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  • Run susie with different priors and see how much prior affects results.

  • Data: ukb chr 17 to chr 22 combined. SNPs are downsampled to 1/10, eQTLs defined by FUSION-TWAS (Adipose/GTEx) lasso effect size > 0 were kept, p= 86k, n = 20k.

library(mr.ash.alpha)
library(data.table)
suppressMessages({library(plotly)})
library(tidyr)
library(plyr)
library(stringr)
library(kableExtra)
source("analysis/summarize_twas_plots.R")

PIP calibration: filter regions

simdatadir <- "~/causalTWAS/simulations/simulation_ashtest_20200721/"
outputdir <- "~/causalTWAS/simulations/simulation_ashtest_20200721/"
susiedir <- "~/causalTWAS/simulations/simulation_susietest_20200721/20200721-1-fixprior_rpip0.5/"

We run 100 simulations and run susie using different priors and L= 1. We only apply susie for regions with mr.ash2 regional PIP > 0.5.

Truth

  • The true parameters we used to simulate data:
par <- read.table(paste0(susiedir, "20200721-1-fixedprior_1.txt"), header = T)
t(par[,2, drop = F])
        gene.pi1    gene.pve     snp.pi1    snp.pve
truth 0.05021174 0.008497975 0.002498094 0.05003487

Using uniform prior:

pipfs <- Sys.glob(paste0(susiedir,"20200721-1-*.fixedprior1.L1.susieres.expr.txt"))
res <- do.call(rbind, lapply(pipfs, read.table, header = T))

cp_plot(res$pip.null, res$ifcausal, main = "SUSIE.uniform PIP")

Use overestimated prior

  • The prior used is:
par <- read.table(paste0(susiedir, "20200721-1-fixedprior_1.txt"), header = T)
t(par[c(1,3),1, drop = F])
          gene.pi1     snp.pi1
estimated 0.131184 0.002274899
  • susie results:
par(mfrow=c(1,2))
cp_plot(res$pip, res$ifcausal, main = "SUSIE.weighted PIP")
cp_plot(res$pip.w0, res$ifcausal, main = "SUSIE.weighted-w-null PIP")

Use priors close to truth

  • The prior used is:
par <- read.table(paste0(susiedir, "20200721-1-fixedprior_2.txt"), header = T)
t(par[c(1,3),1, drop = F])
            gene.pi1     snp.pi1
estimated 0.05118395 0.002274899
pipfs <- Sys.glob(paste0(susiedir,"20200721-1-*.fixedprior2.L1.susieres.expr.txt"))
res <- do.call(rbind, lapply(pipfs, read.table, header = T))

par(mfrow=c(1,2))
cp_plot(res$pip, res$ifcausal, main = "SUSIE.weighted PIP")
cp_plot(res$pip.w0, res$ifcausal, main = "SUSIE.weighted-w-null PIP")

Use under estimated priors

  • The prior used is:
par <- read.table(paste0(susiedir, "20200721-1-fixedprior_3.txt"), header = T)
t(par[c(1,3),1, drop = F])
            gene.pi1     snp.pi1
estimated 0.01118395 0.002274899
  • susie results:
pipfs <- Sys.glob(paste0(susiedir,"20200721-1-*.fixedprior3.L1.susieres.expr.txt"))
res <- do.call(rbind, lapply(pipfs, read.table, header = T))

par(mfrow=c(1,2))
cp_plot(res$pip, res$ifcausal, main = "SUSIE.weighted PIP")
cp_plot(res$pip.w0, res$ifcausal, main = "SUSIE.weighted-w-null PIP")

PIP calibration: use all regions

susiedir <- "~/causalTWAS/simulations/simulation_susietest_20200721/"

We run 100 simulations and run susie using different priors and L= 1. We only apply susie for all regions.

Truth

  • The true parameters we used to simulate data:
par <- read.table(paste0(susiedir, "20200721-1-fixedprior_1.txt"), header = T)
t(par[,2, drop = F])
        gene.pi1    gene.pve     snp.pi1    snp.pve
truth 0.05021174 0.008497975 0.002498094 0.05003487

Using uniform prior:

pipfs <- Sys.glob(paste0(susiedir,"20200721-1-*.fixedprior1.L1.susieres.expr.txt"))
res <- do.call(rbind, lapply(pipfs, read.table, header = T))

cp_plot(res$pip.null, res$ifcausal, main = "SUSIE.uniform PIP")

Use overestimated prior

  • The prior used is:
par <- read.table(paste0(susiedir, "20200721-1-fixedprior_1.txt"), header = T)
t(par[c(1,3),1, drop = F])
          gene.pi1     snp.pi1
estimated 0.131184 0.002274899
  • susie results:
par(mfrow=c(1,2))
cp_plot(res$pip, res$ifcausal, main = "SUSIE.weighted PIP")
cp_plot(res$pip.w0, res$ifcausal, main = "SUSIE.weighted-w-null PIP")

Use priors close to truth

  • The prior used is:
par <- read.table(paste0(susiedir, "20200721-1-fixedprior_2.txt"), header = T)
t(par[c(1,3),1, drop = F])
            gene.pi1     snp.pi1
estimated 0.05118395 0.002274899
pipfs <- Sys.glob(paste0(susiedir,"20200721-1-*.fixedprior2.L1.susieres.expr.txt"))
res <- do.call(rbind, lapply(pipfs, read.table, header = T))

par(mfrow=c(1,2))
cp_plot(res$pip, res$ifcausal, main = "SUSIE.weighted PIP")
cp_plot(res$pip.w0, res$ifcausal, main = "SUSIE.weighted-w-null PIP")

Use under estimated priors

  • The prior used is:
par <- read.table(paste0(susiedir, "20200721-1-fixedprior_3.txt"), header = T)
t(par[c(1,3),1, drop = F])
            gene.pi1     snp.pi1
estimated 0.01118395 0.002274899
  • susie results:
pipfs <- Sys.glob(paste0(susiedir,"20200721-1-*.fixedprior3.L1.susieres.expr.txt"))
res <- do.call(rbind, lapply(pipfs, read.table, header = T))

par(mfrow=c(1,2))
cp_plot(res$pip, res$ifcausal, main = "SUSIE.weighted PIP")
cp_plot(res$pip.w0, res$ifcausal, main = "SUSIE.weighted-w-null PIP")


sessionInfo()
R version 3.5.1 (2018-07-02)
Platform: x86_64-pc-linux-gnu (64-bit)
Running under: Scientific Linux 7.4 (Nitrogen)

Matrix products: default
BLAS/LAPACK: /software/openblas-0.2.19-el7-x86_64/lib/libopenblas_haswellp-r0.2.19.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] stats     graphics  grDevices utils     datasets  methods   base     

other attached packages:
[1] kableExtra_1.2.1    stringr_1.4.0       plyr_1.8.6         
[4] tidyr_0.8.3         plotly_4.9.2.9000   ggplot2_3.3.1      
[7] data.table_1.12.7   mr.ash.alpha_0.1-34

loaded via a namespace (and not attached):
 [1] Rcpp_1.0.4.6      compiler_3.5.1    pillar_1.4.4     
 [4] later_0.7.5       git2r_0.26.1      workflowr_1.6.2  
 [7] tools_3.5.1       digest_0.6.25     viridisLite_0.3.0
[10] jsonlite_1.6.1    evaluate_0.12     tibble_3.0.1     
[13] lifecycle_0.2.0   gtable_0.2.0      lattice_0.20-38  
[16] pkgconfig_2.0.2   rlang_0.4.6       Matrix_1.2-15    
[19] rstudioapi_0.11   yaml_2.2.0        xml2_1.2.0       
[22] httr_1.4.1        withr_2.1.2       dplyr_1.0.0      
[25] knitr_1.20        htmlwidgets_1.3   generics_0.0.2   
[28] fs_1.3.1          vctrs_0.3.1       webshot_0.5.1    
[31] tidyselect_1.1.0  rprojroot_1.3-2   grid_3.5.1       
[34] glue_1.4.1        R6_2.3.0          rmarkdown_1.10   
[37] purrr_0.3.4       magrittr_1.5      backports_1.1.2  
[40] scales_1.0.0      promises_1.0.1    htmltools_0.3.6  
[43] ellipsis_0.3.1    rvest_0.3.2       colorspace_1.3-2 
[46] httpuv_1.4.5      stringi_1.3.1     lazyeval_0.2.1   
[49] munsell_0.5.0     crayon_1.3.4