Functional enrichment analysis with structural variants: pitfalls and strategies.

Journal article

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: Webber, C

• Publication status: Published
• Journal: Cytogenetic and genome research
• Volume: 135
• Issue: 3-4
• Pages: 277-285
• Publication date: 2011-01-01
• DOI: 10.1159/000331670
• EISSN: 1424-859X
• ISSN: 1424-8581
• Language: English
• Keywords: Genomics; Humans; Genetic Variation; DNA Copy Number Variations; Animals; Genetic Association Studies; Chromosome Aberrations