recount2 LVs in more severe or active ANCA-associated vasculitis

J. Taroni 2018

In 21-AAV_DLVE, we identified LVs that are differentially expressed in all the ANCA-associated vasculitis datasets. In this notebook, we’ll do exploratory analyses of some of the recount2 PLIER model LVs that look like they show consistent directionality across the 3 tissues.

Functions and directory set up

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

# plot and result directory setup for this notebook
plot.dir <- file.path("plots", "23")
dir.create(plot.dir, recursive = TRUE, showWarnings = FALSE)
results.dir <- file.path("results", "23")
dir.create(results.dir, recursive = TRUE, showWarnings = FALSE)

Read in data

recount2 PLIER model

recount.plier <- readRDS(file.path("data", "recount2_PLIER_data",
                                   "recount_PLIER_model.RDS"))

Upregulated

LVs that are consistently upregulated in severe or active AAV as compared to controls.

Explore LV10

Let’s look at all the pathways associated with this LV.

recount.plier$summary %>%
  dplyr::filter(`LV index` == 10,
                FDR < 0.05)

data.frame(loadings = sort(recount.plier$Z[, 10], decreasing = TRUE))

Explore LV53

recount.plier$summary %>%
  dplyr::filter(`LV index` == 53,
                FDR < 0.05)

data.frame(loadings = sort(recount.plier$Z[, 53], decreasing = TRUE))

Explore LV63

recount.plier$summary %>%
  dplyr::filter(`LV index` == 63,
                FDR < 0.05)

data.frame(loadings = sort(recount.plier$Z[, 63], decreasing = TRUE))

Explore LV524

recount.plier$summary %>%
  dplyr::filter(`LV index` == 524,
                FDR < 0.05)

This is certainly capturing something about the myeloid lineage. Recall that this LV was correlated with neutrophil count from the Banchereau, et al. dataset when we analyzed it in 07-sle_cell_type_recount2_model.

Let’s take a look at the genes contributing to this signal.

data.frame(loadings = sort(recount.plier$Z[, 524], decreasing = TRUE))

Explore LV624

recount.plier$summary %>%
  dplyr::filter(`LV index` == 624,
                FDR < 0.05)

data.frame(loadings = sort(recount.plier$Z[, 624], decreasing = TRUE))

Explore LV937

recount.plier$summary %>%
  dplyr::filter(`LV index` == 937,
                FDR < 0.05)

data.frame(loadings = sort(recount.plier$Z[, 937], decreasing = TRUE))

Downregulated

LVs that are consistently downregulated in severe or active AAV as compared to controls.

Explore LV139

recount.plier$summary %>%
  dplyr::filter(`LV index` == 139,
                FDR < 0.05)

data.frame(loadings = sort(recount.plier$Z[, 139], decreasing = TRUE))

Explore LV332

recount.plier$summary %>%
  dplyr::filter(`LV index` == 332,
                FDR < 0.05)

data.frame(loadings = sort(recount.plier$Z[, 332], decreasing = TRUE))

Explore LV346

recount.plier$summary %>%
  dplyr::filter(`LV index` == 346,
                FDR < 0.05)

data.frame(loadings = sort(recount.plier$Z[, 346], decreasing = TRUE))

Explore LV631

recount.plier$summary %>%
  dplyr::filter(`LV index` == 631,
                FDR < 0.05)

data.frame(loadings = sort(recount.plier$Z[, 631], decreasing = TRUE))

Explore LV793

recount.plier$summary %>%
  dplyr::filter(`LV index` == 793,
                FDR < 0.05)

data.frame(loadings = sort(recount.plier$Z[, 793], decreasing = TRUE))

Explore LV887

recount.plier$summary %>%
  dplyr::filter(`LV index` == 887,
                FDR < 0.05)

data.frame(loadings = sort(recount.plier$Z[, 887], decreasing = TRUE))

Explore LV909

recount.plier$summary %>%
  dplyr::filter(`LV index` == 909,
                FDR < 0.05)

data.frame(loadings = sort(recount.plier$Z[, 909], decreasing = TRUE))