Last updated: 2021-09-08

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Knit directory: ~/Github/ARIC/

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Liftover

Definitions

conda activate imlabtools
METAXCAN=/Users/sabrinami/Github/MetaXcan/software
DATA=/Users/sabrinami/Github/ARIC/test_data/GWAS
RESULTS=/Users/sabrinami/Github/ARIC/results/SPrediXcan
MODEL=/Users/sabrinami/Github/ARIC/models

Validation

Definitions

.

suppressPackageStartupMessages(library(tidyverse))
suppressPackageStartupMessages(library(qqman))
suppressPackageStartupMessages(library(data.table))
suppressPackageStartupMessages(library(RSQLite))
DATA="/Users/sabrinami/Github/ARIC/test_data/GWAS"
RESULTS="/Users/sabrinami/Github/ARIC/results/SPrediXcan"
MODEL="/Users/sabrinami/Github/ARIC/models"
CODE="/Users/sabrinami/Github/ARIC/code"
source(glue::glue("{CODE}/load_data_functions.R"))
source(glue::glue("{CODE}/plotting_utils_functions.R"))

gencode_df = load_gencode_df()

Run S-PrediXcan

Run S-PrediXcan with the ARIC model.

python $METAXCAN/SPrediXcan.py \
--gwas_file  $DATA/imputed_CARDIoGRAM_C4D_CAD_ADDITIVE.txt.gz \
--snp_column panel_variant_id --effect_allele_column effect_allele --non_effect_allele_column non_effect_allele --zscore_column zscore \
--model_db_path $MODEL/ARIC_EA_hg38.db \
--covariance $MODEL/ARIC_EA_hg38.txt.gz \
--keep_non_rsid --additional_output --model_db_snp_key varID \
--throw \
--output_file $RESULTS/CAD_ARIC_hg38.csv

And the mashr model.

python $METAXCAN/SPrediXcan.py \
--gwas_file  $DATA/imputed_CARDIoGRAM_C4D_CAD_ADDITIVE.txt.gz \
--snp_column panel_variant_id --effect_allele_column effect_allele --non_effect_allele_column non_effect_allele --zscore_column zscore \
--model_db_path $MODEL/mashr_Whole_Blood.db \
--covariance $MODEL/mashr_Whole_Blood.txt.gz \
--keep_non_rsid --additional_output --model_db_snp_key varID \
--throw \
--output_file $RESULTS/CAD_mashr_Whole_Blood.csv

Compare Association Results

spredixcan_association_ARIC = load_spredixcan_association(glue::glue("{RESULTS}/CAD_ARIC_hg38.csv"), gencode_df)
dim(spredixcan_association_ARIC)
[1] 1318   16
significant_genes_ARIC <- spredixcan_association_ARIC %>% filter(pvalue < 0.05/nrow(spredixcan_association_ARIC)) %>% arrange(pvalue)
spredixcan_association_Whole_Blood = load_spredixcan_association(glue::glue("{RESULTS}/CAD_mashr_Whole_Blood.csv"), gencode_df)
dim(spredixcan_association_Whole_Blood)
[1] 12587    16
significant_genes_Whole_Blood <- spredixcan_association_Whole_Blood %>% filter(pvalue < 0.05/nrow(spredixcan_association_Whole_Blood)) %>% arrange(pvalue)

Then compare ARIC and Whole Blood z-scores.

zscores = inner_join(spredixcan_association_Whole_Blood, spredixcan_association_ARIC, by=c("gene"))
dim(zscores)
[1] 815  31
zscores %>% ggplot(aes(zscore.x, zscore.y)) + geom_point() + ggtitle("S-PrediXcan z-score") + xlab("mashr Whole Blood") + ylab("ARIC") + geom_abline(intercept = 0, slope = 1)
Warning: Removed 1 rows containing missing values (geom_point).

We can compare the significant genes found with the ARIC and mashr Whole Blood models.

significant_genes_ARIC[, c(1,2)]
             gene    zscore
1 ENSG00000186063 -6.914873
2 ENSG00000160712 -5.813218
3 ENSG00000169174  5.326004
4 ENSG00000133789 -5.085480
5 ENSG00000107562  4.976651
6 ENSG00000158710  4.567579
7 ENSG00000158710  4.567579
8 ENSG00000175573  4.125269
significant_genes_Whole_Blood[, c(1,2)]
              gene    zscore
1  ENSG00000134222 -9.263287
2  ENSG00000107798  7.525837
3  ENSG00000163596  7.210367
4  ENSG00000138380 -5.982736
5  ENSG00000160712  5.744854
6  ENSG00000127616  5.703439
7  ENSG00000183431 -5.382606
8  ENSG00000182511 -5.373519
9  ENSG00000115486  5.258467
10 ENSG00000084093 -5.204898
11 ENSG00000143498  4.920139
12 ENSG00000031698 -4.747462
13 ENSG00000168906 -4.698991
14 ENSG00000130475 -4.683521
15 ENSG00000119718  4.681344
intersect(significant_genes_ARIC$gene,significant_genes_Whole_Blood$gene)
[1] "ENSG00000160712"

There is only one gene found significant in both, ENSG00000160712


sessionInfo()
R version 4.0.3 (2020-10-10)
Platform: x86_64-apple-darwin17.0 (64-bit)
Running under: macOS Big Sur 10.16

Matrix products: default
BLAS:   /Library/Frameworks/R.framework/Versions/4.0/Resources/lib/libRblas.dylib
LAPACK: /Library/Frameworks/R.framework/Versions/4.0/Resources/lib/libRlapack.dylib

locale:
[1] en_US.UTF-8/en_US.UTF-8/en_US.UTF-8/C/en_US.UTF-8/en_US.UTF-8

attached base packages:
[1] stats     graphics  grDevices utils     datasets  methods   base     

other attached packages:
 [1] RSQLite_2.2.1     data.table_1.13.2 qqman_0.1.4       forcats_0.5.0    
 [5] stringr_1.4.0     dplyr_1.0.2       purrr_0.3.4       readr_1.4.0      
 [9] tidyr_1.1.2       tibble_3.0.4      ggplot2_3.3.2     tidyverse_1.3.0  

loaded via a namespace (and not attached):
 [1] Rcpp_1.0.5       lubridate_1.7.9  assertthat_0.2.1 rprojroot_1.3-2 
 [5] digest_0.6.27    R6_2.4.1         cellranger_1.1.0 backports_1.1.10
 [9] reprex_0.3.0     evaluate_0.14    httr_1.4.2       highr_0.8       
[13] pillar_1.4.6     rlang_0.4.8      readxl_1.3.1     rstudioapi_0.11 
[17] blob_1.2.1       rmarkdown_2.5    labeling_0.4.2   bit_4.0.4       
[21] munsell_0.5.0    broom_0.7.2      compiler_4.0.3   httpuv_1.5.4    
[25] modelr_0.1.8     xfun_0.18        pkgconfig_2.0.3  htmltools_0.5.0 
[29] tidyselect_1.1.0 workflowr_1.6.2  fansi_0.4.1      calibrate_1.7.7 
[33] crayon_1.3.4     dbplyr_1.4.4     withr_2.3.0      later_1.1.0.1   
[37] MASS_7.3-53      grid_4.0.3       jsonlite_1.7.1   gtable_0.3.0    
[41] lifecycle_0.2.0  DBI_1.1.0        git2r_0.27.1     magrittr_1.5    
[45] scales_1.1.1     cli_2.1.0        stringi_1.5.3    farver_2.0.3    
[49] fs_1.5.0         promises_1.1.1   xml2_1.3.2       ellipsis_0.3.1  
[53] generics_0.0.2   vctrs_0.3.4      tools_4.0.3      bit64_4.0.5     
[57] glue_1.4.2       hms_0.5.3        yaml_2.2.1       colorspace_1.4-1
[61] rvest_0.3.6      memoise_1.1.0    knitr_1.30       haven_2.3.1