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Reconstructing mult-omics networks with coglasso

Introduction

This vignette illustrates the basic usage of the coglasso package to reconstruct a multi-omics network. The package implements and R interface to collaborative graphical lasso, a network estimation algorithm based on graphical lasso (Friedman, Hastie and Tibshirani, 2008) and collaborative regression (Gross and Tibshirani, 2015)

Let us first attach coglasso.

library(coglasso)

We then choose the multi-omics data set to use. The coglasso package offers three alternative version of a transcriptomics and metabolomics data set. We will use multi_omics_sd_small. For further explanation about all the multi-omics data sets see help(multi_omics_sd).

colnames(multi_omics_sd_small)
#>  [1] "Cirbp"       "Hspa5"       "P4ha1"       "Spred1"      "Creld2"     
#>  [6] "Pdia6"       "Hsp90b1"     "Hsph1"       "Manf"        "Pdia3"      
#> [11] "Dnajb11"     "Dnajc3"      "BC004004"    "Stip1"       "Phe"        
#> [16] "Trp"         "Putrescine"  "PC aa C36:3" "PC ae C32:2"
nrow(multi_omics_sd_small)
#> [1] 30

This smaller version of multi_omics_sd has 19 variables, 14 genes and 5 metabolites, and 30 samples. We can directly proceed with network reconstruction.

Multi-omics network reconstruction

Our objective is to reconstruct a network from this data set using collaborative graphical lasso. To do so with the coglasso package, we mainly call two functions. First, we use coglasso() to estimate a network for every combination of hyperparameters we want to explore. Following this, we call stars_coglasso() to select the best combination of hyperparameters using stability selection.

The usual application of coglasso() requires to give an input data set to the argument data, the number of variables of the the first type to pX, and hyperparameter settings. Collaborative graphical lasso has three hyperparameters: \(λ_w\), penalizing “within” same-type interactions, \(λ_b\) penalizing “between” different-type interactions, and \(c\), the weight of the collaborative term. In this vignette we choose to explore 15 possible penalty values for both “within” and “between” penalties, and three possible collaboration values. We do so by setting both nlambda_w and nlambda_b to 15, and by setting nc to 3. We also decide to restrict our search to a less extreme penalization, by setting a fixed maximum value for both penalties to 0.85, while by default it is often estimated to a higher value with a data-driven approach. Nevertheless, we also decide to focus our search to the sparse side of possible networks. We achieve this by setting to a fixed value the ratios between the smallest (least penalizing) and the largest (most penalizing) penalty explored. While the default value of these parameters is 0.1, we decide to set the minimum ratio to 0.6 for \(λ_w\) and to 0.4 for \(λ_b\). For further explanation on other arguments of coglasso() and how to use them, please see help(coglasso).

cg <- coglasso(multi_omics_sd_small,
  pX = 14,
  nlambda_w = 15,
  nlambda_b = 15,
  nc = 3,
  lambda_w_max = 0.85,
  lambda_b_max = 0.85,
  lambda_w_min_ratio = 0.6,
  lambda_b_min_ratio = 0.4,
  verbose = FALSE
)

# To see the explored paramaters:
cg$lambda_w
#>  [1] 0.8500000 0.8195446 0.7901804 0.7618683 0.7345706 0.7082511 0.6828745
#>  [8] 0.6584072 0.6348165 0.6120711 0.5901407 0.5689960 0.5486089 0.5289523
#> [15] 0.5100000
cg$lambda_b
#>  [1] 0.8500000 0.7961495 0.7457107 0.6984673 0.6542169 0.6127700 0.5739489
#>  [8] 0.5375872 0.5035292 0.4716288 0.4417495 0.4137631 0.3875498 0.3629971
#> [15] 0.3400000
cg$c
#> [1] 10.000000  3.162278  1.000000

To select the best combination of hyperparameters, we will use stars_coglasso(). This function implements a coglasso-adapted version of StARS, the stability selection method developed by Liu, Roeder and Wasserman (2010). The usual application of stars_coglasso() uses the default options of the function, whose only required input is the object resulting from coglasso().

sel_cg <- stars_coglasso(cg, verbose = FALSE)

# To see the selected parameters:
sel_cg$sel_lambda_w
#> [1] 0.85
sel_cg$sel_lambda_b
#> [1] 0.61277
sel_cg$sel_c
#> [1] 3.162278

With this we have selected the combination of hyperparameters yielding the most stable, yet sparse coglasso network. The adjacency matrix of the selected network is stored in the object sel_cg$sel_adj. We can use this matrix to display the selected network with the R package igraph.

# To create the igraph object from the selected adjacency matrix:
sel_graph <- igraph::graph.adjacency(sel_cg$sel_adj, mode = "undirected")

# Setting some graphical parameters and removing disconnected nodes from the graph
igraph::V(sel_graph)$label <- colnames(multi_omics_sd_small)
igraph::V(sel_graph)$color <- c(rep("#00ccff", 14), rep("#ff9999", 5))
igraph::V(sel_graph)$frame.color <- c(rep("#002060", 14), rep("#800000", 5))
igraph::V(sel_graph)$frame.width <- 2
igraph::V(sel_graph)$size <- c(30)
igraph::E(sel_graph)$width <- 2

lo <- igraph::layout_with_fr(sel_graph)
diconnected <- which(igraph::degree(sel_graph) == 0)
sel_graph2 <- igraph::delete.vertices(sel_graph, diconnected)
lo2 <- lo[-diconnected, ]

# Plotting
plot(sel_graph2, layout = lo2)

References

Friedman, J., Hastie, T., & Tibshirani, R. (2008). Sparse inverse covariance estimation with the graphical lasso. Biostatistics, 9(3), 432–441. https://doi.org/10.1093/biostatistics/kxm045

Gross, S. M., & Tibshirani, R. (2015). Collaborative regression. Biostatistics, 16(2), 326–338. https://doi.org/10.1093/biostatistics/kxu047

Liu, H., Roeder, K., & Wasserman, L. (2010). Stability Approach to Regularization Selection (StARS) for High Dimensional Graphical Models (arXiv:1006.3316). arXiv. https://doi.org/10.48550/arXiv.1006.3316

These binaries (installable software) and packages are in development.
They may not be fully stable and should be used with caution. We make no claims about them.