", position = "dodge") +scale_fill_manual(values = c("MESuSiE" = "#023e8a", "SuSiE" = "#2a9d8f", "Paintor" = "#f4a261")) +
  geom_text(,label = round(Trait_CS_enrichment_long$Prop,2),position = position_dodge(width = 1),vjust=-0.5,size = 5*5/14)+
  xlab("") + ylab("eQTL Fold Enrichment") + ylim(0,max(round(Trait_CS_enrichment_long$Prop))+1)+
  theme_bw() + custom_theme()

p_out<-p_set/p_z/p_eQTL+plot_layout(guides = "collect",heights = c(1.5,1,1))+plot_annotation(tag_levels = 'a')&theme(legend.position = 'bottom',plot.tag = element_text(size = 7, face = "bold"))
p_out

Version Author Date
504f3a9 borangao 2023-10-09

b. Functional enrichment of 95% credible set and top signals

################################################################################
#
#
#     Functional Annotation enrichment for 95% credible set SNPS
#
#
################################################################################
# Enrichment of 95% credible set without by trait
  calc_fold_enrichment_marginal<-function(df, cs_col, ann_col_name) {
    df %>%group_by(Region) %>%
      filter(sum(!!sym(cs_col)) != 0) %>%
      group_by( !!sym(cs_col)) %>%
      summarise(across(ann_col_name, ~ sum(.x, na.rm = TRUE) / n())) %>%
      summarise(across(ann_col_name, ~ .x[!!sym(cs_col) == 1] / .x[!!sym(cs_col) == 0]))
  }
  MESuSiE_PIP_ann <- calc_fold_enrichment_marginal(res_all, "MESuSiE_cs", ann_col_name)
  SuSiE_PIP_ann <- calc_fold_enrichment_marginal(res_all, "SuSiE_cs", ann_col_name)
  Paintor_PIP_ann <- calc_fold_enrichment_marginal(res_all, "Paintor_cs", ann_col_name)
  
  CS_enrichment <- bind_rows(
    MESuSiE_PIP_ann %>% mutate(Method = "MESuSiE"),
    SuSiE_PIP_ann %>% mutate(Method = "SuSiE"),
    Paintor_PIP_ann %>% mutate(Method = "Paintor")
  ) %>% mutate(Method = factor(Method, levels = c("MESuSiE", "SuSiE", "Paintor")))%>% 
    dplyr::rename(Missense = missense ,Synonymous = synonymous,UTR = utr_comb,Promotor = promotor,eQTL = liver_ind_eQTL)
  # Pivot to long format
  CS_enrichment_long <- CS_enrichment %>%
    pivot_longer(cols = -c(Method), names_to = "Cat", values_to = "Prop") %>%
    mutate(Method = factor(Method, levels = c("MESuSiE", "SuSiE", "Paintor"))) %>%
    mutate(Cat = factor(Cat, levels = c("Missense", "Synonymous", "UTR", "Promotor", "CRE","eQTL")))%>%
    mutate(Prop = round(Prop, 2))
p_set <- ggplot(data = CS_enrichment_long,aes(x = Cat, y = Prop, fill = Method)) +
  geom_col(position = "dodge") + scale_fill_manual(values = c("MESuSiE" = "#023e8a", "SuSiE" = "#2a9d8f", "Paintor" = "#f4a261")) +
  geom_text(aes(x=Cat,group=Method,y=Prop,label=Prop),position = position_dodge(width = 1),vjust=-0.5,size = 5/14*5) + 
  geom_hline(yintercept = 1, linetype = "dashed") + 
  xlab("") + ylab("Fold Enrichment Credible Set") +ylim(0,round(max(CS_enrichment_long$Prop))+1) +
  theme_bw() + custom_theme()
################################################################################
#
#
#     Functional Annotation enrichment for top 500 PIP SNPs
#
#
################################################################################    
  # Enrichment of top 500 signal
  top_N_signal = 500
  bg_an<-res_all%>%summarise(across(ann_col_name,~ sum(.x, na.rm = TRUE)/n()))
  MESuSiE_Signal_ann<-res_all%>%filter(MESuSiE_PIP_Shared>0.5|MESuSiE_PIP_WB>0.5|MESuSiE_PIP_BB>0.5)%>% arrange(desc(MESuSiE_PIP_Either))%>%top_n(n = top_N_signal, wt = MESuSiE_PIP_Either)%>%summarise(across(ann_col_name,~ sum(.x, na.rm = TRUE)/n()))/bg_an
  SuSiE_Signal_ann<-res_all%>%filter(SuSiE_PIP>0.5)%>% arrange(desc(SuSiE_PIP))%>%top_n(n = top_N_signal, wt = SuSiE_PIP)%>%summarise(across(ann_col_name,~ sum(.x, na.rm = TRUE)/n()))/bg_an
  Paintor_Signal_ann<-res_all%>%filter(Paintor_PIP>0.5) %>% arrange(desc(Paintor_PIP))%>%top_n(n = top_N_signal, wt = Paintor_PIP)%>%summarise(across(ann_col_name,~ sum(.x, na.rm = TRUE)/n()))/bg_an
  
  Signal_enrichment <- bind_rows(
    MESuSiE_Signal_ann %>% mutate(Method = "MESuSiE"),
    SuSiE_Signal_ann %>% mutate(Method = "SuSiE"),
    Paintor_Signal_ann %>% mutate(Method = "Paintor")
  ) %>% mutate(Method = factor(Method, levels = c("MESuSiE", "SuSiE", "Paintor")))%>% 
    dplyr::rename(Missense = missense ,Synonymous = synonymous,UTR = utr_comb,Promotor = promotor,eQTL = liver_ind_eQTL)
  # Pivot to long format
  Signal_enrichment_long <- Signal_enrichment %>%
    pivot_longer(cols = -c(Method), names_to = "Cat", values_to = "Prop") %>%
    mutate(Method = factor(Method, levels = c("MESuSiE", "SuSiE", "Paintor"))) %>%
    mutate(Cat = factor(Cat, levels = c("Missense", "Synonymous", "UTR", "Promotor", "CRE","eQTL")))%>%
    mutate(Prop = round(Prop, 2))

p_signal <- ggplot(data = Signal_enrichment_long,aes(x = Cat, y = Prop, fill = Method)) +
  geom_col(position = "dodge") + scale_fill_manual(values = c("MESuSiE" = "#023e8a", "SuSiE" = "#2a9d8f", "Paintor" = "#f4a261")) +
  geom_text(aes(x=Cat,group=Method,y=Prop,label=Prop),position = position_dodge(width = 1),vjust=-0.5,size = 5/14*5) + 
  geom_hline(yintercept = 1, linetype = "dashed") + 
  xlab("") + ylab("Fold Enrichment Top Signal") +ylim(0,round(max(Signal_enrichment_long$Prop))+1) +
  theme_bw() + custom_theme()
p_out<-p_set/p_signal+plot_annotation(tag_levels = 'a')&theme(legend.position = 'bottom',plot.tag = element_text(size = 7, face = "bold"))
p_out

Version Author Date
504f3a9 borangao 2023-10-09

sessionInfo()
R version 4.3.1 (2023-06-16)
Platform: x86_64-pc-linux-gnu (64-bit)
Running under: Ubuntu 20.04.6 LTS

Matrix products: default
BLAS:   /usr/lib/x86_64-linux-gnu/openblas-pthread/libblas.so.3 
LAPACK: /usr/lib/x86_64-linux-gnu/openblas-pthread/liblapack.so.3;  LAPACK version 3.9.0

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       

time zone: America/New_York
tzcode source: system (glibc)

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

other attached packages:
 [1] stringr_1.5.0       ggrepel_0.9.1       susieR_0.11.84     
 [4] coin_1.4-2          survival_3.3-1      DescTools_0.99.45  
 [7] ggbreak_0.1.1       gridExtra_2.3       VennDiagram_1.7.3  
[10] futile.logger_1.4.3 ggpmisc_0.4.7       ggpp_0.4.4         
[13] patchwork_1.1.1     tidyr_1.3.0         dplyr_1.1.2        
[16] data.table_1.14.8   ggpubr_0.6.0        ggplot2_3.4.2      
[19] workflowr_1.7.0    

loaded via a namespace (and not attached):
  [1] formatR_1.14         gld_2.6.5            sandwich_3.0-2      
  [4] readxl_1.4.2         rlang_1.1.1          magrittr_2.0.3      
  [7] git2r_0.32.0         multcomp_1.4-25      matrixStats_1.0.0   
 [10] e1071_1.7-13         compiler_4.3.1       getPass_0.2-2       
 [13] callr_3.7.3          vctrs_0.6.2          quantreg_5.95       
 [16] crayon_1.5.2         pkgconfig_2.0.3      fastmap_1.1.1       
 [19] backports_1.4.1      labeling_0.4.2       utf8_1.2.3          
 [22] promises_1.2.0.1     rmarkdown_2.22       ps_1.7.2            
 [25] MatrixModels_0.5-1   purrr_1.0.1          xfun_0.39           
 [28] modeltools_0.2-23    cachem_1.0.8         aplot_0.1.10        
 [31] jsonlite_1.8.3       highr_0.10           later_1.3.1         
 [34] reshape_0.8.9        irlba_2.3.5.1        broom_1.0.5         
 [37] parallel_4.3.1       R6_2.5.1             bslib_0.5.0         
 [40] stringi_1.7.12       car_3.1-2            boot_1.3-28.1       
 [43] jquerylib_0.1.4      cellranger_1.1.0     Rcpp_1.0.11         
 [46] knitr_1.39           zoo_1.8-12           httpuv_1.6.11       
 [49] Matrix_1.5-4.1       splines_4.3.1        tidyselect_1.2.0    
 [52] rstudioapi_0.14      abind_1.4-5          yaml_2.3.7          
 [55] codetools_0.2-19     processx_3.8.0       plyr_1.8.8          
 [58] lattice_0.20-45      tibble_3.2.1         withr_2.5.1         
 [61] evaluate_0.18        gridGraphics_0.5-1   lambda.r_1.2.4      
 [64] proxy_0.4-27         pillar_1.9.0         carData_3.0-5       
 [67] whisker_0.4.1        stats4_4.3.1         ggfun_0.0.9         
 [70] generics_0.1.3       rprojroot_2.0.3      munsell_0.5.0       
 [73] scales_1.2.1         rootSolve_1.8.2.3    class_7.3-20        
 [76] glue_1.6.2           lmom_2.8             tools_4.3.1         
 [79] SparseM_1.81         ggsignif_0.6.4       Exact_3.1           
 [82] fs_1.6.2             mvtnorm_1.1-3        libcoin_1.0-9       
 [85] colorspace_2.1-0     cli_3.6.1            futile.options_1.0.1
 [88] fansi_1.0.5          expm_0.999-7         mixsqp_0.3-48       
 [91] gtable_0.3.1         rstatix_0.7.2        yulab.utils_0.0.4   
 [94] sass_0.4.6           digest_0.6.30        TH.data_1.1-2       
 [97] ggplotify_0.1.0      farver_2.1.1         htmltools_0.5.5     
[100] lifecycle_1.0.3      httr_1.4.6           MASS_7.3-57