UGM: a more stable procedure for large-scale multiple testing problems, new solutions to identify oncogene.

Pub Date : 2019-12-23 DOI:10.1186/s12976-019-0117-1
Chengyou Liu, Leilei Zhou, Yuhe Wang, Shuchang Tian, Junlin Zhu, Hang Qin, Yong Ding, Hongbing Jiang
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Abstract

Variations of gene expression levels play an important role in tumors. There are numerous methods to identify differentially expressed genes in high-throughput sequencing. Several algorithms endeavor to identify distinctive genetic patterns susceptable to particular diseases. Although these processes have been proved successful, the probability that the number of non-differentially expressed genes measured by false discovery rate (FDR) has a large standard deviation, and the misidentification rate (type I error) grows rapidly when the number of genes to be detected become larger. In this study we developed a new method, Unit Gamma Measurement (UGM), accounting for multiple hypotheses test statistics distribution, which could reduce the dependency problem. Simulated expression profile data and breast cancer RNA-Seq data were utilized to testify the accuracy of UGM. The results show that the number of non-differentially expressed genes identified by the UGM is very close to the real-evidence data, and the UGM also has a smaller standard error, range, quartile range and RMS error. In addition, the UGM can be used to screen many breast cancer-associated genes, such as BRCA1, BRCA2, PTEN, BRIP1, etc., provides better accuracy, robustness and efficiency, the method of identification differentially expressed genes in high-throughput sequencing.

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UGM:一个更稳定的程序,大规模的多重测试问题,新的解决方案,以确定致癌基因。
基因表达水平的变化在肿瘤中起着重要的作用。在高通量测序中,有许多方法可以鉴定差异表达基因。一些算法试图识别易受特定疾病影响的独特遗传模式。虽然这些过程已被证明是成功的,但通过错误发现率(FDR)测量的非差异表达基因数量的概率具有较大的标准差,并且当待检测基因数量增加时,错误识别率(I型错误)迅速增长。在本研究中,我们提出了一种新的方法,单位伽马测量(UGM),该方法考虑了多假设检验统计分布,可以减少依赖问题。模拟表达谱数据和乳腺癌RNA-Seq数据验证了UGM的准确性。结果表明,该方法鉴定的非差异表达基因数量与实际证据数据非常接近,且具有较小的标准误差、极差、四分位极差和均方根误差。此外,UGM可用于筛选多种乳腺癌相关基因,如BRCA1、BRCA2、PTEN、BRIP1等,为鉴别差异表达基因的高通量测序方法提供了更好的准确性、稳健性和高效性。
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