Integrating genomic correlation structure improves copy number variations detection

Copy number variation plays important roles in human complex diseases. The detection of copy number variants (CNVs) is identifying mean shift in genetic intensities to locate chromosomal breakpoints, the step of which is referred to as chromosomal segmentation. Many segmentation algorithms have been developed with a strong assumption of independent observations in the genetic loci, and they assume each locus has an equal chance to be a breakpoint (i.e. boundary of CNVs). However, this assumption is violated in the genetics perspective due to the existence of correlation among genomic positions, such as linkage disequilibrium (LD). Our study showed that the LD structure is related to the location distribution of CNVs, which indeed presents a non-random pattern on the genome. To generate more accurate CNVs, we proposed a novel algorithm, LDcnv, that models the CNV data with its biological characteristics relating to genetic dependence structure (i.e. LD).