Skip to contents

Generate multi-omic differential networks

Source: R/core_functions.R
get_diffNetworks.Rd

Generate a multi-layer differential network with interaction p values

Usage

get_diffNetworks(
  assayData,
  metadata,
  category_variable = NULL,
  regression_method = "lm",
  category_subset = NULL,
  network = NULL,
  percentile_vector = seq(0.35, 0.98, by = 0.05),
  padj_method = "bonferroni",
  show_progressBar = TRUE,
  verbose = TRUE,
  cores = parallel::detectCores()/2
)

Arguments

assayData

a matrix or data.frame (or list of matrices or data.frames for multi-omic analysis) containing normalised assay data. Sample IDs must be in columns and probe IDs (genes, proteins...) in rows. For multi omic analysis, it is highly recommended to use a named list of data. If unnamed, sequential names (assayData1, assayData2, etc.) will be assigned to identify each matrix or data.frame.

metadata

a named vector, matrix, or data.frame containing sample annotations or categories. If matrix or data.frame, each row should correspond to a sample, with columns representing different sample characteristics (e.g., treatment group, condition, time point). The colname of the sample characteristic to be used for differential analysis must be specified in category_variable. Rownames must match the sample IDs used in assayData. If named vector, each element must correspond to a sample characteristic to be used for differential analysis, and names must match sample IDs used in the colnames of assayData. Continuous variables are not allowed.

category_variable

when metadata is a matrix or data.frame this is the column name of metadata that contains the sample annotations to be used for differential analysis

regression_method

whether to use robust linear modelling to calculate link p values. Options are 'lm' (default) or 'rlm'. The lm implementation is faster and lighter.

category_subset

optional character vector indicating a subset of categories from the category variable. If not specified, all categories in category_variable will be used.

network

network of biological interactions provided by the user. The network must be provided in the form of a table of class data.frame with only two columns named "from" and "to". If NULL (default) a network of 10,537 molecular interactions obtained from KEGG, mirTARbase, miRecords and transmiR will be used. This has been obtained via the exportgraph function of the MITHrIL tool (Alaimo et al., 2016).

percentile_vector

a numeric vector specifying the percentiles to be used in the percolation analysis. By default, it is defined as seq(0.35, 0.98, by = 0.05), which generates a sequence of percentiles starting at 0.35, meaning that targets (genes/proteins...) whose expression value is under the 35th percentile of the whole matrix will be excluded. This threshold can be modified by specifying a different starting point for seq. For a more granular percolation analysis an higher optimisation of the algorithm, by = 0.05 can be modified in favour of lower values, but this will increase the computational time.

padj_method

a character string indicating the p values correction method for multiple test adjustment. It can be either one of the methods provided by the p.adjust function from stats (bonferroni, BH, hochberg, etc.) or "q.value" for Storey's q values, or "none" for unadjusted p values. When using "q.value" the qvalue package must be installed first.

show_progressBar

logical. Whether to display a progress bar during execution. Default is TRUE.

verbose

logical. Whether to print detailed output messages during processing. Default is TRUE

cores

number of cores to use for parallelisation.

Value

a deggs object containing differential networks incorporating p values or adjusted p values for each link.

Examples

# Single omic analysis:
data("synthetic_metadata")
data("synthetic_rnaseqData")
deggs_object <- get_diffNetworks(assayData = synthetic_rnaseqData,
                                 metadata = synthetic_metadata,
                                 category_variable = "response",
                                 regression_method = "lm",
                                 padj_method = "bonferroni",
                                 verbose = FALSE,
                                 show_progressBar = FALSE,
                                 cores = 1)
 
# multi-omic analysis: 
data("synthetic_metadata")
data("synthetic_rnaseqData")
data("synthetic_proteomicData")
data("synthetic_OlinkData")
assayData_list <- list("RNAseq" = synthetic_rnaseqData,
                       "Proteomics" = synthetic_proteomicData,
                       "Olink" = synthetic_OlinkData)
deggs_object <- get_diffNetworks(assayData = assayData_list,
                                 metadata = synthetic_metadata,
                                 category_variable = "response",
                                 regression_method = "lm",
                                 padj_method = "bonferroni",
                                 verbose = FALSE,
                                 show_progressBar = FALSE,
                                 cores = 1)
                                 
# to use only certain categories for comparison: 
# let's randomly add another level of response to the example metadata
synthetic_metadata$response <- as.character(synthetic_metadata$response)
indices <- sample(1:nrow(synthetic_metadata), 20, replace = FALSE) 
synthetic_metadata$response[indices] <- "Moderate response"
deggs_object <- get_diffNetworks(assayData = assayData_list,
                                 metadata = synthetic_metadata,
                                 category_variable = "response",
                                 category_subset = c("Responder", 
                                                     "Non_responder"),
                                 regression_method = "lm",
                                 verbose = FALSE,
                                 show_progressBar = FALSE,
                                 cores = 1)
                                 
# to be more generous on the targets to be excluded, and lower the expression 
# level threshold to the 25th percentile (or lower): 
deggs_object <- get_diffNetworks(assayData = assayData_list,
                                 metadata = synthetic_metadata,
                                 category_variable = "response",
                                 category_subset = c("Responder", 
                                                     "Non_responder"),
                                 regression_method = "lm",
                                 percentile_vector = seq(0.25, 0.98, by = 0.05),
                                 verbose = FALSE,
                                 show_progressBar = FALSE,
                                 cores = 1)