Check fold-change concordance between studies

Computes pairwise correlations of per-study log2 fold changes over genes measured in both studies. A negative correlation usually means the case/control orientation is flipped in one study, which would invalidate any directional meta-analysis; low correlation flags biologically or technically divergent studies.

Usage

mx_study_concordance(
  de_results,
  genes = c("significant", "all"),
  padj_threshold = 0.05,
  cor_method = c("spearman", "pearson")
)

Arguments

de_results

A named list of data.frame objects (the de_result slots produced by mx_de), or a named list of metaXpressStudy objects after mx_de_all. Required columns: gene_id, log2FC, pvalue, padj; effect-size methods also need lfcSE.

genes

Which genes to correlate: "significant" (default; genes with padj <= padj_threshold in at least one of the two studies) or "all".

padj_threshold

Numeric. Default: 0.05.

cor_method

Correlation method. Default: "spearman".

Value

A data.frame with one row per study pair: study_1, study_2, n_genes, correlation, sign_agreement (fraction of genes with the same log2FC sign) and a flag.

See also

mx_meta, mx_de

Examples

set.seed(1)
base <- rnorm(300)
de <- lapply(c(1, 1, -1), function(dir) {
  lfc <- dir * base + rnorm(300, 0, 0.3); p <- 2 * pnorm(-abs(lfc / 0.3))
  data.frame(gene_id = paste0("G", 1:300), log2FC = lfc, pvalue = p,
             padj = p.adjust(p, "BH"))
})
names(de) <- c("A", "B", "C_flipped")
mx_study_concordance(de)
#> Warning: Negative fold-change correlation between studies: A vs C_flipped; B vs C_flipped. Check that every study uses the same case/control contrast.
#>   study_1   study_2 n_genes correlation sign_agreement
#> 1       A         B     177   0.8957839     0.98305085
#> 2       A C_flipped     177  -0.8905901     0.01694915
#> 3       B C_flipped     176  -0.9020361     0.01704545
#>                                   flag
#> 1                                   ok
#> 2 NEGATIVE: check contrast orientation
#> 3 NEGATIVE: check contrast orientation