Last updated: 2022-03-03

Checks: 5 2

Knit directory: cTWAS_analysis/

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Weight QC

#number of imputed weights
nrow(qclist_all)
[1] 10096
#number of imputed weights by chromosome
table(qclist_all$chr)

  1   2   3   4   5   6   7   8   9  10  11  12  13  14  15  16  17  18  19  20 
970 724 606 388 494 522 474 399 398 404 602 577 222 334 344 461 597 153 768 314 
 21  22 
112 233 
#number of imputed weights without missing variants
sum(qclist_all$nmiss==0)
[1] 8298
#proportion of imputed weights without missing variants
mean(qclist_all$nmiss==0)
[1] 0.8219

Check convergence of parameters

Version Author Date
ff6403a sq-96 2022-02-27
#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 
0.0079186 0.0002633 
#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 
11.493  8.624 
#report sample size
print(sample_size)
[1] 82315
#report group size
group_size <- c(nrow(ctwas_gene_res), n_snps)
print(group_size)
[1]   10096 7573890
#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 
0.01116 0.20896 
#compare sum(PIP*mu2/sample_size) with above PVE calculation
c(sum(ctwas_gene_res$PVE),sum(ctwas_snp_res$PVE))
[1] 0.04909 1.56331

Genes with highest PIPs

Version Author Date
ff6403a sq-96 2022-02-27
          genename region_tag susie_pip   mu2       PVE      z num_eqtl
4961         FURIN      15_42    0.9778 46.16 0.0005483 -7.000        1
10000       ZNF823      19_10    0.9709 29.75 0.0003509  5.455        1
11036   AC012074.2       2_15    0.8479 22.88 0.0002357  4.620        2
247          VSIG2      11_77    0.7885 26.23 0.0002512 -3.818        1
10995    HIST1H2BN       6_21    0.7676 94.50 0.0008812 10.773        1
8494        DIRAS1       19_3    0.7586 25.35 0.0002337  4.867        2
5687       ARFGAP2      11_29    0.6907 24.40 0.0002047  4.740        1
2668        PDCD10      3_103    0.5732 21.86 0.0001522 -4.033        2
2900        MAP7D1       1_22    0.5726 24.30 0.0001691  4.907        1
8526          LY6H       8_94    0.5552 21.43 0.0001446  4.042        2
12597       EBLN3P       9_28    0.5351 23.06 0.0001499 -4.450        1
10218   LIN28B-AS1       6_70    0.5284 23.56 0.0001512 -4.651        1
10923    LINC01305      2_105    0.5020 23.25 0.0001418  4.523        1
5807         PLBD2      12_68    0.4878 21.18 0.0001255  3.986        1
8611       ZNF354C      5_108    0.4600 24.48 0.0001368 -3.965        1
2371           MDK      11_28    0.4596 39.12 0.0002184 -6.357        1
5246        CEP170      1_128    0.4510 25.69 0.0001408 -4.678        1
98           ELAC2      17_11    0.4364 30.58 0.0001622  4.227        1
1618      PPP1R16B      20_23    0.4354 35.67 0.0001887  6.091        1
11529 RP11-65M17.3      11_66    0.4267 22.40 0.0001161  4.330        1

Genes with largest effect sizes

Version Author Date
ff6403a sq-96 2022-02-27
       genename region_tag susie_pip     mu2       PVE       z num_eqtl
6375   ARHGAP27      17_27 0.000e+00 2296.94 0.000e+00 -2.0935        1
62        KMT2E       7_65 1.106e-05 1474.23 1.981e-07 -5.7816        2
8739   HLA-DQB1       6_26 5.596e-14  848.22 5.766e-16  4.1487        1
10292    HSPA1A       6_26 3.034e-13  234.54 8.645e-16  7.1259        1
8149      DCAKD      17_27 0.000e+00  119.02 0.000e+00 -2.8009        2
4321      SRPK2       7_65 0.000e+00   99.65 0.000e+00 -1.1604        1
10995 HIST1H2BN       6_21 7.676e-01   94.50 8.812e-04 10.7729        1
8901      ACBD4      17_27 0.000e+00   91.02 0.000e+00  0.1106        2
10526     CLIC1       6_26 2.818e-13   85.62 2.931e-16  0.4634        1
9454     HEXIM1      17_27 0.000e+00   69.44 0.000e+00 -2.8451        1
9418     BTN3A2       6_20 1.425e-02   67.98 1.177e-05  9.0770        3
2212      GOSR2      17_27 0.000e+00   67.64 0.000e+00 -2.5096        1
10868    SAPCD1       6_26 3.779e-12   64.23 2.949e-15  2.7814        1
10298      MSH5       6_26 5.906e-14   57.52 4.127e-17  0.7907        2
1217       PUS7       7_65 0.000e+00   56.76 0.000e+00 -2.8339        2
8834  HIST1H2BC       6_20 1.538e-02   54.00 1.009e-05 -8.0277        1
9552    ZSCAN23       6_22 4.653e-02   52.42 2.963e-05 -7.5541        2
4600      PGBD1       6_22 8.004e-03   50.72 4.932e-06 -6.3599        2
11951 LINC01415      18_30 1.610e-01   49.98 9.776e-05 -5.3243        1
4961      FURIN      15_42 9.778e-01   46.16 5.483e-04 -7.0004        1

Genes with highest PVE

           genename region_tag susie_pip   mu2       PVE      z num_eqtl
10995     HIST1H2BN       6_21    0.7676 94.50 0.0008812 10.773        1
4961          FURIN      15_42    0.9778 46.16 0.0005483 -7.000        1
10000        ZNF823      19_10    0.9709 29.75 0.0003509  5.455        1
247           VSIG2      11_77    0.7885 26.23 0.0002512 -3.818        1
11036    AC012074.2       2_15    0.8479 22.88 0.0002357  4.620        2
8494         DIRAS1       19_3    0.7586 25.35 0.0002337  4.867        2
2371            MDK      11_28    0.4596 39.12 0.0002184 -6.357        1
5687        ARFGAP2      11_29    0.6907 24.40 0.0002047  4.740        1
1618       PPP1R16B      20_23    0.4354 35.67 0.0001887  6.091        1
426          ARID1B      6_102    0.3795 37.06 0.0001709 -3.907        1
2900         MAP7D1       1_22    0.5726 24.30 0.0001691  4.907        1
98            ELAC2      17_11    0.4364 30.58 0.0001622  4.227        1
2668         PDCD10      3_103    0.5732 21.86 0.0001522 -4.033        2
10218    LIN28B-AS1       6_70    0.5284 23.56 0.0001512 -4.651        1
12597        EBLN3P       9_28    0.5351 23.06 0.0001499 -4.450        1
8526           LY6H       8_94    0.5552 21.43 0.0001446  4.042        2
10923     LINC01305      2_105    0.5020 23.25 0.0001418  4.523        1
5246         CEP170      1_128    0.4510 25.69 0.0001408 -4.678        1
12007 RP11-247A12.7       9_66    0.2911 39.33 0.0001391  4.243        2
8611        ZNF354C      5_108    0.4600 24.48 0.0001368 -3.965        1

Genes with largest z scores

       genename region_tag susie_pip    mu2       PVE      z num_eqtl
10995 HIST1H2BN       6_21 7.676e-01  94.50 8.812e-04 10.773        1
9418     BTN3A2       6_20 1.425e-02  67.98 1.177e-05  9.077        3
8834  HIST1H2BC       6_20 1.538e-02  54.00 1.009e-05 -8.028        1
9552    ZSCAN23       6_22 4.653e-02  52.42 2.963e-05 -7.554        2
2539     TRIM38       6_20 1.187e-02  45.99 6.630e-06 -7.478        2
6323    ZSCAN12       6_22 1.556e-02  39.73 7.511e-06  7.193        2
10292    HSPA1A       6_26 3.034e-13 234.54 8.645e-16  7.126        1
4961      FURIN      15_42 9.778e-01  46.16 5.483e-04 -7.000        1
5665    CYP17A1      10_66 4.682e-03  31.84 1.811e-06 -6.720        1
4600      PGBD1       6_22 8.004e-03  50.72 4.932e-06 -6.360        2
2371        MDK      11_28 4.596e-01  39.12 2.184e-04 -6.357        1
2778     KCNJ13      2_137 1.584e-01  35.34 6.800e-05 -6.333        1
1137   PPP1R13B      14_54 6.061e-02  44.26 3.259e-05 -6.297        1
8821     HARBI1      11_28 1.622e-01  36.44 7.181e-05  6.169        1
10439   DNAJC19      3_111 2.146e-01  37.89 9.879e-05  6.158        1
3921   C12orf65      12_75 3.691e-03  36.50 1.637e-06 -6.141        1
9960        NMB      15_39 1.706e-01  42.26 8.760e-05  6.132        1
9514    ZKSCAN4       6_22 1.111e-02  28.19 3.805e-06 -6.092        1
1618   PPP1R16B      20_23 4.354e-01  35.67 1.887e-04  6.091        1
10577     AS3MT      10_66 6.259e-03  31.85 2.422e-06  6.055        2

Comparing z scores and PIPs

Version Author Date
ff6403a sq-96 2022-02-27

Version Author Date
ff6403a sq-96 2022-02-27
[1] 0.006933

GO enrichment analysis for genes with PIP>0.5

#number of genes for gene set enrichment
length(genes)
[1] 13
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"

Version Author Date
ff6403a sq-96 2022-02-27
                                                                                                                 Term
1                                                             positive regulation of MAP kinase activity (GO:0043406)
2                                                                      regulation of MAP kinase activity (GO:0043405)
3                                        positive regulation of protein serine/threonine kinase activity (GO:0071902)
4                                     negative regulation of transforming growth factor beta1 production (GO:0032911)
5                              regulation of low-density lipoprotein particle receptor catabolic process (GO:0032803)
6  negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis (GO:1903588)
7                                                                        Golgi transport vesicle coating (GO:0048200)
8                                                                          COPI coating of Golgi vesicle (GO:0048205)
9                                                                            COPI-coated vesicle budding (GO:0035964)
10                                             regulation of transforming growth factor beta1 production (GO:0032908)
11                                                                   establishment of Golgi localization (GO:0051683)
12                                     negative regulation of transforming growth factor beta production (GO:0071635)
13                                             negative regulation of cellular protein catabolic process (GO:1903363)
14                                                                    cellular response to acetylcholine (GO:1905145)
15                                                                             signal peptide processing (GO:0006465)
16                                                                                     Golgi inheritance (GO:0048313)
17                                 intrinsic apoptotic signaling pathway in response to oxidative stress (GO:0008631)
18                                                                                    Golgi localization (GO:0051645)
19                              negative regulation of cell migration involved in sprouting angiogenesis (GO:0090051)
20                                                                         regulation of lipase activity (GO:0060191)
21                                                                                 stress fiber assembly (GO:0043149)
22                                        positive regulation of membrane protein ectodomain proteolysis (GO:0051044)
23                                                            contractile actin filament bundle assembly (GO:0030038)
24                                                                     epiboly involved in wound healing (GO:0090505)
25          regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis (GO:1903587)
26                                                                      regulation of Golgi organization (GO:1903358)
27                                                                       regulation of catabolic process (GO:0009894)
28                              positive regulation of stress-activated protein kinase signaling cascade (GO:0070304)
29                                                                   positive regulation of MAPK cascade (GO:0043410)
30                                                              acetylcholine receptor signaling pathway (GO:0095500)
31                                                             regulation of lipoprotein lipase activity (GO:0051004)
32                                                 regulation of membrane protein ectodomain proteolysis (GO:0051043)
33                                                                      regulation of peptidase activity (GO:0052547)
34                                                                     wound healing, spreading of cells (GO:0044319)
   Overlap Adjusted.P.value         Genes
1     2/69          0.04473 PDCD10;DIRAS1
2     2/97          0.04473 PDCD10;DIRAS1
3    2/106          0.04473 PDCD10;DIRAS1
4      1/5          0.04473         FURIN
5      1/5          0.04473         FURIN
6      1/6          0.04473        PDCD10
7      1/6          0.04473       ARFGAP2
8      1/6          0.04473       ARFGAP2
9      1/6          0.04473       ARFGAP2
10     1/7          0.04473         FURIN
11     1/8          0.04473        PDCD10
12    1/10          0.04473         FURIN
13    1/10          0.04473         FURIN
14    1/10          0.04473          LY6H
15    1/11          0.04473         FURIN
16    1/11          0.04473        PDCD10
17    1/12          0.04473        PDCD10
18    1/12          0.04473        PDCD10
19    1/14          0.04473        PDCD10
20    1/14          0.04473         FURIN
21    1/15          0.04473        PDCD10
22    1/15          0.04473         FURIN
23    1/15          0.04473        PDCD10
24    1/16          0.04473        PDCD10
25    1/16          0.04473        PDCD10
26    1/17          0.04490        PDCD10
27    1/18          0.04490         FURIN
28    1/18          0.04490        PDCD10
29   2/274          0.04727 PDCD10;DIRAS1
30    1/21          0.04727          LY6H
31    1/21          0.04727         FURIN
32    1/22          0.04796         FURIN
33    1/23          0.04861         FURIN
34    1/24          0.04921        PDCD10
[1] "GO_Cellular_Component_2021"

Version Author Date
ff6403a sq-96 2022-02-27
[1] Term             Overlap          Adjusted.P.value Genes           
<0 rows> (or 0-length row.names)
[1] "GO_Molecular_Function_2021"

Version Author Date
ff6403a sq-96 2022-02-27
                                         Term Overlap Adjusted.P.value Genes
1    nerve growth factor binding (GO:0048406)     1/5          0.03978 FURIN
2 acetylcholine receptor binding (GO:0033130)     1/8          0.03978  LY6H
3           neurotrophin binding (GO:0043121)     1/8          0.03978 FURIN

DisGeNET enrichment analysis for genes with PIP>0.5

                                Description      FDR Ratio  BgRatio
13       Cerebral Cavernous Malformations 3 0.002319   1/3   1/9703
15 Familial cerebral cavernous malformation 0.002319   1/3   1/9703
14            Cavernous Hemangioma of Brain 0.004637   1/3   3/9703
1                                 Carcinoma 0.062703   1/3 164/9703
3                  Animal Mammary Neoplasms 0.062703   1/3 142/9703
4           Mammary Neoplasms, Experimental 0.062703   1/3 155/9703
6                      Anaplastic carcinoma 0.062703   1/3 163/9703
7                   Carcinoma, Spindle-Cell 0.062703   1/3 163/9703
8                Undifferentiated carcinoma 0.062703   1/3 163/9703
9                            Carcinomatosis 0.062703   1/3 163/9703

WebGestalt enrichment analysis for genes with PIP>0.5

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

PIP Manhattan Plot

Version Author Date
ff6403a sq-96 2022-02-27

Sensitivity, specificity and precision for silver standard genes

#number of genes in known annotations
print(length(known_annotations))
[1] 130
#number of genes in known annotations with imputed expression
print(sum(known_annotations %in% ctwas_gene_res$genename))
[1] 58
#significance threshold for TWAS
print(sig_thresh)
[1] 4.567
#number of ctwas genes
length(ctwas_genes)
[1] 3
#number of TWAS genes
length(twas_genes)
[1] 70
#show novel genes (ctwas genes with not in TWAS genes)
ctwas_gene_res[ctwas_gene_res$genename %in% novel_genes,report_cols]
[1] genename   region_tag susie_pip  mu2        PVE        z          num_eqtl  
<0 rows> (or 0-length row.names)
#sensitivity / recall
print(sensitivity)
  ctwas    TWAS 
0.01538 0.04615 
#specificity
print(specificity)
 ctwas   TWAS 
0.9999 0.9936 
#precision / PPV
print(precision)
  ctwas    TWAS 
0.66667 0.08571 

Version Author Date
75a1466 sq-96 2022-02-27
ff6403a sq-96 2022-02-27

cTWAS is more precise than TWAS in distinguishing silver standard and bystander genes

#number of genes in known annotations (with imputed expression)
print(length(known_annotations))
[1] 58
#number of bystander genes (with imputed expression)
print(length(unrelated_genes))
[1] 619
#subset results to genes in known annotations or bystanders
ctwas_gene_res_subset <- ctwas_gene_res[ctwas_gene_res$genename %in% c(known_annotations, unrelated_genes),]

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

#significance threshold for TWAS
print(sig_thresh)
[1] 4.567
#number of ctwas genes (in known annotations or bystanders)
length(ctwas_genes)
[1] 2
#number of TWAS genes (in known annotations or bystanders)
length(twas_genes)
[1] 22
#sensitivity / recall
sensitivity
  ctwas    TWAS 
0.03448 0.10345 
#specificity / (1 - False Positive Rate)
specificity
 ctwas   TWAS 
1.0000 0.9742 
#precision / PPV / (1 - False Discovery Rate)
precision
 ctwas   TWAS 
1.0000 0.2727 

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_subset$genename[ctwas_gene_res_subset$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), main="", xlab="1 - Specificity", ylab="Sensitivity")
title(expression("ROC Curve for cTWAS (black) and TWAS (" * phantom("red") * ")"))
title(expression(phantom("ROC Curve for cTWAS (black) and TWAS (") * "red" * phantom(")")), col.main="red")

sig_thresh_range <- seq(from=0, to=max(abs(ctwas_gene_res_subset$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_subset$genename[abs(ctwas_gene_res_subset$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=1)

abline(a=0,b=1,lty=3)

#add previously computed points from the analysis
ctwas_genes <- ctwas_gene_res_subset$genename[ctwas_gene_res_subset$susie_pip>0.8]
twas_genes <- ctwas_gene_res_subset$genename[abs(ctwas_gene_res_subset$z)>sig_thresh]

points(1-specificity_plot["ctwas"], sensitivity_plot["ctwas"], pch=21, bg="black")
points(1-specificity_plot["TWAS"], sensitivity_plot["TWAS"], pch=21, bg="red")

Undetected silver standard genes have low TWAS z-scores or stronger signal from nearby variants

#table of outcomes for silver standard genes
-sort(-table(silver_standard_case))
silver_standard_case
          Not Imputed Insignificant z-score         Nearby SNP(s) 
                   72                    52                     4 
 Detected (PIP > 0.8) 
                    2 
#show inconclusive genes
silver_standard_case[silver_standard_case=="Inconclusive"]
named character(0)


sessionInfo()
R version 3.6.1 (2019-07-05)
Platform: x86_64-pc-linux-gnu (64-bit)
Running under: Scientific Linux 7.4 (Nitrogen)

Matrix products: default
BLAS/LAPACK: /software/openblas-0.2.19-el7-x86_64/lib/libopenblas_haswellp-r0.2.19.so

locale:
 [1] LC_CTYPE=en_US.UTF-8       LC_NUMERIC=C              
 [3] LC_TIME=en_US.UTF-8        LC_COLLATE=en_US.UTF-8    
 [5] LC_MONETARY=en_US.UTF-8    LC_MESSAGES=en_US.UTF-8   
 [7] LC_PAPER=en_US.UTF-8       LC_NAME=C                 
 [9] LC_ADDRESS=C               LC_TELEPHONE=C            
[11] LC_MEASUREMENT=en_US.UTF-8 LC_IDENTIFICATION=C       

attached base packages:
[1] parallel  stats4    stats     graphics  grDevices utils     datasets 
[8] methods   base     

other attached packages:
 [1] GenomicRanges_1.36.1 GenomeInfoDb_1.20.0  IRanges_2.18.1      
 [4] S4Vectors_0.22.1     BiocGenerics_0.30.0  biomaRt_2.40.1      
 [7] readxl_1.3.1         forcats_0.5.1        stringr_1.4.0       
[10] dplyr_1.0.7          purrr_0.3.4          readr_2.1.1         
[13] tidyr_1.1.4          tidyverse_1.3.1      tibble_3.1.6        
[16] WebGestaltR_0.4.4    disgenet2r_0.99.2    enrichR_3.0         
[19] cowplot_1.0.0        ggplot2_3.3.5        workflowr_1.7.0     

loaded via a namespace (and not attached):
  [1] ggbeeswarm_0.6.0       colorspace_2.0-2       rjson_0.2.20          
  [4] ellipsis_0.3.2         rprojroot_2.0.2        XVector_0.24.0        
  [7] fs_1.5.2               rstudioapi_0.13        farver_2.1.0          
 [10] ggrepel_0.9.1          bit64_4.0.5            AnnotationDbi_1.46.0  
 [13] fansi_1.0.2            lubridate_1.8.0        xml2_1.3.3            
 [16] codetools_0.2-16       doParallel_1.0.17      cachem_1.0.6          
 [19] knitr_1.36             jsonlite_1.7.2         apcluster_1.4.8       
 [22] Cairo_1.5-12.2         broom_0.7.10           dbplyr_2.1.1          
 [25] compiler_3.6.1         httr_1.4.2             backports_1.4.1       
 [28] assertthat_0.2.1       Matrix_1.2-18          fastmap_1.1.0         
 [31] cli_3.1.0              later_0.8.0            prettyunits_1.1.1     
 [34] htmltools_0.5.2        tools_3.6.1            igraph_1.2.10         
 [37] GenomeInfoDbData_1.2.1 gtable_0.3.0           glue_1.6.2            
 [40] reshape2_1.4.4         doRNG_1.8.2            Rcpp_1.0.8            
 [43] Biobase_2.44.0         cellranger_1.1.0       jquerylib_0.1.4       
 [46] vctrs_0.3.8            svglite_1.2.2          iterators_1.0.14      
 [49] xfun_0.29              ps_1.6.0               rvest_1.0.2           
 [52] lifecycle_1.0.1        rngtools_1.5.2         XML_3.99-0.3          
 [55] zlibbioc_1.30.0        getPass_0.2-2          scales_1.1.1          
 [58] vroom_1.5.7            hms_1.1.1              promises_1.0.1        
 [61] yaml_2.2.1             curl_4.3.2             memoise_2.0.1         
 [64] ggrastr_1.0.1          gdtools_0.1.9          stringi_1.7.6         
 [67] RSQLite_2.2.8          highr_0.9              foreach_1.5.2         
 [70] rlang_1.0.1            pkgconfig_2.0.3        bitops_1.0-7          
 [73] evaluate_0.14          lattice_0.20-38        labeling_0.4.2        
 [76] bit_4.0.4              processx_3.5.2         tidyselect_1.1.1      
 [79] plyr_1.8.6             magrittr_2.0.2         R6_2.5.1              
 [82] generics_0.1.1         DBI_1.1.2              pillar_1.6.4          
 [85] haven_2.4.3            whisker_0.3-2          withr_2.4.3           
 [88] RCurl_1.98-1.5         modelr_0.1.8           crayon_1.5.0          
 [91] utf8_1.2.2             tzdb_0.2.0             rmarkdown_2.11        
 [94] progress_1.2.2         grid_3.6.1             data.table_1.14.2     
 [97] blob_1.2.2             callr_3.7.0            git2r_0.26.1          
[100] reprex_2.0.1           digest_0.6.29          httpuv_1.5.1          
[103] munsell_0.5.0          beeswarm_0.2.3         vipor_0.4.5