Journal
BRIEFINGS IN BIOINFORMATICS
Volume 15, Issue 6, Pages 919-928Publisher
OXFORD UNIV PRESS
DOI: 10.1093/bib/bbt053
Keywords
genome-wide enrichment; statistical significance; permutation strategy; null distribution
Funding
- NCI Physical Sciences Oncology Center [U54CA143798]
- American Cancer Society [ACS IRG 57-001-53]
- University of Colorado School of Medicine
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Integrative analyses of genomic, epigenomic and transcriptomic features for human and various model organisms have revealed that many such features are nonrandomly distributed in the genome. Significant enrichment (or depletion) of genomic features is anticipated to be biologically important. Detection of genomic regions having enrichment of certain features and estimation of corresponding statistical significance rely on the expected null distribution generated by a permutation model. We discuss different genome-wide permutation approaches, present examples where the permutation strategy affects the null model and show that the confidence in estimating statistical significance of genome-wide enrichment might depend on the choice of the permutation approach. In those cases, where biologically relevant constraints are unclear, it is preferable to examine whether key conclusions are consistent, irrespective of the choice of the randomization strategy.
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