DETECTING AND ANALYZING COPY NUMBER ALTERNATIONS IN ARRAY-BASED CGH DATA

摘要

Copy number changes or alterations are a form of genetic variation in the human genome. Genomic DNA copy number alterations (CNAs) are associated with the development and progression of cancers. Array-based comparative genomic hybridization (a-CGH) is a technique used to identify copy number changes in genomic DNA. It yields data consisting of fluorescence intensity ratios of test and reference DNA samples. The intensity ratios provide information about the number of copies in DNA. Practical issues such as the contamination of tumor cells in tissue specimens and normalization errors necessitate the use of automated statistics algorithms for learning about the genomic alterations from array CGH data. Specifically, there is a need for algorithms that can identify gains and losses in the number of copies based on statistical considerations, rather than merely detect trends in the data. For this purpose the proposed study introduces three different approaches; Circular binary segmentation, Bayesian approach, relying on the hidden Markov model and effective Gaussian mixture (GM) clustering for the analysis of array CGH profiles. Publicly available data on pancreatic adenocarcinoma and Coriell cell line bacterial artificial chromosome (BAC) array were used for the analysis to illustrate the reliability and success of the techniques.