Gene set analysis methods: a systematic comparison.

Gene set analysis methods: a systematic comparison.
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DOI:
10.1186/s13040-018-0166-8
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发表时间:
2018
期刊:
影响因子:
4.5
通讯作者:
Motsinger-Reif A
Motsinger-Reif A
中科院分区:
生物学3区
文献类型:
--
作者:
Mathur R;Rotroff D;Ma J;Shojaie A;Motsinger-Reif A

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基因集分析是一个有价值的工具,总结高维基因表达数据的生物学相关的集合。这是一个活跃的研究领域,已经开发了许多基因集分析方法。尽管如此,系统的比较研究在范围上受到限制。在这项研究中,我们提出了一个半合成模拟研究,使用真实的数据集,以测试和比较常用的方法。一个软件流水线,新基因集模拟的灵活算法(FANGS)开发了基于前列腺癌数据集的模拟数据,其中KRAS和TGF-β通路差异表达。FANGS软件与其他数据集和路径兼容。针对基因集富集分析(GSEA)、功能和表达的显著性分析(SAFE)、sigPathway和相关性调整的平均RANK(CAMERA)方法呈现基因集分析方法的比较。使用来自MSigDB知识库的基因集测试所有基因集分析方法。估计并提供假阳性率和功效以供比较。建议的效用的默认设置的方法和每种方法的灵敏度对各种效果大小。本研究的结果为基因集分析方法的使用者提供了实证指导。FANGS软件可供研究人员继续进行方法比较。本文的在线版本(10.1186/s13040-018-0166-8)包含补充材料,可供授权用户使用。
Gene set analysis is a valuable tool to summarize high-dimensional gene expression data in terms of biologically relevant sets. This is an active area of research and numerous gene set analysis methods have been developed. Despite this popularity, systematic comparative studies have been limited in scope. In this study we present a semi-synthetic simulation study using real datasets in order to test and compare commonly used methods. A software pipeline, Flexible Algorithm for Novel Gene set Simulation (FANGS) develops simulated data based on a prostate cancer dataset where the KRAS and TGF-β pathways were differentially expressed. The FANGS software is compatible with other datasets and pathways. Comparisons of gene set analysis methods are presented for Gene Set Enrichment Analysis (GSEA), Significance Analysis of Function and Expression (SAFE), sigPathway, and Correlation Adjusted Mean RAnk (CAMERA) methods. All gene set analysis methods are tested using gene sets from the MSigDB knowledge base. The false positive rate and power are estimated and presented for comparison. Recommendations are made for the utility of the default settings of methods and each method’s sensitivity towards various effect sizes. The results of this study provide empirical guidance to users of gene set analysis methods. The FANGS software is available for researchers for continued methods comparisons. The online version of this article (10.1186/s13040-018-0166-8) contains supplementary material, which is available to authorized users.
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