Last updated: 2024-08-09

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Knit directory: multigroup_ctwas_analysis/

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We compare the results from Munro weights & predictdb weights here. We are figuring out how the number of high PIP genes compare with PredictDB results with the same tissues?

Settings

6 modalities from Munro

  1. Weight processing:

PredictDB:

all the PredictDB are converted from FUSION weights

  • drop_strand_ambig = TRUE,
  • scale_by_ld_variance = F (FUSION converted weights)
  • load_predictdb_LD = F,
  1. Parameter estimation and fine-mapping
  • niter_prefit = 5,
  • niter = 60,
  • L: determined by uniform susie,
  • group_prior_var_structure = “shared_type”,
  • maxSNP = 20000,
  • min_nonSNP_PIP = 0.5,

weights from predictdb

  1. Weight processing:

PredictDB (eqtl, sqtl)

  • drop_strand_ambig = TRUE,
  • scale_by_ld_variance = T
  • load_predictdb_LD = F,
  1. Parameter estimation and fine-mapping
  • niter_prefit = 5,
  • niter = 60,
  • L: determined by uniform susie,
  • group_prior_var_structure = “shared_type”,
  • maxSNP = 20000,
  • min_nonSNP_PIP = 0.5,

mem: 150g 5cores

Results

LDL - Liver

Predictdb: eqtl and sqtl

2024-08-09 11:44:45 INFO::Annotating ctwas finemapping result ...
2024-08-09 11:44:55 INFO::add gene_name and gene_type
2024-08-09 11:44:55 INFO::split PIPs for traits mapped to multiple genes
2024-08-09 11:44:56 INFO::use gene mid positions
2024-08-09 11:44:56 INFO::add SNP positions

Munro et al : 6 modalities

2024-08-09 11:45:17 INFO::Annotating ctwas finemapping result ...
2024-08-09 11:45:22 INFO::add gene_name and gene_type
2024-08-09 11:45:22 INFO::use gene mid positions
2024-08-09 11:45:22 INFO::add SNP positions

Compare the results from Predictdb & Munro weights

If we filter by combined pip >0.8 in both settings, we have

Checking why Predicdb results missed many Munro genes

[1] "# of Unique munro genes = 25"
[1] "# of Unique munro genes included in predictdb data = 18"

IBD – Colon_Transverse

Predictdb: eqtl and sqtl

2024-08-09 11:45:43 INFO::Annotating ctwas finemapping result ...
2024-08-09 11:45:48 INFO::add gene_name and gene_type
2024-08-09 11:45:48 INFO::split PIPs for traits mapped to multiple genes
2024-08-09 11:45:48 INFO::use gene mid positions
2024-08-09 11:45:48 INFO::add SNP positions

Munro et al : 6 modalities

2024-08-09 11:46:04 INFO::Annotating ctwas finemapping result ...
2024-08-09 11:46:09 INFO::add gene_name and gene_type
2024-08-09 11:46:10 INFO::use gene mid positions
2024-08-09 11:46:10 INFO::add SNP positions

Compare the results from Predictdb & Munro weights

If we filter by combined pip >0.8 in both settings, we have

There’s no overlapped genes at combined_pip > 0.8.

We noticed that, when using Munro’s weights, we have GNA12 as the top1 IBD risk gene, which has been reported by literature. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10323775/

But when using predictdb weights, we missed this gene.

Checking why Predicdb results missed many Munro genes

[1] "# of Unique munro genes = 22"
[1] "# of Unique munro genes included in predictdb data = 16"

sessionInfo()
R version 4.2.0 (2022-04-22)
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] C

attached base packages:
[1] stats4    stats     graphics  grDevices utils     datasets  methods  
[8] base     

other attached packages:
 [1] cowplot_1.1.1             ggrepel_0.9.1            
 [3] locuszoomr_0.2.1          logging_0.10-108         
 [5] EnsDb.Hsapiens.v86_2.99.0 ensembldb_2.20.2         
 [7] AnnotationFilter_1.20.0   GenomicFeatures_1.48.3   
 [9] AnnotationDbi_1.58.0      Biobase_2.56.0           
[11] GenomicRanges_1.48.0      GenomeInfoDb_1.39.9      
[13] IRanges_2.30.0            S4Vectors_0.34.0         
[15] BiocGenerics_0.42.0       gridExtra_2.3            
[17] forcats_0.5.1             stringr_1.5.1            
[19] dplyr_1.1.4               purrr_1.0.2              
[21] readr_2.1.2               tidyr_1.3.0              
[23] tibble_3.2.1              ggplot2_3.5.1            
[25] tidyverse_1.3.1           data.table_1.14.2        
[27] ctwas_0.4.5              

loaded via a namespace (and not attached):
  [1] colorspace_2.0-3            rjson_0.2.21               
  [3] ellipsis_0.3.2              rprojroot_2.0.3            
  [5] XVector_0.36.0              fs_1.5.2                   
  [7] rstudioapi_0.13             farver_2.1.0               
  [9] DT_0.22                     bit64_4.0.5                
 [11] lubridate_1.8.0             fansi_1.0.3                
 [13] xml2_1.3.3                  codetools_0.2-18           
 [15] cachem_1.0.6                knitr_1.39                 
 [17] jsonlite_1.8.0              workflowr_1.7.0            
 [19] Rsamtools_2.12.0            broom_0.8.0                
 [21] dbplyr_2.1.1                png_0.1-7                  
 [23] compiler_4.2.0              httr_1.4.3                 
 [25] backports_1.4.1             assertthat_0.2.1           
 [27] Matrix_1.5-3                fastmap_1.1.0              
 [29] lazyeval_0.2.2              cli_3.6.1                  
 [31] later_1.3.0                 htmltools_0.5.2            
 [33] prettyunits_1.1.1           tools_4.2.0                
 [35] gtable_0.3.0                glue_1.6.2                 
 [37] GenomeInfoDbData_1.2.8      rappdirs_0.3.3             
 [39] Rcpp_1.0.12                 cellranger_1.1.0           
 [41] jquerylib_0.1.4             vctrs_0.6.5                
 [43] Biostrings_2.64.0           rtracklayer_1.56.0         
 [45] crosstalk_1.2.0             xfun_0.41                  
 [47] rvest_1.0.2                 lifecycle_1.0.4            
 [49] irlba_2.3.5                 restfulr_0.0.14            
 [51] XML_3.99-0.14               zlibbioc_1.42.0            
 [53] zoo_1.8-10                  scales_1.3.0               
 [55] gggrid_0.2-0                hms_1.1.1                  
 [57] promises_1.2.0.1            MatrixGenerics_1.8.0       
 [59] ProtGenerics_1.28.0         parallel_4.2.0             
 [61] SummarizedExperiment_1.26.1 LDlinkR_1.2.3              
 [63] yaml_2.3.5                  curl_4.3.2                 
 [65] memoise_2.0.1               sass_0.4.1                 
 [67] biomaRt_2.54.1              stringi_1.7.6              
 [69] RSQLite_2.3.1               highr_0.9                  
 [71] BiocIO_1.6.0                filelock_1.0.2             
 [73] BiocParallel_1.30.3         rlang_1.1.2                
 [75] pkgconfig_2.0.3             matrixStats_0.62.0         
 [77] bitops_1.0-7                evaluate_0.15              
 [79] lattice_0.20-45             labeling_0.4.2             
 [81] GenomicAlignments_1.32.0    htmlwidgets_1.5.4          
 [83] bit_4.0.4                   tidyselect_1.2.0           
 [85] magrittr_2.0.3              R6_2.5.1                   
 [87] generics_0.1.2              DelayedArray_0.22.0        
 [89] DBI_1.2.2                   withr_2.5.0                
 [91] haven_2.5.0                 pgenlibr_0.3.3             
 [93] pillar_1.9.0                KEGGREST_1.36.3            
 [95] RCurl_1.98-1.7              mixsqp_0.3-43              
 [97] modelr_0.1.8                crayon_1.5.1               
 [99] utf8_1.2.2                  BiocFileCache_2.4.0        
[101] plotly_4.10.0               tzdb_0.4.0                 
[103] rmarkdown_2.25              progress_1.2.2             
[105] readxl_1.4.0                grid_4.2.0                 
[107] blob_1.2.3                  git2r_0.30.1               
[109] reprex_2.0.1                digest_0.6.29              
[111] httpuv_1.6.5                munsell_0.5.0              
[113] viridisLite_0.4.0           bslib_0.3.1