J. Taroni 2018

Are the expression values of the neutrophil-associated latent variables correlated with MCPCounter (Becht, et al.) neutrophil estimates?

The correlations between the neutrophil counts and the LV expression levels are modest. (This question has come up more than once!) We think this is likely because neutrophils are terminally differentiated cells, so it is a limitation of using gene expression as a measure of neutrophil count rather than a limitation intrinsic to PLIER models or the MultiPLIER approach.

So, we’ll check to see if the two estimates from expression are highly correlated, which would lend support to this notion.

Set up

# magrittr pipe
`%>%` <- dplyr::`%>%`

Directory setup

# plot and result directory setup for this notebook
plot.dir <- file.path("plots", "40")
dir.create(plot.dir, recursive = TRUE, showWarnings = FALSE)
results.dir <- file.path("results", "40")
dir.create(results.dir, recursive = TRUE, showWarnings = FALSE)

Read in data

The SLE whole blood expression data

sle.wb.file <- 
  file.path("data", "expression_data", 
            "SLE_WB_all_microarray_QN_zto_before_with_GeneSymbol.pcl")
exprs.mat <- readr::read_tsv(sle.wb.file) %>%
  dplyr::select(-EntrezID) %>%
  tibble::column_to_rownames("GeneSymbol") %>%
  as.matrix()
Parsed with column specification:
cols(
  .default = col_double(),
  EntrezID = col_integer(),
  GeneSymbol = col_character()
)
See spec(...) for full column specifications.

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Setting row names on a tibble is deprecated.

We’d like to compare this to results from 07-sle_cell_type_recount2_model.

plier.neutrophil.file <- file.path("results", "07", 
                                   "neutrophil_count_LV_both_models.tsv")
plier.neutrophil.df <- readr::read_tsv(plier.neutrophil.file)
Parsed with column specification:
cols(
  Sample = col_character(),
  LV2 = col_double(),
  LV27 = col_double(),
  LV34 = col_double(),
  LV87 = col_double(),
  Neutrophil.Count = col_double(),
  recount2_LV524 = col_double(),
  recount2_LV603 = col_double(),
  recount2_LV985 = col_double()
)

MCPCounter

# get cell type estimates with MCPcounter
mcp.results <- 
  MCPcounter::MCPcounter.estimate(expression = exprs.mat,
                                  featuresType = "HUGO_symbols")
# we're only interested in the neutrophil counts
neutrophil.df <- reshape2::melt(mcp.results) %>%
  dplyr::filter(Var1 == "Neutrophils") %>% 
  dplyr::select(-Var1)
colnames(neutrophil.df) <- c("Sample", "Neutrophil_estimate")

Compare

joined.neutrophil.df <- dplyr::inner_join(neutrophil.df, plier.neutrophil.df,
                                          by = "Sample")
Column `Sample` joining factor and character vector, coercing into character vector
cor(joined.neutrophil.df$recount2_LV603,
    joined.neutrophil.df$Neutrophil_estimate, 
    method = "pearson") ^ 2
[1] 0.8305573

Save results

readr::write_tsv(joined.neutrophil.df,
                 path = file.path(results.dir, 
                                  "Banchereau_MCPcounter_neutrophil_LV.tsv"))
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