Reconstruction of Ring Chromosomes Using Paired-End Sequencing Data

摘要

Ring chromosomes are genomic abnormalities that occur when DNA is lost at the p-arm and q-arm telomeres, causing the fusion of the altered chromosomal arms into a ring-like shape. Ring chromosomes cause genetic disorders that lead to diseases such as epilepsy and Turner syndrome. Algorithms to detect ring chromosomes using next-generation sequencing (NGS) data can provide rapid and high-resolution methods to detect these abnormalities in utero, which is essential for genetic counseling and diagnosis. However, to date, there are no algorithms that exist for the problem of detecting ring chromosomes using NGS data. In this study, we present an algorithm called RingScreen that uses paired-end sequencing data to determine the presence if ring chromosomes. On simulated data, the method accurately predicted the presence of synthetic rings on 18 of 23 human chromosomes. The method takes advantage of several hallmarks of ring chromosome onset that are reflected in the paired reads that map the p-arm/q-arm junction, and in the read depth in areas flanking the breakpoint.