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A Pairwise-Gaussian-Merging Approach: Towards Genome Segmentation for Copy Number Analysis

Authors: Chih-Hao Chen, Hsing-Chung Lee, Qingdong Ling, Hsiao-Jung Chen, Sun-Chong Wang, Li-Ching Wu, H.C. Lee

Abstract:

Segmentation, filtering out of measurement errors and identification of breakpoints are integral parts of any analysis of microarray data for the detection of copy number variation (CNV). Existing algorithms designed for these tasks have had some successes in the past, but they tend to be O(N2) in either computation time or memory requirement, or both, and the rapid advance of microarray resolution has practically rendered such algorithms useless. Here we propose an algorithm, SAD, that is much faster and much less thirsty for memory – O(N) in both computation time and memory requirement -- and offers higher accuracy. The two key ingredients of SAD are the fundamental assumption in statistics that measurement errors are normally distributed and the mathematical relation that the product of two Gaussians is another Gaussian (function). We have produced a computer program for analyzing CNV based on SAD. In addition to being fast and small it offers two important features: quantitative statistics for predictions and, with only two user-decided parameters, ease of use. Its speed shows little dependence on genomic profile. Running on an average modern computer, it completes CNV analyses for a 262 thousand-probe array in ~1 second and a 1.8 million-probe array in 9 seconds

Keywords: Cancer, pathogenesis, chromosomal aberration, copy number variation, segmentation analysis.

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1082655

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