Improved statistical analysis for array CGH-based DNA copy number aberrations

Array-based comparative genomic hybridization (aCGH) allows measuring DNA copy number at the whole genome scale. In cancer studies, one may be interested in identifying DNA copy number aberrations (CNAs) associated with certain clinicopathological characteristics such as cancer metastasis. We proposed to defne test regions based on copy number pattern profles across multiple samples, using either smoothed log₂-ratio or discrete data of copy number gain/loss calls. Association test performed on the refned test regions instead of the probes has improved power due to reduced number of tests. We also compared three types of measurement of copy number levels, normalized log₂-ratio, smoothed log₂-ratio, and copy number gain or loss calls in statistical hypothesis testing. The relative strengths and weaknesses of the proposed method were demonstrated using both simulation studies and real data analysis of a liver cancer study.