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Stage two of DIALOGUE: for every ordered pair of cell types and every candidate gene, a random-intercept mixed model over samples asking whether a cell's own programme score tracks the partner cell type's expression of that gene in the same sample.

Usage

params_dialogue_hlm(
  min_cells_per_sample = 2L,
  use_tme_qc = TRUE,
  use_cell_quality = TRUE,
  satterthwaite = TRUE
)

Arguments

min_cells_per_sample

Integer. Minimum cells a sample must contribute, in both cell types of a pair, before it takes part in that pair's models. Defaults to 2L.

use_tme_qc

Boolean. Include the partner cell type's mean quality in that sample as a fixed effect. Upstream's tme.qc. Defaults to TRUE.

use_cell_quality

Boolean. Include the responding cell's own quality as a fixed effect. Upstream's cellQ. Defaults to TRUE.

satterthwaite

Boolean. Compute Satterthwaite denominator degrees of freedom, as lmerTest does. Defaults to TRUE.

Value

A named list with the following elements:

  • min_cells_per_sample - Integer. Minimum cells a sample must contribute, in both cell types of a pair, before it takes part in that pair's models. Defaults to 2L.

  • use_tme_qc - Boolean. Include the partner cell type's mean quality in that sample as a fixed effect. Upstream's tme.qc. Defaults to TRUE.

  • use_cell_quality - Boolean. Include the responding cell's own quality as a fixed effect. Upstream's cellQ. Defaults to TRUE.

  • satterthwaite - Boolean. Compute Satterthwaite denominator degrees of freedom, as lmerTest does. Defaults to TRUE.

Details

This stage dominates the runtime, and satterthwaite is the knob that decides how badly. Turning it off falls back to the residual count for the denominator degrees of freedom, which is far cheaper and barely differs once a cell type has thousands of cells.

use_cell_quality conditions on the cell's own quality covariate, which stage one has already regressed out of the scores by ordinary least squares. The default conditions on it twice, because upstream does.

References

Jerby-Arnon & Regev, Nature Biotechnology, 2022