title: The dilemma of choosing the ideal permutation strategy while estimating statistical significance of genome-wide enrichment.
abstract: 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.
authors: Subhajyoti
authors: S
authors: De
authors: Brent S
authors: BS
authors: Pedersen
authors: Katerina
authors: K
authors: Kechris
mesh_terms: D001665:Binding Sites / Q000235:genetics; D000076246:CCCTC-Binding Factor; D019295:Computational Biology; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D057890:Epigenomics / Q000706:statistics & numerical data; D054856:G-Quadruplexes; D020869:Gene Expression Profiling / Q000706:statistics & numerical data; D015894:Genome, Human; D055106:Genome-Wide Association Study / Q000706:statistics & numerical data*; D023281:Genomics / Q000706:statistics & numerical data; D059014:High-Throughput Nucleotide Sequencing / Q000706:statistics & numerical data; D006801:Humans; D008957:Models, Genetic; D015233:Models, Statistical; D012097:Repressor Proteins / Q000378:metabolism; D050795:STAT2 Transcription Factor / Q000378:metabolism; D012984:Software
chemical_list: D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D012097:Repressor Proteins; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human; D004247:DNA
keywords: genome-wide enrichment; null distribution; permutation strategy; statistical significance
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