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A simulation of expression and splicing traits from three tissues is conducted to evaluate cTWAS performance (parameter estimation, PIP calibration …). Three tissues used in this simulation are Liver, Lung, Spleen.

It current has three settings:

  • One tissue case: 3% PVE, 0.9% \(\pi\) for E and S from Liver and 30% PVE, 2.5e-4 \(\pi\) for SNP.
  • 3% PVE, 0.9% \(\pi\) for E from three tissues, 0% PVE, 0% \(\pi\) for S from three tissues and 30% PVE, 2.5e-4 \(\pi\) for SNP.
  • 3% PVE, 0.9% \(\pi\) for Liver E, Liver S and Lung E, 0% PVE, 0% \(\pi\) for the others and 30% PVE, 2.5e-4 \(\pi\) for SNP.

Findings: I think there are still correlations between E and S within a tissues. For example, in the first case, we see inflations in the PIP calibration plots.

Simulation 1: Expression and Splicing from Liver (3% PVE)

Results using PIP Threshold

  simutag n_causal n_detected_pip n_detected_pip_in_causal
1     1-1      339             51                       48
2     1-2      314             36                       32
3     1-3      296             44                       38
4     1-4      308             34                       28
5     1-5      329             33                       29
[1] 0.8838384

Estimated Prior Inclusion Probability

Version Author Date
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Estimated PVE

Version Author Date
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Estimated Prior Variance

Version Author Date
7a7c814 sq-96 2024-01-19
6637147 sq-96 2024-01-19

Estimated Enrichment

Version Author Date
7a7c814 sq-96 2024-01-19
6637147 sq-96 2024-01-19

PIP Calibration Plot

Version Author Date
6637147 sq-96 2024-01-19

Simulation 2: Expression traits from three tissues are causal (3% PVE).

Results using PIP Threshold

  simutag n_causal n_detected_pip n_detected_pip_in_causal
1     2-1      222             33                       27
2     2-2      259             37                       32
3     2-3      241             32                       30
4     2-4      246             30                       26
5     2-5      248             19                       16
[1] 0.8675497

Estimated Prior Inclusion Probability

Version Author Date
7a7c814 sq-96 2024-01-19
6637147 sq-96 2024-01-19

Estimated PVE

Version Author Date
7a7c814 sq-96 2024-01-19
6637147 sq-96 2024-01-19

Estimated Prior Variance

Version Author Date
6637147 sq-96 2024-01-19

Estimated Enrichment

Version Author Date
6637147 sq-96 2024-01-19

PIP Calibration Plot

Version Author Date
6637147 sq-96 2024-01-19

Simulation 2: Expression traits from Liver and Lung and Splicing traits from Liver are causal (3% PVE).

Results using PIP Threshold

  simutag n_causal n_detected_pip n_detected_pip_in_causal
1     3-1      274             25                       24
2     3-2      292             21                       20
3     3-3      290             13                       12
4     3-4      291             30                       26
5     3-5      268             15                       12
[1] 0.9038462

Estimated Prior Inclusion Probability

Version Author Date
7a7c814 sq-96 2024-01-19
6637147 sq-96 2024-01-19

Estimated PVE

Version Author Date
7a7c814 sq-96 2024-01-19
6637147 sq-96 2024-01-19

Estimated Prior Variance

Version Author Date
6637147 sq-96 2024-01-19

Estimated Enrichment

Version Author Date
7a7c814 sq-96 2024-01-19
6637147 sq-96 2024-01-19

PIP Calibration Plot

Version Author Date
6637147 sq-96 2024-01-19

Simulation 4: Expression traits from Liver and Lung and Splicing traits from Liver are causal (3% PVE).

Results using PIP Threshold

  simutag n_causal n_detected_pip n_detected_pip_in_causal
1     4-1      779             34                       28
2     4-2      731             27                       22
3     4-3      764             32                       24
4     4-4      740             26                       22
5     4-5      853             43                       36
[1] 0.8148148

Estimated Prior Inclusion Probability

Estimated PVE

Estimated Prior Variance

Estimated Enrichment

PIP Calibration Plot

Simulation 5: Expression and Splicing traits from Liver are causal(3% PVE).

Results using PIP Threshold

  simutag n_causal n_detected_pip n_detected_pip_in_causal
1     5-1      198             24                       20
2     5-2      191             14                       13
3     5-3      197             17                       17
4     5-4      181             26                       20
5     5-5      203             11                       10
[1] 0.8695652

Estimated Prior Inclusion Probability

Estimated PVE

Estimated Prior Variance

Estimated Enrichment

PIP Calibration Plot

PIP Calibration Plot (L1=1)

PIP Calibration Plot (True parameters)


sessionInfo()
R version 4.1.0 (2021-05-18)
Platform: x86_64-pc-linux-gnu (64-bit)
Running under: CentOS Linux 7 (Core)

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] plyr_1.8.8        ggpubr_0.6.0      plotrix_3.8-4     cowplot_1.1.1    
[5] ggplot2_3.4.0     latex2exp_0.9.6   data.table_1.14.6 ctwas_0.1.40     
[9] workflowr_1.7.0  

loaded via a namespace (and not attached):
 [1] Rcpp_1.0.9       lattice_0.20-44  tidyr_1.3.0      getPass_0.2-2   
 [5] ps_1.7.2         assertthat_0.2.1 rprojroot_2.0.3  digest_0.6.31   
 [9] foreach_1.5.2    utf8_1.2.2       R6_2.5.1         backports_1.2.1 
[13] evaluate_0.19    highr_0.9        httr_1.4.4       pillar_1.8.1    
[17] rlang_1.1.1      rstudioapi_0.14  car_3.1-1        whisker_0.4.1   
[21] callr_3.7.3      jquerylib_0.1.4  Matrix_1.3-3     rmarkdown_2.19  
[25] labeling_0.4.2   stringr_1.5.0    munsell_0.5.0    broom_1.0.2     
[29] compiler_4.1.0   httpuv_1.6.7     xfun_0.35        pkgconfig_2.0.3 
[33] htmltools_0.5.4  tidyselect_1.2.0 tibble_3.1.8     logging_0.10-108
[37] codetools_0.2-18 fansi_1.0.3      dplyr_1.0.10     withr_2.5.0     
[41] later_1.3.0      grid_4.1.0       jsonlite_1.8.4   gtable_0.3.1    
[45] lifecycle_1.0.3  DBI_1.1.3        git2r_0.30.1     magrittr_2.0.3  
[49] scales_1.2.1     carData_3.0-4    cli_3.6.1        stringi_1.7.8   
[53] cachem_1.0.6     farver_2.1.0     ggsignif_0.6.4   fs_1.5.2        
[57] promises_1.2.0.1 pgenlibr_0.3.2   bslib_0.4.1      vctrs_0.6.3     
[61] generics_0.1.3   iterators_1.0.14 tools_4.1.0      glue_1.6.2      
[65] purrr_1.0.2      abind_1.4-5      processx_3.8.0   fastmap_1.1.0   
[69] yaml_2.3.6       colorspace_2.0-3 rstatix_0.7.2    knitr_1.41      
[73] sass_0.4.4