Browsing by Author "Zhang, Shengli"

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    Comparative Analysis of Methods for Identifying Recurrent Copy Number Alterations in Cancer
    Yuan, Xiguo; Zhang, Junying; Zhang, Shengli; Yu, Guoqiang; Wang, Yue (PLOS, 2012-12-20)
    Recurrent copy number alterations (CNAs) play an important role in cancer genesis. While a number of computational methods have been proposed for identifying such CNAs, their relative merits remain largely unknown in practice since very few efforts have been focused on comparative analysis of the methods. To facilitate studies of recurrent CNA identification in cancer genome, it is imperative to conduct a comprehensive comparison of performance and limitations among existing methods. In this paper, six representative methods proposed in the latest six years are compared. These include one-stage and two-stage approaches, working with raw intensity ratio data and discretized data respectively. They are based on various techniques such as kernel regression, correlation matrix diagonal segmentation, semi-parametric permutation and cyclic permutation schemes. We explore multiple criteria including type I error rate, detection power, Receiver Operating Characteristics (ROC) curve and the area under curve (AUC), and computational complexity, to evaluate performance of the methods under multiple simulation scenarios. We also characterize their abilities on applications to two real datasets obtained from cancers with lung adenocarcinoma and glioblastoma. This comparison study reveals general characteristics of the existing methods for identifying recurrent CNAs, and further provides new insights into their strengths and weaknesses. It is believed helpful to accelerate the development of novel and improved methods.
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    TAGCNA: A Method to Identify Significant Consensus Events of Copy Number Alterations in Cancer
    Yuan, Xiguo; Zhang, Junying; Yang, Liying; Zhang, Shengli; Chen, Baodi; Geng, Yaojun; Wang, Yue (PLOS, 2012-07-18)
    Somatic copy number alteration (CNA) is a common phenomenon in cancer genome. Distinguishing significant consensus events (SCEs) from random background CNAs in a set of subjects has been proven to be a valuable tool to study cancer. In order to identify SCEs with an acceptable type I error rate, better computational approaches should be developed based on reasonable statistics and null distributions. In this article, we propose a new approach named TAGCNA for identifying SCEs in somatic CNAs that may encompass cancer driver genes. TAGCNA employs a peel-off permutation scheme to generate a reasonable null distribution based on a prior step of selecting tag CNA markers from the genome being considered. We demonstrate the statistical power of TAGCNA on simulated ground truth data, and validate its applicability using two publicly available cancer datasets: lung and prostate adenocarcinoma. TAGCNA identifies SCEs that are known to be involved with proto-oncogenes (e.g. EGFR, CDK4) and tumor suppressor genes (e.g. CDKN2A, CDKN2B), and provides many additional SCEs with potential biological relevance in these data. TAGCNA can be used to analyze the significance of CNAs in various cancers. It is implemented in R and is freely available at http://tagcna.sourceforge.net/.