SCZ 2018 - Brain_Anterior_cingulate_cortex_BA24

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Last updated: 2022-05-19

Checks: 5 2

Knit directory: cTWAS_analysis/

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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] 18988

#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 
1766 1297 1118  729  754  987 1093  674  787  871 1192 1048  389  666  643  793 
  17   18   19   20   21   22 
1329  261 1342  620   35  594 

#number of imputed weights without missing variants
sum(qclist_all$nmiss==0)

[1] 16837

#proportion of imputed weights without missing variants
mean(qclist_all$nmiss==0)

[1] 0.8867

INFO:numexpr.utils:Note: NumExpr detected 56 cores but "NUMEXPR_MAX_THREADS" not set, so enforcing safe limit of 8.

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

Past versions of unnamed-chunk-12-1.png

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

     gene       snp 
0.0068134 0.0003114 

 gene   snp 
15.56 10.20 

[1] 105318

[1]    7115 6309950

    gene      snp 
0.007161 0.190316 

[1] 0.01572 1.10677

Genes with highest PIPs

Past versions of unnamed-chunk-14-1.png

Version	Author	Date
bcaadf3	sq-96	2022-05-19
be614ed	sq-96	2022-05-19
2749be9	sq-96	2022-05-12

       genename region_tag susie_pip    mu2       PVE       z num_intron
765      BTN2A1       6_20    1.0491 157.37 1.570e-03 -13.238          6
3347       LRP8       1_33    1.0010  25.97 2.331e-04   4.820          6
3331     LPCAT4      15_10    0.9457  26.08 2.141e-04   4.892          4
772  BUB1B-PAK6      15_14    0.9157  31.13 2.438e-04  -5.588          3
4084      NRXN2      11_36    0.8999  25.63 1.950e-04   4.723          4
5808     SPECC1      17_16    0.8947  26.90 2.013e-04  -5.038          3
627      B3GAT1      11_84    0.8865  22.73 1.578e-04   4.343          9
3740     MRPS33       7_87    0.8542  21.83 1.489e-04  -4.304          4
6155      THAP8      19_25    0.8477  20.15 1.375e-04   3.847          2
265        AKT3      1_128    0.8362  36.35 2.280e-04  -6.350          7
419      APOPT1      14_54    0.8209  50.53 3.169e-04   7.429          7
691        BDNF      11_19    0.8143  24.21 1.499e-04   4.348          3
1867     DPYSL3       5_86    0.7890  23.30 1.377e-04   4.157          1
2489     GIGYF1       7_62    0.7603  28.78 1.561e-04   5.266          2
3985       NGEF      2_137    0.7358  31.04 1.576e-04   6.994          2
1656      DBF4B      17_26    0.7211  19.92 9.437e-05  -3.890          5
4832     R3HDM2      12_36    0.6939  22.64 1.027e-04  -4.237          2
5749     SNRPA1      15_50    0.6925  22.95 1.029e-04  -3.948          2
2820      HSPA9       5_82    0.6773  28.81 1.255e-04   5.633          1
138      ACTR1B       2_57    0.6669  21.84 9.034e-05  -3.978          4
     num_sqtl
765         7
3347        6
3331        4
772         3
4084        4
5808        4
627        14
3740        4
6155        2
265         8
419         9
691         4
1867        1
2489        2
3985        2
1656        5
4832        3
5749        3
2820        1
138         4

Genes with highest PVE

       genename region_tag susie_pip    mu2       PVE       z num_intron
765      BTN2A1       6_20    1.0491 157.37 0.0015695 -13.238          6
3381       LSM2       6_26    0.3709 658.01 0.0008595 -11.599          1
418        APOM       6_26    0.2474 649.69 0.0003774  11.590          2
419      APOPT1      14_54    0.8209  50.53 0.0003169   7.429          7
772  BUB1B-PAK6      15_14    0.9157  31.13 0.0002438  -5.588          3
3347       LRP8       1_33    1.0010  25.97 0.0002331   4.820          6
265        AKT3      1_128    0.8362  36.35 0.0002280  -6.350          7
3331     LPCAT4      15_10    0.9457  26.08 0.0002141   4.892          4
5808     SPECC1      17_16    0.8947  26.90 0.0002013  -5.038          3
4084      NRXN2      11_36    0.8999  25.63 0.0001950   4.723          4
627      B3GAT1      11_84    0.8865  22.73 0.0001578   4.343          9
3985       NGEF      2_137    0.7358  31.04 0.0001576   6.994          2
2489     GIGYF1       7_62    0.7603  28.78 0.0001561   5.266          2
3751       MSH5       6_26    0.1568 654.60 0.0001528  11.531          2
691        BDNF      11_19    0.8143  24.21 0.0001499   4.348          3
3740     MRPS33       7_87    0.8542  21.83 0.0001489  -4.304          4
1867     DPYSL3       5_86    0.7890  23.30 0.0001377   4.157          1
6155      THAP8      19_25    0.8477  20.15 0.0001375   3.847          2
6685       VARS       6_26    0.1464 650.58 0.0001324 -11.548          1
2308        FES      15_42    0.6005  37.84 0.0001270   5.964          3
     num_sqtl
765         7
3381        1
418         2
419         9
772         3
3347        6
265         8
3331        4
5808        4
4084        4
627        14
3985        2
2489        2
3751        2
691         4
3740        4
1867        1
6155        2
6685        1
2308        4

Comparing z scores and PIPs

Past versions of unnamed-chunk-16-1.png

Version	Author	Date
be614ed	sq-96	2022-05-19
2749be9	sq-96	2022-05-12

Past versions of unnamed-chunk-16-2.png

Version	Author	Date
bcaadf3	sq-96	2022-05-19
be614ed	sq-96	2022-05-19
2749be9	sq-96	2022-05-12

[1] 0.01673

         genename region_tag susie_pip    mu2       PVE       z num_intron
765        BTN2A1       6_20 1.049e+00 157.37 1.570e-03 -13.238          6
4373        PGBD1       6_22 2.219e-02 167.48 4.926e-07 -13.087          2
3381         LSM2       6_26 3.709e-01 658.01 8.595e-04 -11.599          1
418          APOM       6_26 2.474e-01 649.69 3.774e-04  11.590          2
6685         VARS       6_26 1.464e-01 650.58 1.324e-04 -11.548          1
3751         MSH5       6_26 1.568e-01 654.60 1.528e-04  11.531          2
1693         DDR1       6_25 2.429e-01 105.31 5.771e-05  11.175          3
894      C6orf136       6_24 1.025e-01  84.83 8.464e-06  11.031          2
2345        FLOT1       6_24 2.514e-01  83.46 4.991e-05  10.981          7
768        BTN3A2       6_20 1.281e-01 102.85 5.057e-06 -10.732          5
643          BAG6       6_26 8.739e-10 518.30 3.759e-21  10.247          7
4649         PPT2       6_26 4.838e-13 483.22 1.074e-27 -10.061          4
2597        GPSM3       6_26 2.154e-14 431.49 1.901e-30   9.377          2
1084       CCHCR1       6_25 3.360e-02  63.97 3.100e-07  -9.244          9
2755      HLA-DMA       6_27 4.764e-02  70.44 8.914e-07   8.781          4
5239 RP5-874C20.8       6_22 2.995e-02  56.35 2.939e-07   8.672          4
4099        NT5C2      10_66 4.423e-01  49.30 8.938e-05  -8.541          9
513         AS3MT      10_66 3.247e-01  46.06 4.535e-05   8.051          5
7107      ZSCAN16       6_22 2.986e-02  56.18 3.388e-07   7.468          4
419        APOPT1      14_54 8.209e-01  50.53 3.169e-04   7.429          7
     num_sqtl
765         7
4373        2
3381        1
418         2
6685        1
3751        2
1693        3
894         2
2345        7
768         6
643         7
4649        4
2597        2
1084       13
2755        4
5239        4
4099       12
513         5
7107        4
419         9

GO enrichment analysis for genes with PIP>0.5

#number of genes for gene set enrichment
length(genes)

[1] 45

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"

Past versions of unnamed-chunk-19-1.png

Version	Author	Date
bcaadf3	sq-96	2022-05-19
be614ed	sq-96	2022-05-19
2749be9	sq-96	2022-05-12

                                                               Term Overlap
1 positive regulation of neuron projection development (GO:0010976)    4/88
2         modulation of chemical synaptic transmission (GO:0050804)   4/109
  Adjusted.P.value                 Genes
1          0.01853  BDNF;FES;DPYSL3;LRP8
2          0.02136 BDNF;LRP8;DGKZ;BEGAIN
[1] "GO_Cellular_Component_2021"

Past versions of unnamed-chunk-19-2.png

Version	Author	Date
bcaadf3	sq-96	2022-05-19
be614ed	sq-96	2022-05-19
2749be9	sq-96	2022-05-12

                                              Term Overlap Adjusted.P.value
1 protein phosphatase type 2A complex (GO:0000159)    2/17          0.03624
            Genes
1 PPP2R5B;PPP2R2A
[1] "GO_Molecular_Function_2021"

Past versions of unnamed-chunk-19-3.png

Version	Author	Date
bcaadf3	sq-96	2022-05-19
be614ed	sq-96	2022-05-19
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
12                                                Renal Cell Carcinoma 0.0342
36                                                             Measles 0.0342
137                                   Chromophobe Renal Cell Carcinoma 0.0342
138                                   Sarcomatoid Renal Cell Carcinoma 0.0342
139                            Collecting Duct Carcinoma of the Kidney 0.0342
142                                     Papillary Renal Cell Carcinoma 0.0342
152                                 Maple Syrup Urine Disease, Type IA 0.0342
157          HEMOLYTIC UREMIC SYNDROME, ATYPICAL, SUSCEPTIBILITY TO, 2 0.0342
166               MITOCHONDRIAL COMPLEX III DEFICIENCY, NUCLEAR TYPE 5 0.0342
174 MEGALENCEPHALY-POLYMICROGYRIA-POLYDACTYLY-HYDROCEPHALUS SYNDROME 2 0.0342
    Ratio  BgRatio
12   3/20 128/9703
36   1/20   1/9703
137  3/20 128/9703
138  3/20 128/9703
139  3/20 128/9703
142  3/20 128/9703
152  1/20   1/9703
157  1/20   1/9703
166  1/20   1/9703
174  1/20   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: 5 unlabeled data points (too many overlaps). Consider
increasing max.overlaps

Past versions of unnamed-chunk-22-1.png

Version	Author	Date
bcaadf3	sq-96	2022-05-19
be614ed	sq-96	2022-05-19
7d08c9b	sq-96	2022-05-18
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] 51

#significance threshold for TWAS
print(sig_thresh)

[1] 4.493

#number of ctwas genes
length(ctwas_genes)

[1] 12

#number of TWAS genes
length(twas_genes)

[1] 119

#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_intron num_sqtl
627    B3GAT1      11_84    0.8865 22.73 0.0001578  4.343          9       14
691      BDNF      11_19    0.8143 24.21 0.0001499  4.348          3        4
3740   MRPS33       7_87    0.8542 21.83 0.0001489 -4.304          4        4
6155    THAP8      19_25    0.8477 20.15 0.0001375  3.847          2        2

#sensitivity / recall
print(sensitivity)

  ctwas    TWAS 
0.01538 0.08462 

#specificity
print(specificity)

 ctwas   TWAS 
0.9986 0.9847 

#precision / PPV
print(precision)

  ctwas    TWAS 
0.16667 0.09244 

Session information

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_1.25   workflowr_1.7.0  

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  processx_3.5.2    curl_4.3.2        compiler_4.1.0   
[21] git2r_0.28.0      rvest_1.0.0       cli_3.0.0         Cairo_1.5-15     
[25] xml2_1.3.2        labeling_0.4.2    sass_0.4.0        scales_1.1.1     
[29] callr_3.7.0       systemfonts_1.0.4 apcluster_1.4.9   digest_0.6.27    
[33] rmarkdown_2.9     svglite_2.0.0     pkgconfig_2.0.3   htmltools_0.5.1.1
[37] dbplyr_2.1.1      highr_0.9         rlang_1.0.2       rstudioapi_0.13  
[41] jquerylib_0.1.4   farver_2.1.0      generics_0.1.0    jsonlite_1.7.2   
[45] magrittr_2.0.1    Matrix_1.3-3      ggbeeswarm_0.6.0  Rcpp_1.0.7       
[49] munsell_0.5.0     fansi_0.5.0       lifecycle_1.0.0   stringi_1.6.2    
[53] whisker_0.4       yaml_2.2.1        plyr_1.8.6        grid_4.1.0       
[57] ggrepel_0.9.1     parallel_4.1.0    promises_1.2.0.1  crayon_1.4.1     
[61] lattice_0.20-44   haven_2.4.1       hms_1.1.0         knitr_1.33       
[65] ps_1.6.0          pillar_1.7.0      igraph_1.2.6      rjson_0.2.20     
[69] rngtools_1.5      reshape2_1.4.4    codetools_0.2-18  reprex_2.0.0     
[73] glue_1.4.2        evaluate_0.14     getPass_0.2-2     modelr_0.1.8     
[77] data.table_1.14.0 png_0.1-7         vctrs_0.3.8       httpuv_1.6.1     
[81] foreach_1.5.1     cellranger_1.1.0  gtable_0.3.0      assertthat_0.2.1 
[85] xfun_0.24         broom_0.7.8       later_1.2.0       iterators_1.0.13 
[89] beeswarm_0.4.0    ellipsis_0.3.2    here_1.0.1