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Considering Dependencies Amongst Genes Helps to Adjust the Significance Rank of DEGs
Authors:Liu Qi  Ding Guohui  Huang Tao  Tan Yejun  Dai Hongyue  Xie Lu  Li Yixue
Institution:1. School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China;2. Shanghai Center for Bioinformation Technology, Shanghai 200235, China;3. Merck Research Laboratory, Boston and Rahway, U.S.A.
Abstract:Lists of differentially expressed genes (DEGs) detected often show low reproducibility even in technique replicate experiments. The reproducibility is even lower for those real cancer data with large biological variations and limited number of samples. Since existing methods for identifying differentially expressed genes treat each gene separately, they cannot circumvent the problem of low reproducibility. Considering correlation structures of genes may help to mitigate the effect of errors on individual gene estimates and thus get more reliable lists of DEGs. We borrowed information from large amount of existing microarray data to define the expression dependencies amongst genes. We use this prior knowledge of dependencies amongst genes to adjust the significance rank of DEGs. We applied our method and four popular ranking algorithms including mean fold change (FC), SAM, t‐statistic and Wilcoxon rank sum‐test on two cancer microarray datasets. Our method achieved higher reproducibility than other methods across a range of sample sizes. Furthermore, our method obtained higher accuracy than other methods, especially when the sample size is small. The results demonstrate that considering the dependencies amongst genes helps to adjust the significance rank of genes and find those truly differentially expressed genes.
Keywords:dependencies amongst genes  significance rank  microarrays  gene expression
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