Last updated: 2022-02-13

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Rmd 87fee8b sq-96 2022-02-13 update

Introduction

Weight QC

qclist_all <- list()

qc_files <- paste0(results_dir, "/", list.files(results_dir, pattern="exprqc.Rd"))

for (i in 1:length(qc_files)){
  load(qc_files[i])
  chr <- unlist(strsplit(rev(unlist(strsplit(qc_files[i], "_")))[1], "[.]"))[1]
  qclist_all[[chr]] <- cbind(do.call(rbind, lapply(qclist,unlist)), as.numeric(substring(chr,4)))
}

qclist_all <- data.frame(do.call(rbind, qclist_all))
colnames(qclist_all)[ncol(qclist_all)] <- "chr"

rm(qclist, wgtlist, z_gene_chr)

#number of imputed weights
nrow(qclist_all)
[1] 12414
#number of imputed weights by chromosome
table(qclist_all$chr)

   1    2    3    4    5    6    7    8    9   10   11   12   13   14   15   16 
1223  885  712  493  574  708  607  468  472  481  750  671  248  411  431  580 
  17   18   19   20   21   22 
 758  186  940  370  138  308 
#number of imputed weights without missing variants
sum(qclist_all$nmiss==0)
[1] 8861
#proportion of imputed weights without missing variants
mean(qclist_all$nmiss==0)
[1] 0.7137909

Load ctwas results

Check convergence of parameters

library(ggplot2)
library(cowplot)

********************************************************
Note: As of version 1.0.0, cowplot does not change the
  default ggplot2 theme anymore. To recover the previous
  behavior, execute:
  theme_set(theme_cowplot())
********************************************************
load(paste0(results_dir, "/", analysis_id, "_ctwas.s2.susieIrssres.Rd"))
  
df <- data.frame(niter = rep(1:ncol(group_prior_rec), 2),
                 value = c(group_prior_rec[1,], group_prior_rec[2,]),
                 group = rep(c("Gene", "SNP"), each = ncol(group_prior_rec)))
df$group <- as.factor(df$group)

df$value[df$group=="SNP"] <- df$value[df$group=="SNP"]*thin #adjust parameter to account for thin argument

p_pi <- ggplot(df, aes(x=niter, y=value, group=group)) +
  geom_line(aes(color=group)) +
  geom_point(aes(color=group)) +
  xlab("Iteration") + ylab(bquote(pi)) +
  ggtitle("Prior mean") +
  theme_cowplot()

df <- data.frame(niter = rep(1:ncol(group_prior_var_rec), 2),
                 value = c(group_prior_var_rec[1,], group_prior_var_rec[2,]),
                 group = rep(c("Gene", "SNP"), each = ncol(group_prior_var_rec)))
df$group <- as.factor(df$group)
p_sigma2 <- ggplot(df, aes(x=niter, y=value, group=group)) +
  geom_line(aes(color=group)) +
  geom_point(aes(color=group)) +
  xlab("Iteration") + ylab(bquote(sigma^2)) +
  ggtitle("Prior variance") +
  theme_cowplot()

plot_grid(p_pi, p_sigma2)

#estimated group prior
estimated_group_prior <- group_prior_rec[,ncol(group_prior_rec)]
names(estimated_group_prior) <- c("gene", "snp")
estimated_group_prior["snp"] <- estimated_group_prior["snp"]*thin #adjust parameter to account for thin argument
print(estimated_group_prior)
        gene          snp 
0.0066047523 0.0001681642 
#estimated group prior variance
estimated_group_prior_var <- group_prior_var_rec[,ncol(group_prior_var_rec)]
names(estimated_group_prior_var) <- c("gene", "snp")
print(estimated_group_prior_var)
    gene      snp 
3.629571 1.542519 
#report sample size
print(sample_size)
[1] 337159
#report group size
group_size <- c(nrow(ctwas_gene_res), n_snps)
print(group_size)
[1]   12414 7535010
#estimated group PVE
estimated_group_pve <- estimated_group_prior_var*estimated_group_prior*group_size/sample_size #check PVE calculation
names(estimated_group_pve) <- c("gene", "snp")
print(estimated_group_pve)
        gene          snp 
0.0008826506 0.0057971306 
#compare sum(PIP*mu2/sample_size) with above PVE calculation
c(sum(ctwas_gene_res$PVE),sum(ctwas_snp_res$PVE))
[1] 0.008240852 0.104643058

Genes with highest PIPs

#distribution of PIPs
hist(ctwas_gene_res$susie_pip, xlim=c(0,1), main="Distribution of Gene PIPs")

#genes with PIP>0.8 or 20 highest PIPs
head(ctwas_gene_res[order(-ctwas_gene_res$susie_pip),report_cols], max(sum(ctwas_gene_res$susie_pip>0.8), 20))
         genename region_tag susie_pip      mu2          PVE         z num_eqtl
3633        CCND2       12_4 0.9960588 26.82338 7.924350e-05  5.640253        2
4039         DAW1      2_134 0.6520366 24.10133 4.660990e-05  4.212144        2
3927        KLHL7       7_20 0.3117293 28.82218 2.664831e-05  3.761454        2
1055        ADCY2        5_7 0.3110596 29.13539 2.688004e-05 -3.602686        1
5948         SAT2       17_7 0.3034725 27.90152 2.511380e-05  3.462292        1
8729       ZNF180      19_31 0.2994262 28.43816 2.525553e-05  3.487253        2
7067         NUS1       6_78 0.2961966 28.74758 2.525496e-05  3.716370        1
14507 RP6-65G23.5      14_33 0.2820679 26.95154 2.254771e-05  3.369949        1
2137       NIPAL2       8_67 0.2774893 29.77768 2.450769e-05 -3.500588        2
2923       GNPTAB      12_61 0.2585525 26.98745 2.069549e-05  3.600816        1
7368        AP3S2      15_41 0.2457994 26.57908 1.937697e-05 -3.675343        2
11538       RABL6       9_74 0.2439157 26.89396 1.945627e-05 -3.491221        1
8342       MAMDC2       9_31 0.2436855 27.46993 1.985420e-05  3.779388        1
7460        PINK1       1_14 0.2391013 26.38648 1.871237e-05  3.208561        1
5761       DIAPH3      13_28 0.2384631 26.45894 1.871366e-05 -3.353072        1
11408       RRP7A      22_18 0.2329284 25.57072 1.766569e-05  3.082913        4
7974        LMOD1      1_102 0.2310904 25.35682 1.737969e-05  3.200403        1
9603         HPSE       4_56 0.2282649 26.26893 1.778471e-05 -3.109502        1
10568        LIPF      10_56 0.2252638 26.18648 1.749580e-05  2.991710        1
12381      KCTD11       17_6 0.2232470 25.41206 1.682638e-05  3.070309        2

Genes with largest effect sizes

#plot PIP vs effect size
plot(ctwas_gene_res$susie_pip, ctwas_gene_res$mu2, xlab="PIP", ylab="mu^2", main="Gene PIPs vs Effect Size")

#genes with 20 largest effect sizes
head(ctwas_gene_res[order(-ctwas_gene_res$mu2),report_cols],20)
         genename region_tag susie_pip      mu2          PVE         z num_eqtl
2137       NIPAL2       8_67 0.2774893 29.77768 2.450769e-05 -3.500588        2
1055        ADCY2        5_7 0.3110596 29.13539 2.688004e-05 -3.602686        1
3927        KLHL7       7_20 0.3117293 28.82218 2.664831e-05  3.761454        2
7067         NUS1       6_78 0.2961966 28.74758 2.525496e-05  3.716370        1
12700   LINC01537      11_41 0.1922338 28.61611 1.631569e-05 -3.271391        2
8729       ZNF180      19_31 0.2994262 28.43816 2.525553e-05  3.487253        2
5948         SAT2       17_7 0.3034725 27.90152 2.511380e-05  3.462292        1
8342       MAMDC2       9_31 0.2436855 27.46993 1.985420e-05  3.779388        1
2923       GNPTAB      12_61 0.2585525 26.98745 2.069549e-05  3.600816        1
14507 RP6-65G23.5      14_33 0.2820679 26.95154 2.254771e-05  3.369949        1
13511  AP001257.1      11_34 0.1747441 26.93090 1.395786e-05  3.363327        2
11538       RABL6       9_74 0.2439157 26.89396 1.945627e-05 -3.491221        1
3633        CCND2       12_4 0.9960588 26.82338 7.924350e-05  5.640253        2
7368        AP3S2      15_41 0.2457994 26.57908 1.937697e-05 -3.675343        2
5761       DIAPH3      13_28 0.2384631 26.45894 1.871366e-05 -3.353072        1
7460        PINK1       1_14 0.2391013 26.38648 1.871237e-05  3.208561        1
9603         HPSE       4_56 0.2282649 26.26893 1.778471e-05 -3.109502        1
12996       ZBED5       11_8 0.1569989 26.26162 1.222879e-05 -3.094448        2
10568        LIPF      10_56 0.2252638 26.18648 1.749580e-05  2.991710        1
9172         SIK2      11_66 0.2107616 25.57879 1.598957e-05 -3.728002        1

Genes with highest PVE

#genes with 20 highest pve
head(ctwas_gene_res[order(-ctwas_gene_res$PVE),report_cols],20)
         genename region_tag susie_pip      mu2          PVE         z num_eqtl
3633        CCND2       12_4 0.9960588 26.82338 7.924350e-05  5.640253        2
4039         DAW1      2_134 0.6520366 24.10133 4.660990e-05  4.212144        2
1055        ADCY2        5_7 0.3110596 29.13539 2.688004e-05 -3.602686        1
3927        KLHL7       7_20 0.3117293 28.82218 2.664831e-05  3.761454        2
8729       ZNF180      19_31 0.2994262 28.43816 2.525553e-05  3.487253        2
7067         NUS1       6_78 0.2961966 28.74758 2.525496e-05  3.716370        1
5948         SAT2       17_7 0.3034725 27.90152 2.511380e-05  3.462292        1
2137       NIPAL2       8_67 0.2774893 29.77768 2.450769e-05 -3.500588        2
14507 RP6-65G23.5      14_33 0.2820679 26.95154 2.254771e-05  3.369949        1
2923       GNPTAB      12_61 0.2585525 26.98745 2.069549e-05  3.600816        1
8342       MAMDC2       9_31 0.2436855 27.46993 1.985420e-05  3.779388        1
11538       RABL6       9_74 0.2439157 26.89396 1.945627e-05 -3.491221        1
7368        AP3S2      15_41 0.2457994 26.57908 1.937697e-05 -3.675343        2
5761       DIAPH3      13_28 0.2384631 26.45894 1.871366e-05 -3.353072        1
7460        PINK1       1_14 0.2391013 26.38648 1.871237e-05  3.208561        1
9603         HPSE       4_56 0.2282649 26.26893 1.778471e-05 -3.109502        1
11408       RRP7A      22_18 0.2329284 25.57072 1.766569e-05  3.082913        4
10568        LIPF      10_56 0.2252638 26.18648 1.749580e-05  2.991710        1
7974        LMOD1      1_102 0.2310904 25.35682 1.737969e-05  3.200403        1
12381      KCTD11       17_6 0.2232470 25.41206 1.682638e-05  3.070309        2

Genes with largest z scores

#genes with 20 largest z scores
head(ctwas_gene_res[order(-abs(ctwas_gene_res$z)),report_cols],20)
       genename region_tag  susie_pip      mu2          PVE         z num_eqtl
3633      CCND2       12_4 0.99605876 26.82338 7.924350e-05  5.640253        2
4039       DAW1      2_134 0.65203660 24.10133 4.660990e-05  4.212144        2
8342     MAMDC2       9_31 0.24368551 27.46993 1.985420e-05  3.779388        1
3927      KLHL7       7_20 0.31172926 28.82218 2.664831e-05  3.761454        2
9172       SIK2      11_66 0.21076159 25.57879 1.598957e-05 -3.728002        1
7067       NUS1       6_78 0.29619664 28.74758 2.525496e-05  3.716370        1
7368      AP3S2      15_41 0.24579938 26.57908 1.937697e-05 -3.675343        2
1055      ADCY2        5_7 0.31105965 29.13539 2.688004e-05 -3.602686        1
2923     GNPTAB      12_61 0.25855245 26.98745 2.069549e-05  3.600816        1
6954    ZFP36L2       2_27 0.09181774 19.66710 5.355897e-06 -3.577139        2
1731       RBX1      22_17 0.17255431 22.56815 1.155013e-05 -3.521311        1
14659 LINC01126       2_27 0.08675796 19.20577 4.942040e-06  3.518883        2
2137     NIPAL2       8_67 0.27748935 29.77768 2.450769e-05 -3.500588        2
11538     RABL6       9_74 0.24391565 26.89396 1.945627e-05 -3.491221        1
8729     ZNF180      19_31 0.29942623 28.43816 2.525553e-05  3.487253        2
8071      SPDYA       2_17 0.13662530 21.97074 8.903094e-06 -3.478973        2
5948       SAT2       17_7 0.30347254 27.90152 2.511380e-05  3.462292        1
9512     DNAJB7      22_17 0.15659375 21.74971 1.010167e-05  3.462008        1
5651     CNOT6L       4_52 0.20603518 25.05407 1.531034e-05  3.460483        1
12362    PPP1CB       2_17 0.12457721 21.20505 7.835074e-06  3.405525        1

Comparing z scores and PIPs

#set nominal signifiance threshold for z scores
alpha <- 0.05

#bonferroni adjusted threshold for z scores
sig_thresh <- qnorm(1-(alpha/nrow(ctwas_gene_res)/2), lower=T)

#Q-Q plot for z scores
obs_z <- ctwas_gene_res$z[order(ctwas_gene_res$z)]
exp_z <- qnorm((1:nrow(ctwas_gene_res))/nrow(ctwas_gene_res))

plot(exp_z, obs_z, xlab="Expected z", ylab="Observed z", main="Gene z score Q-Q plot")
abline(a=0,b=1)

#plot z score vs PIP
plot(abs(ctwas_gene_res$z), ctwas_gene_res$susie_pip, xlab="abs(z)", ylab="PIP")
abline(v=sig_thresh, col="red", lty=2)

#proportion of significant z scores
mean(abs(ctwas_gene_res$z) > sig_thresh)
[1] 8.055421e-05
#genes with most significant z scores
head(ctwas_gene_res[order(-abs(ctwas_gene_res$z)),report_cols],20)
       genename region_tag  susie_pip      mu2          PVE         z num_eqtl
3633      CCND2       12_4 0.99605876 26.82338 7.924350e-05  5.640253        2
4039       DAW1      2_134 0.65203660 24.10133 4.660990e-05  4.212144        2
8342     MAMDC2       9_31 0.24368551 27.46993 1.985420e-05  3.779388        1
3927      KLHL7       7_20 0.31172926 28.82218 2.664831e-05  3.761454        2
9172       SIK2      11_66 0.21076159 25.57879 1.598957e-05 -3.728002        1
7067       NUS1       6_78 0.29619664 28.74758 2.525496e-05  3.716370        1
7368      AP3S2      15_41 0.24579938 26.57908 1.937697e-05 -3.675343        2
1055      ADCY2        5_7 0.31105965 29.13539 2.688004e-05 -3.602686        1
2923     GNPTAB      12_61 0.25855245 26.98745 2.069549e-05  3.600816        1
6954    ZFP36L2       2_27 0.09181774 19.66710 5.355897e-06 -3.577139        2
1731       RBX1      22_17 0.17255431 22.56815 1.155013e-05 -3.521311        1
14659 LINC01126       2_27 0.08675796 19.20577 4.942040e-06  3.518883        2
2137     NIPAL2       8_67 0.27748935 29.77768 2.450769e-05 -3.500588        2
11538     RABL6       9_74 0.24391565 26.89396 1.945627e-05 -3.491221        1
8729     ZNF180      19_31 0.29942623 28.43816 2.525553e-05  3.487253        2
8071      SPDYA       2_17 0.13662530 21.97074 8.903094e-06 -3.478973        2
5948       SAT2       17_7 0.30347254 27.90152 2.511380e-05  3.462292        1
9512     DNAJB7      22_17 0.15659375 21.74971 1.010167e-05  3.462008        1
5651     CNOT6L       4_52 0.20603518 25.05407 1.531034e-05  3.460483        1
12362    PPP1CB       2_17 0.12457721 21.20505 7.835074e-06  3.405525        1

Sensitivity, specificity and precision for silver standard genes

library("readxl")

known_annotations <- read_xlsx("data/summary_known_genes_annotations.xlsx", sheet="T2D")
known_annotations <- unique(known_annotations$`Gene Symbol`)

unrelated_genes <- ctwas_gene_res$genename[!(ctwas_gene_res$genename %in% known_annotations)]

#number of genes in known annotations
print(length(known_annotations))
[1] 72
#number of genes in known annotations with imputed expression
print(sum(known_annotations %in% ctwas_gene_res$genename))
[1] 35
#assign ctwas, TWAS, and bystander genes
ctwas_genes <- ctwas_gene_res$genename[ctwas_gene_res$susie_pip>0.8]
twas_genes <- ctwas_gene_res$genename[abs(ctwas_gene_res$z)>sig_thresh]
novel_genes <- ctwas_genes[!(ctwas_genes %in% twas_genes)]

#significance threshold for TWAS
print(sig_thresh)
[1] 4.609947
#number of ctwas genes
length(ctwas_genes)
[1] 1
#number of TWAS genes
length(twas_genes)
[1] 1
#show novel genes (ctwas genes with not in TWAS genes)
ctwas_gene_res[ctwas_gene_res$genename %in% novel_genes,report_cols]
[1] genename   region_tag susie_pip  mu2        PVE        z          num_eqtl  
<0 rows> (or 0-length row.names)
#sensitivity / recall
sensitivity <- rep(NA,2)
names(sensitivity) <- c("ctwas", "TWAS")
sensitivity["ctwas"] <- sum(ctwas_genes %in% known_annotations)/length(known_annotations)
sensitivity["TWAS"] <- sum(twas_genes %in% known_annotations)/length(known_annotations)
sensitivity
ctwas  TWAS 
    0     0 
#specificity
specificity <- rep(NA,2)
names(specificity) <- c("ctwas", "TWAS")
specificity["ctwas"] <- sum(!(unrelated_genes %in% ctwas_genes))/length(unrelated_genes)
specificity["TWAS"] <- sum(!(unrelated_genes %in% twas_genes))/length(unrelated_genes)
specificity
    ctwas      TWAS 
0.9999192 0.9999192 
#precision / PPV
precision <- rep(NA,2)
names(precision) <- c("ctwas", "TWAS")
precision["ctwas"] <- sum(ctwas_genes %in% known_annotations)/length(ctwas_genes)
precision["TWAS"] <- sum(twas_genes %in% known_annotations)/length(twas_genes)
precision
ctwas  TWAS 
    0     0 
#ROC curves

pip_range <- (0:1000)/1000
sensitivity <- rep(NA, length(pip_range))
specificity <- rep(NA, length(pip_range))

for (index in 1:length(pip_range)){
  pip <- pip_range[index]
  ctwas_genes <- ctwas_gene_res$genename[ctwas_gene_res$susie_pip>=pip]
  sensitivity[index] <- sum(ctwas_genes %in% known_annotations)/length(known_annotations)
  specificity[index] <- sum(!(unrelated_genes %in% ctwas_genes))/length(unrelated_genes)
}

plot(1-specificity, sensitivity, type="l", xlim=c(0,1), ylim=c(0,1))

sig_thresh_range <- seq(from=0, to=max(abs(ctwas_gene_res$z)), length.out=length(pip_range))

for (index in 1:length(sig_thresh_range)){
  sig_thresh_plot <- sig_thresh_range[index]
  twas_genes <- ctwas_gene_res$genename[abs(ctwas_gene_res$z)>=sig_thresh_plot]
  sensitivity[index] <- sum(twas_genes %in% known_annotations)/length(known_annotations)
  specificity[index] <- sum(!(unrelated_genes %in% twas_genes))/length(unrelated_genes)
}

lines(1-specificity, sensitivity, xlim=c(0,1), ylim=c(0,1), col="red", lty=2)

Sensitivity, specificity and precision for silver standard genes - bystanders only

This section first uses all silver standard genes to identify bystander genes within 1Mb. The silver standard and bystander gene lists are then subset to only genes with imputed expression in this analysis. Then, the ctwas and TWAS gene lists from this analysis are subset to only genes that are in the (subset) silver standard and bystander genes. These gene lists are then used to compute sensitivity, specificity and precision for ctwas and TWAS.

library(biomaRt)
library(GenomicRanges)
Loading required package: stats4
Loading required package: BiocGenerics
Loading required package: parallel

Attaching package: 'BiocGenerics'
The following objects are masked from 'package:parallel':

    clusterApply, clusterApplyLB, clusterCall, clusterEvalQ,
    clusterExport, clusterMap, parApply, parCapply, parLapply,
    parLapplyLB, parRapply, parSapply, parSapplyLB
The following objects are masked from 'package:stats':

    IQR, mad, sd, var, xtabs
The following objects are masked from 'package:base':

    anyDuplicated, append, as.data.frame, basename, cbind, colnames,
    dirname, do.call, duplicated, eval, evalq, Filter, Find, get, grep,
    grepl, intersect, is.unsorted, lapply, Map, mapply, match, mget,
    order, paste, pmax, pmax.int, pmin, pmin.int, Position, rank,
    rbind, Reduce, rownames, sapply, setdiff, sort, table, tapply,
    union, unique, unsplit, which, which.max, which.min
Loading required package: S4Vectors

Attaching package: 'S4Vectors'
The following object is masked from 'package:base':

    expand.grid
Loading required package: IRanges
Loading required package: GenomeInfoDb
ensembl <- useEnsembl(biomart="ENSEMBL_MART_ENSEMBL", dataset="hsapiens_gene_ensembl")
G_list <- getBM(filters= "chromosome_name", attributes= c("hgnc_symbol","chromosome_name","start_position","end_position","gene_biotype"), values=1:22, mart=ensembl)
G_list <- G_list[G_list$hgnc_symbol!="",]
G_list <- G_list[G_list$gene_biotype %in% c("protein_coding","lncRNA"),]
G_list$start <- G_list$start_position
G_list$end <- G_list$end_position
G_list_granges <- makeGRangesFromDataFrame(G_list, keep.extra.columns=T)

known_annotations_positions <- G_list[G_list$hgnc_symbol %in% known_annotations,]
half_window <- 1000000
known_annotations_positions$start <- known_annotations_positions$start_position - half_window
known_annotations_positions$end <- known_annotations_positions$end_position + half_window
known_annotations_positions$start[known_annotations_positions$start<1] <- 1
known_annotations_granges <- makeGRangesFromDataFrame(known_annotations_positions, keep.extra.columns=T)

bystanders <- findOverlaps(known_annotations_granges,G_list_granges)
bystanders <- unique(subjectHits(bystanders))
bystanders <- G_list$hgnc_symbol[bystanders]
bystanders <- bystanders[!(bystanders %in% known_annotations)]
unrelated_genes <- bystanders

#number of genes in known annotations
print(length(known_annotations))
[1] 72
#number of genes in known annotations with imputed expression
print(sum(known_annotations %in% ctwas_gene_res$genename))
[1] 35
#number of bystander genes
print(length(unrelated_genes))
[1] 1847
#number of bystander genes with imputed expression
print(sum(unrelated_genes %in% ctwas_gene_res$genename))
[1] 941
#remove genes without imputed expression from gene lists
known_annotations <- known_annotations[known_annotations %in% ctwas_gene_res$genename]
unrelated_genes <- unrelated_genes[unrelated_genes %in% ctwas_gene_res$genename]

#assign ctwas and TWAS genes
ctwas_genes <- ctwas_gene_res$genename[ctwas_gene_res$susie_pip>0.8]
twas_genes <- ctwas_gene_res$genename[abs(ctwas_gene_res$z)>sig_thresh]

#significance threshold for TWAS
print(sig_thresh)
[1] 4.609947
#number of ctwas genes
length(ctwas_genes)
[1] 1
#number of ctwas genes in known annotations or bystanders
sum(ctwas_genes %in% c(known_annotations, unrelated_genes))
[1] 0
#number of ctwas genes
length(twas_genes)
[1] 1
#number of TWAS genes
sum(twas_genes %in% c(known_annotations, unrelated_genes))
[1] 0
#remove genes not in known or bystander lists from results
ctwas_genes <- ctwas_genes[ctwas_genes %in% c(known_annotations, unrelated_genes)]
twas_genes <- twas_genes[twas_genes %in% c(known_annotations, unrelated_genes)]

#sensitivity / recall
sensitivity <- rep(NA,2)
names(sensitivity) <- c("ctwas", "TWAS")
sensitivity["ctwas"] <- sum(ctwas_genes %in% known_annotations)/length(known_annotations)
sensitivity["TWAS"] <- sum(twas_genes %in% known_annotations)/length(known_annotations)
sensitivity
ctwas  TWAS 
    0     0 
#specificity
specificity <- rep(NA,2)
names(specificity) <- c("ctwas", "TWAS")
specificity["ctwas"] <- sum(!(unrelated_genes %in% ctwas_genes))/length(unrelated_genes)
specificity["TWAS"] <- sum(!(unrelated_genes %in% twas_genes))/length(unrelated_genes)
specificity
ctwas  TWAS 
    1     1 
#precision / PPV
precision <- rep(NA,2)
names(precision) <- c("ctwas", "TWAS")
precision["ctwas"] <- sum(ctwas_genes %in% known_annotations)/length(ctwas_genes)
precision["TWAS"] <- sum(twas_genes %in% known_annotations)/length(twas_genes)
precision
ctwas  TWAS 
  NaN   NaN 

sessionInfo()
R version 3.6.1 (2019-07-05)
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] parallel  stats4    stats     graphics  grDevices utils     datasets 
[8] methods   base     

other attached packages:
 [1] GenomicRanges_1.36.1 GenomeInfoDb_1.20.0  IRanges_2.18.1      
 [4] S4Vectors_0.22.1     BiocGenerics_0.30.0  biomaRt_2.40.1      
 [7] readxl_1.3.1         cowplot_1.0.0        ggplot2_3.3.5       
[10] workflowr_1.6.2     

loaded via a namespace (and not attached):
 [1] Rcpp_1.0.7             prettyunits_1.1.1      assertthat_0.2.1      
 [4] rprojroot_2.0.2        digest_0.6.29          utf8_1.2.2            
 [7] R6_2.5.1               cellranger_1.1.0       RSQLite_2.2.8         
[10] evaluate_0.14          httr_1.4.2             highr_0.9             
[13] pillar_1.6.4           zlibbioc_1.30.0        progress_1.2.2        
[16] rlang_0.4.12           curl_4.3.2             data.table_1.14.2     
[19] whisker_0.3-2          jquerylib_0.1.4        blob_1.2.2            
[22] rmarkdown_2.11         labeling_0.4.2         stringr_1.4.0         
[25] RCurl_1.98-1.5         bit_4.0.4              munsell_0.5.0         
[28] compiler_3.6.1         httpuv_1.5.1           xfun_0.29             
[31] pkgconfig_2.0.3        htmltools_0.5.2        tidyselect_1.1.1      
[34] GenomeInfoDbData_1.2.1 tibble_3.1.6           XML_3.99-0.3          
[37] fansi_0.5.0            crayon_1.4.2           dplyr_1.0.7           
[40] withr_2.4.3            later_0.8.0            bitops_1.0-7          
[43] grid_3.6.1             gtable_0.3.0           lifecycle_1.0.1       
[46] DBI_1.1.1              git2r_0.26.1           magrittr_2.0.1        
[49] scales_1.1.1           stringi_1.7.6          cachem_1.0.6          
[52] XVector_0.24.0         farver_2.1.0           fs_1.5.2              
[55] promises_1.0.1         ellipsis_0.3.2         generics_0.1.1        
[58] vctrs_0.3.8            tools_3.6.1            bit64_4.0.5           
[61] Biobase_2.44.0         glue_1.5.1             purrr_0.3.4           
[64] hms_1.1.1              fastmap_1.1.0          yaml_2.2.1            
[67] AnnotationDbi_1.46.0   colorspace_2.0-2       memoise_2.0.1         
[70] knitr_1.36