An integrative approach to assess X-chromosome inactivation using allele-specific expression with applications to epithelial ovarian cancer.

ABSTRACT: X-chromosome inactivation (XCI) epigenetically silences transcription of an X chromosome in females; patterns of XCI are thought to be aberrant in women's cancers, but are understudied due to statistical challenges. We develop a two-stage statistical framework to assess skewed XCI and evaluate gene-level patterns of XCI for an individual sample by integration of RNA sequence, copy number alteration, and genotype data. Our method relies on allele-specific expression (ASE) to directly measure XCI and does not rely on male samples or paired normal tissue for comparison. We model ASE using a two-component mixture of beta distributions, allowing estimation for a given sample of the degree of skewness (based on a composite likelihood ratio test) and the posterior probability that a given gene es

SUBMITTER: Larson NB 

PROVIDER: S-EPMC5726546 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature