vignettes/others/repeat_Fig5_Pathway_Separation.Rmd
repeat_Fig5_Pathway_Separation.RmdAbstract
Source CodeWe 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.
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"cutoff_n argument of checkPathwaySeparation function decides how many enriched pathways are used for the comparison. We tried both top 5 and top 1.
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] TRUENeutrophil 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] TRUEG1 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#> R version 4.1.2 (2021-11-01)
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