In shbrief/GenomicSuperSignaturePaper: Reproduce GenomicSuperSignature paper

knitr::opts_chunk$set(
  comment = "#>", message = FALSE, warning = FALSE, collapse = FALSE
)

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.

Load packages

suppressPackageStartupMessages({
  library(GenomicSuperSignaturePaper)
  library(GenomicSuperSignature)
  library(dplyr)
})

RAVmodel

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

## If GenomicSuperSignaturePaper is built locally with RAVmodel in inst/extdata
data.dir <- system.file("extdata", package = "GenomicSuperSignaturePaper")
RAVmodel <- readRDS(file.path(data.dir, "RAVmodel_PLIERpriors.rds"))

RAVmodel <- getModel("PLIERpriors", load=TRUE)

RAVmodel

version(RAVmodel)

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)
checkPathwaySeparation(RAVmodel, ifn.alpha.set, ifn.gamma.set, cutoff_n = 1)

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) 
checkPathwaySeparation(RAVmodel, neutrophil.set, monocyte.set, cutoff_n = 1)

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) 
checkPathwaySeparation(RAVmodel, g1.set, g2.set, cutoff_n = 1)