get.conservative.fold.enrichment.profile: Estimate minimal fold enrichment/depletion along the chromosomes

Description

The method provides a statistical assessment of enrichment/depletion along the chromosomes. To assess tag density enrichment/depletion, a sliding window of a specified size (fws) is used to calculate the density of the foreground tags (ftl). Multiple, typically larger windows are used to estimate background tag (btl) density around the same location. The densities are compared as ratios of two Poisson processes to estimate lower bound of foreground enrichment, or upper bound of foreground depletion. If multiple window sizes were used to estimate the background tag density, the most conservative one is chosen for each point.

Usage

get.conservative.fold.enrichment.profile(ftl, 
    btl, 
    fws, 
    bwsl = c(1, 5, 25, 50) * fws, 
    step = 50, 
    tag.shift = 146/2, 
    alpha = 0.05, 
    use.most.informative.scale = F, 
    quick.calculation = T,
    background.density.scaling = T, 
    bg.weight = NULL, 
    posl= NULL, 
    return.mle = F)

Arguments

ftl

foreground tag vector list

btl

background tag vector list

fws

foreground window size

bwsl

background window scales. The size(s) of background windows will be fws*bwsl.

step

spacing between positions at which the enrichment/depletion is evaluated

tag.shift

number of basepairs by which positive and negative tag coordinates should be shifted towards eachother (half of binding peak separation distance)

alpha

desired level of statistical significance

use.most.informative.scale

for each position, instead of evaluating enrichment ratio bounds for all background window scales, choose the one with the highest observed density to speed up the calculations

quick.calculation

Use square root transformation method instead of a Bayesian method. This speeds up the caclulation considerably and is turned on by default.

background.density.scaling

If TRUE, regions of significant tag enrichment will be masked out when calculating size ratio of the signal to control datasets (to estimate ratio of the background tag density). If FALSE, the dataset ratio will be equal to the ratio of the number of tags in each dataset.

bg.weight

optional weight by which the background density should be multipled for scaling. If not supplied, the weight is calculated based on the ratio of the reduced ChIP to input dataset sizes.

posl

return.mle

Value

A list of elements corresponding to chromosomes, with each element being an $x/$y data.frame giving the position and the log2 conservative estimate of enrichment/depletion fold ratios around that position. Use writewig to output the structure to a WIG file.

References

R.M.Price, D.G. Bonett "Estimating the ratio fo two Poisson rates", Comp. Stat & Data Anal. 32(2000) 345

Examples

Run this code

# NOT RUN {
    enrichment.estimates <- get.conservative.fold.enrichment.profile(chip.data,
      input.data,
      fws=2*binding.characteristics$whs,
      step=100,
      alpha=0.01);
    writewig(enrichment.estimates,
      "example.enrichment.estimates.wig",
      "Example conservative fold-enrichment/depletion estimates shown on log2 scale");
  
# }