Last updated: 2021-09-13
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Knit directory: ctwas_applied/
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File | Version | Author | Date | Message |
---|---|---|---|---|
Rmd | 72c8ef7 | wesleycrouse | 2021-09-13 | changing mart for biomart |
Rmd | a49c40e | wesleycrouse | 2021-09-13 | updating with bystander analysis |
html | 7e22565 | wesleycrouse | 2021-09-13 | updating reports |
Rmd | 3a7fbc1 | wesleycrouse | 2021-09-08 | generating reports for known annotations |
Rmd | cbf7408 | wesleycrouse | 2021-09-08 | adding enrichment to reports |
These are the results of a ctwas
analysis of the UK Biobank trait Glucose
using Adipose_Subcutaneous
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-30740_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 Adipose_Subcutaneous
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])
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] 12961
#number of imputed weights by chromosome
table(qclist_all$chr)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
1278 918 741 500 602 740 638 485 494 502 777 731 256 426 444
16 17 18 19 20 21 22
610 799 198 977 380 144 321
#proportion of imputed weights without missing variants
mean(qclist_all$nmiss==0)
[1] 0.7639843
#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$region_tag2, sep="_")
#load z scores for SNPs and collect sample size
load(paste0(results_dir, "/", analysis_id, "_expr_z_snp.Rd"))
sample_size <- z_snp$ss
sample_size <- as.numeric(names(which.max(table(sample_size))))
#compute PVE for each gene/SNP
ctwas_res$PVE = ctwas_res$susie_pip*ctwas_res$mu2/sample_size
#separate gene and SNP results
ctwas_gene_res <- ctwas_res[ctwas_res$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$gene), c("genename", "gene_type")])
#add z scores to results
load(paste0(results_dir, "/", analysis_id, "_expr_z_gene.Rd"))
ctwas_gene_res$z <- z_gene[ctwas_gene_res$id,]$z
z_snp <- z_snp[z_snp$id %in% ctwas_snp_res$id,]
ctwas_snp_res$z <- z_snp$z[match(ctwas_snp_res$id, z_snp$id)]
#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_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$type=="SNP")/thin
rm(ctwas_res_s1)
library(ggplot2)
library(cowplot)
********************************************************
Note: As of version 1.0.0, cowplot does not change the
default ggplot2 theme anymore. To recover the previous
behavior, execute:
theme_set(theme_cowplot())
********************************************************
load(paste0(results_dir, "/", analysis_id, "_ctwas.s2.susieIrssres.Rd"))
df <- data.frame(niter = rep(1:ncol(group_prior_rec), 2),
value = c(group_prior_rec[1,], group_prior_rec[2,]),
group = rep(c("Gene", "SNP"), each = ncol(group_prior_rec)))
df$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$group)
p_sigma2 <- ggplot(df, aes(x=niter, y=value, group=group)) +
geom_line(aes(color=group)) +
geom_point(aes(color=group)) +
xlab("Iteration") + ylab(bquote(sigma^2)) +
ggtitle("Prior variance") +
theme_cowplot()
plot_grid(p_pi, p_sigma2)
Version | Author | Date |
---|---|---|
7e22565 | wesleycrouse | 2021-09-13 |
#estimated group prior
estimated_group_prior <- group_prior_rec[,ncol(group_prior_rec)]
names(estimated_group_prior) <- c("gene", "snp")
estimated_group_prior["snp"] <- estimated_group_prior["snp"]*thin #adjust parameter to account for thin argument
print(estimated_group_prior)
gene snp
0.0131489668 0.0001435707
#estimated group prior variance
estimated_group_prior_var <- group_prior_var_rec[,ncol(group_prior_var_rec)]
names(estimated_group_prior_var) <- c("gene", "snp")
print(estimated_group_prior_var)
gene snp
10.71966 10.47239
#report sample size
print(sample_size)
[1] 314916
#report group size
group_size <- c(nrow(ctwas_gene_res), n_snps)
print(group_size)
[1] 12961 8696600
#estimated group PVE
estimated_group_pve <- estimated_group_prior_var*estimated_group_prior*group_size/sample_size #check PVE calculation
names(estimated_group_pve) <- c("gene", "snp")
print(estimated_group_pve)
gene snp
0.005801183 0.041520854
#compare sum(PIP*mu2/sample_size) with above PVE calculation
c(sum(ctwas_gene_res$PVE),sum(ctwas_snp_res$PVE))
[1] 0.02579552 0.27574421
#distribution of PIPs
hist(ctwas_gene_res$susie_pip, xlim=c(0,1), main="Distribution of Gene PIPs")
Version | Author | Date |
---|---|---|
7e22565 | wesleycrouse | 2021-09-13 |
#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
3633 CCND2 12_4 0.994 116.64 3.7e-04 -11.03
4200 PPDPF 20_37 0.987 26.32 8.3e-05 -5.04
11938 CHAMP1 13_62 0.979 28.90 9.0e-05 5.30
9666 CHD2 15_43 0.967 31.34 9.6e-05 -5.58
1237 CPNE3 8_62 0.966 26.16 8.0e-05 4.97
6954 ZFP36L2 2_27 0.957 80.13 2.4e-04 10.17
8836 FAM234A 16_1 0.943 50.88 1.5e-04 8.39
7223 NAT2 8_20 0.929 23.78 7.0e-05 -4.74
2816 MADD 11_29 0.911 33.39 9.7e-05 7.42
7048 JAZF1 7_23 0.908 35.74 1.0e-04 -6.09
6020 AKT1 14_55 0.859 20.40 5.6e-05 -4.14
6523 GIGYF1 7_62 0.843 38.89 1.0e-04 -6.95
66 FAM214B 9_27 0.831 21.22 5.6e-05 -4.20
3620 ABCG2 4_59 0.812 19.76 5.1e-05 -4.10
11303 C15orf52 15_14 0.788 23.00 5.8e-05 -4.41
1526 CWF19L1 10_64 0.766 20.81 5.1e-05 -4.18
92 ABCC8 11_12 0.742 19.98 4.7e-05 3.48
5790 WARS 14_52 0.734 24.11 5.6e-05 4.88
5881 MAP1LC3B 16_52 0.733 20.79 4.8e-05 3.96
7529 ACE 17_37 0.732 22.21 5.2e-05 4.42
#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 |
---|---|---|
7e22565 | wesleycrouse | 2021-09-13 |
#genes with 20 largest effect sizes
head(ctwas_gene_res[order(-ctwas_gene_res$mu2),report_cols],20)
genename region_tag susie_pip mu2 PVE z
6925 G6PC2 2_102 0.000 1201.61 1.3e-11 -40.22
6924 SPC25 2_102 0.000 131.08 4.0e-12 10.06
3633 CCND2 12_4 0.994 116.64 3.7e-04 -11.03
8011 RPL22L1 3_104 0.055 103.82 1.8e-05 10.33
3270 SNX17 2_16 0.096 96.74 2.9e-05 -9.53
2474 GCK 7_32 0.000 90.52 6.4e-11 14.68
3267 NRBP1 2_16 0.040 83.19 1.0e-05 -9.09
6954 ZFP36L2 2_27 0.957 80.13 2.4e-04 10.17
7920 NOSTRIN 2_102 0.000 70.08 1.4e-13 -8.43
14678 LINC00506 3_57 0.000 61.82 0.0e+00 -1.21
8941 FEN1 11_34 0.656 52.38 1.1e-04 7.56
11270 NCR3LG1 11_12 0.660 51.60 1.1e-04 -7.01
8836 FAM234A 16_1 0.943 50.88 1.5e-04 8.39
4388 RNF6 13_6 0.188 50.02 3.0e-05 7.67
3368 THADA 2_27 0.023 49.46 3.7e-06 7.66
4875 CDK8 13_6 0.184 47.29 2.8e-05 -6.42
8010 EIF5A2 3_104 0.016 46.29 2.4e-06 8.68
2476 YKT6 7_32 0.005 43.65 7.3e-07 11.82
12250 MANSC4 12_19 0.629 43.06 8.6e-05 -6.66
14659 LINC01126 2_27 0.014 42.87 2.0e-06 -6.91
#genes with 20 highest pve
head(ctwas_gene_res[order(-ctwas_gene_res$PVE),report_cols],20)
genename region_tag susie_pip mu2 PVE z
3633 CCND2 12_4 0.994 116.64 3.7e-04 -11.03
6954 ZFP36L2 2_27 0.957 80.13 2.4e-04 10.17
8836 FAM234A 16_1 0.943 50.88 1.5e-04 8.39
11270 NCR3LG1 11_12 0.660 51.60 1.1e-04 -7.01
8941 FEN1 11_34 0.656 52.38 1.1e-04 7.56
7048 JAZF1 7_23 0.908 35.74 1.0e-04 -6.09
6523 GIGYF1 7_62 0.843 38.89 1.0e-04 -6.95
2816 MADD 11_29 0.911 33.39 9.7e-05 7.42
9666 CHD2 15_43 0.967 31.34 9.6e-05 -5.58
12080 RNF5 6_26 0.709 40.82 9.2e-05 -6.52
11938 CHAMP1 13_62 0.979 28.90 9.0e-05 5.30
12250 MANSC4 12_19 0.629 43.06 8.6e-05 -6.66
4200 PPDPF 20_37 0.987 26.32 8.3e-05 -5.04
3652 CTNNAL1 9_56 0.701 36.37 8.1e-05 -5.88
1237 CPNE3 8_62 0.966 26.16 8.0e-05 4.97
9852 ARHGAP1 11_28 0.559 39.99 7.1e-05 -6.18
7223 NAT2 8_20 0.929 23.78 7.0e-05 -4.74
10743 AIFM3 22_4 0.706 28.47 6.4e-05 -4.76
7490 UBE2Z 17_28 0.580 33.80 6.2e-05 -5.77
11303 C15orf52 15_14 0.788 23.00 5.8e-05 -4.41
#genes with 20 largest z scores
head(ctwas_gene_res[order(-abs(ctwas_gene_res$z)),report_cols],20)
genename region_tag susie_pip mu2 PVE z
6925 G6PC2 2_102 0.000 1201.61 1.3e-11 -40.22
2474 GCK 7_32 0.000 90.52 6.4e-11 14.68
2476 YKT6 7_32 0.005 43.65 7.3e-07 11.82
3633 CCND2 12_4 0.994 116.64 3.7e-04 -11.03
8011 RPL22L1 3_104 0.055 103.82 1.8e-05 10.33
6954 ZFP36L2 2_27 0.957 80.13 2.4e-04 10.17
6924 SPC25 2_102 0.000 131.08 4.0e-12 10.06
3270 SNX17 2_16 0.096 96.74 2.9e-05 -9.53
3267 NRBP1 2_16 0.040 83.19 1.0e-05 -9.09
8010 EIF5A2 3_104 0.016 46.29 2.4e-06 8.68
7920 NOSTRIN 2_102 0.000 70.08 1.4e-13 -8.43
8836 FAM234A 16_1 0.943 50.88 1.5e-04 8.39
10698 FAM46C 1_72 0.450 35.86 5.1e-05 7.73
4388 RNF6 13_6 0.188 50.02 3.0e-05 7.67
3368 THADA 2_27 0.023 49.46 3.7e-06 7.66
8941 FEN1 11_34 0.656 52.38 1.1e-04 7.56
2816 MADD 11_29 0.911 33.39 9.7e-05 7.42
4009 KBTBD4 11_29 0.019 34.04 2.0e-06 -7.05
11270 NCR3LG1 11_12 0.660 51.60 1.1e-04 -7.01
6523 GIGYF1 7_62 0.843 38.89 1.0e-04 -6.95
#set nominal signifiance threshold for z scores
alpha <- 0.05
#bonferroni adjusted threshold for z scores
sig_thresh <- qnorm(1-(alpha/nrow(ctwas_gene_res)/2), lower=T)
#Q-Q plot for z scores
obs_z <- ctwas_gene_res$z[order(ctwas_gene_res$z)]
exp_z <- qnorm((1:nrow(ctwas_gene_res))/nrow(ctwas_gene_res))
plot(exp_z, obs_z, xlab="Expected z", ylab="Observed z", main="Gene z score Q-Q plot")
abline(a=0,b=1)
Version | Author | Date |
---|---|---|
7e22565 | wesleycrouse | 2021-09-13 |
#plot z score vs PIP
plot(abs(ctwas_gene_res$z), ctwas_gene_res$susie_pip, xlab="abs(z)", ylab="PIP")
abline(v=sig_thresh, col="red", lty=2)
Version | Author | Date |
---|---|---|
7e22565 | wesleycrouse | 2021-09-13 |
#proportion of significant z scores
mean(abs(ctwas_gene_res$z) > sig_thresh)
[1] 0.006712445
#genes with most significant z scores
head(ctwas_gene_res[order(-abs(ctwas_gene_res$z)),report_cols],20)
genename region_tag susie_pip mu2 PVE z
6925 G6PC2 2_102 0.000 1201.61 1.3e-11 -40.22
2474 GCK 7_32 0.000 90.52 6.4e-11 14.68
2476 YKT6 7_32 0.005 43.65 7.3e-07 11.82
3633 CCND2 12_4 0.994 116.64 3.7e-04 -11.03
8011 RPL22L1 3_104 0.055 103.82 1.8e-05 10.33
6954 ZFP36L2 2_27 0.957 80.13 2.4e-04 10.17
6924 SPC25 2_102 0.000 131.08 4.0e-12 10.06
3270 SNX17 2_16 0.096 96.74 2.9e-05 -9.53
3267 NRBP1 2_16 0.040 83.19 1.0e-05 -9.09
8010 EIF5A2 3_104 0.016 46.29 2.4e-06 8.68
7920 NOSTRIN 2_102 0.000 70.08 1.4e-13 -8.43
8836 FAM234A 16_1 0.943 50.88 1.5e-04 8.39
10698 FAM46C 1_72 0.450 35.86 5.1e-05 7.73
4388 RNF6 13_6 0.188 50.02 3.0e-05 7.67
3368 THADA 2_27 0.023 49.46 3.7e-06 7.66
8941 FEN1 11_34 0.656 52.38 1.1e-04 7.56
2816 MADD 11_29 0.911 33.39 9.7e-05 7.42
4009 KBTBD4 11_29 0.019 34.04 2.0e-06 -7.05
11270 NCR3LG1 11_12 0.660 51.60 1.1e-04 -7.01
6523 GIGYF1 7_62 0.843 38.89 1.0e-04 -6.95
ctwas_gene_res_sortz <- ctwas_gene_res[order(-abs(ctwas_gene_res$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: 2_102"
genename region_tag susie_pip mu2 PVE z
7920 NOSTRIN 2_102 0 70.08 1.4e-13 -8.43
6924 SPC25 2_102 0 131.08 4.0e-12 10.06
6925 G6PC2 2_102 0 1201.61 1.3e-11 -40.22
Version | Author | Date |
---|---|---|
7e22565 | wesleycrouse | 2021-09-13 |
[1] "Region: 7_32"
genename region_tag susie_pip mu2 PVE z
17 HECW1 7_32 0.000 8.59 5.1e-12 2.49
2465 COA1 7_32 0.000 20.57 7.3e-11 -2.05
2466 BLVRA 7_32 0.000 5.58 2.4e-12 -1.26
627 MRPS24 7_32 0.000 12.24 1.4e-11 0.07
1072 UBE2D4 7_32 0.000 39.47 1.7e-11 -6.85
2467 URGCP 7_32 0.000 18.44 2.6e-11 1.49
12733 AC004951.6 7_32 0.000 9.17 4.2e-12 -0.37
12967 LINC00957 7_32 0.000 7.13 3.4e-12 2.46
3938 POLM 7_32 0.000 8.05 4.5e-12 -1.05
2472 POLD2 7_32 0.000 25.22 1.3e-10 3.04
2474 GCK 7_32 0.000 90.52 6.4e-11 14.68
2476 YKT6 7_32 0.005 43.65 7.3e-07 11.82
270 NUDCD3 7_32 0.000 12.17 7.0e-12 -1.53
268 NPC1L1 7_32 0.000 14.68 2.2e-11 -0.43
5285 DDX56 7_32 0.000 12.88 1.3e-11 1.54
7441 TMED4 7_32 0.000 16.32 2.8e-11 1.42
2384 OGDH 7_32 0.000 25.61 1.6e-10 -2.17
Version | Author | Date |
---|---|---|
7e22565 | wesleycrouse | 2021-09-13 |
[1] "Region: 12_4"
genename region_tag susie_pip mu2 PVE z
4562 CRACR2A 12_4 0.010 8.32 2.6e-07 1.13
2871 PARP11 12_4 0.011 8.64 3.0e-07 1.04
3633 CCND2 12_4 0.994 116.64 3.7e-04 -11.03
Version | Author | Date |
---|---|---|
7e22565 | wesleycrouse | 2021-09-13 |
[1] "Region: 3_104"
genename region_tag susie_pip mu2 PVE z
13155 LINC02082 3_104 0.015 9.14 4.5e-07 1.08
14310 RP11-368I23.3 3_104 0.009 4.61 1.3e-07 0.14
10810 ACTRT3 3_104 0.015 9.70 4.5e-07 1.50
9407 LRRC34 3_104 0.100 26.10 8.3e-06 -2.45
173 SEC62 3_104 0.010 6.33 2.1e-07 -0.96
9702 GPR160 3_104 0.009 5.43 1.6e-07 -0.78
9701 PHC3 3_104 0.011 5.86 2.0e-07 -0.03
8004 PRKCI 3_104 0.009 6.14 1.8e-07 1.46
242 CLDN11 3_104 0.010 4.90 1.5e-07 -0.22
8011 RPL22L1 3_104 0.055 103.82 1.8e-05 10.33
8010 EIF5A2 3_104 0.016 46.29 2.4e-06 8.68
Version | Author | Date |
---|---|---|
7e22565 | wesleycrouse | 2021-09-13 |
[1] "Region: 2_27"
genename region_tag susie_pip mu2 PVE z
6954 ZFP36L2 2_27 0.957 80.13 2.4e-04 10.17
14659 LINC01126 2_27 0.014 42.87 2.0e-06 -6.91
3368 THADA 2_27 0.023 49.46 3.7e-06 7.66
12562 C1GALT1C1L 2_27 0.013 4.62 1.9e-07 -0.10
6956 PLEKHH2 2_27 0.016 5.83 2.9e-07 0.45
5539 DYNC2LI1 2_27 0.037 15.07 1.8e-06 -2.00
5552 LRPPRC 2_27 0.021 8.94 6.1e-07 -1.16
Version | Author | Date |
---|---|---|
7e22565 | wesleycrouse | 2021-09-13 |
#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
54769 rs79687284 1_109 1.000 110.51 3.5e-04 -12.08
75841 rs780093 2_16 1.000 187.59 6.0e-04 -14.95
81780 rs2121564 2_28 1.000 59.90 1.9e-04 -8.01
166409 rs148685409 3_57 1.000 853.37 2.7e-03 2.99
176521 rs72964564 3_76 1.000 235.76 7.5e-04 16.88
196568 rs4234603 3_115 1.000 39.15 1.2e-04 -5.05
322828 rs76623841 6_7 1.000 56.94 1.8e-04 6.80
385777 rs10225316 7_15 1.000 45.08 1.4e-04 -7.51
395269 rs138917529 7_32 1.000 78.08 2.5e-04 10.45
434650 rs7012814 8_12 1.000 62.58 2.0e-04 9.18
528687 rs61856594 10_33 1.000 38.34 1.2e-04 6.23
548498 rs12244851 10_70 1.000 291.83 9.3e-04 -16.46
556804 rs3842727 11_3 1.000 99.24 3.1e-04 8.57
559533 rs3750952 11_6 1.000 52.60 1.7e-04 7.40
644589 rs576674 13_11 1.000 104.18 3.3e-04 10.82
692315 rs35889227 14_45 1.000 115.48 3.7e-04 11.34
869379 rs2232318 2_102 1.000 118.88 3.8e-04 -2.07
869385 rs560887 2_102 1.000 2693.07 8.6e-03 -57.71
869395 rs71397670 2_102 1.000 839.32 2.7e-03 -42.67
114580 rs12692596 2_96 0.999 45.79 1.5e-04 -7.24
287368 rs12189028 5_45 0.999 33.95 1.1e-04 5.08
477622 rs10758593 9_4 0.999 70.73 2.2e-04 -8.64
54778 rs3754140 1_109 0.998 57.31 1.8e-04 10.01
235039 rs11728350 4_69 0.998 42.34 1.3e-04 -6.68
510433 rs115478735 9_70 0.997 81.69 2.6e-04 -9.52
754067 rs28489441 17_15 0.997 32.27 1.0e-04 5.83
810592 rs34783010 19_32 0.995 32.77 1.0e-04 6.40
322847 rs55792466 6_7 0.994 97.58 3.1e-04 9.67
484862 rs572168822 9_16 0.993 40.97 1.3e-04 6.61
658936 rs1327315 13_40 0.992 34.72 1.1e-04 7.02
869466 rs56100844 2_102 0.991 152.72 4.8e-04 17.86
635707 rs4765221 12_76 0.989 33.47 1.1e-04 -5.80
395249 rs17769733 7_32 0.986 132.27 4.1e-04 7.76
547950 rs11195508 10_70 0.986 60.78 1.9e-04 10.76
556809 rs10743152 11_3 0.983 39.26 1.2e-04 -1.91
411852 rs4729755 7_63 0.982 26.37 8.2e-05 -4.96
475580 rs4977218 8_94 0.975 29.86 9.2e-05 5.34
484857 rs1333045 9_16 0.975 40.69 1.3e-04 -6.62
702978 rs12912777 15_13 0.974 25.21 7.8e-05 -3.77
627206 rs6538805 12_58 0.973 31.92 9.9e-05 6.74
755 rs60330317 1_2 0.968 36.62 1.1e-04 6.18
34659 rs893230 1_72 0.968 39.62 1.2e-04 7.56
642899 rs60353775 13_7 0.968 82.20 2.5e-04 -9.78
191411 rs10653660 3_104 0.967 346.87 1.1e-03 23.54
174555 rs9875598 3_73 0.962 27.15 8.3e-05 5.10
466327 rs4433184 8_78 0.960 52.39 1.6e-04 -4.78
395261 rs10259649 7_32 0.949 396.06 1.2e-03 -28.65
511723 rs28624681 9_73 0.941 51.50 1.5e-04 -7.55
169326 rs62276527 3_63 0.938 33.19 9.9e-05 -5.85
699455 rs35767992 15_4 0.936 24.57 7.3e-05 -4.72
571437 rs117396352 11_28 0.930 27.38 8.1e-05 -4.93
832926 rs6026545 20_34 0.928 31.93 9.4e-05 -5.72
755576 rs543720569 17_18 0.924 44.21 1.3e-04 7.03
454682 rs10957704 8_54 0.923 24.50 7.2e-05 -4.68
796901 rs10410896 19_5 0.917 27.00 7.9e-05 -5.04
560955 rs34718245 11_9 0.916 32.22 9.4e-05 5.37
710385 rs11637069 15_29 0.913 28.11 8.2e-05 -5.00
574641 rs7941126 11_36 0.911 31.41 9.1e-05 5.63
572457 rs182512331 11_31 0.899 27.53 7.9e-05 5.05
561887 rs117720468 11_11 0.890 44.43 1.3e-04 -6.82
336539 rs62396405 6_31 0.887 25.89 7.3e-05 4.78
287429 rs6887019 5_45 0.886 26.51 7.5e-05 -5.23
359059 rs118126621 6_73 0.881 25.14 7.0e-05 -4.67
638739 rs1882297 12_82 0.875 38.50 1.1e-04 -6.47
793684 rs41404946 18_44 0.870 24.21 6.7e-05 -4.56
572039 rs139913257 11_30 0.857 31.37 8.5e-05 5.63
659287 rs79317015 13_40 0.840 24.30 6.5e-05 -4.40
365537 rs112388031 6_87 0.838 26.15 7.0e-05 4.65
154838 rs3172494 3_34 0.837 26.99 7.2e-05 5.09
257174 rs62332172 4_113 0.833 24.67 6.5e-05 -4.54
19026 rs6699568 1_42 0.827 27.21 7.1e-05 -5.02
397605 rs11763778 7_36 0.817 41.83 1.1e-04 7.61
116081 rs112308555 2_103 0.815 24.92 6.4e-05 -4.32
196108 rs73185688 3_114 0.807 25.15 6.4e-05 -4.69
605021 rs12582270 12_17 0.806 25.76 6.6e-05 4.72
576671 rs11603349 11_41 0.805 44.79 1.1e-04 6.78
#plot PIP vs effect size
plot(ctwas_snp_res$susie_pip, ctwas_snp_res$mu2, xlab="PIP", ylab="mu^2", main="SNP PIPs vs Effect Size")
Version | Author | Date |
---|---|---|
7e22565 | wesleycrouse | 2021-09-13 |
#SNPs with 50 largest effect sizes
head(ctwas_snp_res[order(-ctwas_snp_res$mu2),report_cols_snps],50)
id region_tag susie_pip mu2 PVE z
869385 rs560887 2_102 1.000 2693.07 8.6e-03 -57.71
869374 rs573225 2_102 0.000 2299.86 5.9e-11 -54.23
869362 rs13431652 2_102 0.000 2198.87 1.1e-10 53.00
869519 rs853787 2_102 0.004 2158.94 2.4e-05 -53.06
869516 rs853789 2_102 0.003 2155.95 2.1e-05 -53.04
869546 rs853777 2_102 0.002 2121.19 1.2e-05 -52.75
869411 rs537183 2_102 0.000 2098.86 1.8e-09 -52.66
869409 rs563694 2_102 0.000 2093.73 1.8e-09 -52.60
869434 rs557462 2_102 0.000 2093.31 1.7e-09 -52.60
869413 rs502570 2_102 0.000 2061.83 1.3e-09 -52.14
869427 rs475612 2_102 0.000 2050.99 5.8e-10 -52.14
869430 rs518598 2_102 0.000 2050.44 5.8e-10 -52.13
869423 rs578763 2_102 0.000 2047.87 7.2e-10 -52.08
869418 rs580670 2_102 0.000 2036.60 6.2e-10 -51.95
869462 rs508506 2_102 0.000 1988.79 3.4e-09 -51.54
869453 rs569829 2_102 0.000 1985.83 2.9e-09 -51.52
869474 rs494874 2_102 0.000 1985.61 4.0e-09 -51.48
869481 rs552976 2_102 0.000 1977.83 3.9e-09 -51.36
869420 rs580613 2_102 0.000 1977.14 4.8e-10 -51.23
869419 rs580639 2_102 0.000 1963.41 1.4e-09 -51.53
869449 rs486981 2_102 0.000 1945.21 1.1e-09 -51.05
869450 rs485094 2_102 0.000 1943.80 1.1e-09 -51.04
869456 rs566879 2_102 0.000 1942.59 1.0e-09 -51.03
869455 rs579060 2_102 0.000 1940.45 1.0e-09 -51.00
869454 rs569805 2_102 0.000 1937.19 1.1e-09 -50.95
869432 rs796703396 2_102 0.000 1857.75 4.8e-12 -49.98
869407 rs504979 2_102 0.000 1785.37 4.4e-12 -49.37
869451 rs484066 2_102 0.000 1717.34 2.8e-12 -48.49
869525 rs71397677 2_102 0.000 1661.43 1.0e-10 -47.29
869364 rs12475700 2_102 0.000 1322.20 2.4e-14 -38.64
869494 rs2544360 2_102 0.000 1286.73 1.7e-11 -39.60
869490 rs508743 2_102 0.000 1282.53 1.1e-11 39.58
869521 rs862662 2_102 0.000 1273.92 1.0e-11 -39.50
869493 rs79933700 2_102 0.000 1273.37 8.8e-12 39.46
869540 rs1101532 2_102 0.000 1268.64 1.2e-11 -39.54
869500 rs2685807 2_102 0.000 1259.72 7.9e-12 -39.24
869514 rs853791 2_102 0.000 1255.90 6.5e-12 -39.21
869511 rs2250677 2_102 0.000 1250.19 5.6e-12 -39.12
869472 rs531772 2_102 0.000 1234.27 7.6e-13 -38.74
869549 rs853775 2_102 0.000 1234.14 5.0e-12 -39.04
869445 rs575671 2_102 0.000 1229.97 6.6e-13 -38.66
869486 rs567074 2_102 0.000 1227.64 2.1e-12 38.66
869443 rs473351 2_102 0.000 1223.97 5.9e-13 -38.57
869530 rs853781 2_102 0.000 1212.94 2.2e-12 -38.77
869529 rs853782 2_102 0.000 1210.48 2.0e-12 -38.75
869425 rs500432 2_102 0.000 1205.74 9.9e-14 -37.99
869551 rs853773 2_102 0.000 1201.04 4.1e-11 -39.87
869518 rs853788 2_102 0.000 1124.29 1.1e-13 -37.47
869539 rs35351007 2_102 0.000 1123.25 2.8e-13 -37.70
869522 rs853785 2_102 0.000 1122.24 9.8e-14 -37.45
#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
869385 rs560887 2_102 1.000 2693.07 0.00860 -57.71
166409 rs148685409 3_57 1.000 853.37 0.00270 2.99
869395 rs71397670 2_102 1.000 839.32 0.00270 -42.67
869387 rs492594 2_102 0.764 795.31 0.00190 -17.82
166411 rs1436648 3_57 0.505 875.28 0.00140 3.09
166412 rs7619398 3_57 0.518 875.49 0.00140 3.08
395274 rs917793 7_32 0.582 704.38 0.00130 -33.28
395261 rs10259649 7_32 0.949 396.06 0.00120 -28.65
191411 rs10653660 3_104 0.967 346.87 0.00110 23.54
166413 rs2256473 3_57 0.367 874.83 0.00100 3.06
548498 rs12244851 10_70 1.000 291.83 0.00093 -16.46
166410 rs2575789 3_57 0.314 874.71 0.00087 3.06
176521 rs72964564 3_76 1.000 235.76 0.00075 16.88
75841 rs780093 2_16 1.000 187.59 0.00060 -14.95
395278 rs2908282 7_32 0.258 702.30 0.00057 -33.26
869466 rs56100844 2_102 0.991 152.72 0.00048 17.86
385837 rs1974619 7_15 0.606 241.15 0.00046 -16.89
395249 rs17769733 7_32 0.986 132.27 0.00041 7.76
869379 rs2232318 2_102 1.000 118.88 0.00038 -2.07
692315 rs35889227 14_45 1.000 115.48 0.00037 11.34
869391 rs567243 2_102 0.145 797.22 0.00037 -17.95
395268 rs4607517 7_32 0.160 702.26 0.00036 -33.23
54769 rs79687284 1_109 1.000 110.51 0.00035 -12.08
644589 rs576674 13_11 1.000 104.18 0.00033 10.82
322847 rs55792466 6_7 0.994 97.58 0.00031 9.67
556804 rs3842727 11_3 1.000 99.24 0.00031 8.57
510433 rs115478735 9_70 0.997 81.69 0.00026 -9.52
395269 rs138917529 7_32 1.000 78.08 0.00025 10.45
642899 rs60353775 13_7 0.968 82.20 0.00025 -9.78
869390 rs570876 2_102 0.090 796.62 0.00023 -18.01
477622 rs10758593 9_4 0.999 70.73 0.00022 -8.64
292632 rs17085655 5_57 0.547 118.27 0.00021 11.48
916610 rs11039165 11_29 0.653 101.61 0.00021 11.82
434650 rs7012814 8_12 1.000 62.58 0.00020 9.18
81780 rs2121564 2_28 1.000 59.90 0.00019 -8.01
547950 rs11195508 10_70 0.986 60.78 0.00019 10.76
54778 rs3754140 1_109 0.998 57.31 0.00018 10.01
322828 rs76623841 6_7 1.000 56.94 0.00018 6.80
548492 rs117764423 10_70 0.726 76.01 0.00018 5.24
385835 rs10228796 7_15 0.221 238.64 0.00017 -16.82
559533 rs3750952 11_6 1.000 52.60 0.00017 7.40
261258 rs12499544 4_119 0.723 67.95 0.00016 8.39
466327 rs4433184 8_78 0.960 52.39 0.00016 -4.78
823488 rs111405491 20_16 0.674 74.16 0.00016 8.97
114580 rs12692596 2_96 0.999 45.79 0.00015 -7.24
327439 rs2206734 6_15 0.740 64.95 0.00015 -8.26
466351 rs28529793 8_78 0.688 69.90 0.00015 6.80
511723 rs28624681 9_73 0.941 51.50 0.00015 -7.55
385777 rs10225316 7_15 1.000 45.08 0.00014 -7.51
235039 rs11728350 4_69 0.998 42.34 0.00013 -6.68
#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
869385 rs560887 2_102 1.000 2693.07 8.6e-03 -57.71
869374 rs573225 2_102 0.000 2299.86 5.9e-11 -54.23
869519 rs853787 2_102 0.004 2158.94 2.4e-05 -53.06
869516 rs853789 2_102 0.003 2155.95 2.1e-05 -53.04
869362 rs13431652 2_102 0.000 2198.87 1.1e-10 53.00
869546 rs853777 2_102 0.002 2121.19 1.2e-05 -52.75
869411 rs537183 2_102 0.000 2098.86 1.8e-09 -52.66
869409 rs563694 2_102 0.000 2093.73 1.8e-09 -52.60
869434 rs557462 2_102 0.000 2093.31 1.7e-09 -52.60
869413 rs502570 2_102 0.000 2061.83 1.3e-09 -52.14
869427 rs475612 2_102 0.000 2050.99 5.8e-10 -52.14
869430 rs518598 2_102 0.000 2050.44 5.8e-10 -52.13
869423 rs578763 2_102 0.000 2047.87 7.2e-10 -52.08
869418 rs580670 2_102 0.000 2036.60 6.2e-10 -51.95
869462 rs508506 2_102 0.000 1988.79 3.4e-09 -51.54
869419 rs580639 2_102 0.000 1963.41 1.4e-09 -51.53
869453 rs569829 2_102 0.000 1985.83 2.9e-09 -51.52
869474 rs494874 2_102 0.000 1985.61 4.0e-09 -51.48
869481 rs552976 2_102 0.000 1977.83 3.9e-09 -51.36
869420 rs580613 2_102 0.000 1977.14 4.8e-10 -51.23
869449 rs486981 2_102 0.000 1945.21 1.1e-09 -51.05
869450 rs485094 2_102 0.000 1943.80 1.1e-09 -51.04
869456 rs566879 2_102 0.000 1942.59 1.0e-09 -51.03
869455 rs579060 2_102 0.000 1940.45 1.0e-09 -51.00
869454 rs569805 2_102 0.000 1937.19 1.1e-09 -50.95
869432 rs796703396 2_102 0.000 1857.75 4.8e-12 -49.98
869407 rs504979 2_102 0.000 1785.37 4.4e-12 -49.37
869451 rs484066 2_102 0.000 1717.34 2.8e-12 -48.49
869525 rs71397677 2_102 0.000 1661.43 1.0e-10 -47.29
869395 rs71397670 2_102 1.000 839.32 2.7e-03 -42.67
869551 rs853773 2_102 0.000 1201.04 4.1e-11 -39.87
869494 rs2544360 2_102 0.000 1286.73 1.7e-11 -39.60
869490 rs508743 2_102 0.000 1282.53 1.1e-11 39.58
869540 rs1101532 2_102 0.000 1268.64 1.2e-11 -39.54
869521 rs862662 2_102 0.000 1273.92 1.0e-11 -39.50
869493 rs79933700 2_102 0.000 1273.37 8.8e-12 39.46
869500 rs2685807 2_102 0.000 1259.72 7.9e-12 -39.24
869514 rs853791 2_102 0.000 1255.90 6.5e-12 -39.21
869511 rs2250677 2_102 0.000 1250.19 5.6e-12 -39.12
869549 rs853775 2_102 0.000 1234.14 5.0e-12 -39.04
869530 rs853781 2_102 0.000 1212.94 2.2e-12 -38.77
869529 rs853782 2_102 0.000 1210.48 2.0e-12 -38.75
869472 rs531772 2_102 0.000 1234.27 7.6e-13 -38.74
869445 rs575671 2_102 0.000 1229.97 6.6e-13 -38.66
869486 rs567074 2_102 0.000 1227.64 2.1e-12 38.66
869364 rs12475700 2_102 0.000 1322.20 2.4e-14 -38.64
869443 rs473351 2_102 0.000 1223.97 5.9e-13 -38.57
869425 rs500432 2_102 0.000 1205.74 9.9e-14 -37.99
869539 rs35351007 2_102 0.000 1123.25 2.8e-13 -37.70
869542 rs853778 2_102 0.000 1112.85 7.9e-14 -37.54
#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] 14
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")])
}
Uploading data to Enrichr... Done.
Querying GO_Biological_Process_2021... Done.
Querying GO_Cellular_Component_2021... Done.
Querying GO_Molecular_Function_2021... Done.
Parsing results... Done.
[1] "GO_Biological_Process_2021"
Term
1 insulin-like growth factor receptor signaling pathway (GO:0048009)
2 positive regulation of cyclin-dependent protein serine/threonine kinase activity (GO:0045737)
3 positive regulation of cyclin-dependent protein kinase activity (GO:1904031)
4 positive regulation of G1/S transition of mitotic cell cycle (GO:1900087)
5 cellular response to growth factor stimulus (GO:0071363)
6 positive regulation of cell cycle G1/S phase transition (GO:1902808)
7 response to growth factor (GO:0070848)
8 positive regulation of mitotic cell cycle phase transition (GO:1901992)
9 ERBB signaling pathway (GO:0038127)
10 positive regulation of cell cycle (GO:0045787)
11 regulation of G1/S transition of mitotic cell cycle (GO:2000045)
12 regulation of fat cell differentiation (GO:0045598)
13 regulation of cyclin-dependent protein serine/threonine kinase activity (GO:0000079)
14 positive regulation of protein serine/threonine kinase activity (GO:0071902)
15 response to tumor necrosis factor (GO:0034612)
16 regulation of protein serine/threonine kinase activity (GO:0071900)
17 regulation of mRNA catabolic process (GO:0061013)
18 positive regulation of deoxyribonuclease activity (GO:0032077)
19 cellular response to metal ion (GO:0071248)
20 cellular response to granulocyte macrophage colony-stimulating factor stimulus (GO:0097011)
21 regulation of long-chain fatty acid import across plasma membrane (GO:0010746)
22 response to granulocyte macrophage colony-stimulating factor (GO:0097012)
23 positive regulation of I-kappaB phosphorylation (GO:1903721)
24 xenobiotic transport across blood-brain barrier (GO:1990962)
25 regulation of mRNA stability (GO:0043488)
26 regulation of Rab protein signal transduction (GO:0032483)
27 cellular response to interleukin-18 (GO:0071351)
28 negative regulation of cell cycle phase transition (GO:1901988)
29 sphingosine-1-phosphate receptor signaling pathway (GO:0003376)
30 regulation of I-kappaB phosphorylation (GO:1903719)
31 T cell apoptotic process (GO:0070231)
32 definitive hemopoiesis (GO:0060216)
33 interleukin-18-mediated signaling pathway (GO:0035655)
34 positive regulation of mitochondrial membrane potential (GO:0010918)
35 mammary gland epithelial cell differentiation (GO:0060644)
36 negative regulation of fatty acid oxidation (GO:0046322)
37 regulation of endodeoxyribonuclease activity (GO:0032071)
38 protein localization to microtubule (GO:0035372)
39 protein localization to microtubule cytoskeleton (GO:0072698)
40 regulation of glucan biosynthetic process (GO:0010962)
41 anoikis (GO:0043276)
42 glycerolipid biosynthetic process (GO:0045017)
43 positive regulation of membrane potential (GO:0045838)
44 cellular response to oxidised low-density lipoprotein particle stimulus (GO:0140052)
45 negative regulation of transmembrane transport (GO:0034763)
46 regulation of type B pancreatic cell development (GO:2000074)
47 T cell homeostasis (GO:0043029)
48 tetrahydrobiopterin metabolic process (GO:0046146)
49 regulation of lymphocyte migration (GO:2000401)
50 urate metabolic process (GO:0046415)
51 negative regulation of lymphocyte migration (GO:2000402)
52 cellular response to tumor necrosis factor (GO:0071356)
53 regulation of programmed cell death (GO:0043067)
54 regulation of glycogen metabolic process (GO:0070873)
55 regulation of leukocyte cell-cell adhesion (GO:1903037)
56 attachment of mitotic spindle microtubules to kinetochore (GO:0051315)
57 protein localization to condensed chromosome (GO:1903083)
58 negative regulation of stem cell differentiation (GO:2000737)
59 pteridine-containing compound metabolic process (GO:0042558)
60 positive regulation of cellular carbohydrate metabolic process (GO:0010676)
61 negative regulation of mononuclear cell migration (GO:0071676)
62 protein localization to mitochondrion (GO:0070585)
63 positive regulation of protein modification process (GO:0031401)
64 regulation of fatty acid beta-oxidation (GO:0031998)
65 T cell differentiation in thymus (GO:0033077)
66 positive regulation of glucose metabolic process (GO:0010907)
67 positive regulation of glycogen biosynthetic process (GO:0045725)
68 response to UV-A (GO:0070141)
69 protein localization to kinetochore (GO:0034501)
70 positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay (GO:1900153)
71 mammary gland epithelium development (GO:0061180)
72 nitric oxide biosynthetic process (GO:0006809)
73 positive regulation of glycogen metabolic process (GO:0070875)
74 regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay (GO:1900151)
75 3'-UTR-mediated mRNA destabilization (GO:0061158)
76 nitric oxide metabolic process (GO:0046209)
77 positive regulation of small molecule metabolic process (GO:0062013)
78 transepithelial transport (GO:0070633)
79 heme catabolic process (GO:0042167)
80 porphyrin-containing compound catabolic process (GO:0006787)
81 cellular response to corticosteroid stimulus (GO:0071384)
82 negative regulation of release of cytochrome c from mitochondria (GO:0090201)
83 protein localization to chromosome, centromeric region (GO:0071459)
84 cellular response to glucocorticoid stimulus (GO:0071385)
85 positive regulation of nitric-oxide synthase activity (GO:0051000)
86 regulation of B cell differentiation (GO:0045577)
87 negative regulation of leukocyte cell-cell adhesion (GO:1903038)
88 negative regulation of lipid catabolic process (GO:0050995)
89 regulation of oxidative stress-induced intrinsic apoptotic signaling pathway (GO:1902175)
90 cell migration involved in sprouting angiogenesis (GO:0002042)
91 positive regulation of phosphorylation (GO:0042327)
92 excitatory postsynaptic potential (GO:0060079)
93 maintenance of protein localization in organelle (GO:0072595)
94 diol metabolic process (GO:0034311)
95 negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway (GO:1902176)
96 regulation of apoptotic process (GO:0042981)
97 regulation of lymphocyte differentiation (GO:0045619)
98 xenobiotic transport (GO:0042908)
99 regulation of protein phosphorylation (GO:0001932)
100 cellular response to nerve growth factor stimulus (GO:1990090)
101 heme biosynthetic process (GO:0006783)
102 negative regulation of signal transduction in absence of ligand (GO:1901099)
103 ERK1 and ERK2 cascade (GO:0070371)
104 negative regulation of extrinsic apoptotic signaling pathway in absence of ligand (GO:2001240)
105 blood vessel endothelial cell migration (GO:0043534)
106 regulation of monooxygenase activity (GO:0032768)
107 protein kinase B signaling (GO:0043491)
108 porphyrin-containing compound biosynthetic process (GO:0006779)
109 chemical synaptic transmission, postsynaptic (GO:0099565)
110 positive regulation of ERBB signaling pathway (GO:1901186)
111 positive regulation of lipid metabolic process (GO:0045834)
112 regulation of glycogen biosynthetic process (GO:0005979)
113 TOR signaling (GO:0031929)
114 positive regulation of glucose import (GO:0046326)
115 negative regulation of macroautophagy (GO:0016242)
116 positive regulation of nitric oxide biosynthetic process (GO:0045429)
117 response to glucocorticoid (GO:0051384)
118 cellular response to cadmium ion (GO:0071276)
119 regulation of extrinsic apoptotic signaling pathway in absence of ligand (GO:2001239)
120 positive regulation of nitric oxide metabolic process (GO:1904407)
121 amide transport (GO:0042886)
122 sulfur compound transport (GO:0072348)
123 regulation of B cell activation (GO:0050864)
124 negative regulation of oxidative stress-induced cell death (GO:1903202)
125 regulation of plasma membrane bounded cell projection organization (GO:0120035)
126 positive regulation of monooxygenase activity (GO:0032770)
127 cellular response to epidermal growth factor stimulus (GO:0071364)
Overlap Adjusted.P.value Genes
1 2/11 0.008103861 GIGYF1;AKT1
2 2/17 0.009298289 CCND2;AKT1
3 2/20 0.009298289 CCND2;AKT1
4 2/26 0.010736217 CCND2;AKT1
5 3/158 0.010736217 AKT1;CPNE3;ZFP36L2
6 2/35 0.014472206 CCND2;AKT1
7 2/41 0.017054687 AKT1;CPNE3
8 2/58 0.029878625 CCND2;AKT1
9 2/66 0.030918376 AKT1;CPNE3
10 2/66 0.030918376 CCND2;AKT1
11 2/71 0.032497906 CCND2;AKT1
12 2/80 0.036587970 AKT1;ZFP36L2
13 2/82 0.036587970 CCND2;AKT1
14 2/106 0.044174001 CCND2;AKT1
15 2/110 0.044174001 AKT1;ZFP36L2
16 2/111 0.044174001 CCND2;AKT1
17 2/122 0.044174001 AKT1;ZFP36L2
18 1/5 0.044174001 AKT1
19 2/131 0.044174001 AKT1;CPNE3
20 1/6 0.044174001 ZFP36L2
21 1/6 0.044174001 AKT1
22 1/6 0.044174001 ZFP36L2
23 1/6 0.044174001 AKT1
24 1/6 0.044174001 ABCG2
25 2/146 0.044174001 AKT1;ZFP36L2
26 1/7 0.044174001 MADD
27 1/7 0.044174001 AKT1
28 1/7 0.044174001 ZFP36L2
29 1/7 0.044174001 AKT1
30 1/7 0.044174001 AKT1
31 1/7 0.044174001 AKT1
32 1/7 0.044174001 ZFP36L2
33 1/7 0.044174001 AKT1
34 1/7 0.044174001 AKT1
35 1/8 0.044174001 AKT1
36 1/8 0.044174001 AKT1
37 1/8 0.044174001 AKT1
38 1/8 0.044174001 CHAMP1
39 1/8 0.044174001 CHAMP1
40 1/9 0.044174001 AKT1
41 1/9 0.044174001 AKT1
42 1/9 0.044174001 CPNE3
43 1/9 0.044174001 AKT1
44 1/10 0.044174001 AKT1
45 1/10 0.044174001 AKT1
46 1/10 0.044174001 AKT1
47 1/11 0.044174001 AKT1
48 1/11 0.044174001 AKT1
49 1/11 0.044174001 AKT1
50 1/11 0.044174001 ABCG2
51 1/11 0.044174001 AKT1
52 2/194 0.044174001 AKT1;ZFP36L2
53 2/194 0.044174001 MADD;AKT1
54 1/12 0.044174001 AKT1
55 1/12 0.044174001 AKT1
56 1/12 0.044174001 CHAMP1
57 1/12 0.044174001 CHAMP1
58 1/13 0.044174001 ZFP36L2
59 1/13 0.044174001 AKT1
60 1/13 0.044174001 AKT1
61 1/13 0.044174001 AKT1
62 1/13 0.044174001 AKT1
63 2/214 0.044174001 CCND2;AKT1
64 1/14 0.044174001 AKT1
65 1/14 0.044174001 ZFP36L2
66 1/14 0.044174001 AKT1
67 1/14 0.044174001 AKT1
68 1/14 0.044174001 AKT1
69 1/14 0.044174001 CHAMP1
70 1/15 0.044174001 ZFP36L2
71 1/15 0.044174001 AKT1
72 1/15 0.044174001 AKT1
73 1/15 0.044174001 AKT1
74 1/15 0.044174001 ZFP36L2
75 1/16 0.044174001 ZFP36L2
76 1/16 0.044174001 AKT1
77 1/16 0.044174001 AKT1
78 1/16 0.044174001 ABCG2
79 1/16 0.044174001 ABCG2
80 1/16 0.044174001 ABCG2
81 1/16 0.044174001 ZFP36L2
82 1/16 0.044174001 AKT1
83 1/17 0.045234301 CHAMP1
84 1/18 0.045234301 ZFP36L2
85 1/18 0.045234301 AKT1
86 1/18 0.045234301 ZFP36L2
87 1/18 0.045234301 AKT1
88 1/18 0.045234301 AKT1
89 1/18 0.045234301 AKT1
90 1/18 0.045234301 AKT1
91 2/253 0.045234301 CCND2;AKT1
92 1/19 0.045234301 AKT1
93 1/19 0.045234301 AKT1
94 1/19 0.045234301 AKT1
95 1/19 0.045234301 AKT1
96 3/742 0.046142478 CCND2;MADD;AKT1
97 1/20 0.046142478 ZFP36L2
98 1/20 0.046142478 ABCG2
99 2/266 0.047378384 CCND2;AKT1
100 1/22 0.049217157 AKT1
101 1/22 0.049217157 ABCG2
102 1/23 0.049478084 AKT1
103 1/23 0.049478084 ZFP36L2
104 1/23 0.049478084 AKT1
105 1/23 0.049478084 AKT1
106 1/24 0.049719225 AKT1
107 1/24 0.049719225 AKT1
108 1/24 0.049719225 ABCG2
109 1/25 0.049719225 AKT1
110 1/25 0.049719225 AKT1
111 1/25 0.049719225 AKT1
112 1/26 0.049719225 AKT1
113 1/26 0.049719225 AKT1
114 1/26 0.049719225 AKT1
115 1/26 0.049719225 AKT1
116 1/27 0.049719225 AKT1
117 1/27 0.049719225 ZFP36L2
118 1/27 0.049719225 AKT1
119 1/28 0.049719225 AKT1
120 1/28 0.049719225 AKT1
121 1/28 0.049719225 ABCG2
122 1/28 0.049719225 ABCG2
123 1/28 0.049719225 ZFP36L2
124 1/28 0.049719225 AKT1
125 1/28 0.049719225 AKT1
126 1/28 0.049719225 AKT1
127 1/28 0.049719225 ZFP36L2
[1] "GO_Cellular_Component_2021"
[1] Term Overlap Adjusted.P.value Genes
<0 rows> (or 0-length row.names)
[1] "GO_Molecular_Function_2021"
Term Overlap
1 protein kinase regulator activity (GO:0019887) 2/98
2 urate transmembrane transporter activity (GO:0015143) 1/5
3 potassium channel activator activity (GO:0099104) 1/5
4 riboflavin transmembrane transporter activity (GO:0032217) 1/5
Adjusted.P.value Genes
1 0.03408014 CCND2;MADD
2 0.03408014 ABCG2
3 0.03408014 AKT1
4 0.03408014 ABCG2
MADD gene(s) from the input list not found in DisGeNET CURATEDPPDPF gene(s) from the input list not found in DisGeNET CURATEDFAM214B gene(s) from the input list not found in DisGeNET CURATEDGIGYF1 gene(s) from the input list not found in DisGeNET CURATED
Description FDR
65 Prostatic Neoplasms 0.001129474
127 Malignant neoplasm of prostate 0.001129474
18 Colorectal Neoplasms 0.008314537
23 Diabetes Mellitus, Non-Insulin-Dependent 0.022319439
29 Fibrosis 0.022319439
163 Squamous cell carcinoma of the head and neck 0.022319439
180 Cirrhosis 0.022319439
181 URIC ACID CONCENTRATION, SERUM, QUANTITATIVE TRAIT LOCUS 1 0.022319439
189 Precursor T-Cell Lymphoblastic Leukemia-Lymphoma 0.022319439
197 COWDEN SYNDROME 6 0.022319439
Ratio BgRatio
65 6/10 616/9703
127 6/10 616/9703
18 4/10 277/9703
23 3/10 221/9703
29 2/10 50/9703
163 2/10 52/9703
180 2/10 50/9703
181 1/10 1/9703
189 2/10 53/9703
197 1/10 1/9703
******************************************
* *
* Welcome to WebGestaltR ! *
* *
******************************************
Loading the functional categories...
Loading the ID list...
Loading the reference list...
Performing the enrichment analysis...
Warning in oraEnrichment(interestGeneList, referenceGeneList, geneSet,
minNum = minNum, : No significant gene set is identified based on FDR 0.05!
NULL
library("readxl")
known_annotations <- read_xlsx("data/summary_known_genes_annotations.xlsx", sheet="Glucose")
known_annotations <- unique(known_annotations$`Gene Symbol`)
unrelated_genes <- ctwas_gene_res$genename[!(ctwas_gene_res$genename %in% known_annotations)]
#number of genes in known annotations
print(length(known_annotations))
[1] 87
#number of genes in known annotations with imputed expression
print(sum(known_annotations %in% ctwas_gene_res$genename))
[1] 39
#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] 4.618904
#number of ctwas genes
length(ctwas_genes)
[1] 14
#number of TWAS genes
length(twas_genes)
[1] 87
#show novel genes (ctwas genes with not in TWAS genes)
ctwas_gene_res[ctwas_gene_res$genename %in% novel_genes,report_cols]
genename region_tag susie_pip mu2 PVE z
3620 ABCG2 4_59 0.812 19.76 5.1e-05 -4.10
66 FAM214B 9_27 0.831 21.22 5.6e-05 -4.20
6020 AKT1 14_55 0.859 20.40 5.6e-05 -4.14
#sensitivity / recall
sensitivity <- rep(NA,2)
names(sensitivity) <- c("ctwas", "TWAS")
sensitivity["ctwas"] <- sum(ctwas_genes %in% known_annotations)/length(known_annotations)
sensitivity["TWAS"] <- sum(twas_genes %in% known_annotations)/length(known_annotations)
sensitivity
ctwas TWAS
0.00000000 0.03448276
#specificity
specificity <- rep(NA,2)
names(specificity) <- c("ctwas", "TWAS")
specificity["ctwas"] <- sum(!(unrelated_genes %in% ctwas_genes))/length(unrelated_genes)
specificity["TWAS"] <- sum(!(unrelated_genes %in% twas_genes))/length(unrelated_genes)
specificity
ctwas TWAS
0.9989166 0.9934995
#precision / PPV
precision <- rep(NA,2)
names(precision) <- c("ctwas", "TWAS")
precision["ctwas"] <- sum(ctwas_genes %in% known_annotations)/length(ctwas_genes)
precision["TWAS"] <- sum(twas_genes %in% known_annotations)/length(twas_genes)
precision
ctwas TWAS
0.00000000 0.03448276
#ROC curves
pip_range <- (0:1000)/1000
sensitivity <- rep(NA, length(pip_range))
specificity <- rep(NA, length(pip_range))
for (index in 1:length(pip_range)){
pip <- pip_range[index]
ctwas_genes <- ctwas_gene_res$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)
Version | Author | Date |
---|---|---|
7e22565 | wesleycrouse | 2021-09-13 |
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] 87
#number of genes in known annotations with imputed expression
print(sum(known_annotations %in% ctwas_gene_res$genename))
[1] 39
#number of bystander genes
print(length(unrelated_genes))
[1] 1944
#number of bystander genes with imputed expression
print(sum(unrelated_genes %in% ctwas_gene_res$genename))
[1] 1086
#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] 4.618904
#number of ctwas genes
length(ctwas_genes)
[1] 14
#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] 87
#number of TWAS genes
sum(twas_genes %in% c(known_annotations, unrelated_genes))
[1] 13
#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
0.00000000 0.07692308
#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
1.0000000 0.9907919
#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 0.2307692
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_1.36.0 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 WebGestaltR_0.4.4 disgenet2r_0.99.2
[10] enrichR_3.0 cowplot_1.0.0 ggplot2_3.3.3
loaded via a namespace (and not attached):
[1] bitops_1.0-6 fs_1.3.1 bit64_4.0.5
[4] doParallel_1.0.16 progress_1.2.2 httr_1.4.1
[7] rprojroot_2.0.2 tools_3.6.1 doRNG_1.8.2
[10] utf8_1.2.1 R6_2.5.0 DBI_1.1.1
[13] colorspace_1.4-1 withr_2.4.1 tidyselect_1.1.0
[16] prettyunits_1.0.2 bit_4.0.4 curl_3.3
[19] compiler_3.6.1 git2r_0.26.1 Biobase_2.44.0
[22] labeling_0.3 scales_1.1.0 readr_1.4.0
[25] stringr_1.4.0 apcluster_1.4.8 digest_0.6.20
[28] rmarkdown_1.13 svglite_1.2.2 XVector_0.24.0
[31] pkgconfig_2.0.3 htmltools_0.3.6 fastmap_1.1.0
[34] rlang_0.4.11 RSQLite_2.2.7 farver_2.1.0
[37] generics_0.0.2 jsonlite_1.6 dplyr_1.0.7
[40] RCurl_1.98-1.1 magrittr_2.0.1 GenomeInfoDbData_1.2.1
[43] Matrix_1.2-18 Rcpp_1.0.6 munsell_0.5.0
[46] fansi_0.5.0 gdtools_0.1.9 lifecycle_1.0.0
[49] stringi_1.4.3 whisker_0.3-2 yaml_2.2.0
[52] zlibbioc_1.30.0 plyr_1.8.4 grid_3.6.1
[55] blob_1.2.1 promises_1.0.1 crayon_1.4.1
[58] lattice_0.20-38 hms_1.1.0 knitr_1.23
[61] pillar_1.6.1 igraph_1.2.4.1 rjson_0.2.20
[64] rngtools_1.5 reshape2_1.4.3 codetools_0.2-16
[67] XML_3.98-1.20 glue_1.4.2 evaluate_0.14
[70] data.table_1.14.0 vctrs_0.3.8 httpuv_1.5.1
[73] foreach_1.5.1 cellranger_1.1.0 gtable_0.3.0
[76] purrr_0.3.4 assertthat_0.2.1 cachem_1.0.5
[79] xfun_0.8 later_0.8.0 tibble_3.1.2
[82] iterators_1.0.13 AnnotationDbi_1.46.0 memoise_2.0.0
[85] workflowr_1.6.2 ellipsis_0.3.2