Last updated: 2021-09-09

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File Version Author Date Message
Rmd cbf7408 wesleycrouse 2021-09-08 adding enrichment to reports
html cbf7408 wesleycrouse 2021-09-08 adding enrichment to reports
Rmd 4970e3e wesleycrouse 2021-09-08 updating reports
html 4970e3e wesleycrouse 2021-09-08 updating reports
Rmd 627a4e1 wesleycrouse 2021-09-07 adding heritability
Rmd dfd2b5f wesleycrouse 2021-09-07 regenerating reports
html dfd2b5f wesleycrouse 2021-09-07 regenerating reports
Rmd 61b53b3 wesleycrouse 2021-09-06 updated PVE calculation
html 61b53b3 wesleycrouse 2021-09-06 updated PVE calculation
Rmd 837dd01 wesleycrouse 2021-09-01 adding additional fixedsigma report
Rmd d0a5417 wesleycrouse 2021-08-30 adding new reports to the index
Rmd 0922de7 wesleycrouse 2021-08-18 updating all reports with locus plots
html 0922de7 wesleycrouse 2021-08-18 updating all reports with locus plots
html 1c62980 wesleycrouse 2021-08-11 Updating reports
Rmd 5981e80 wesleycrouse 2021-08-11 Adding more reports
html 5981e80 wesleycrouse 2021-08-11 Adding more reports
Rmd 05a98b7 wesleycrouse 2021-08-07 adding additional results
html 05a98b7 wesleycrouse 2021-08-07 adding additional results
html 03e541c wesleycrouse 2021-07-29 Cleaning up report generation
Rmd 276893d wesleycrouse 2021-07-29 Updating reports
html 276893d wesleycrouse 2021-07-29 Updating reports

Overview

These are the results of a ctwas analysis of the UK Biobank trait Oestradiol (quantile) using Liver gene weights.

The GWAS was conducted by the Neale Lab, and the biomarker traits we analyzed are discussed here. Summary statistics were obtained from IEU OpenGWAS using GWAS ID: ukb-d-30800_irnt. Results were obtained from from IEU rather than Neale Lab because they are in a standardard format (GWAS VCF). Note that 3 of the 34 biomarker traits were not available from IEU and were excluded from analysis.

The weights are mashr GTEx v8 models on Liver eQTL obtained from PredictDB. We performed a full harmonization of the variants, including recovering strand ambiguous variants. This procedure is discussed in a separate document. (TO-DO: add report that describes harmonization)

LD matrices were computed from a 10% subset of Neale lab subjects. Subjects were matched using the plate and well information from genotyping. We included only biallelic variants with MAF>0.01 in the original Neale Lab GWAS. (TO-DO: add more details [number of subjects, variants, etc])

Weight QC

TO-DO: add enhanced QC reporting (total number of weights, why each variant was missing for all genes)

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] 10901
#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 
1070  768  652  417  494  611  548  408  405  434  634  629  195  365  354 
  16   17   18   19   20   21   22 
 526  663  160  859  306  114  289 
#proportion of imputed weights without missing variants
mean(qclist_all$nmiss==0)
[1] 0.8366205

Load ctwas results

#load ctwas results
ctwas_res <- data.table::fread(paste0(results_dir, "/", analysis_id, "_ctwas.susieIrss.txt"))

#make unique identifier for regions
ctwas_res$region_tag <- paste(ctwas_res$region_tag1, ctwas_res$region_tag2, sep="_")

#compute PVE for each gene/SNP
ctwas_res$PVE = ctwas_res$susie_pip*ctwas_res$mu2/sample_size #check PVE calculation

#separate gene and SNP results
ctwas_gene_res <- ctwas_res[ctwas_res$type == "gene", ]
ctwas_gene_res <- data.frame(ctwas_gene_res)
ctwas_snp_res <- ctwas_res[ctwas_res$type == "SNP", ]
ctwas_snp_res <- data.frame(ctwas_snp_res)

#add gene information to results
sqlite <- RSQLite::dbDriver("SQLite")
db = RSQLite::dbConnect(sqlite, paste0("/project2/compbio/predictdb/mashr_models/mashr_", weight, ".db"))
query <- function(...) RSQLite::dbGetQuery(db, ...)
gene_info <- query("select gene, genename from extra")
gene_info <- query("select gene, genename, gene_type from extra")
RSQLite::dbDisconnect(db)

ctwas_gene_res <- cbind(ctwas_gene_res, gene_info[sapply(ctwas_gene_res$id, match, gene_info$gene), c("genename", "gene_type")])

#add z score to results
load(paste0(results_dir, "/", analysis_id, "_expr_z_gene.Rd"))
ctwas_gene_res$z <- z_gene[ctwas_gene_res$id,]$z

#load(paste0(results_dir, "/", analysis_id, "_expr_z_snp.Rd")) #for new version, stored after harmonization
z_snp <- readRDS(paste0(results_dir, "/", trait_id, ".RDS")) #for old version, unharmonized

z_snp <- z_snp[z_snp$id %in% ctwas_snp_res$id,] #subset snps to those included in analysis, note some are duplicated, need to match which allele was used
ctwas_snp_res$z <- z_snp$z[match(ctwas_snp_res$id, z_snp$id)] #for duplicated snps, this arbitrarily uses the first allele
ctwas_snp_res$z_flag <- as.numeric(ctwas_snp_res$id %in% z_snp$id[duplicated(z_snp$id)]) #mark the unclear z scores, flag=1

#formatting and rounding for tables
ctwas_gene_res$z <- round(ctwas_gene_res$z,2)
ctwas_snp_res$z <- round(ctwas_snp_res$z,2)
ctwas_gene_res$susie_pip <- round(ctwas_gene_res$susie_pip,3)
ctwas_snp_res$susie_pip <- round(ctwas_snp_res$susie_pip,3)
ctwas_gene_res$mu2 <- round(ctwas_gene_res$mu2,2)
ctwas_snp_res$mu2 <- round(ctwas_snp_res$mu2,2)
ctwas_gene_res$PVE <- signif(ctwas_gene_res$PVE, 2)
ctwas_snp_res$PVE <- signif(ctwas_snp_res$PVE, 2)

#merge gene and snp results with added information
ctwas_gene_res$z_flag=NA
ctwas_snp_res$genename=NA
ctwas_snp_res$gene_type=NA

ctwas_res <- rbind(ctwas_gene_res,
                   ctwas_snp_res[,colnames(ctwas_gene_res)])

#store columns to report
report_cols <- colnames(ctwas_gene_res)[!(colnames(ctwas_gene_res) %in% c("type", "region_tag1", "region_tag2", "cs_index", "gene_type", "z_flag", "id", "chrom", "pos"))]
first_cols <- c("genename", "region_tag")
report_cols <- c(first_cols, report_cols[!(report_cols %in% first_cols)])

report_cols_snps <- c("id", report_cols[-1])

#get number of SNPs from s1 results; adjust for thin
ctwas_res_s1 <- data.table::fread(paste0(results_dir, "/", analysis_id, "_ctwas.s1.susieIrss.txt"))
n_snps <- sum(ctwas_res_s1$type=="SNP")/thin
rm(ctwas_res_s1)

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)

Version Author Date
dfd2b5f wesleycrouse 2021-09-07
#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 
0.0008474940 0.0001366605 
#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 
0.7217176 1.1250624 
#report sample size
print(sample_size)
[1] 54498
#report group size
group_size <- c(nrow(ctwas_gene_res), n_snps)
print(group_size)
[1]   10901 8697330
#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 
0.000122346 0.024537192 
#compare sum(PIP*mu2/sample_size) with above PVE calculation
c(sum(ctwas_gene_res$PVE),sum(ctwas_snp_res$PVE))
[1] 0.002731761 0.502393806

Genes with highest PIPs

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

Version Author Date
dfd2b5f wesleycrouse 2021-09-07
#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
2518     LIN7A      12_49     0.036 12.01 7.8e-06 -3.42
5908    GTF3C5       9_70     0.035 11.71 7.6e-06 -3.35
2586    GOLT1B      12_16     0.025 11.56 5.2e-06 -3.46
4693    SETDB2      13_21     0.025 10.81 5.0e-06  3.48
8233     KCNS3       2_10     0.024 10.88 4.7e-06  3.66
11       RAD52       12_1     0.024 10.70 4.7e-06 -3.31
3991    ATP1B2       17_7     0.024 11.86 5.2e-06 -4.47
10146   MVB12B       9_65     0.022 10.32 4.2e-06  3.24
11309 C12orf75      12_63     0.022 10.24 4.2e-06  3.57
4223    DNAJB1      19_12     0.021  9.95 3.9e-06 -3.15
1006    COBLL1      2_100     0.020  9.97 3.7e-06  3.36
8238    CHCHD7       8_44     0.020 10.17 3.7e-06  3.09
5115     NUP58       13_6     0.020  9.83 3.6e-06  3.01
3881      VIL1      2_129     0.019  9.64 3.4e-06 -3.24
11478  HLA-DMB       6_27     0.019  9.08 3.1e-06 -3.05
10260     BCO2      11_66     0.019  9.81 3.4e-06 -3.12
5305     PELP1       17_4     0.019 10.25 3.6e-06  4.25
7089    IGFBP7       4_41     0.018 10.20 3.3e-06  3.13
3265      DLST      14_34     0.018 10.24 3.4e-06 -3.45
1672      TTI1      20_22     0.018  9.10 2.9e-06 -2.85

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")

Version Author Date
dfd2b5f wesleycrouse 2021-09-07
#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
2518     LIN7A      12_49     0.036 12.01 7.8e-06 -3.42
3991    ATP1B2       17_7     0.024 11.86 5.2e-06 -4.47
5908    GTF3C5       9_70     0.035 11.71 7.6e-06 -3.35
2586    GOLT1B      12_16     0.025 11.56 5.2e-06 -3.46
8233     KCNS3       2_10     0.024 10.88 4.7e-06  3.66
4693    SETDB2      13_21     0.025 10.81 5.0e-06  3.48
11       RAD52       12_1     0.024 10.70 4.7e-06 -3.31
10642    HLA-C       6_25     0.011 10.41 2.2e-06 -4.52
854     EXOSC7       3_31     0.017 10.34 3.3e-06  3.54
10146   MVB12B       9_65     0.022 10.32 4.2e-06  3.24
5305     PELP1       17_4     0.019 10.25 3.6e-06  4.25
11309 C12orf75      12_63     0.022 10.24 4.2e-06  3.57
3265      DLST      14_34     0.018 10.24 3.4e-06 -3.45
7089    IGFBP7       4_41     0.018 10.20 3.3e-06  3.13
8238    CHCHD7       8_44     0.020 10.17 3.7e-06  3.09
1006    COBLL1      2_100     0.020  9.97 3.7e-06  3.36
4223    DNAJB1      19_12     0.021  9.95 3.9e-06 -3.15
5115     NUP58       13_6     0.020  9.83 3.6e-06  3.01
10260     BCO2      11_66     0.019  9.81 3.4e-06 -3.12
6880   TNFSF13       17_7     0.014  9.68 2.5e-06  4.26

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
2518     LIN7A      12_49     0.036 12.01 7.8e-06 -3.42
5908    GTF3C5       9_70     0.035 11.71 7.6e-06 -3.35
2586    GOLT1B      12_16     0.025 11.56 5.2e-06 -3.46
3991    ATP1B2       17_7     0.024 11.86 5.2e-06 -4.47
4693    SETDB2      13_21     0.025 10.81 5.0e-06  3.48
8233     KCNS3       2_10     0.024 10.88 4.7e-06  3.66
11       RAD52       12_1     0.024 10.70 4.7e-06 -3.31
10146   MVB12B       9_65     0.022 10.32 4.2e-06  3.24
11309 C12orf75      12_63     0.022 10.24 4.2e-06  3.57
4223    DNAJB1      19_12     0.021  9.95 3.9e-06 -3.15
1006    COBLL1      2_100     0.020  9.97 3.7e-06  3.36
8238    CHCHD7       8_44     0.020 10.17 3.7e-06  3.09
5115     NUP58       13_6     0.020  9.83 3.6e-06  3.01
5305     PELP1       17_4     0.019 10.25 3.6e-06  4.25
3881      VIL1      2_129     0.019  9.64 3.4e-06 -3.24
10260     BCO2      11_66     0.019  9.81 3.4e-06 -3.12
3265      DLST      14_34     0.018 10.24 3.4e-06 -3.45
854     EXOSC7       3_31     0.017 10.34 3.3e-06  3.54
7089    IGFBP7       4_41     0.018 10.20 3.3e-06  3.13
11478  HLA-DMB       6_27     0.019  9.08 3.1e-06 -3.05

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
10642    HLA-C       6_25     0.011 10.41 2.2e-06 -4.52
3991    ATP1B2       17_7     0.024 11.86 5.2e-06 -4.47
6880   TNFSF13       17_7     0.014  9.68 2.5e-06  4.26
5305     PELP1       17_4     0.019 10.25 3.6e-06  4.25
5308     ARRB2       17_4     0.013  8.60 2.0e-06 -3.96
8233     KCNS3       2_10     0.024 10.88 4.7e-06  3.66
11309 C12orf75      12_63     0.022 10.24 4.2e-06  3.57
854     EXOSC7       3_31     0.017 10.34 3.3e-06  3.54
4693    SETDB2      13_21     0.025 10.81 5.0e-06  3.48
2586    GOLT1B      12_16     0.025 11.56 5.2e-06 -3.46
3265      DLST      14_34     0.018 10.24 3.4e-06 -3.45
2518     LIN7A      12_49     0.036 12.01 7.8e-06 -3.42
1410    RNF215      22_10     0.017  9.55 3.0e-06 -3.41
1006    COBLL1      2_100     0.020  9.97 3.7e-06  3.36
5908    GTF3C5       9_70     0.035 11.71 7.6e-06 -3.35
7177    CLEC3B       3_31     0.014  9.33 2.4e-06  3.33
11       RAD52       12_1     0.024 10.70 4.7e-06 -3.31
9074     TCAIM       3_31     0.011  8.32 1.7e-06 -3.29
11399  TNFSF12       17_7     0.006  6.17 7.0e-07  3.28
5643    ZNF660       3_31     0.010  7.86 1.4e-06  3.27

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)

Version Author Date
dfd2b5f wesleycrouse 2021-09-07
#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)

Version Author Date
dfd2b5f wesleycrouse 2021-09-07
#proportion of significant z scores
mean(abs(ctwas_gene_res$z) > sig_thresh)
[1] 0
#genes with most significant z scores
head(ctwas_gene_res[order(-abs(ctwas_gene_res$z)),report_cols],20)
      genename region_tag susie_pip   mu2     PVE     z
10642    HLA-C       6_25     0.011 10.41 2.2e-06 -4.52
3991    ATP1B2       17_7     0.024 11.86 5.2e-06 -4.47
6880   TNFSF13       17_7     0.014  9.68 2.5e-06  4.26
5305     PELP1       17_4     0.019 10.25 3.6e-06  4.25
5308     ARRB2       17_4     0.013  8.60 2.0e-06 -3.96
8233     KCNS3       2_10     0.024 10.88 4.7e-06  3.66
11309 C12orf75      12_63     0.022 10.24 4.2e-06  3.57
854     EXOSC7       3_31     0.017 10.34 3.3e-06  3.54
4693    SETDB2      13_21     0.025 10.81 5.0e-06  3.48
2586    GOLT1B      12_16     0.025 11.56 5.2e-06 -3.46
3265      DLST      14_34     0.018 10.24 3.4e-06 -3.45
2518     LIN7A      12_49     0.036 12.01 7.8e-06 -3.42
1410    RNF215      22_10     0.017  9.55 3.0e-06 -3.41
1006    COBLL1      2_100     0.020  9.97 3.7e-06  3.36
5908    GTF3C5       9_70     0.035 11.71 7.6e-06 -3.35
7177    CLEC3B       3_31     0.014  9.33 2.4e-06  3.33
11       RAD52       12_1     0.024 10.70 4.7e-06 -3.31
9074     TCAIM       3_31     0.011  8.32 1.7e-06 -3.29
11399  TNFSF12       17_7     0.006  6.17 7.0e-07  3.28
5643    ZNF660       3_31     0.010  7.86 1.4e-06  3.27

Locus plots for genes and SNPs

ctwas_gene_res_sortz <- ctwas_gene_res[order(-abs(ctwas_gene_res$z)),]

n_plots <- 5
for (region_tag_plot in head(unique(ctwas_gene_res_sortz$region_tag), n_plots)){
  ctwas_res_region <-  ctwas_res[ctwas_res$region_tag==region_tag_plot,]
  start <- min(ctwas_res_region$pos)
  end <- max(ctwas_res_region$pos)
  
  ctwas_res_region <- ctwas_res_region[order(ctwas_res_region$pos),]
  ctwas_res_region_gene <- ctwas_res_region[ctwas_res_region$type=="gene",]
  ctwas_res_region_snp <- ctwas_res_region[ctwas_res_region$type=="SNP",]
  
  #region name
  print(paste0("Region: ", region_tag_plot))
  
  #table of genes in region
  print(ctwas_res_region_gene[,report_cols])
  
  par(mfrow=c(4,1))
  
  #gene z scores
  plot(ctwas_res_region_gene$pos, abs(ctwas_res_region_gene$z), xlab="Position", ylab="abs(gene_z)", xlim=c(start,end),
   ylim=c(0,max(sig_thresh, abs(ctwas_res_region_gene$z))),
   main=paste0("Region: ", region_tag_plot))
  abline(h=sig_thresh,col="red",lty=2)
  
  #significance threshold for SNPs
  alpha_snp <- 5*10^(-8)
  sig_thresh_snp <- qnorm(1-alpha_snp/2, lower=T)
  
  #snp z scores
  plot(ctwas_res_region_snp$pos, abs(ctwas_res_region_snp$z), xlab="Position", ylab="abs(snp_z)",xlim=c(start,end),
   ylim=c(0,max(sig_thresh_snp, max(abs(ctwas_res_region_snp$z)))))
  abline(h=sig_thresh_snp,col="purple",lty=2)
  
  #gene pips
  plot(ctwas_res_region_gene$pos, ctwas_res_region_gene$susie_pip, xlab="Position", ylab="Gene PIP", xlim=c(start,end), ylim=c(0,1))
  abline(h=0.8,col="blue",lty=2)
  
  #snp pips
  plot(ctwas_res_region_snp$pos, ctwas_res_region_snp$susie_pip, xlab="Position", ylab="SNP PIP", xlim=c(start,end), ylim=c(0,1))
  abline(h=0.8,col="blue",lty=2)
}
[1] "Region: 6_25"
               genename region_tag susie_pip   mu2     PVE     z
10653              DDR1       6_25     0.002  2.26 6.7e-08  0.28
4838              VARS2       6_25     0.003  4.38 2.2e-07  2.25
10854            GTF2H4       6_25     0.003  4.57 2.4e-07 -2.17
10044             SFTA2       6_25     0.002  2.31 7.0e-08 -0.97
10646          PSORS1C1       6_25     0.002  3.81 1.6e-07  2.11
10645          PSORS1C2       6_25     0.002  2.11 6.0e-08 -0.32
11297             HLA-B       6_25     0.002  2.10 6.0e-08 -0.08
4832              TCF19       6_25     0.002  2.16 6.3e-08 -0.31
10644            CCHCR1       6_25     0.002  2.16 6.3e-08 -0.31
10643            POU5F1       6_25     0.002  2.79 9.4e-08 -1.22
10771             HCG27       6_25     0.004  6.15 4.6e-07  3.05
10642             HLA-C       6_25     0.011 10.41 2.2e-06 -4.52
12306 XXbac-BPG181B23.7       6_25     0.002  2.95 1.0e-07 -1.22
10640              MICA       6_25     0.002  2.98 1.1e-07  1.78
10639              MICB       6_25     0.002  2.43 7.5e-08 -0.54
10417            DDX39B       6_25     0.002  3.57 1.5e-07  1.29
10637           NFKBIL1       6_25     0.002  2.13 6.1e-08  0.13
10852          ATP6V1G2       6_25     0.002  2.10 6.0e-08 -0.02
11110               LTA       6_25     0.002  2.26 6.7e-08 -0.54
11237               TNF       6_25     0.002  3.07 1.1e-07 -1.09
10635              NCR3       6_25     0.002  3.32 1.3e-07  1.45

Version Author Date
dfd2b5f wesleycrouse 2021-09-07
[1] "Region: 17_7"
          genename region_tag susie_pip   mu2     PVE     z
9229       TMEM102       17_7     0.003  2.47 1.2e-07 -1.04
6882         FGF11       17_7     0.009  7.83 1.3e-06  2.59
11885      SLC35G6       17_7     0.002  2.32 1.0e-07  0.82
11399      TNFSF12       17_7     0.006  6.17 7.0e-07  3.28
6880       TNFSF13       17_7     0.014  9.68 2.5e-06  4.26
6881         SENP3       17_7     0.003  2.68 1.3e-07 -0.61
6883        EIF4A1       17_7     0.002  2.32 1.0e-07 -1.05
5313          SAT2       17_7     0.002  2.10 9.0e-08 -0.13
3991        ATP1B2       17_7     0.024 11.86 5.2e-06 -4.47
5311        WRAP53       17_7     0.004  4.76 3.8e-07 -2.14
9477         DNAH2       17_7     0.006  5.76 5.9e-07  2.76
7853        TMEM88       17_7     0.003  2.55 1.2e-07  0.85
9115    AC025335.1       17_7     0.003  2.63 1.3e-07  0.90
8143        KCNAB3       17_7     0.002  2.17 9.4e-08 -0.34
8142        CNTROB       17_7     0.002  2.23 9.9e-08 -0.44
10982        VAMP2       17_7     0.003  2.92 1.5e-07  0.99
9063       TMEM107       17_7     0.003  3.01 1.6e-07 -1.01
9059         AURKB       17_7     0.002  2.12 9.1e-08  0.17
9053          CTC1       17_7     0.002  2.11 9.0e-08  0.13
9046          PFAS       17_7     0.011  8.58 1.7e-06  2.75
12191 RP11-849F2.9       17_7     0.002  2.22 9.7e-08 -0.32
3703      SLC25A35       17_7     0.002  2.14 9.2e-08  0.21
9538         KRBA2       17_7     0.002  2.17 9.4e-08 -0.33

Version Author Date
dfd2b5f wesleycrouse 2021-09-07
[1] "Region: 17_4"
     genename region_tag susie_pip   mu2     PVE     z
1024    ITGAE       17_4     0.006  5.36 5.8e-07  1.93
811    ATP2A3       17_4     0.005  4.76 4.5e-07  1.86
819     ZZEF1       17_4     0.003  2.10 1.0e-07 -0.02
4260   UBE2G1       17_4     0.004  3.50 2.4e-07  1.32
9334    SPNS3       17_4     0.003  2.12 1.1e-07  0.14
7828     GGT6       17_4     0.003  2.25 1.2e-07  0.33
4257  MYBBP1A       17_4     0.003  2.26 1.2e-07 -0.73
5305    PELP1       17_4     0.019 10.25 3.6e-06  4.25
5308    ARRB2       17_4     0.013  8.60 2.0e-06 -3.96
6876    MED11       17_4     0.003  2.29 1.2e-07  0.63
5310  ZMYND15       17_4     0.004  3.40 2.3e-07 -1.06
9363     VMO1       17_4     0.005  4.93 4.8e-07 -1.99

Version Author Date
dfd2b5f wesleycrouse 2021-09-07
[1] "Region: 2_10"
      genename region_tag susie_pip   mu2     PVE     z
10301   FAM49A       2_10     0.003  2.26 1.3e-07  0.45
10925 RAD51AP2       2_10     0.005  3.92 3.3e-07  1.60
7032     VSNL1       2_10     0.003  2.76 1.7e-07  0.92
8996      GEN1       2_10     0.003  2.61 1.6e-07 -0.94
7031      SMC6       2_10     0.004  3.20 2.3e-07  1.31
8233     KCNS3       2_10     0.024 10.88 4.7e-06  3.66

Version Author Date
dfd2b5f wesleycrouse 2021-09-07
[1] "Region: 12_63"
      genename region_tag susie_pip   mu2     PVE    z
4676   SLC41A2      12_63     0.004  2.69 1.8e-07 0.79
6082  C12orf45      12_63     0.003  2.15 1.3e-07 0.28
4675    WASHC4      12_63     0.005  3.53 3.0e-07 1.45
11309 C12orf75      12_63     0.022 10.24 4.2e-06 3.57
4672     APPL2      12_63     0.005  3.59 3.0e-07 1.52

Version Author Date
dfd2b5f wesleycrouse 2021-09-07

SNPs with highest PIPs

#snps with PIP>0.8 or 20 highest PIPs
head(ctwas_snp_res[order(-ctwas_snp_res$susie_pip),report_cols_snps],
max(sum(ctwas_snp_res$susie_pip>0.8), 20))
                id region_tag susie_pip   mu2     PVE     z
140037  rs75620930        3_1     0.242 23.92 1.1e-04  4.34
396298  rs62444120       7_28     0.242 23.84 1.1e-04 -4.35
476904 rs112371525       8_89     0.219 23.32 9.4e-05  4.23
761470   rs4968212       17_7     0.217 25.19 1.0e-04 -5.30
761480  rs62059839       17_7     0.205 24.86 9.4e-05  5.31
679108   rs1959607       14_1     0.202 22.92 8.5e-05  4.21
526099 rs551737161      10_16     0.187 24.22 8.3e-05  3.60
813811  rs73000658      19_16     0.184 22.18 7.5e-05 -4.06
761458   rs9892862       17_7     0.177 23.99 7.8e-05  5.26
319306  rs13160700      5_104     0.175 22.38 7.2e-05 -4.06
165332   rs9813399       3_53     0.174 21.67 6.9e-05  4.14
806869 rs117700303       19_2     0.170 22.08 6.9e-05 -4.07
70306   rs13429539        2_7     0.167 22.83 7.0e-05 -4.12
513886  rs10760461       9_65     0.167 22.03 6.8e-05  4.10
417774    rs876169       7_68     0.161 21.86 6.5e-05  4.31
272419 rs112157462       5_14     0.160 21.39 6.3e-05  3.98
761460   rs8073177       17_7     0.160 23.44 6.9e-05  5.21
154020  rs76750610       3_28     0.155 21.22 6.0e-05 -3.93
459963 rs553564201       8_57     0.155 22.03 6.3e-05  3.99
381048 rs113784847        7_1     0.151 21.78 6.0e-05 -4.04

SNPs with largest effect sizes

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

Version Author Date
dfd2b5f wesleycrouse 2021-09-07
#SNPs with 50 largest effect sizes
head(ctwas_snp_res[order(-ctwas_snp_res$mu2),report_cols_snps],50)
                id region_tag susie_pip   mu2     PVE     z
761470   rs4968212       17_7     0.217 25.19 1.0e-04 -5.30
761480  rs62059839       17_7     0.205 24.86 9.4e-05  5.31
526099 rs551737161      10_16     0.187 24.22 8.3e-05  3.60
761458   rs9892862       17_7     0.177 23.99 7.8e-05  5.26
140037  rs75620930        3_1     0.242 23.92 1.1e-04  4.34
396298  rs62444120       7_28     0.242 23.84 1.1e-04 -4.35
761460   rs8073177       17_7     0.160 23.44 6.9e-05  5.21
476904 rs112371525       8_89     0.219 23.32 9.4e-05  4.23
679108   rs1959607       14_1     0.202 22.92 8.5e-05  4.21
70306   rs13429539        2_7     0.167 22.83 7.0e-05 -4.12
761500   rs1641549       17_7     0.139 22.61 5.7e-05 -4.62
319306  rs13160700      5_104     0.175 22.38 7.2e-05 -4.06
813811  rs73000658      19_16     0.184 22.18 7.5e-05 -4.06
806869 rs117700303       19_2     0.170 22.08 6.9e-05 -4.07
459963 rs553564201       8_57     0.155 22.03 6.3e-05  3.99
513886  rs10760461       9_65     0.167 22.03 6.8e-05  4.10
39473  rs192164271       1_80     0.129 21.89 5.2e-05  3.94
761464  rs11078694       17_7     0.122 21.89 4.9e-05 -5.05
417774    rs876169       7_68     0.161 21.86 6.5e-05  4.31
381048 rs113784847        7_1     0.151 21.78 6.0e-05 -4.04
165332   rs9813399       3_53     0.174 21.67 6.9e-05  4.14
327669 rs192338591       6_13     0.144 21.57 5.7e-05  3.94
138489   rs3791461      2_142     0.150 21.42 5.9e-05 -3.97
761474 rs149932962       17_7     0.112 21.41 4.4e-05  5.03
272419 rs112157462       5_14     0.160 21.39 6.3e-05  3.98
96986  rs187600283       2_58     0.133 21.22 5.2e-05  3.88
154020  rs76750610       3_28     0.155 21.22 6.0e-05 -3.93
742136 rs143894776      16_23     0.138 21.20 5.4e-05 -3.90
642695 rs146568110      12_75     0.125 21.17 4.9e-05  3.84
423042   rs9640863       7_80     0.141 21.14 5.5e-05 -3.96
238187 rs142227684       4_72     0.074 21.08 2.9e-05  3.79
2845     rs2274332        1_6     0.149 21.06 5.8e-05 -3.89
106803  rs62162215       2_78     0.144 20.98 5.5e-05 -3.94
598854  rs73008432      11_70     0.146 20.95 5.6e-05  4.04
182446   rs9823043       3_85     0.127 20.94 4.9e-05 -4.05
64719   rs79505543      1_129     0.143 20.92 5.5e-05  3.85
710597  rs76553406       15_9     0.133 20.91 5.1e-05  3.91
582710 rs140333597      11_37     0.137 20.90 5.2e-05  3.86
819786 rs544367902      19_27     0.132 20.82 5.0e-05  3.82
368002 rs148062999       6_88     0.129 20.80 4.9e-05  3.84
763904  rs58335060      17_13     0.133 20.74 5.1e-05 -4.13
199766 rs115771219      3_119     0.100 20.64 3.8e-05 -3.74
24562   rs41284595       1_52     0.138 20.62 5.2e-05 -3.85
468856 rs149885805       8_74     0.124 20.59 4.7e-05 -3.82
611212   rs7308471      12_15     0.081 20.59 3.1e-05  3.96
394648  rs11371390       7_26     0.114 20.57 4.3e-05 -4.04
56411   rs78763889      1_111     0.133 20.53 5.0e-05 -4.03
382126  rs10951073        7_5     0.099 20.49 3.7e-05 -3.93
257296  rs13121691      4_110     0.126 20.47 4.7e-05 -3.84
645510   rs1696452      12_80     0.132 20.46 5.0e-05  3.78

SNPs with highest PVE

#SNPs with 50 highest pve
head(ctwas_snp_res[order(-ctwas_snp_res$PVE),report_cols_snps],50)
                id region_tag susie_pip   mu2     PVE     z
140037  rs75620930        3_1     0.242 23.92 1.1e-04  4.34
396298  rs62444120       7_28     0.242 23.84 1.1e-04 -4.35
761470   rs4968212       17_7     0.217 25.19 1.0e-04 -5.30
476904 rs112371525       8_89     0.219 23.32 9.4e-05  4.23
761480  rs62059839       17_7     0.205 24.86 9.4e-05  5.31
679108   rs1959607       14_1     0.202 22.92 8.5e-05  4.21
526099 rs551737161      10_16     0.187 24.22 8.3e-05  3.60
761458   rs9892862       17_7     0.177 23.99 7.8e-05  5.26
813811  rs73000658      19_16     0.184 22.18 7.5e-05 -4.06
319306  rs13160700      5_104     0.175 22.38 7.2e-05 -4.06
70306   rs13429539        2_7     0.167 22.83 7.0e-05 -4.12
165332   rs9813399       3_53     0.174 21.67 6.9e-05  4.14
761460   rs8073177       17_7     0.160 23.44 6.9e-05  5.21
806869 rs117700303       19_2     0.170 22.08 6.9e-05 -4.07
513886  rs10760461       9_65     0.167 22.03 6.8e-05  4.10
417774    rs876169       7_68     0.161 21.86 6.5e-05  4.31
272419 rs112157462       5_14     0.160 21.39 6.3e-05  3.98
459963 rs553564201       8_57     0.155 22.03 6.3e-05  3.99
154020  rs76750610       3_28     0.155 21.22 6.0e-05 -3.93
381048 rs113784847        7_1     0.151 21.78 6.0e-05 -4.04
138489   rs3791461      2_142     0.150 21.42 5.9e-05 -3.97
2845     rs2274332        1_6     0.149 21.06 5.8e-05 -3.89
327669 rs192338591       6_13     0.144 21.57 5.7e-05  3.94
761500   rs1641549       17_7     0.139 22.61 5.7e-05 -4.62
598854  rs73008432      11_70     0.146 20.95 5.6e-05  4.04
64719   rs79505543      1_129     0.143 20.92 5.5e-05  3.85
106803  rs62162215       2_78     0.144 20.98 5.5e-05 -3.94
423042   rs9640863       7_80     0.141 21.14 5.5e-05 -3.96
742136 rs143894776      16_23     0.138 21.20 5.4e-05 -3.90
24562   rs41284595       1_52     0.138 20.62 5.2e-05 -3.85
39473  rs192164271       1_80     0.129 21.89 5.2e-05  3.94
96986  rs187600283       2_58     0.133 21.22 5.2e-05  3.88
582710 rs140333597      11_37     0.137 20.90 5.2e-05  3.86
351728  rs78874260       6_54     0.137 20.40 5.1e-05 -3.79
710597  rs76553406       15_9     0.133 20.91 5.1e-05  3.91
763904  rs58335060      17_13     0.133 20.74 5.1e-05 -4.13
56411   rs78763889      1_111     0.133 20.53 5.0e-05 -4.03
645510   rs1696452      12_80     0.132 20.46 5.0e-05  3.78
819786 rs544367902      19_27     0.132 20.82 5.0e-05  3.82
182446   rs9823043       3_85     0.127 20.94 4.9e-05 -4.05
368002 rs148062999       6_88     0.129 20.80 4.9e-05  3.84
642695 rs146568110      12_75     0.125 21.17 4.9e-05  3.84
761464  rs11078694       17_7     0.122 21.89 4.9e-05 -5.05
764807 rs139270577      17_15     0.130 20.22 4.8e-05 -3.76
99704    rs3113783       2_65     0.126 20.12 4.7e-05 -3.99
257296  rs13121691      4_110     0.126 20.47 4.7e-05 -3.84
362887   rs2350814       6_76     0.127 20.25 4.7e-05  3.91
468856 rs149885805       8_74     0.124 20.59 4.7e-05 -3.82
758122  rs11076740      16_53     0.126 20.41 4.7e-05 -3.98
685436 rs117875427      14_11     0.124 20.04 4.6e-05 -3.85

SNPs with largest z scores

#SNPs with 50 largest z scores
head(ctwas_snp_res[order(-abs(ctwas_snp_res$z)),report_cols_snps],50)
                id region_tag susie_pip   mu2     PVE     z
761480  rs62059839       17_7     0.205 24.86 9.4e-05  5.31
761470   rs4968212       17_7     0.217 25.19 1.0e-04 -5.30
761458   rs9892862       17_7     0.177 23.99 7.8e-05  5.26
761460   rs8073177       17_7     0.160 23.44 6.9e-05  5.21
761464  rs11078694       17_7     0.122 21.89 4.9e-05 -5.05
761474 rs149932962       17_7     0.112 21.41 4.4e-05  5.03
333973   rs6913470       6_25     0.043 18.28 1.4e-05  4.92
333928    rs915660       6_25     0.041 18.11 1.4e-05  4.89
333967   rs7453202       6_25     0.040 17.98 1.3e-05  4.89
333971   rs6907451       6_25     0.040 17.93 1.3e-05  4.89
333930   rs9357109       6_25     0.041 18.08 1.4e-05  4.88
333957  rs28360066       6_25     0.040 17.94 1.3e-05  4.88
333964   rs9380223       6_25     0.040 17.92 1.3e-05  4.88
333953   rs9391819       6_25     0.039 17.82 1.3e-05  4.86
333960   rs9404983       6_25     0.039 17.81 1.3e-05  4.86
333947  rs28360062       6_25     0.036 17.33 1.1e-05  4.82
333938   rs6899875       6_25     0.035 17.29 1.1e-05  4.81
333940   rs9357115       6_25     0.035 17.28 1.1e-05  4.81
333942   rs9378115       6_25     0.035 17.30 1.1e-05  4.81
333976  rs17191237       6_25     0.033 16.86 1.0e-05  4.78
760375  rs55884013       17_4     0.095 19.67 3.4e-05 -4.75
760372  rs55677157       17_4     0.084 19.01 2.9e-05 -4.69
760370 rs142108572       17_4     0.079 18.68 2.7e-05 -4.67
334039  rs28749561       6_25     0.026 15.61 7.4e-06  4.64
760373  rs11658808       17_4     0.084 19.01 2.9e-05  4.64
334022  rs28397294       6_25     0.025 15.42 7.1e-06  4.62
760371   rs2174830       17_4     0.080 18.78 2.8e-05  4.62
761500   rs1641549       17_7     0.139 22.61 5.7e-05 -4.62
334019   rs7745906       6_25     0.025 15.32 6.9e-06  4.60
760368   rs9904358       17_4     0.069 17.91 2.3e-05  4.58
760364  rs55780247       17_4     0.059 17.09 1.9e-05 -4.49
760367   rs4538065       17_4     0.055 16.66 1.7e-05  4.44
334078  rs35556213       6_25     0.025 15.37 7.0e-06  4.41
334079  rs35303934       6_25     0.024 15.23 6.7e-06  4.39
333956  rs28749557       6_25     0.021 14.62 5.8e-06  4.38
334087  rs35482069       6_25     0.023 15.00 6.4e-06  4.36
334088  rs34247821       6_25     0.023 14.98 6.3e-06  4.36
396298  rs62444120       7_28     0.242 23.84 1.1e-04 -4.35
140037  rs75620930        3_1     0.242 23.92 1.1e-04  4.34
760381  rs55999196       17_4     0.046 15.79 1.3e-05 -4.33
417774    rs876169       7_68     0.161 21.86 6.5e-05  4.31
572473  rs11031033      11_21     0.083 18.52 2.8e-05 -4.30
572475  rs10835646      11_21     0.082 18.44 2.8e-05 -4.30
333985  rs10947149       6_25     0.018 13.72 4.6e-06  4.27
155047  rs13092460       3_31     0.082 19.40 2.9e-05 -4.26
333986   rs9263947       6_25     0.024 15.18 6.6e-06  4.26
333935   rs9468882       6_25     0.019 13.95 4.9e-06  4.25
333983  rs34480332       6_25     0.018 13.63 4.5e-06  4.25
333988   rs3869109       6_25     0.024 15.13 6.6e-06  4.25
760363  rs12941694       17_4     0.045 15.66 1.3e-05  4.25

Gene set enrichment for genes with PIP>0.8

#GO enrichment analysis
library(enrichR)
Welcome to enrichR
Checking connection ... 
Enrichr ... Connection is Live!
FlyEnrichr ... Connection is available!
WormEnrichr ... Connection is available!
YeastEnrichr ... Connection is available!
FishEnrichr ... Connection is available!
dbs <- c("GO_Biological_Process_2021", "GO_Cellular_Component_2021", "GO_Molecular_Function_2021")
genes <- ctwas_gene_res$genename[ctwas_gene_res$susie_pip>0.8]

#number of genes for gene set enrichment
length(genes)
[1] 0
if (length(genes)>0){
  GO_enrichment <- enrichr(genes, dbs)

  for (db in dbs){
    print(db)
    df <- GO_enrichment[[db]]
    df <- df[df$Adjusted.P.value<0.05,c("Term", "Overlap", "Adjusted.P.value", "Genes")]
    print(df)
  }
  
  #DisGeNET enrichment
  
  # devtools::install_bitbucket("ibi_group/disgenet2r")
  library(disgenet2r)
  
  disgenet_api_key <- get_disgenet_api_key(
                    email = "wesleycrouse@gmail.com", 
                    password = "uchicago1" )
  
  Sys.setenv(DISGENET_API_KEY= disgenet_api_key)
  
  res_enrich <-disease_enrichment(entities=genes, vocabulary = "HGNC",
                               database = "CURATED" )
  
  df <- res_enrich@qresult[1:10, c("Description", "FDR", "Ratio",  "BgRatio")]
  print(df)
  
  #WebGestalt enrichment
  library(WebGestaltR)
  
  background <- ctwas_gene_res$genename
  
  #listGeneSet()
  databases <- c("pathway_KEGG", "disease_GLAD4U", "disease_OMIM")
  
  enrichResult <- WebGestaltR(enrichMethod="ORA", organism="hsapiens",
                              interestGene=genes, referenceGene=background,
                              enrichDatabase=databases, interestGeneType="genesymbol",
                              referenceGeneType="genesymbol", isOutput=F)
  print(enrichResult[,c("description", "size", "overlap", "FDR", "database", "userId")])
}

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] stats     graphics  grDevices utils     datasets  methods   base     

other attached packages:
[1] enrichR_3.0   cowplot_1.0.0 ggplot2_3.3.3

loaded via a namespace (and not attached):
 [1] Biobase_2.44.0              httr_1.4.1                 
 [3] bit64_4.0.5                 assertthat_0.2.1           
 [5] stats4_3.6.1                blob_1.2.1                 
 [7] BSgenome_1.52.0             GenomeInfoDbData_1.2.1     
 [9] Rsamtools_2.0.0             yaml_2.2.0                 
[11] progress_1.2.2              pillar_1.6.1               
[13] RSQLite_2.2.7               lattice_0.20-38            
[15] glue_1.4.2                  digest_0.6.20              
[17] GenomicRanges_1.36.0        promises_1.0.1             
[19] XVector_0.24.0              colorspace_1.4-1           
[21] htmltools_0.3.6             httpuv_1.5.1               
[23] Matrix_1.2-18               XML_3.98-1.20              
[25] pkgconfig_2.0.3             biomaRt_2.40.1             
[27] zlibbioc_1.30.0             purrr_0.3.4                
[29] scales_1.1.0                whisker_0.3-2              
[31] later_0.8.0                 BiocParallel_1.18.0        
[33] git2r_0.26.1                tibble_3.1.2               
[35] farver_2.1.0                generics_0.0.2             
[37] IRanges_2.18.1              ellipsis_0.3.2             
[39] withr_2.4.1                 cachem_1.0.5               
[41] SummarizedExperiment_1.14.1 GenomicFeatures_1.36.3     
[43] BiocGenerics_0.30.0         magrittr_2.0.1             
[45] crayon_1.4.1                memoise_2.0.0              
[47] evaluate_0.14               fs_1.3.1                   
[49] fansi_0.5.0                 tools_3.6.1                
[51] data.table_1.14.0           prettyunits_1.0.2          
[53] hms_1.1.0                   lifecycle_1.0.0            
[55] matrixStats_0.57.0          stringr_1.4.0              
[57] S4Vectors_0.22.1            munsell_0.5.0              
[59] DelayedArray_0.10.0         AnnotationDbi_1.46.0       
[61] Biostrings_2.52.0           compiler_3.6.1             
[63] GenomeInfoDb_1.20.0         rlang_0.4.11               
[65] grid_3.6.1                  RCurl_1.98-1.1             
[67] rjson_0.2.20                VariantAnnotation_1.30.1   
[69] labeling_0.3                bitops_1.0-6               
[71] rmarkdown_1.13              gtable_0.3.0               
[73] curl_3.3                    DBI_1.1.1                  
[75] R6_2.5.0                    GenomicAlignments_1.20.1   
[77] dplyr_1.0.7                 knitr_1.23                 
[79] rtracklayer_1.44.0          utf8_1.2.1                 
[81] fastmap_1.1.0               bit_4.0.4                  
[83] workflowr_1.6.2             rprojroot_2.0.2            
[85] stringi_1.4.3               parallel_3.6.1             
[87] Rcpp_1.0.6                  vctrs_0.3.8                
[89] tidyselect_1.1.0            xfun_0.8