arXivDaily arXiv每日学术速递 周一至周五更新
arXiv 1203.4445stat.AP
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双通道细胞RNAi重复数据的贝叶斯测量误差模型

A Bayesian measurement error model for two-channel cell-based RNAi data with replicates

Chung-Hsing Chen, Wen-Chi Su, Chih-Yu Chen, Jing-Ying Huang, Fang-Yu Tsai, Wen-Chang Wang, Chao A. Hsiung, King-Song Jeng, I-Shou Chang

摘要:

RNA干扰(RNA interference,RNAi)是一种内源性的细胞内过程,小的双链RNA导致具有互补核苷序列的mRNA被破坏。随着RNAi文库的产生,可以在人类细胞中进行大规模RNAi筛选,以鉴定参与生物途径的未知基因。研究人员面临的一个挑战是如何处理多重检验问题以及相关的假阳性率(FDR)和假阴性率(FNR)。本文提出了一种贝叶斯分层测量误差模型,用于分析重复的双通道RNAi高通量实验的数据,在该实验中,对特定生物通路的活性和细胞活力进行监测,目标是识别影响通路活性而不影响细胞活性的短发夹RNA(shRNAs)。模拟研究证明了贝叶斯方法的灵活性和鲁棒性,以及在实验中重复的好处。通过分析RNAi高通量筛选的数据来说明这种方法,该筛选在不影响细胞活力的情况下搜索影响HCV复制的细胞因子;包括本HCV研究的结果与文献中报道的一些结果的比较。

英文摘要:

RNA interference (RNAi) is an endogenous cellular process in which small double-stranded RNAs lead to the destruction of mRNAs with complementary nucleoside sequence. With the production of RNAi libraries, large-scale RNAi screening in human cells can be conducted to identify unknown genes involved in a biological pathway. One challenge researchers face is how to deal with the multiple testing issue and the related false positive rate (FDR) and false negative rate (FNR). This paper proposes a Bayesian hierarchical measurement error model for the analysis of data from a two-channel RNAi high-throughput experiment with replicates, in which both the activity of a particular biological pathway and cell viability are monitored and the goal is to identify short hair-pin RNAs (shRNAs) that affect the pathway activity without affecting cell activity. Simulation studies demonstrate the flexibility and robustness of the Bayesian method and the benefits of having replicates in the experiment. This method is illustrated through analyzing the data from a RNAi high-throughput screening that searches for cellular factors affecting HCV replication without affecting cell viability; comparisons of the results from this HCV study and some of those reported in the literature are included.

机构、总结、中文摘要均由AI分析而来,可能存在错误,请以论文正文为准。

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