A Local Polynomial Method for Detection of Gene Copy Number Changes in Human Cancer

• Activity Number: 477
• Type: Topic Contributed
• Date/Time: Thursday, August 11, 2005 : 8:30 AM to 10:20 AM
• Sponsor: Biometrics Section
• Author(s): Lexin Li*+ and Hongzhe Li
• Companies: University of California, Davis and University of California, Davis
• Keywords: Array CGH ; Change-point ; Local polynomial regression

Abstract

Cancer progression often involves alterations in DNA copy number, which measures the number of copies of DNA at a region of a genome. Because an aberration at a particular genome location may indicate the presence of a tumor suppressor gene or an oncogene, it is important to identify the chromosome regions with abnormal copy numbers precisely. Array comparative genomic hybridization (array CGH) is an effective tool for genome-wide scanning of DNA copy numbers. However, the experiments are subjected to many sources of noise. In this article, we propose a simple but effective method to determine objectively the locations of DNA copy number alterations. The problem was formulated by a change-point model and a nonparametric local polynomial method was developed to evaluate the observed copy number variations at each chromosomal location. The proposed method assumes no parametric form for the distribution of the copy numbers and requires no computationally intensive method such as data permutation. The computation involved is simple and fast. The effectiveness of the proposed method has been demonstrated by both simulations and a real BAC array data with 15 fibroblast cell lines.