title: Functional enrichment analysis with structural variants: pitfalls and strategies.
abstract: Interpreting the phenotypic consequences of human structural variation remains challenging. Functional enrichment analysis, which can identify functional enrichments among genes affected by structural variants, is providing significant biological insights into the genotype-phenotype relationship. In this review, we discuss the different approaches and choices in the application of this technique to human structural variation. We consider the importance of choosing the right background distribution for detection, the significance of the gene selection criteria, the effects of tissue-specific gene length biases and discuss sources of functional annotations with a focus on Gene Ontology and mouse phenotypic resources. Throughout this review, we highlight potential sources of significant bias that are of particular concern to the analysis of structural variants, and illustrate the importance of examining the expectations upon which enrichment analysis techniques depend.
authors: Department of Physiology, Anatomy and Genetics, MRC Functional Genomics Unit, University of Oxford, Oxford, UK. caleb.webber@dpag.ox.ac.uk
authors: C
authors: C
authors: Webber
mesh_terms: D000818:Animals; D002869:Chromosome Aberrations; D056915:DNA Copy Number Variations; D056726:Genetic Association Studies / Q000379:methods*; D014644:Genetic Variation; D023281:Genomics; D006801:Humans