Overview

The following vignette describes the nullranges implementation of the block bootstrap with respect to a genomic segmentation. See the main nullranges vignette for an overview of the idea of bootstrapping, or below diagram, and there is additionally a vignette on block boostrapping without respect to segmentation-Unsegmented block bootstrap.

As proposed by Bickel et al. (2010), nullranges contains an implementation of a block bootstrap, such that features are sampled from the genome in blocks. The original block bootstrapping algorithm is implemented in a python software called Genome Structure Correlation, GSC.

Our description of the bootRanges methods is described in Mu et al. (2022).

In a segmented block bootstrap, the blocks are sampled and placed within regions of a genome segmentation. That is, for a genome segmented into states 1,2,…,S, blocks from state s will be used to tile the ranges of state s in each bootstrap sample. The process can be visualized in (A), a block with length \(L_b\) is \(\color{brown}{\text{randomly}}\) selected from state “red” and move to a \(\color{brown}{\text{tile}}\) block across chromosome within same states.

An example workflow of bootRanges used in combination with plyranges is diagrammed in (B), and can be summarized as:

  1. Compute overlap between GRanges of feature \(x\) and GRanges of feature \(y\) to assess overlap or to derive other statistic of interest
  2. bootRanges() with optional segmentation and exclude to create a bootRanges object \(y'\)
  3. Compute overlap between GRanges of feature \(x\) and \(y'\) to derive bootstrap distribution of statistics
  4. A \(z\) test can be performed for testing the null hypothesis that there is no true biological enrichment of the original data (that bootstrap data often has as high an enrichment as the observed data)