Last updated: 2022-05-18

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Knit directory: cTWAS_analysis/

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File Version Author Date Message
Rmd 2749be9 sq-96 2022-05-12 update
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library(reticulate)
use_python("/scratch/midway2/shengqian/miniconda3/envs/PythonForR/bin/python",required=T)

Weight QC

#number of imputed weights
nrow(qclist_all)
[1] 21642
#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 
1929 1532 1343  876  885 1118 1258  748  873 1021 1288 1205  442  765  754  863 
  17   18   19   20   21   22 
1460  296 1534  750   40  662 
#number of imputed weights without missing variants
sum(qclist_all$nmiss==0)
[1] 18965
#proportion of imputed weights without missing variants
mean(qclist_all$nmiss==0)
[1] 0.8763
finish

Attaching package: 'dplyr'
The following objects are masked from 'package:stats':

    filter, lag
The following objects are masked from 'package:base':

    intersect, setdiff, setequal, union

Check convergence of parameters

Version Author Date
2749be9 sq-96 2022-05-12
     gene       snp 
0.0063107 0.0003111 
 gene   snp 
10.20 10.34 
[1] 105318
[1]    7779 6309950
    gene      snp 
0.004756 0.192769 
[1] 0.01421 1.10685

Genes with highest PIPs

Version Author Date
2749be9 sq-96 2022-05-12
     genename region_tag susie_pip   mu2       PVE      z num_intron num_sqtl
3588     LRP8       1_33    1.1028 32.85 2.908e-04 -4.820          5        5
7470  ZDHHC20       13_2    0.9020 24.49 1.796e-04 -4.784          5        6
2627   GIGYF1       7_62    0.8896 26.12 1.951e-04 -5.266          4        4
4603     PAK6      15_14    0.8434 29.84 2.016e-04  5.588          1        1
6998  TSNARE1       8_93    0.8350 27.20 1.779e-04  5.555         11       11
3573   LPCAT4      15_10    0.8112 26.23 1.599e-04  4.892          3        5
574    ATP2B2        3_8    0.7968 26.02 1.436e-04  4.229          5        6
6666    THAP8      19_25    0.7784 20.83 1.195e-04  3.847          2        2
253      AKT3      1_128    0.7627 34.93 1.831e-04 -6.350          6        6
861   C2orf80      2_123    0.7584 24.25 9.972e-05  3.053         12       13
1934   DPYSL3       5_86    0.7575 23.63 1.287e-04  4.157          1        1
4310     NGEF      2_137    0.7346 30.69 1.537e-04  7.036          3        3
118    ACTR1B       2_57    0.7234 20.56 1.003e-04 -3.978          5        5
4385 NPIPB14P      16_37    0.7132 17.79 8.171e-05 -3.742         12       12
744     BRCA1      17_25    0.7052 31.00 8.244e-05 -3.837         20       22
3968 MPHOSPH9      12_75    0.6872 60.79 2.709e-04 -8.201          2        4
695      BDNF      11_19    0.6805 23.22 1.021e-04  4.348          1        1
2217     ESAM      11_77    0.6792 35.97 1.325e-04  5.889          2        2
7331    WDR27      6_111    0.6484 16.96 3.988e-05  2.235         21       33
1792     DHPS      19_10    0.6472 25.49 1.014e-04 -4.396          1        1

Genes with highest PVE

     genename region_tag susie_pip    mu2       PVE       z num_intron num_sqtl
3588     LRP8       1_33    1.1028  32.85 0.0002908  -4.820          5        5
3968 MPHOSPH9      12_75    0.6872  60.79 0.0002709  -8.201          2        4
4603     PAK6      15_14    0.8434  29.84 0.0002016   5.588          1        1
415      APOM       6_26    0.1818 627.31 0.0001967  11.590          2        2
2627   GIGYF1       7_62    0.8896  26.12 0.0001951  -5.266          4        4
253      AKT3      1_128    0.7627  34.93 0.0001831  -6.350          6        6
7470  ZDHHC20       13_2    0.9020  24.49 0.0001796  -4.784          5        6
6998  TSNARE1       8_93    0.8350  27.20 0.0001779   5.555         11       11
3573   LPCAT4      15_10    0.8112  26.23 0.0001599   4.892          3        5
3627     LSM2       6_26    0.1619 635.43 0.0001581 -11.599          1        1
6542    TAOK2      16_24    0.6049  46.28 0.0001540   7.024          5        6
4310     NGEF      2_137    0.7346  30.69 0.0001537   7.036          3        3
7237    VARS1       6_26    0.1563 629.91 0.0001462 -11.620          1        1
4445    NT5C2      10_66    0.5910  46.04 0.0001450  -8.511         11       15
574    ATP2B2        3_8    0.7968  26.02 0.0001436   4.229          5        6
2217     ESAM      11_77    0.6792  35.97 0.0001325   5.889          2        2
1934   DPYSL3       5_86    0.7575  23.63 0.0001287   4.157          1        1
6666    THAP8      19_25    0.7784  20.83 0.0001195   3.847          2        2
695      BDNF      11_19    0.6805  23.22 0.0001021   4.348          1        1
1431     COA8      14_54    0.5012  43.66 0.0001015   7.265          4        7

Comparing z scores and PIPs

Version Author Date
2749be9 sq-96 2022-05-12

Version Author Date
2749be9 sq-96 2022-05-12
[1] 0.01825
     genename region_tag susie_pip    mu2       PVE       z num_intron num_sqtl
7237    VARS1       6_26   0.15633 629.91 1.462e-04 -11.620          1        1
3627     LSM2       6_26   0.16187 635.43 1.581e-04 -11.599          1        1
415      APOM       6_26   0.18177 627.31 1.967e-04  11.590          2        2
645      BAG6       6_26   0.11475 627.31 7.843e-05 -11.590          7        7
1656  CYP21A2       6_26   0.01511 659.18 1.430e-06 -11.340          1        1
7238    VARS2       6_25   0.05583 101.38 3.000e-06 -11.137          1        1
877  C6orf136       6_24   0.06069  79.63 2.785e-06 -11.031          2        2
2465    FLOT1       6_24   0.14500  78.29 1.560e-05  10.981          6        7
776    BTN3A2       6_20   0.08647  90.16 2.598e-06 -10.659          3        3
773    BTN2A1       6_20   0.08574  82.29 3.455e-06  10.110          5        6
1087   CCHCR1       6_25   0.05360  62.58 9.944e-07  -9.358         10       14
1728     DDR1       6_25   0.01101  67.83 7.808e-08   9.016          1        1
2927  HLA-DMA       6_27   0.05258  65.16 9.905e-07   8.596          4        7
4445    NT5C2      10_66   0.59099  46.04 1.450e-04  -8.511         11       15
3671   MAD1L1        7_3   0.31932  63.77 4.772e-05  -8.215          3        3
3968 MPHOSPH9      12_75   0.68723  60.79 2.709e-04  -8.201          2        4
512     AS3MT      10_66   0.21828  44.51 1.947e-05   8.051          6        7
4055     MSH5       6_26   0.00000 236.73 0.000e+00  -7.892          3        3
802  C12orf65      12_75   0.04490  54.18 9.788e-07  -7.754          2        2
7762  ZSCAN16       6_22   0.01873  53.24 8.925e-08  -7.468          2        2

GO enrichment analysis for genes with PIP>0.5

#number of genes for gene set enrichment
length(genes)
[1] 38
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
2749be9 sq-96 2022-05-12
[1] Term             Overlap          Adjusted.P.value Genes           
<0 rows> (or 0-length row.names)
[1] "GO_Cellular_Component_2021"

Version Author Date
2749be9 sq-96 2022-05-12
[1] Term             Overlap          Adjusted.P.value Genes           
<0 rows> (or 0-length row.names)
[1] "GO_Molecular_Function_2021"

Version Author Date
2749be9 sq-96 2022-05-12
[1] Term             Overlap          Adjusted.P.value Genes           
<0 rows> (or 0-length row.names)

DisGeNET enrichment analysis for genes with PIP>0.5

                                                  Description     FDR Ratio
48                                                    Measles 0.02668  1/20
69                                              Schizophrenia 0.02668  7/20
86                              Electroencephalogram abnormal 0.02668  1/20
181                                 Sporadic Breast Carcinoma 0.02668  1/20
184                              Primary peritoneal carcinoma 0.02668  1/20
193     BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 1 0.02668  1/20
194             BREAST CANCER, FAMILIAL, SUSCEPTIBILITY TO, 1 0.02668  1/20
195            OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 1 0.02668  1/20
196 HEMOLYTIC UREMIC SYNDROME, ATYPICAL, SUSCEPTIBILITY TO, 2 0.02668  1/20
201                                   SENIOR-LOKEN SYNDROME 7 0.02668  1/20
     BgRatio
48    1/9703
69  883/9703
86    1/9703
181   1/9703
184   1/9703
193   1/9703
194   1/9703
195   1/9703
196   1/9703
201   1/9703

WebGestalt enrichment analysis for genes with PIP>0.5

Warning: replacing previous import 'lifecycle::last_warnings' by
'rlang::last_warnings' when loading 'hms'
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

Warning: ggrepel: 3 unlabeled data points (too many overlaps). Consider
increasing max.overlaps

Version Author Date
2749be9 sq-96 2022-05-12

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$genename))
[1] 53
#significance threshold for TWAS
print(sig_thresh)
[1] 4.512
#number of ctwas genes
length(ctwas_genes)
[1] 6
#number of TWAS genes
length(twas_genes)
[1] 142
#show novel genes (ctwas genes with not in TWAS genes)
ctwas_gene_res[ctwas_gene_res$genename %in% novel_genes,report_cols]
[1] genename   region_tag susie_pip  mu2        PVE        z          num_intron
[8] num_sqtl  
<0 rows> (or 0-length row.names)
#sensitivity / recall
print(sensitivity)
  ctwas    TWAS 
0.01538 0.10769 
#specificity
print(specificity)
 ctwas   TWAS 
0.9995 0.9834 
#precision / PPV
print(precision)
  ctwas    TWAS 
0.33333 0.09859 

sessionInfo()
R version 4.1.0 (2021-05-18)
Platform: x86_64-pc-linux-gnu (64-bit)
Running under: Scientific Linux 7.4 (Nitrogen)

Matrix products: default
BLAS/LAPACK: /software/openblas-0.3.13-el7-x86_64/lib/libopenblas_haswellp-r0.3.13.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_1.4.0      forcats_0.5.1     stringr_1.4.0     purrr_0.3.4      
 [5] readr_1.4.0       tidyr_1.1.3       tidyverse_1.3.1   tibble_3.1.7     
 [9] WebGestaltR_0.4.4 disgenet2r_0.99.2 enrichR_3.0       cowplot_1.1.1    
[13] ggplot2_3.3.5     dplyr_1.0.7       reticulate_1.20   workflowr_1.6.2  

loaded via a namespace (and not attached):
 [1] fs_1.5.0          lubridate_1.7.10  doParallel_1.0.16 httr_1.4.2       
 [5] rprojroot_2.0.2   tools_4.1.0       backports_1.2.1   doRNG_1.8.2      
 [9] bslib_0.2.5.1     utf8_1.2.1        R6_2.5.0          vipor_0.4.5      
[13] DBI_1.1.1         colorspace_2.0-2  withr_2.4.2       ggrastr_1.0.1    
[17] tidyselect_1.1.1  curl_4.3.2        compiler_4.1.0    git2r_0.28.0     
[21] rvest_1.0.0       cli_3.0.0         Cairo_1.5-15      xml2_1.3.2       
[25] labeling_0.4.2    sass_0.4.0        scales_1.1.1      systemfonts_1.0.4
[29] apcluster_1.4.9   digest_0.6.27     rmarkdown_2.9     svglite_2.0.0    
[33] pkgconfig_2.0.3   htmltools_0.5.1.1 dbplyr_2.1.1      highr_0.9        
[37] rlang_1.0.2       rstudioapi_0.13   jquerylib_0.1.4   farver_2.1.0     
[41] generics_0.1.0    jsonlite_1.7.2    magrittr_2.0.1    Matrix_1.3-3     
[45] ggbeeswarm_0.6.0  Rcpp_1.0.7        munsell_0.5.0     fansi_0.5.0      
[49] lifecycle_1.0.0   stringi_1.6.2     whisker_0.4       yaml_2.2.1       
[53] plyr_1.8.6        grid_4.1.0        ggrepel_0.9.1     parallel_4.1.0   
[57] promises_1.2.0.1  crayon_1.4.1      lattice_0.20-44   haven_2.4.1      
[61] hms_1.1.0         knitr_1.33        pillar_1.7.0      igraph_1.2.6     
[65] rjson_0.2.20      rngtools_1.5      reshape2_1.4.4    codetools_0.2-18 
[69] reprex_2.0.0      glue_1.4.2        evaluate_0.14     data.table_1.14.0
[73] modelr_0.1.8      png_0.1-7         vctrs_0.3.8       httpuv_1.6.1     
[77] foreach_1.5.1     cellranger_1.1.0  gtable_0.3.0      assertthat_0.2.1 
[81] xfun_0.24         broom_0.7.8       later_1.2.0       iterators_1.0.13 
[85] beeswarm_0.4.0    ellipsis_0.3.2