Last updated: 2022-04-18

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Knit directory: cTWAS_analysis/

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brain_tissue <- list.files("/project2/xinhe/shengqian/cTWAS/cTWAS_analysis/data/SCZ_2014_EUR/")
top_genes <- c()
all_genes <- c()
for(i in brain_tissue){
  df <- readRDS(paste0("/project2/xinhe/shengqian/cTWAS/cTWAS_analysis/data/SCZ_2014_EUR/",i,"/SCZ_",i,"_ctwas_gene_res.RDS"))
  all_genes <- c(all_genes,df$genename)
  df <- df[df$susie_pip>=0.5,]
  top_genes <- c(top_genes,df$genename)
}
top_genes <- unique(top_genes)
all_genes <- unique(all_genes)
set.seed(2022)
random_genes <- sample(all_genes,1000)
library(readxl)
Supplementary_Table_15_MAGMA <- read_excel("data/Supplementary Table 15 - MAGMA.xlsx", 
    sheet = "Gene Lists")

summary_known_genes_annotations <- read_excel("data/summary_known_genes_annotations.xlsx", 
    sheet = "SCZ")

SCHEMA_genes <- Supplementary_Table_15_MAGMA$`SCHEMA (p<0.001)`
SCHEMA_genes <- SCHEMA_genes[!is.na(SCHEMA_genes)]

ASD_genes <- Supplementary_Table_15_MAGMA$`ASD (Satterstrom et al. 2019)`
ASD_genes <- ASD_genes[!is.na(ASD_genes)]

DDD_genes <- Supplementary_Table_15_MAGMA$`DDD (Kaplanis et al. 2019)`
DDD_genes <- DDD_genes[!is.na(DDD_genes)]


PGC3_genes <- summary_known_genes_annotations$`Gene Symbol`
PGC3_genes <- PGC3_genes[!is.na(PGC3_genes)]
Supplementary_Table_20_Prioritised_Genes <- read_excel("data/Supplementary Table 20 - Prioritised Genes.xlsx", 
    sheet = "ST20 all criteria")

SMR_genes <- Supplementary_Table_20_Prioritised_Genes[,c("Symbol.ID","SMRmap","SMRsingleGene","HI.C.SMR")]
SMR_genes["index"] <- (SMR_genes$SMRmap==1) | (SMR_genes$SMRsingleGene==1) | (SMR_genes$HI.C.SMR==1)
SMR_genes <- SMR_genes[SMR_genes$index==1,]$Symbol.ID
sum(top_genes %in% SCHEMA_genes)
[1] 2
sum(top_genes %in% ASD_genes)
[1] 1
sum(top_genes %in% DDD_genes)
[1] 5
sum(top_genes %in% PGC3_genes)
[1] 9
sum(top_genes %in% setdiff(PGC3_genes,SMR_genes))
[1] 1
sum(random_genes %in% SCHEMA_genes)
[1] 3
sum(random_genes %in% ASD_genes)
[1] 7
sum(random_genes %in% DDD_genes)
[1] 14
sum(random_genes %in% PGC3_genes)
[1] 6
sum(random_genes %in% setdiff(PGC3_genes,SMR_genes))
[1] 4
fisher.test(matrix(c(sum(top_genes %in% SCHEMA_genes),length(top_genes)-sum(top_genes %in% SCHEMA_genes),sum(random_genes %in% SCHEMA_genes),1000-sum(random_genes %in% SCHEMA_genes)),ncol=2))

    Fisher's Exact Test for Count Data

data:  
p-value = 0.1413
alternative hypothesis: true odds ratio is not equal to 1
95 percent confidence interval:
  0.350347 37.179757
sample estimates:
odds ratio 
  4.225739 
fisher.test(matrix(c(sum(top_genes %in% ASD_genes),length(top_genes)-sum(top_genes %in% ASD_genes),sum(random_genes %in% ASD_genes),1000-sum(random_genes %in% ASD_genes)),ncol=2))

    Fisher's Exact Test for Count Data

data:  
p-value = 1
alternative hypothesis: true odds ratio is not equal to 1
95 percent confidence interval:
 0.01979746 7.06655191
sample estimates:
odds ratio 
  0.897886 
fisher.test(matrix(c(sum(top_genes %in% DDD_genes),length(top_genes)-sum(top_genes %in% DDD_genes),sum(random_genes %in% DDD_genes),1000-sum(random_genes %in% DDD_genes)),ncol=2))

    Fisher's Exact Test for Count Data

data:  
p-value = 0.1657
alternative hypothesis: true odds ratio is not equal to 1
95 percent confidence interval:
 0.6348484 6.8334851
sample estimates:
odds ratio 
  2.284503 
fisher.test(matrix(c(sum(top_genes %in% PGC3_genes),length(top_genes)-sum(top_genes %in% PGC3_genes),sum(random_genes %in% PGC3_genes),1000-sum(random_genes %in% PGC3_genes)),ncol=2))

    Fisher's Exact Test for Count Data

data:  
p-value = 3.34e-05
alternative hypothesis: true odds ratio is not equal to 1
95 percent confidence interval:
  3.09800 34.34657
sample estimates:
odds ratio 
  9.904212 
fisher.test(matrix(c(sum(top_genes %in% setdiff(PGC3_genes,SMR_genes)),length(top_genes)-sum(top_genes %in% setdiff(PGC3_genes,SMR_genes)),sum(random_genes %in% setdiff(PGC3_genes,SMR_genes)),1000-sum(random_genes %in% setdiff(PGC3_genes,SMR_genes))),ncol=2))

    Fisher's Exact Test for Count Data

data:  
p-value = 0.5225
alternative hypothesis: true odds ratio is not equal to 1
95 percent confidence interval:
  0.03180166 16.04506772
sample estimates:
odds ratio 
  1.575219 
library(enrichR)
Welcome to enrichR
Checking connection ... 
Enrichr ... Connection is Live!
FlyEnrichr ... Connection is available!
WormEnrichr ... Connection is available!
YeastEnrichr ... Connection is available!
FishEnrichr ... Connection is available!
dbs <- c("GO_Biological_Process_2021", "GO_Cellular_Component_2021", "GO_Molecular_Function_2021")

if (length(top_genes)>0){
  GO_enrichment <- enrichr(top_genes, dbs)

  for (db in dbs){
    print(db)
    df <- GO_enrichment[[db]]
    print(plotEnrich(GO_enrichment[[db]]))
    df <- df[df$Adjusted.P.value<0.05,c("Term", "Overlap", "Adjusted.P.value", "Genes")]
    print(df)
  }
}
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
0552ba2 sq-96 2022-04-18
[1] Term             Overlap          Adjusted.P.value Genes           
<0 rows> (or 0-length row.names)
[1] "GO_Cellular_Component_2021"

Version Author Date
0552ba2 sq-96 2022-04-18
[1] Term             Overlap          Adjusted.P.value Genes           
<0 rows> (or 0-length row.names)
[1] "GO_Molecular_Function_2021"

Version Author Date
0552ba2 sq-96 2022-04-18
[1] Term             Overlap          Adjusted.P.value Genes           
<0 rows> (or 0-length row.names)
                                       Description        FDR Ratio  BgRatio
84                                         Measles 0.04999924  1/65   1/9703
106                                  Schizophrenia 0.04999924 13/65 883/9703
108                                   Spasmophilia 0.04999924  1/65   1/9703
116                                    Tachycardia 0.04999924  2/65  18/9703
117                                         Tetany 0.04999924  1/65   1/9703
123                                Tachyarrhythmia 0.04999924  2/65  18/9703
179                               Alstrom Syndrome 0.04999924  1/65   1/9703
180                               Tetany, Neonatal 0.04999924  1/65   1/9703
210 Renal dysplasia and retinal aplasia (disorder) 0.04999924  2/65  12/9703
277                          Bardet-Biedl Syndrome 0.04999924  2/65  13/9703

sessionInfo()
R version 3.6.1 (2019-07-05)
Platform: x86_64-pc-linux-gnu (64-bit)
Running under: Scientific Linux 7.4 (Nitrogen)

Matrix products: default
BLAS/LAPACK: /software/openblas-0.2.19-el7-x86_64/lib/libopenblas_haswellp-r0.2.19.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] disgenet2r_0.99.2 enrichR_3.0       readxl_1.3.1      workflowr_1.7.0  

loaded via a namespace (and not attached):
 [1] tidyselect_1.1.1 xfun_0.29        reshape2_1.4.4   purrr_0.3.4     
 [5] colorspace_2.0-2 vctrs_0.3.8      generics_0.1.1   htmltools_0.5.2 
 [9] yaml_2.2.1       utf8_1.2.2       rlang_1.0.1      later_0.8.0     
[13] pillar_1.6.4     jquerylib_0.1.4  glue_1.6.2       DBI_1.1.2       
[17] plyr_1.8.6       lifecycle_1.0.1  stringr_1.4.0    munsell_0.5.0   
[21] gtable_0.3.0     cellranger_1.1.0 evaluate_0.14    labeling_0.4.2  
[25] knitr_1.36       callr_3.7.0      fastmap_1.1.0    httpuv_1.5.1    
[29] ps_1.6.0         curl_4.3.2       fansi_1.0.2      highr_0.9       
[33] Rcpp_1.0.8       promises_1.0.1   scales_1.1.1     jsonlite_1.7.2  
[37] farver_2.1.0     fs_1.5.2         rjson_0.2.20     ggplot2_3.3.5   
[41] digest_0.6.29    stringi_1.7.6    processx_3.5.2   dplyr_1.0.7     
[45] getPass_0.2-2    rprojroot_2.0.2  grid_3.6.1       cli_3.1.0       
[49] tools_3.6.1      magrittr_2.0.2   tibble_3.1.6     crayon_1.5.0    
[53] whisker_0.3-2    pkgconfig_2.0.3  ellipsis_0.3.2   assertthat_0.2.1
[57] rmarkdown_2.11   httr_1.4.2       rstudioapi_0.13  R6_2.5.1        
[61] git2r_0.26.1     compiler_3.6.1