varRatio: Compare Variance Ratio Factors of Two 'bioCond' Objects

In MAnorm2: Tools for Normalizing and Comparing ChIP-seq Samples

Compare Variance Ratio Factors of Two bioCond Objects

Description

Given two bioCond objects, varRatio robustly estimates the ratio between their variance ratio factors, assuming they are associated with the same mean-variance curve and using the genomic intervals expected to have invariant signal intensities across the two biological conditions (see "Details").

Usage

varRatio(cond1, cond2, invariant = NULL)

Arguments

cond1, cond2	Two bioCond objects.
invariant	An optional non-negative real specifying the upper bound of difference in mean signal intensity for a genomic interval to be treated as invariant between cond1 and cond2. By default, intervals occupied by both conditions are treated as invariant.

Details

MAnorm2 models ChIP-seq samples as grouped by biological conditions. It constructs a bioCond object to represent each biological condition, which contains a set of ChIP-seq samples belonging to the condition.

Given multiple bioCond objects, MAnorm2 could fit a single curve to model the mean-variance dependence across genomic intervals. Each genomic interval in each bioCond object that contains replicate samples serves as an observation for the fitting process.

To account for the global difference in variation level of signal intensities between two conditions, MAnorm2 involves a "variance ratio factor" for each condition. Specifically, given two bioCond objects associated with the same mean-variance curve (say condition 1 and 2), we have

cov(Xi,1 | vi) = (r1 * vi) * Si,1

and

cov(Xi,2 | vi) = (r2 * vi) * Si,2

for any genomic interval i that is not differentially represented between the two conditions. Here, Xi,j is the vector of signal intensities of interval i in condition j, rj is the variance ratio factor (a scalar) of condition j, vi is the unscaled variance (a scalar) of signal intensities in interval i, and Si,j is the structure matrix of interval i in condition j (see bioCond and setWeight for a detailed description of structure matrix).

Under this formulation, varRatio estimates the ratio of the variance ratio factor of cond2 to that of cond1, using the intervals with invariant signal intensities across the two conditions. The argument invariant controls the set of such intervals. By default, intervals occupied by both conditions constitute the set. Alternatively, giving invariant a non-negative value specifies these intervals to be invariant that have a difference in average signal intensity between the two conditions less than or equal to the value.

In most cases, you don't need to call this function directly. It's typically used by fitMeanVarCurve for fitting a mean-variance trend on a set of bioCond objects.

Value

The estimated ratio of the variance ratio factor of cond2 to that of cond1. Note that the function returns NA if there are not sufficient invariant intervals for estimating it.

References

Tu, S., et al., MAnorm2 for quantitatively comparing groups of ChIP-seq samples. Genome Res, 2021. 31(1): p. 131-145.

See Also

bioCond for creating a bioCond object; setWeight for a detailed description of structure matrix; fitMeanVarCurve for fitting a mean-variance curve given a set of bioCond objects.

Examples

data(H3K27Ac, package = "MAnorm2")
attr(H3K27Ac, "metaInfo")

## Compare variance ratio factor between cell lines.

# Perform the MA normalization and construct bioConds to represent cell
# lines.
norm <- normalize(H3K27Ac, 4, 9)
norm <- normalize(norm, 5:6, 10:11)
norm <- normalize(norm, 7:8, 12:13)
conds <- list(GM12890 = bioCond(norm[4], norm[9], name = "GM12890"),
              GM12891 = bioCond(norm[5:6], norm[10:11], name = "GM12891"),
              GM12892 = bioCond(norm[7:8], norm[12:13], name = "GM12892"))
autosome <- !(H3K27Ac$chrom %in% c("chrX", "chrY"))
conds <- normBioCond(conds, common.peak.regions = autosome)

# Compare the variance ratio factor of GM12892 to that of GM12891.
varRatio(conds$GM12891, conds$GM12892)

# Such a comparison is only possible when both bioConds have replicate
# samples.
varRatio(conds$GM12891, conds$GM12890)

MAnorm2 documentation built on Oct. 29, 2022, 1:12 a.m.