Detection of Simultaneous Group Effects in MicroRNA Expression and Related Target Gene Sets

被引:20
作者
Artmann, Stephan [1 ]
Jung, Klaus [1 ]
Bleckmann, Annalen [1 ,2 ]
Beissbarth, Tim [1 ]
机构
[1] Univ Med Ctr Gottingen, Dept Med Stat, Gottingen, Germany
[2] Univ Med Ctr Gottingen, Dept Hematol & Oncol, Gottingen, Germany
关键词
GLOBAL TEST; PROFILES; VARIANCE;
D O I
10.1371/journal.pone.0038365
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
Expression levels of mRNAs are among other factors regulated by microRNAs. A particular microRNA can bind specifically to several target mRNAs and lead to their degradation. Expression levels of both, mRNAs and microRNAs, can be obtained by microarray experiments. In order to increase the power of detecting microRNAs that are differentially expressed between two different groups of samples, we incorporate expression levels of their related target gene sets. Group effects are determined individually for each microRNA, and by enrichment tests and global tests for target gene sets. The resulting lists of p-values from individual and set-wise testing are combined by means of meta analysis. We propose a new approach to connect microRNA-wise and gene set-wise information by means of p-value combination as often used in meta-analysis. In this context, we evaluate the usefulness of different approaches of gene set tests. In a simulation study we reveal that our combination approach is more powerful than microRNA-wise testing alone. Furthermore, we show that combining microRNA-wise results with 'competitive' gene set tests maintains a pre-specified false discovery rate. In contrast, a combination with 'self-contained' gene set tests can harm the false discovery rate, particularly when gene sets are not disjunct.
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页数:11
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