Abstract

Source Code

Setup

We benchmark one of the model validation measures, named as pathway separation, from the previous study (Figure 5). Briefly, pathway separation is defined as the ability of the signature model to keep non-overlapping signatures that can differentiate biologically similar pathways.

RAVmodel

To directly compare with the previous publication, we used the RAVmodel annotated with the same priors: bloodCellMarkersIRISDMAP, svmMarkers, and canonicalPathways.

RAVmodel <- getModel("PLIERpriors", load=TRUE)
RAVmodel
#> class: PCAGenomicSignatures 
#> dim: 13934 4764 
#> metadata(8): cluster size ... version geneSets
#> assays(1): RAVindex
#> rownames(13934): CASKIN1 DDX3Y ... CTC-457E21.9 AC007966.1
#> rowData names(0):
#> colnames(4764): RAV1 RAV2 ... RAV4763 RAV4764
#> colData names(4): RAV studies silhouetteWidth gsea
#> trainingData(2): PCAsummary MeSH
#> trainingData names(536): DRP000987 SRP059172 ... SRP164913 SRP188526
version(RAVmodel)
#> [1] "1.1.1"

Pathway Separation

cutoff_n argument of checkPathwaySeparation function decides how many enriched pathways are used for the comparison. We tried both top 5 and top 1.

Type I and type II interferon

ifn.alpha.set <- c("REACTOME_INTERFERON_ALPHA_BETA_SIGNALING")
ifn.gamma.set <- c("REACTOME_INTERFERON_GAMMA_SIGNALING")

checkPathwaySeparation(RAVmodel, ifn.alpha.set, ifn.gamma.set, 
                       cutoff_nes = NULL, cutoff_n = 5)
#> [1] TRUE
checkPathwaySeparation(RAVmodel, ifn.alpha.set, ifn.gamma.set, cutoff_n = 1)
#> [1] TRUE

Myeloid lineage

Neutrophil vs. Monocyte

neutrophil.set <- c("DMAP_GRAN3", "IRIS_Neutrophil-Resting", "SVM Neutrophils")
monocyte.set <- c("IRIS_Monocyte-Day0", "IRIS_Monocyte-Day1", 
                  "IRIS_Monocyte-Day7", "DMAP_MONO2", "SVM Monocytes",
                  "SVM Macrophages M0", "SVM Macrophages M1", 
                  "SVM Macrophages M2")

checkPathwaySeparation(RAVmodel, neutrophil.set, monocyte.set, 
                       cutoff_nes = NULL, cutoff_n = 5) 
#> [1] TRUE
checkPathwaySeparation(RAVmodel, neutrophil.set, monocyte.set, cutoff_n = 1)
#> [1] TRUE

Proliferation

G1 vs. G2 cell cycle phases

g1.set <- c("REACTOME_G1_S_TRANSITION", "REACTOME_M_G1_TRANSITION",
            "REACTOME_APC_C_CDH1_MEDIATED_DEGRADATION_OF_CDC20_AND_OTHER_APC_C_CDH1_TARGETED_PROTEINS_IN_LATE_MITOSIS_EARLY_G1", 
            "REACTOME_CYCLIN_E_ASSOCIATED_EVENTS_DURING_G1_S_TRANSITION_", 
            "REACTOME_G1_PHASE", "REACTOME_MITOTIC_M_M_G1_PHASES",
            "REACTOME_P53_DEPENDENT_G1_DNA_DAMAGE_RESPONSE", 
            "REACTOME_MITOTIC_G1_G1_S_PHASES", 
            "REACTOME_P53_INDEPENDENT_G1_S_DNA_DAMAGE_CHECKPOINT")
g2.set <- c("REACTOME_MITOTIC_G2_G2_M_PHASES", "REACTOME_G2_M_CHECKPOINTS")

checkPathwaySeparation(RAVmodel, g1.set, g2.set, 
                       cutoff_nes = NULL, cutoff_n = 5) 
#> [1] TRUE
checkPathwaySeparation(RAVmodel, g1.set, g2.set, cutoff_n = 1)
#> [1] TRUE

Session Info

#> R version 4.1.2 (2021-11-01)
#> Platform: x86_64-pc-linux-gnu (64-bit)
#> Running under: Ubuntu 20.04.3 LTS
#> 
#> Matrix products: default
#> BLAS/LAPACK: /usr/lib/x86_64-linux-gnu/openblas-pthread/libopenblasp-r0.3.8.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] stats4    stats     graphics  grDevices utils     datasets  methods  
#> [8] base     
#> 
#> other attached packages:
#>  [1] dplyr_1.0.8                      GenomicSuperSignature_1.3.6     
#>  [3] SummarizedExperiment_1.24.0      Biobase_2.54.0                  
#>  [5] GenomicRanges_1.46.1             GenomeInfoDb_1.30.1             
#>  [7] IRanges_2.28.0                   S4Vectors_0.32.3                
#>  [9] BiocGenerics_0.40.0              MatrixGenerics_1.6.0            
#> [11] matrixStats_0.61.0               GenomicSuperSignaturePaper_1.1.1
#> [13] BiocStyle_2.22.0                
#> 
#> loaded via a namespace (and not attached):
#>  [1] bitops_1.0-7           fs_1.5.2               bit64_4.0.5           
#>  [4] filelock_1.0.2         httr_1.4.2             doParallel_1.0.17     
#>  [7] RColorBrewer_1.1-2     rprojroot_2.0.2        tools_4.1.2           
#> [10] backports_1.4.1        bslib_0.3.1            utf8_1.2.2            
#> [13] R6_2.5.1               DBI_1.1.2              colorspace_2.0-3      
#> [16] GetoptLong_1.0.5       tidyselect_1.1.2       curl_4.3.2            
#> [19] bit_4.0.4              compiler_4.1.2         textshaping_0.3.6     
#> [22] cli_3.2.0              desc_1.4.1             DelayedArray_0.20.0   
#> [25] bookdown_0.25          sass_0.4.0             scales_1.1.1          
#> [28] rappdirs_0.3.3         pkgdown_2.0.2          systemfonts_1.0.4     
#> [31] stringr_1.4.0          digest_0.6.29          rmarkdown_2.13        
#> [34] XVector_0.34.0         pkgconfig_2.0.3        htmltools_0.5.2       
#> [37] dbplyr_2.1.1           fastmap_1.1.0          rlang_1.0.2           
#> [40] GlobalOptions_0.1.2    RSQLite_2.2.10         shape_1.4.6           
#> [43] jquerylib_0.1.4        generics_0.1.2         jsonlite_1.8.0        
#> [46] car_3.0-12             RCurl_1.98-1.6         magrittr_2.0.2        
#> [49] GenomeInfoDbData_1.2.7 Matrix_1.4-0           Rcpp_1.0.8.3          
#> [52] munsell_0.5.0          fansi_1.0.2            abind_1.4-5           
#> [55] lifecycle_1.0.1        stringi_1.7.6          yaml_2.3.5            
#> [58] carData_3.0-5          zlibbioc_1.40.0        BiocFileCache_2.2.1   
#> [61] blob_1.2.2             grid_4.1.2             parallel_4.1.2        
#> [64] crayon_1.5.0           lattice_0.20-45        circlize_0.4.14       
#> [67] knitr_1.37             ComplexHeatmap_2.10.0  pillar_1.7.0          
#> [70] ggpubr_0.4.0           rjson_0.2.21           ggsignif_0.6.3        
#> [73] codetools_0.2-18       glue_1.6.2             evaluate_0.15         
#> [76] BiocManager_1.30.16    png_0.1-7              vctrs_0.3.8           
#> [79] foreach_1.5.2          gtable_0.3.0           purrr_0.3.4           
#> [82] tidyr_1.2.0            clue_0.3-60            assertthat_0.2.1      
#> [85] cachem_1.0.6           ggplot2_3.3.5          xfun_0.30             
#> [88] broom_0.7.12           rstatix_0.7.0          ragg_1.2.2            
#> [91] tibble_3.1.6           iterators_1.0.14       memoise_2.0.1         
#> [94] cluster_2.1.2          ellipsis_0.3.2