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# Load packages
library(viper)
Loading required package: Biobase
Loading required package: BiocGenerics

Attaching package: 'BiocGenerics'
The following objects are masked from 'package:stats':

    IQR, mad, sd, var, xtabs
The following objects are masked from 'package:base':

    anyDuplicated, aperm, append, as.data.frame, basename, cbind,
    colnames, dirname, do.call, duplicated, eval, evalq, Filter, Find,
    get, grep, grepl, intersect, is.unsorted, lapply, Map, mapply,
    match, mget, order, paste, pmax, pmax.int, pmin, pmin.int,
    Position, rank, rbind, Reduce, rownames, sapply, setdiff, table,
    tapply, union, unique, unsplit, which.max, which.min
Welcome to Bioconductor

    Vignettes contain introductory material; view with
    'browseVignettes()'. To cite Bioconductor, see
    'citation("Biobase")', and for packages 'citation("pkgname")'.
library(aracne.networks)
# Names of the individual context-specific networks
print(data(package="aracne.networks")$results[, "Item"])
 [1] "regulonblca" "regulonbrca" "reguloncesc" "reguloncoad" "regulonesca"
 [6] "regulongbm"  "regulonhnsc" "regulonkirc" "regulonkirp" "regulonlaml"
[11] "regulonlihc" "regulonluad" "regulonlusc" "regulonnet"  "regulonov"  
[16] "regulonpaad" "regulonpcpg" "regulonprad" "regulonread" "regulonsarc"
[21] "regulonstad" "regulontgct" "regulonthca" "regulonthym" "regulonucec"
print(data(package="aracne.networks"))
data(bcellViper, package="bcellViper")
adjfile <- system.file("aracne", "bcellaracne.adj", package = "bcellViper")
regul <- aracne2regulon(adjfile, dset, verbose = FALSE)
number of iterations= 301 
signature <- rowTtest(dset, "description", c("CB", "CC"), "N")
signature <- (qnorm(signature$p.value/2, lower.tail = FALSE) * + sign(signature$statistic))[, 1]
nullmodel <- ttestNull(dset, "description", c("CB", "CC"), "N", per = 1000, repos = TRUE, verbose = FALSE)
mrs <- msviper(signature, regulon, nullmodel, verbose = FALSE)
summary(mrs)
        Regulon Size   NES  p.value   FDR
TCF3       TCF3  298  3.30 0.000962 0.028
BCL6       BCL6  401  3.28 0.001030 0.028
KLF10     KLF10  254  3.25 0.001170 0.028
MYBL2     MYBL2  240  3.22 0.001300 0.028
TSC22D3 TSC22D3  333 -3.17 0.001520 0.028
HES1       HES1  360 -3.18 0.001470 0.028
ZNF32     ZNF32  291 -3.19 0.001420 0.028
ZMYND11 ZMYND11  452 -3.20 0.001380 0.028
ZNF101   ZNF101  301 -3.22 0.001300 0.028
KLF9       KLF9  337 -3.24 0.001190 0.028
plot(mrs, cex = .7)

Version Author Date
68d3a8b Zhen Zuo 2024-05-21
mrs <- ledge(mrs)
summary(mrs)
        Regulon Size   NES  p.value   FDR
TCF3       TCF3  298  3.30 0.000962 0.028
BCL6       BCL6  401  3.28 0.001030 0.028
KLF10     KLF10  254  3.25 0.001170 0.028
MYBL2     MYBL2  240  3.22 0.001300 0.028
TSC22D3 TSC22D3  333 -3.17 0.001520 0.028
HES1       HES1  360 -3.18 0.001470 0.028
ZNF32     ZNF32  291 -3.19 0.001420 0.028
ZMYND11 ZMYND11  452 -3.20 0.001380 0.028
ZNF101   ZNF101  301 -3.22 0.001300 0.028
KLF9       KLF9  337 -3.24 0.001190 0.028
                                              Ledge
TCF3    SMARCA4, MCM7, TRAF3IP3, NDC80, + 110 genes
BCL6        KIF14, BUB1, DLGAP4, GINS1, + 217 genes
KLF10       TRIP13, NDC80, AHNAK, KIF2C, + 99 genes
MYBL2     SMARCA4, MCM7, TRIP13, GINS1, + 138 genes
TSC22D3      NOTCH2, RAD1, RBM19, MLEC, + 190 genes
HES1          CDK4, SHC1, STX7, MAN1A1, + 104 genes
ZNF32       GNA12, PLAG1, PSMB1, CARM1, + 145 genes
ZMYND11   ANKRD26, EXTL2, IGFBP4, CTSC, + 234 genes
ZNF101     SLC46A3, GCLM, TCEA2, HMOX2, + 128 genes
KLF9          IFIT1, LPAR1, NID1, STOM, + 158 genes
signature <- bootstrapTtest(dset, "description", c("CB", "CC"), "N", verbose = FALSE)
mrs <- msviper(signature, regulon, nullmodel, verbose = FALSE)
mrs <- bootstrapmsviper(mrs, "mode")
plot(mrs, cex = .7)

Version Author Date
68d3a8b Zhen Zuo 2024-05-21
mrshadow <- shadow(mrs, regulators = 25, verbose = FALSE)
summary(mrshadow)
$msviper.results
        Regulon Size   NES p.value    FDR
BCL6       BCL6  401  3.18 0.00146 0.0709
MYBL2     MYBL2  240  3.12 0.00184 0.0709
WHSC1     WHSC1  257  3.07 0.00213 0.0709
TOP2A     TOP2A  749  3.06 0.00222 0.0709
MYBL1     MYBL1  225  3.04 0.00239 0.0709
PTTG1     PTTG1  471  3.00 0.00273 0.0709
NR1D2     NR1D2  259 -3.00 0.00266 0.0709
TSC22D3 TSC22D3  313 -3.02 0.00255 0.0709
ZNF274   ZNF274  160 -3.04 0.00235 0.0709
ZMYND11 ZMYND11  452 -3.06 0.00220 0.0709

$Shadow.pairs
 [1] "BCL6 -> TCF3"      "BCL6 -> HES1"      "MYBL2 -> ZNF32"   
 [4] "MYBL2 -> HES1"     "MYBL2 -> ZNF23"    "MYBL2 -> MEIS2"   
 [7] "KLF10 -> ZNF101"   "KLF10 -> HES1"     "KLF9 -> HES1"     
[10] "ZNF32 -> HES1"     "WHSC1 -> TSC22D3"  "WHSC1 -> ZNF101"  
[13] "WHSC1 -> IRF5"     "WHSC1 -> KDM1A"    "WHSC1 -> E2F2"    
[16] "TSC22D3 -> HES1"   "TSC22D3 -> ZNF23"  "TOP2A -> CREB3L2" 
[19] "TOP2A -> E2F2"     "TOP2A -> HES1"     "TOP2A -> HMGB2"   
[22] "TOP2A -> MEIS2"    "ZMYND11 -> IRF5"   "ZMYND11 -> E2F2"  
[25] "ZMYND11 -> HES1"   "ZMYND11 -> MEIS2"  "CREB3L2 -> E2F2"  
[28] "PRKDC -> HES1"     "IRF5 -> HES1"      "PTTG1 -> E2F2"    
[31] "ZNF274 -> E2F2"    "ZNF274 -> ZNF23"   "ZNF274 -> MEIS2"  
[34] "NR1D2 -> HES1"     "NR1D2 -> HMGB2"    "HES1 -> HMGB2"    
[37] "WHSC1 -> KLF10"    "TSC22D3 -> KLF10"  "PRKDC -> KLF10"   
[40] "ZNF274 -> KLF10"   "KDM1A -> KLF10"    "ZNF23 -> KLF10"   
[43] "HMGB2 -> KLF10"    "MEIS2 -> KLF10"    "ZNF32 -> KLF9"    
[46] "PRKDC -> KLF9"     "MYBL1 -> KLF9"     "IRF5 -> KLF9"     
[49] "ZNF274 -> KLF9"    "WHSC1 -> ZNF32"    "TSC22D3 -> ZNF32" 
[52] "KDM1A -> ZNF32"    "HMGB2 -> ZNF32"    "PRKDC -> TCF3"    
[55] "MYBL1 -> TCF3"     "IRF5 -> TCF3"      "PTTG1 -> TCF3"    
[58] "KDM1A -> TCF3"     "HMGB2 -> TCF3"     "TOP2A -> ZNF101"  
[61] "PRKDC -> ZNF101"   "MYBL1 -> ZNF101"   "PTTG1 -> ZNF101"  
[64] "ZNF274 -> ZNF101"  "NR1D2 -> ZNF101"   "PTTG1 -> CREB3L2" 
[67] "ZNF274 -> CREB3L2" "HMGB2 -> CREB3L2"  "MYBL1 -> PRKDC"   
[70] "HMGB2 -> MYBL1"    "ZNF274 -> PTTG1"   "HMGB2 -> KDM1A"   
[73] "NR1D2 -> E2F2"    

sessionInfo()
R version 4.4.0 (2024-04-24)
Platform: aarch64-apple-darwin20
Running under: macOS Sonoma 14.5

Matrix products: default
BLAS:   /Library/Frameworks/R.framework/Versions/4.4-arm64/Resources/lib/libRblas.0.dylib 
LAPACK: /Library/Frameworks/R.framework/Versions/4.4-arm64/Resources/lib/libRlapack.dylib;  LAPACK version 3.12.0

locale:
[1] en_US.UTF-8/en_US.UTF-8/en_US.UTF-8/C/en_US.UTF-8/en_US.UTF-8

time zone: America/New_York
tzcode source: internal

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

other attached packages:
[1] aracne.networks_1.30.0 viper_1.38.0           Biobase_2.64.0        
[4] BiocGenerics_0.50.0   

loaded via a namespace (and not attached):
 [1] gtable_0.3.5       xfun_0.44          bslib_0.7.0        ggplot2_3.5.1     
 [5] htmlwidgets_1.6.4  lattice_0.22-6     vctrs_0.6.5        tools_4.4.0       
 [9] generics_0.1.3     parallel_4.4.0     tibble_3.2.1       proxy_0.4-27      
[13] fansi_1.0.6        highr_0.10         pkgconfig_2.0.3    Matrix_1.7-0      
[17] KernSmooth_2.23-24 data.table_1.15.4  lifecycle_1.0.4    compiler_4.4.0    
[21] stringr_1.5.1      git2r_0.33.0       mixtools_2.0.0     munsell_0.5.1     
[25] httpuv_1.6.15      htmltools_0.5.8.1  class_7.3-22       sass_0.4.9        
[29] yaml_2.3.8         lazyeval_0.2.2     plotly_4.10.4      later_1.3.2       
[33] pillar_1.9.0       jquerylib_0.1.4    whisker_0.4.1      tidyr_1.3.1       
[37] MASS_7.3-60.2      cachem_1.1.0       nlme_3.1-164       tidyselect_1.2.1  
[41] digest_0.6.35      stringi_1.8.4      kernlab_0.9-32     dplyr_1.1.4       
[45] purrr_1.0.2        splines_4.4.0      rprojroot_2.0.4    fastmap_1.2.0     
[49] grid_4.4.0         colorspace_2.1-0   cli_3.6.2          magrittr_2.0.3    
[53] survival_3.6-4     utf8_1.2.4         e1071_1.7-14       scales_1.3.0      
[57] promises_1.3.0     segmented_2.1-0    rmarkdown_2.27     httr_1.4.7        
[61] workflowr_1.7.1    evaluate_0.23      knitr_1.46         viridisLite_0.4.2 
[65] rlang_1.1.3        Rcpp_1.0.12        glue_1.7.0         rstudioapi_0.16.0 
[69] jsonlite_1.8.8     R6_2.5.1           fs_1.6.4