SCZ 2018 - Brain_Cerebellum

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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] 27353

#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 
2535 1830 1661  982 1135 1371 1536  916 1175 1171 1678 1471  543  971  987 1200 
  17   18   19   20   21   22 
1981  337 2002  917   48  906 

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

[1] 23734

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

[1] 0.8677

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 
0.0088825 0.0002955 

 gene   snp 
12.43 10.04 

[1] 105318

[1]    8002 6309950

    gene      snp 
0.008389 0.177721 

[1] 0.01561 1.06067

Genes with highest PIPs

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

Version	Author	Date
7d08c9b	sq-96	2022-05-18
2749be9	sq-96	2022-05-12

        genename region_tag susie_pip    mu2       PVE      z num_intron
5397      R3HDM2      12_36    0.9739  44.06 4.190e-04  6.634         10
854   BUB1B-PAK6      15_14    0.9156  30.33 2.452e-04 -5.588          4
4518      NPIPA1      16_15    0.9142  24.97 2.005e-04  4.689          3
3632   LINC00320       21_6    0.8839  29.24 2.240e-04 -5.336          3
1449       CLCN3      4_110    0.7913  29.64 1.762e-04  5.470          1
2078      DPYSL3       5_86    0.7675  21.98 1.229e-04  4.157          1
4586       NTRK3      15_41    0.7571  24.66 1.310e-04  4.457          2
1318       CENPM      22_17    0.7509  57.80 3.094e-04 -6.506          1
765         BDNF      11_19    0.7364  23.81 1.415e-04  4.348          3
1952        DHPS      19_10    0.7273  24.50 1.241e-04 -4.396          3
6899       THAP8      19_25    0.7268  22.04 1.105e-04 -3.840          1
6497      SPECC1      17_16    0.7238  25.92 1.289e-04 -4.822          1
3563       LAMA5      20_36    0.7061  23.61 1.554e-04  4.603         24
6429      SNRPA1      15_50    0.6840  21.86 1.028e-04 -3.896          6
360       ANAPC7      12_67    0.6619  37.61 1.771e-04  6.385          7
151        ACTG1      17_46    0.6582  25.43 1.074e-04 -4.250          2
849       BTN3A1       6_20    0.6374 146.39 5.732e-04 13.091          8
1700 CTB-31O20.2       19_2    0.6348  22.98 8.791e-05  4.456          1
1109       CASP2       7_89    0.6145  20.64 7.400e-05 -3.889          1
7160      TRANK1       3_27    0.6112  39.04 1.565e-04 -6.365          8
     num_sqtl
5397       12
854         5
4518        3
3632        3
1449        2
2078        1
4586        2
1318        1
765         3
1952        3
6899        1
6497        1
3563       38
6429        7
360         7
151         4
849         8
1700        1
1109        1
7160        8

Genes with highest PVE

       genename region_tag susie_pip    mu2       PVE       z num_intron
849      BTN3A1       6_20    0.6374 146.39 0.0005732  13.091          8
468        APOM       6_26    0.2337 623.03 0.0005094  11.590          3
5397     R3HDM2      12_36    0.9739  44.06 0.0004190   6.634         10
1318      CENPM      22_17    0.7509  57.80 0.0003094  -6.506          1
854  BUB1B-PAK6      15_14    0.9156  30.33 0.0002452  -5.588          4
7547       VWA7       6_26    0.1940 627.25 0.0002242  11.553          1
3632  LINC00320       21_6    0.8839  29.24 0.0002240  -5.336          3
4518     NPIPA1      16_15    0.9142  24.97 0.0002005   4.689          3
360      ANAPC7      12_67    0.6619  37.61 0.0001771   6.385          7
1449      CLCN3      4_110    0.7913  29.64 0.0001762   5.470          1
6119      SF3B1      2_117    0.4372  45.88 0.0001728   7.053          5
299        AKT3      1_128    0.5124  35.61 0.0001595   6.350          6
7160     TRANK1       3_27    0.6112  39.04 0.0001565  -6.365          8
3563      LAMA5      20_36    0.7061  23.61 0.0001554   4.603         24
4179       MSH5       6_26    0.1588 627.91 0.0001503 -11.538          3
469      APOPT1      14_54    0.4092  43.21 0.0001444   7.429          6
765        BDNF      11_19    0.7364  23.81 0.0001415   4.348          3
4586      NTRK3      15_41    0.7571  24.66 0.0001310   4.457          2
6497     SPECC1      17_16    0.7238  25.92 0.0001289  -4.822          1
1952       DHPS      19_10    0.7273  24.50 0.0001241  -4.396          3
     num_sqtl
849         8
468         3
5397       12
1318        1
854         5
7547        1
3632        3
4518        3
360         7
1449        2
6119        5
299         7
7160        8
3563       38
4179        3
469         7
765         3
4586        2
6497        1
1952        3

Comparing z scores and PIPs

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

Version	Author	Date
7d08c9b	sq-96	2022-05-18
2749be9	sq-96	2022-05-12

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

Version	Author	Date
7d08c9b	sq-96	2022-05-18
2749be9	sq-96	2022-05-12

[1] 0.02124

         genename region_tag susie_pip    mu2       PVE       z num_intron
849        BTN3A1       6_20 6.374e-01 146.39 5.732e-04  13.091          8
4876        PGBD1       6_22 3.519e-02 160.95 2.473e-06  13.087          5
468          APOM       6_26 2.337e-01 623.03 5.094e-04  11.590          3
7547         VWA7       6_26 1.940e-01 627.25 2.242e-04  11.553          1
7489         VARS       6_26 1.402e-01 623.95 1.165e-04 -11.548          2
4179         MSH5       6_26 1.588e-01 627.91 1.503e-04 -11.538          3
1888         DDR1       6_25 1.531e-01 105.86 2.397e-05 -11.175          3
7490        VARS2       6_25 1.076e-01 104.74 1.161e-05  11.137          2
979      C6orf136       6_25 3.795e-02  87.21 2.386e-06 -11.031          2
2623        FLOT1       6_25 2.776e-02  87.22 3.503e-06 -10.981          7
850        BTN3A2       6_20 1.254e-01  94.96 9.019e-06 -10.694          3
2841         GNL1       6_25 2.920e-03  78.25 6.334e-09 -10.645          1
7183       TRIM39       6_25 7.839e-03  82.27 4.800e-08 -10.616          1
716          BAG6       6_26 1.491e-09 498.08 1.051e-20  10.247          6
5195         PPT2       6_26 3.900e-12 464.25 1.341e-25 -10.061         10
5261        PRRT1       6_26 2.706e-12 462.51 3.216e-26 -10.018          1
2909        GPSM3       6_26 8.360e-14 414.68 2.752e-29  -9.377          1
1203       CCHCR1       6_25 1.796e-02  69.57 2.332e-07  -9.358         17
7105         TNXB       6_26 1.527e-13 452.13 1.000e-28   9.001          6
5832 RP5-874C20.8       6_22 1.377e-02  53.73 3.284e-07   8.672          6
     num_sqtl
849         8
4876        6
468         3
7547        1
7489        2
4179        3
1888        3
7490        2
979         2
2623        7
850         5
2841        1
7183        1
716         7
5195       12
5261        1
2909        1
1203       30
7105        7
5832        6

GO enrichment analysis for genes with PIP>0.5

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

[1] 29

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
7d08c9b	sq-96	2022-05-18
2749be9	sq-96	2022-05-12

                                                               Term Overlap
1              morphogenesis of a polarized epithelium (GO:0001738)    2/12
2 positive regulation of neuron projection development (GO:0010976)    3/88
3    cellular response to nerve growth factor stimulus (GO:1990090)    2/22
4  positive regulation of cell projection organization (GO:0031346)   3/117
  Adjusted.P.value             Genes
1          0.03944       LAMA5;ACTG1
2          0.04111 BDNF;NTRK3;DPYSL3
3          0.04560        BDNF;NTRK3
4          0.04737 BDNF;NTRK3;DPYSL3
[1] "GO_Cellular_Component_2021"

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

Version	Author	Date
7d08c9b	sq-96	2022-05-18
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"

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

Version	Author	Date
7d08c9b	sq-96	2022-05-18
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 BgRatio
78                   Electroencephalogram abnormal 0.009968  1/15  1/9703
97                             Short upturned nose 0.009968  1/15  1/9703
159                       Abnormality of the pinna 0.009968  1/15  1/9703
176   Progressive sensorineural hearing impairment 0.009968  1/15  1/9703
177                                   Pointed chin 0.009968  1/15  1/9703
178                         Long palpebral fissure 0.009968  1/15  1/9703
182                Deafness, Autosomal Dominant 20 0.009968  1/15  1/9703
183 TOBACCO ADDICTION, SUSCEPTIBILITY TO (finding) 0.009968  2/15 12/9703
185                                  Long philtrum 0.009968  1/15  1/9703
186                       Thin upper lip vermilion 0.009968  1/15  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
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] 59

#significance threshold for TWAS
print(sig_thresh)

[1] 4.518

#number of ctwas genes
length(ctwas_genes)

[1] 4

#number of TWAS genes
length(twas_genes)

[1] 170

#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 0.17692 

#specificity
print(specificity)

 ctwas   TWAS 
0.9997 0.9815 

#precision / PPV
print(precision)

 ctwas   TWAS 
0.5000 0.1353 

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