A CUSUM approach to the detection of copy-number neutral loss of heterozygosity

Abstract

Several genetic alterations are involved in the genesis and development of cancers. The determination of whether and how each genetic alterations contributes to cancer development is fundamental for a complete understanding of the human cancer etiology. Loss of heterozygosity (LOH) is one of such genetic phenomenon linked to a variate of diseases and characterized by the change from heterozygosity (the presence of both alleles of a gene) to to homozygosity (presence of only one type of allele) in a particular DNA locus. Thus identification of DNA regions where LOH has taken place is a important issue in the health sciences. In this article we formulate the LOH detection as the identification of change-points in the parameters of a mixture model and present a detection algorithm based on the cumulative sums (CUSUM) method. We found that even under mild contamination our proposal is a fast and reliable method.