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Fit the NEBULA negative binomial gamma mixed model over single cells

rs_nebula_sc.Rd

[Experimental] Fits NEBULA to every requested gene, streaming the counts out of the gene-major store in batches. NEBULA is gene-independent, so the batching changes nothing about the answer. Cells do not have to arrive grouped by subject: the Rust side sorts them and permutes the design and offsets to match.

Usage

rs_nebula_sc(
  f_path_genes,
  f_path_cells,
  cells_to_keep,
  gene_indices,
  subject_ids,
  design,
  offset,
  nebula_params,
  verbose
)

Arguments

f_path_genes

String. Path to the counts_genes.bin file.

f_path_cells

String. Path to the counts_cells.bin file. Only read when offset is NULL, to take the library sizes.

cells_to_keep

Integer vector. 0-indexed(!) global positions of the cells to analyse, in any order. Must not hold duplicates.

gene_indices

Integer vector. 0-indexed(!) positions of the genes to fit.

subject_ids

Integer vector. 0-indexed(!) subject label per global cell. One entry per cell in the store, not per cell in cells_to_keep.

design

Numeric matrix. Predictors of cells x coefficients, rows aligned to cells_to_keep and including an intercept.

offset

Optional numeric vector. Strictly positive scaling factor per selected cell, aligned to cells_to_keep. NULL uses the library sizes.

nebula_params

Named list. The NEBULA parameters, see params_nebula(), plus either coef (a 0-indexed(!) coefficient) or contrast (one weight per coefficient).

verbose

Integer. 0L - quiet; 1L - normal verbosity; 2L - detailed verbosity.

Value

A list with the following elements

  • gene_idx - Integer. 0-indexed positions of the genes that survived NEBULA's own expression filter.

  • coefficients - Numeric matrix of genes x coefficients. The fixed effects on the design scale.

  • se - Numeric matrix of genes x coefficients. The standard errors.

  • subject_overdispersion - Numeric. NEBULA's sigma^2.

  • cell_overdispersion - Numeric. NEBULA's phi^-1.

  • cell_overdispersion_shrunk - Numeric or NULL. The cell-level overdispersion after empirical Bayes shrinkage, when it was requested.

  • convergence - Integer. NEBULA's convergence code. At or below -20 is a likely failure.

  • sigma_at_bound - Boolean. Whether the subject-level variance finished pinned on its lower bound, i.e. the mixed model collapsed to a plain negative binomial.

  • log_fc - Numeric. Effect of the tested coefficient or contrast, on the natural log scale.

  • effect_se - Numeric. Standard error of that effect.

  • z - Numeric. The Wald statistic.

  • p_values - Numeric. Two-sided p-values.

  • fdr - Numeric. Benjamini-Hochberg adjusted p-values.

References

He, et al., Commun Biol, 2021