A hierarchical clustering method for estimating copy number variation

Abstract

Microarray technologies allow for simultaneous measurement of DNA copy number at thousands of positions in a genome. Gains and losses of DNA sequences reveal themselves through characteristic patterns of hybridization intensity. To identify change points along the chromosomes, we develop a marker clustering method which consists of 2 parts. First, a "circular clustering tree test statistic" attaches a statistic to each marker that measures the likelihood that it is a change point. Then construction of the marker statistics is followed by outlier detection approaches. The method provides a new way to build up a binary tree that can accurately capture change-point signals and is easy to perform. A simulation study shows good performance in change-point detection, and cancer cell line data are used to illustrate performance when regions of true copy number changes are known. © The Author 2006. Published by Oxford University Press. All rights reserved.