libraries, data loading and feature selection
# We advise to instal from github to get the latest version of the tool.
# if (!requireNamespace("devtools", quietly = TRUE))
# install.packages("devtools")
#
# devtools::install_github("saezlab/cosmosR")
library(cosmosR)
library(reshape2)
library(readr)
data("meta_network")
meta_network <- meta_network_cleanup(meta_network)
## Warning: `summarise_each()` was deprecated in dplyr 0.7.0.
## ℹ Please use `across()` instead.
## ℹ The deprecated feature was likely used in the cosmosR package.
## Please report the issue at <https://github.com/saezlab/COSMOSR/issues>.
## This warning is displayed once every 8 hours.
## Call `lifecycle::last_lifecycle_warnings()` to see where this warning was
## generated.
## Warning: `funs()` was deprecated in dplyr 0.8.0.
## ℹ Please use a list of either functions or lambdas:
##
## # Simple named list: list(mean = mean, median = median)
##
## # Auto named with `tibble::lst()`: tibble::lst(mean, median)
##
## # Using lambdas list(~ mean(., trim = .2), ~ median(., na.rm = TRUE))
## ℹ The deprecated feature was likely used in the cosmosR package.
## Please report the issue at <https://github.com/saezlab/COSMOSR/issues>.
## This warning is displayed once every 8 hours.
## Call `lifecycle::last_lifecycle_warnings()` to see where this warning was
## generated.
load("data/cosmos/cosmos_inputs.RData")
names(cosmos_inputs)
## [1] "786-0" "A498" "A549/ATCC" "ACHN" "BT-549"
## [6] "CAKI-1" "CCRF-CEM" "COLO 205" "DU-145" "EKVX"
## [11] "HCC-2998" "HCT-116" "HCT-15" "HL-60(TB)" "HOP-62"
## [16] "HOP-92" "HS 578T" "HT29" "IGROV1" "K-562"
## [21] "KM12" "LOX IMVI" "M14" "MALME-3M" "MCF7"
## [26] "MDA-MB-435" "MOLT-4" "NCI-H226" "NCI-H23" "NCI-H322M"
## [31] "NCI-H460" "NCI-H522" "NCI/ADR-RES" "OVCAR-3" "OVCAR-4"
## [36] "OVCAR-5" "OVCAR-8" "PC-3" "RPMI-8226" "SF-268"
## [41] "SF-295" "SF-539" "SK-MEL-28" "SK-MEL-5" "SK-OV-3"
## [46] "SN12C" "SNB-19" "SNB-75" "SR" "SW-620"
## [51] "T-47D" "TK-10" "U251" "UACC-257" "UACC-62"
## [56] "UO-31"
cell_line <- "786-0"
#see scripts/prepare_cosmos_inputs.R
sig_input <- cosmos_inputs[[cell_line]]$TF_scores
metab_input <- cosmos_inputs[[cell_line]]$metabolomic
RNA_input <- cosmos_inputs[[cell_line]]$RNA
#Choose which compartment to assign to the metabolic measurments
metab_input <- prepare_metab_inputs(metab_input, c("c","m"))
## [1] "Adding compartment codes."
##Filter significant inputs
sig_input <- sig_input[abs(sig_input) > 2]
# metab_input <- metab_input[abs(metab_input) > 2]
#Remove genes that are not expressed from the meta_network
meta_network <- cosmosR:::filter_pkn_expressed_genes(names(RNA_input), meta_pkn = meta_network)
## [1] "COSMOS: removing unexpressed nodes from PKN..."
## [1] "COSMOS: 20357 interactions removed"
#Filter inputs and prune the meta_network to only keep nodes that can be found downstream of the inputs
#The number of step is quite flexible, 7 steps already covers most of the network
n_steps <- 6
# in this step we prune the network to keep only the relevant part between upstream and downstream nodes
sig_input <- cosmosR:::filter_input_nodes_not_in_pkn(sig_input, meta_network)
## [1] "COSMOS: 12 input/measured nodes are not in PKN any more: CEBPA, ESR1, FOS, FOXA1, GATA3, HNF4A and 6 more."
meta_network <- cosmosR:::keep_controllable_neighbours(meta_network, n_steps, names(sig_input))
## [1] "COSMOS: removing nodes that are not reachable from inputs within 6 steps"
## [1] "COSMOS: 26540 from 37740 interactions are removed from the PKN"
metab_input <- cosmosR:::filter_input_nodes_not_in_pkn(metab_input, meta_network)
## [1] "COSMOS: 195 input/measured nodes are not in PKN any more: Metab__HMDB0011747_c, Metab__HMDB0000755_c, Metab__HMDB0000905_c, Metab__HMDB0001191_c, Metab__HMDB0000355_c, Metab__HMDB0000479_c and 189 more."
meta_network <- cosmosR:::keep_observable_neighbours(meta_network, n_steps, names(metab_input))
## [1] "COSMOS: removing nodes that are not observable by measurements within 6 steps"
## [1] "COSMOS: 3657 from 11200 interactions are removed from the PKN"
sig_input <- cosmosR:::filter_input_nodes_not_in_pkn(sig_input, meta_network)
## [1] "COSMOS: 4 input/measured nodes are not in PKN any more: CTCF, EPAS1, ETS1, USF1 and 0 more."
#compress the network
meta_network_compressed_list <- compress_same_children(meta_network, sig_input = sig_input, metab_input = metab_input)
meta_network_compressed <- meta_network_compressed_list$compressed_network
node_signatures <- meta_network_compressed_list$node_signatures
duplicated_parents <- meta_network_compressed_list$duplicated_signatures
meta_network_compressed <- meta_network_cleanup(meta_network_compressed)
run MOON ot score the and contextualise the PKN
load("support/dorothea_reg.RData")
meta_network_TF_to_metab <- meta_network_compressed
before <- 1
after <- 0
i <- 1
while (before != after & i < 10) {
before <- length(meta_network_TF_to_metab[,1])
moon_res <- moon(upstream_input = sig_input,
downstream_input = metab_input,
meta_network = meta_network_TF_to_metab,
n_layers = n_steps,
statistic = "ulm")
meta_network_TF_to_metab <- filter_incohrent_TF_target(moon_res, dorothea_reg, meta_network_TF_to_metab, RNA_input)
after <- length(meta_network_TF_to_metab[,1])
i <- i + 1
}
## [1] 2
## [1] 3
## [1] 4
## [1] 5
## [1] 6
## [1] 2
## [1] 3
## [1] 4
## [1] 5
## [1] 6
## [1] 2
## [1] 3
## [1] 4
## [1] 5
## [1] 6
if(i < 10)
{
print(paste("Converged after ",paste(i-1," iterations", sep = ""),sep = ""))
} else
{
print(paste("Interupted after ",paste(i," iterations. Convergence uncertain.", sep = ""),sep = ""))
}
## [1] "Converged after 3 iterations"
#####
write_csv(moon_res, file = paste("results/moon/",paste(cell_line, "_ATT_decouplerino_full.csv",sep = ""), sep = ""))
source("scripts/support_decompression.R")
moon_res <- decompress_moon_result(moon_res, meta_network_compressed_list, meta_network_TF_to_metab)
plot(density(moon_res$score))
abline(v = 1)
abline(v = -1)
solution_network <- reduce_solution_network(decoupleRnival_res = moon_res,
meta_network = meta_network,
cutoff = 0.5,
upstream_input = sig_input,
RNA_input = RNA_input,
n_steps = n_steps)
## [1] "COSMOS: removing nodes that are not reachable from inputs within 6 steps"
## [1] "COSMOS: 458 from 1747 interactions are removed from the PKN"
SIF <- solution_network$SIF
names(SIF)[3] <- "sign"
ATT <- solution_network$ATT
data("HMDB_mapper_vec")
translated_res <- translate_res(SIF,ATT,HMDB_mapper_vec)
SIF <- translated_res[[1]]
ATT <- translated_res[[2]]
write_csv(SIF, file = paste("results/",paste(cell_line, "_dec_compressed_SIF.csv",sep = ""), sep = ""))
write_csv(ATT, file = paste("results/",paste(cell_line, "_dec_compressed_ATT.csv",sep = ""), sep = ""))
sessionInfo()
## R version 4.2.0 (2022-04-22)
## Platform: aarch64-apple-darwin20 (64-bit)
## Running under: macOS Monterey 12.6
##
## Matrix products: default
## BLAS: /Library/Frameworks/R.framework/Versions/4.2-arm64/Resources/lib/libRblas.0.dylib
## LAPACK: /Library/Frameworks/R.framework/Versions/4.2-arm64/Resources/lib/libRlapack.dylib
##
## locale:
## [1] en_US.UTF-8/en_US.UTF-8/en_US.UTF-8/C/en_US.UTF-8/en_US.UTF-8
##
## attached base packages:
## [1] stats graphics grDevices utils datasets methods base
##
## other attached packages:
## [1] readr_2.1.4 reshape2_1.4.4 cosmosR_1.5.2
##
## loaded via a namespace (and not attached):
## [1] Rcpp_1.0.10 highr_0.10 plyr_1.8.8 pillar_1.9.0
## [5] compiler_4.2.0 prettyunits_1.1.1 tools_4.2.0 progress_1.2.2
## [9] bit_4.0.5 digest_0.6.31 evaluate_0.20 lifecycle_1.0.3
## [13] tibble_3.2.1 lattice_0.20-45 pkgconfig_2.0.3 rlang_1.1.0
## [17] igraph_1.4.2 Matrix_1.5-3 cli_3.6.1 rstudioapi_0.14
## [21] yaml_2.3.7 parallel_4.2.0 xfun_0.42 fastmap_1.1.1
## [25] withr_2.5.0 dplyr_1.1.3 stringr_1.5.0 knitr_1.42
## [29] generics_0.1.3 vctrs_0.6.1 hms_1.1.3 bit64_4.0.5
## [33] grid_4.2.0 tidyselect_1.2.0 glue_1.6.2 R6_2.5.1
## [37] fansi_1.0.4 parallelly_1.34.0 vroom_1.6.1 rmarkdown_2.21
## [41] tzdb_0.3.0 tidyr_1.3.0 purrr_1.0.1 decoupleR_2.9.1
## [45] magrittr_2.0.3 htmltools_0.5.5 utf8_1.2.3 stringi_1.7.12
## [49] crayon_1.5.2
