Last updated: 2022-02-27
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Knit directory: cTWAS_analysis/
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#number of imputed weights
nrow(qclist_all)
[1] 11152
#number of imputed weights by chromosome
table(qclist_all$chr)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
1097 778 665 440 568 568 537 435 425 444 658 638 212 359 377 502
17 18 19 20 21 22
679 169 849 331 133 288
#number of imputed weights without missing variants
sum(qclist_all$nmiss==0)
[1] 8929
#proportion of imputed weights without missing variants
mean(qclist_all$nmiss==0)
[1] 0.8007
#estimated group prior
estimated_group_prior <- group_prior_rec[,ncol(group_prior_rec)]
names(estimated_group_prior) <- c("gene", "snp")
estimated_group_prior["snp"] <- estimated_group_prior["snp"]*thin #adjust parameter to account for thin argument
print(estimated_group_prior)
gene snp
0.0148454 0.0002505
#estimated group prior variance
estimated_group_prior_var <- group_prior_var_rec[,ncol(group_prior_var_rec)]
names(estimated_group_prior_var) <- c("gene", "snp")
print(estimated_group_prior_var)
gene snp
11.589 8.483
#report sample size
print(sample_size)
[1] 82315
#report group size
group_size <- c(nrow(ctwas_gene_res), n_snps)
print(group_size)
[1] 11152 7573890
#estimated group PVE
estimated_group_pve <- estimated_group_prior_var*estimated_group_prior*group_size/sample_size #check PVE calculation
names(estimated_group_pve) <- c("gene", "snp")
print(estimated_group_pve)
gene snp
0.02331 0.19553
#compare sum(PIP*mu2/sample_size) with above PVE calculation
c(sum(ctwas_gene_res$PVE),sum(ctwas_snp_res$PVE))
[1] 0.1358 1.4127
genename region_tag susie_pip mu2 PVE z num_eqtl
3376 CRHR1 17_27 1.0000 3865.12 0.0469552 3.362 1
3993 SPECC1 17_16 0.9949 32.10 0.0003879 5.624 2
5324 FURIN 15_42 0.9892 46.47 0.0005584 -7.000 1
10843 ZNF823 19_10 0.9867 29.93 0.0003588 5.479 2
6111 ARFGAP2 11_29 0.9408 24.98 0.0002856 4.740 1
1089 RRN3 16_15 0.9222 24.23 0.0002714 -4.560 2
11997 AC012074.2 2_15 0.9186 21.83 0.0002436 4.620 2
7382 THOC7 3_43 0.8943 31.42 0.0003414 -5.578 1
2970 SF3B1 2_117 0.8932 44.56 0.0004835 6.725 1
11948 HIST1H2BN 6_21 0.8616 93.98 0.0009837 10.773 1
6802 CDC25C 5_82 0.8496 25.55 0.0002637 -5.591 1
3381 CAAP1 9_20 0.8063 24.10 0.0002361 4.751 2
9203 DIRAS1 19_3 0.8016 24.23 0.0002360 4.765 2
8764 FUT9 6_65 0.7872 29.99 0.0002868 5.427 1
11985 AC073283.4 2_30 0.7857 20.57 0.0001964 -3.881 3
11817 LINC00242 6_112 0.7772 20.55 0.0001940 3.921 2
10218 TMEM222 1_19 0.7456 22.33 0.0002023 3.902 1
7356 SERPINI1 3_103 0.7420 20.10 0.0001812 -4.038 1
3112 MAP7D1 1_22 0.7364 24.37 0.0002180 4.907 1
434 ARID1B 6_102 0.7239 21.68 0.0001906 -3.907 1
genename region_tag susie_pip mu2 PVE z num_eqtl
3376 CRHR1 17_27 1.000e+00 3865.12 4.696e-02 3.3623 1
10942 HLA-DRB5 6_26 0.000e+00 921.30 0.000e+00 2.9680 1
11166 MSH5 6_26 5.429e-09 839.87 5.539e-11 8.8255 2
10534 HLA-DRB1 6_26 0.000e+00 677.09 0.000e+00 5.1518 1
10645 HLA-DQA1 6_26 0.000e+00 376.40 0.000e+00 -1.6175 1
11162 HSPA1A 6_26 0.000e+00 359.84 0.000e+00 7.1259 1
11158 SLC44A4 6_26 0.000e+00 313.06 0.000e+00 6.1896 1
12073 HLA-DQA2 6_26 0.000e+00 306.49 0.000e+00 0.2164 1
11418 CLIC1 6_26 0.000e+00 262.34 0.000e+00 -0.4634 1
9485 HLA-DQB1 6_26 0.000e+00 217.87 0.000e+00 -1.4137 1
9661 ACBD4 17_27 0.000e+00 196.79 0.000e+00 1.6219 2
11620 C4B 6_26 0.000e+00 158.66 0.000e+00 -4.9282 1
11888 CYP21A2 6_26 0.000e+00 157.05 0.000e+00 3.7459 1
10008 FMNL1 17_27 0.000e+00 152.89 0.000e+00 0.6638 1
11948 HIST1H2BN 6_21 8.616e-01 93.98 9.837e-04 10.7729 1
11799 SAPCD1 6_26 0.000e+00 87.82 0.000e+00 -2.7814 1
2335 GOSR2 17_27 0.000e+00 76.11 0.000e+00 -2.5096 1
2736 PRSS16 6_21 1.002e-01 64.78 7.883e-05 -8.5674 1
11150 STK19 6_26 0.000e+00 56.67 0.000e+00 -2.0635 1
9592 HIST1H2BC 6_20 2.545e-02 54.50 1.685e-05 -8.0277 1
genename region_tag susie_pip mu2 PVE z num_eqtl
3376 CRHR1 17_27 1.0000 3865.12 0.0469552 3.362 1
11948 HIST1H2BN 6_21 0.8616 93.98 0.0009837 10.773 1
5324 FURIN 15_42 0.9892 46.47 0.0005584 -7.000 1
2970 SF3B1 2_117 0.8932 44.56 0.0004835 6.725 1
3993 SPECC1 17_16 0.9949 32.10 0.0003879 5.624 2
10843 ZNF823 19_10 0.9867 29.93 0.0003588 5.479 2
7382 THOC7 3_43 0.8943 31.42 0.0003414 -5.578 1
2829 PCCB 3_84 0.7124 35.08 0.0003036 -6.358 1
8764 FUT9 6_65 0.7872 29.99 0.0002868 5.427 1
6111 ARFGAP2 11_29 0.9408 24.98 0.0002856 4.740 1
1089 RRN3 16_15 0.9222 24.23 0.0002714 -4.560 2
6802 CDC25C 5_82 0.8496 25.55 0.0002637 -5.591 1
1685 PPP1R16B 20_23 0.6083 35.39 0.0002615 6.091 1
11997 AC012074.2 2_15 0.9186 21.83 0.0002436 4.620 2
3381 CAAP1 9_20 0.8063 24.10 0.0002361 4.751 2
9203 DIRAS1 19_3 0.8016 24.23 0.0002360 4.765 2
2505 MDK 11_28 0.4635 38.86 0.0002188 -6.357 1
3112 MAP7D1 1_22 0.7364 24.37 0.0002180 4.907 1
6178 TAOK2 16_24 0.4564 37.80 0.0002096 6.189 1
3041 ALMS1 2_48 0.6430 26.52 0.0002072 -5.154 1
genename region_tag susie_pip mu2 PVE z num_eqtl
11948 HIST1H2BN 6_21 8.616e-01 93.98 9.837e-04 10.773 1
11166 MSH5 6_26 5.429e-09 839.87 5.539e-11 8.825 2
2736 PRSS16 6_21 1.002e-01 64.78 7.883e-05 -8.567 1
10214 BTN3A2 6_20 1.908e-02 53.75 1.246e-05 8.047 3
9592 HIST1H2BC 6_20 2.545e-02 54.50 1.685e-05 -8.028 1
2696 TRIM38 6_20 1.994e-02 49.73 1.205e-05 -7.769 2
11162 HSPA1A 6_26 0.000e+00 359.84 0.000e+00 7.126 1
5324 FURIN 15_42 9.892e-01 46.47 5.584e-04 -7.000 1
2970 SF3B1 2_117 8.932e-01 44.56 4.835e-04 6.725 1
10360 ZSCAN23 6_22 1.101e-01 46.18 6.177e-05 -6.717 2
1571 ZFYVE21 14_54 1.435e-01 40.59 7.079e-05 -6.708 1
3855 XRCC3 14_54 1.179e-01 42.60 6.100e-05 6.690 1
9715 ARL6IP4 12_75 1.257e-02 40.62 6.201e-06 6.491 1
10694 ZSCAN26 6_22 2.479e-02 28.09 8.460e-06 6.389 2
2829 PCCB 3_84 7.124e-01 35.08 3.036e-04 -6.358 1
2505 MDK 11_28 4.635e-01 38.86 2.188e-04 -6.357 1
11158 SLC44A4 6_26 0.000e+00 313.06 0.000e+00 6.190 1
6178 TAOK2 16_24 4.564e-01 37.80 2.096e-04 6.189 1
12000 ZSCAN31 6_22 1.972e-02 33.00 7.908e-06 -6.182 3
9577 HARBI1 11_28 1.681e-01 36.17 7.388e-05 6.169 1
[1] 0.007443
genename region_tag susie_pip mu2 PVE z num_eqtl
11948 HIST1H2BN 6_21 8.616e-01 93.98 9.837e-04 10.773 1
11166 MSH5 6_26 5.429e-09 839.87 5.539e-11 8.825 2
2736 PRSS16 6_21 1.002e-01 64.78 7.883e-05 -8.567 1
10214 BTN3A2 6_20 1.908e-02 53.75 1.246e-05 8.047 3
9592 HIST1H2BC 6_20 2.545e-02 54.50 1.685e-05 -8.028 1
2696 TRIM38 6_20 1.994e-02 49.73 1.205e-05 -7.769 2
11162 HSPA1A 6_26 0.000e+00 359.84 0.000e+00 7.126 1
5324 FURIN 15_42 9.892e-01 46.47 5.584e-04 -7.000 1
2970 SF3B1 2_117 8.932e-01 44.56 4.835e-04 6.725 1
10360 ZSCAN23 6_22 1.101e-01 46.18 6.177e-05 -6.717 2
1571 ZFYVE21 14_54 1.435e-01 40.59 7.079e-05 -6.708 1
3855 XRCC3 14_54 1.179e-01 42.60 6.100e-05 6.690 1
9715 ARL6IP4 12_75 1.257e-02 40.62 6.201e-06 6.491 1
10694 ZSCAN26 6_22 2.479e-02 28.09 8.460e-06 6.389 2
2829 PCCB 3_84 7.124e-01 35.08 3.036e-04 -6.358 1
2505 MDK 11_28 4.635e-01 38.86 2.188e-04 -6.357 1
11158 SLC44A4 6_26 0.000e+00 313.06 0.000e+00 6.190 1
6178 TAOK2 16_24 4.564e-01 37.80 2.096e-04 6.189 1
12000 ZSCAN31 6_22 1.972e-02 33.00 7.908e-06 -6.182 3
9577 HARBI1 11_28 1.681e-01 36.17 7.388e-05 6.169 1
#number of genes for gene set enrichment
length(genes)
[1] 35
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"
[1] Term Overlap Adjusted.P.value Genes
<0 rows> (or 0-length row.names)
[1] "GO_Cellular_Component_2021"
[1] Term Overlap Adjusted.P.value Genes
<0 rows> (or 0-length row.names)
[1] "GO_Molecular_Function_2021"
[1] Term Overlap Adjusted.P.value Genes
<0 rows> (or 0-length row.names)
Description FDR Ratio
11 Involutional Depression 0.01732 2/12
17 Hirschsprung Disease 0.01732 2/12
63 Alstrom Syndrome 0.01732 1/12
109 Involutional paraphrenia 0.01732 2/12
110 Psychosis, Involutional 0.01732 2/12
113 Familial encephalopathy with neuroserpin inclusion bodies 0.01732 1/12
114 Childhood-onset truncal obesity 0.01732 1/12
123 NOONAN SYNDROME 8 0.01732 1/12
125 EPILEPSY, FAMILIAL TEMPORAL LOBE, 8 0.01732 1/12
106 Cardiomyopathy, Familial Idiopathic 0.02095 2/12
BgRatio
11 25/9703
17 31/9703
63 1/9703
109 25/9703
110 25/9703
113 1/9703
114 1/9703
123 1/9703
125 1/9703
106 50/9703
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
#number of genes in known annotations
print(length(known_annotations))
[1] 41
#number of genes in known annotations with imputed expression
print(sum(known_annotations %in% ctwas_gene_res$genename))
[1] 22
#significance threshold for TWAS
print(sig_thresh)
[1] 4.588
#number of ctwas genes
length(ctwas_genes)
[1] 13
#number of TWAS genes
length(twas_genes)
[1] 83
#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 num_eqtl
1089 RRN3 16_15 0.9222 24.23 0.0002714 -4.560 2
3376 CRHR1 17_27 1.0000 3865.12 0.0469552 3.362 1
#sensitivity / recall
print(sensitivity)
ctwas TWAS
0 0
#specificity
print(specificity)
ctwas TWAS
0.9988 0.9925
#precision / PPV
print(precision)
ctwas TWAS
0 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] stats graphics grDevices utils datasets methods base
other attached packages:
[1] readxl_1.3.1 forcats_0.5.1 stringr_1.4.0 dplyr_1.0.7
[5] purrr_0.3.4 readr_2.1.1 tidyr_1.1.4 tidyverse_1.3.1
[9] tibble_3.1.6 WebGestaltR_0.4.4 disgenet2r_0.99.2 enrichR_3.0
[13] cowplot_1.0.0 ggplot2_3.3.5 workflowr_1.6.2
loaded via a namespace (and not attached):
[1] fs_1.5.2 lubridate_1.8.0 bit64_4.0.5 doParallel_1.0.17
[5] httr_1.4.2 rprojroot_2.0.2 tools_3.6.1 backports_1.4.1
[9] doRNG_1.8.2 utf8_1.2.2 R6_2.5.1 vipor_0.4.5
[13] DBI_1.1.2 colorspace_2.0-2 withr_2.4.3 ggrastr_1.0.1
[17] tidyselect_1.1.1 bit_4.0.4 curl_4.3.2 compiler_3.6.1
[21] git2r_0.26.1 rvest_1.0.2 cli_3.1.0 Cairo_1.5-12.2
[25] xml2_1.3.3 labeling_0.4.2 scales_1.1.1 apcluster_1.4.8
[29] digest_0.6.29 rmarkdown_2.11 svglite_1.2.2 pkgconfig_2.0.3
[33] htmltools_0.5.2 dbplyr_2.1.1 fastmap_1.1.0 highr_0.9
[37] rlang_1.0.1 rstudioapi_0.13 RSQLite_2.2.8 jquerylib_0.1.4
[41] farver_2.1.0 generics_0.1.1 jsonlite_1.7.2 vroom_1.5.7
[45] magrittr_2.0.2 Matrix_1.2-18 ggbeeswarm_0.6.0 Rcpp_1.0.8
[49] munsell_0.5.0 fansi_1.0.2 gdtools_0.1.9 lifecycle_1.0.1
[53] stringi_1.7.6 whisker_0.3-2 yaml_2.2.1 plyr_1.8.6
[57] grid_3.6.1 blob_1.2.2 ggrepel_0.9.1 parallel_3.6.1
[61] promises_1.0.1 crayon_1.5.0 lattice_0.20-38 haven_2.4.3
[65] hms_1.1.1 knitr_1.36 pillar_1.6.4 igraph_1.2.10
[69] rjson_0.2.20 rngtools_1.5.2 reshape2_1.4.4 codetools_0.2-16
[73] reprex_2.0.1 glue_1.6.2 evaluate_0.14 data.table_1.14.2
[77] modelr_0.1.8 vctrs_0.3.8 tzdb_0.2.0 httpuv_1.5.1
[81] foreach_1.5.2 cellranger_1.1.0 gtable_0.3.0 assertthat_0.2.1
[85] cachem_1.0.6 xfun_0.29 broom_0.7.10 later_0.8.0
[89] iterators_1.0.14 beeswarm_0.2.3 memoise_2.0.1 ellipsis_0.3.2