Modular network construction using eQTL data: an analysis of computational costs and benefits.
Modular network construction using eQTL data: an analysis of computational costs and benefits.
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DOI：
10.3389/fgene.2014.00040
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发表时间：
2014
影响因子：
3.7
通讯作者：
Parmigiani G
中科院分区：
文献类型：
--
作者：
Ho YY;Cope LM;Parmigiani G
背景资料：在本文中，我们考虑的分析方法，基因组DNA变异和mRNA表达（也称为eQTL数据）的综合分析，发现与感兴趣的复杂性状的遗传网络。我们的重点是系统地评估这些网络构建中网络规模和网络搜索效率之间的权衡。结果如下：我们开发了一种模块化的网络构建方法，从较小的网络构建到较大的网络，从而减少了搜索空间，同时在分析中包含更多的变量。我们的目标是实现更低的计算成本，同时保持所得网络的高置信度。仿真结果表明，与贪婪搜索相比，用这种方法构建的网络具有较低的节点/边错误发现率（FDR）和较高的边敏感性。我们进一步证明了我们的方法在两种化疗药物的细胞反应的数据集：多西他赛和5-氟尿嘧啶（5-FU），并确定生物学上合理的网络，可能会描述这些药物的耐药性。结论：在这项研究中，我们建议引导全面搜索吝啬的网络应被视为一种替代贪婪的网络搜索。
Background: In this paper, we consider analytic methods for the integrated analysis of genomic DNA variation and mRNA expression (also named as eQTL data), to discover genetic networks that are associated with a complex trait of interest. Our focus is the systematic evaluation of the trade-off between network size and network search efficiency in the construction of these networks. Results: We developed a modular approach to network construction, building from smaller networks to larger ones, thereby reducing the search space while including more variables in the analysis. The goal is achieving a lower computational cost while maintaining high confidence in the resulting networks. As demonstrated in our simulation results, networks built in this way have low node/edge false discovery rate (FDR) and high edge sensitivity comparing to greedy search. We further demonstrate our method in a data set of cellular responses to two chemotherapeutic agents: docetaxel and 5-fluorouracil (5-FU), and identify biologically plausible networks that might describe resistances to these drugs. Conclusion: In this study, we suggest that guided comprehensive searches for parsimonious networks should be considered as an alternative to greedy network searches.