Summarise the fraction of hyper-stable methylated regions (GRCh38 only)

For each sample, compute the proportion of Edgar et al. “ultra-stable” windows that are clearly methylated (beta >= minBeta) after filtering by CpG density (>= minDensity). The result is added to the sample table as hyperStableEdgar (overwriting any existing column of that name).

addHyperStableFraction(qseaSet, minDensity = 5, minBeta = 0.8)

Arguments

qseaSet: qseaSet. Input object (must be GRCh38). Default: none (must be supplied).
minDensity: numeric(1). Minimum CpG_density to keep a window. Default: 5.
minBeta: numeric(1). Beta threshold to call a window methylated. Default: 0.8.

Value

The input qseaSet with its sampleTable augmented by a numeric column hyperStableEdgar (range 0–1) giving, per sample, the fraction of ultra-stable windows called methylated.

Details

Genome restriction. Only supported for "BSgenome.Hsapiens.NCBI.GRCh38"; the function stops otherwise (checked via qsea::getParameters()).
Regions used. Uses mesa::hg38UltraStableProbes, a GRCh38 set derived from array data (Edgar et al., 2014).
Computation. Windows overlapping the ultra-stable set are extracted, beta values are computed via qsea::makeTable(norm_methods = "beta"), windows with CpG_density < minDensity are dropped, NA beta are treated as 0 for thresholding, and the per-sample fraction with beta >= minBeta is returned.

References

Edgar R, Tan PPC, Portales-Casamar E, Pavlidis P (2014). Meta-analysis of human methylomes reveals stably methylated sequences surrounding CpG islands associated with high gene expression. doi:10.1186/1756-8935-7-28

Examples

data(exampleTumourNormal, package = "mesa")

# Run only if the example windows overlap the ultra-stable probes
exampleTumourNormal %>%
    {
        has_ov <- sum(
            GenomicRanges::countOverlaps(
                qsea::getRegions(.),
                mesa::hg38UltraStableProbes
            )
        ) > 0

        if (has_ov) addHyperStableFraction(.) else {
            message(
                "No overlap with hg38UltraStableProbes in this toy dataset;",
                " skipping."
            )
            .
        }
    } %>%
    qsea::getSampleTable() %>%
    dplyr::select(sample_name, dplyr::any_of("hyperStableEdgar")) %>%
    head()
#> No overlap with hg38UltraStableProbes in this toy dataset; skipping.
#>          sample_name
#> Colon1_N    Colon1_N
#> Colon1_T    Colon1_T
#> Colon2_N    Colon2_N
#> Colon2_T    Colon2_T
#> Lung1_N      Lung1_N
#> Lung1_T      Lung1_T