design and statistical analysis of pooled next generation sequencing for rare variants池的设计和统计分析下一代测序罕见变异.pdfVIP

Hindawi Publishing Corporation Journal of Probability and Statistics Volume 2012, Article ID 524724, 19 pages doi:10.1155/2012/524724 Research Article Design and Statistical Analysis of Pooled Next Generation Sequencing for Rare Variants Tao Wang,1 Chang-Yun Lin,2 Yuanhao Zhang,3 Ruofeng Wen,3 and Kenny Ye1 1 Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, NY 10461, USA 2 Department of Applied Mathematics and Institute of Statistics, National Chung Hsing University, Taichung 402, Taiwan 3 Department of Applied Mathematics and Statistics, Stony Brook University, New York, NY 11794, USA Correspondence should be addressed to Tao Wang, tao.wang@ Received 23 March 2012; Accepted 6 June 2012 Academic Editor: Wei T. Pan Copyright q 2012 Tao Wang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Next generation sequencing NGS is a revolutionary technology for biomedical research. One highly cost-efficient application of NGS is to detect disease association based on pooled DNA samples. However, several key issues need to be addressed for pooled NGS. One of them is the high sequencing error rate and its high variability across genomic positions and experiment runs, which, if not well considered in the experimental design and analysis, could lead to either inflated false positive rates or loss in statistical power. Another important issue is how to test association of a group of rare variants. To address the first issue, we proposed a new blocked pooling design in which multiple pools