Phylogeny-guided microbiome OTU-specific association test (POST).
Phylogeny-guided microbiome OTU-specific association test (POST).
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DOI：
10.1186/s40168-022-01266-3
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发表时间：
2022-06-07
期刊：
影响因子：
15.5
通讯作者：
Tzeng, Jung-Ying
中科院分区：
文献类型：
--
作者：
Huang, Caizhi;Callahan, Benjamin John;Wu, Michael C.;Holloway, Shannon T.;Brochu, Hayden;Lu, Wenbin;Peng, Xinxia;Tzeng, Jung-Ying
宿主条件和微生物组谱之间的关系通常以操作分类单位（OTU）为特征，包含有关微生物在人类健康中的作用的重要信息。传统的关联测试框架受到典型微生物组特征的高维性和稀疏性的挑战。系统发育信息往往被纳入到解决这些挑战的假设，进化相似的类群往往表现相似。然而，由于微生物的复杂影响，这种假设可能并不总是有效的，系统发育信息应该以数据监督的方式纳入。在这项工作中，我们提出了一种局部崩溃测试，称为遗传学引导的微生物组OTU特异性关联测试（POST）。在POST中，是否从系统发生树中的相邻OTU借用信息以及借用多少信息由系统发生距离和结果-OTU关联来监督。POST是在内核机器框架下构建的，以适应复杂的OTU效应，并将内核机器微生物组测试从社区级别扩展到OTU级别。使用模拟研究，我们表明，当系统发育树是翔实的，POST有更好的性能比现有的OTU级关联测试。当系统发育树没有信息时，POST实现了与现有方法相似的性能。最后，在细菌性阴道病和早产的真实的数据应用中，我们发现POST可以识别与现有方法相比具有生物学相关性的类似或更多结果相关的OTU。使用POST，我们表明，自适应地利用系统发育信息可以通过改善整体真阳性和假阳性检测来提高相关微生物组特征的选择性能。我们开发了一个用户友好的R包POSTm，它可以在CRAN上免费获得（https：//CRAN.R-project.org/package=POSTm）。视频摘要。在线版本包含补充材料，可在（10.1186/s40168-022-01266-3）获得。
The relationship between host conditions and microbiome profiles, typically characterized by operational taxonomic units (OTUs), contains important information about the microbial role in human health. Traditional association testing frameworks are challenged by the high dimensionality and sparsity of typical microbiome profiles. Phylogenetic information is often incorporated to address these challenges with the assumption that evolutionarily similar taxa tend to behave similarly. However, this assumption may not always be valid due to the complex effects of microbes, and phylogenetic information should be incorporated in a data-supervised fashion. In this work, we propose a local collapsing test called phylogeny-guided microbiome OTU-specific association test (POST). In POST, whether or not to borrow information and how much information to borrow from the neighboring OTUs in the phylogenetic tree are supervised by phylogenetic distance and the outcome-OTU association. POST is constructed under the kernel machine framework to accommodate complex OTU effects and extends kernel machine microbiome tests from community level to OTU level. Using simulation studies, we show that when the phylogenetic tree is informative, POST has better performance than existing OTU-level association tests. When the phylogenetic tree is not informative, POST achieves similar performance as existing methods. Finally, in real data applications on bacterial vaginosis and on preterm birth, we find that POST can identify similar or more outcome-associated OTUs that are of biological relevance compared to existing methods. Using POST, we show that adaptively leveraging the phylogenetic information can enhance the selection performance of associated microbiome features by improving the overall true-positive and false-positive detection. We developed a user friendly R package POSTm which is freely available on CRAN (https://CRAN.R-project.org/package=POSTm). Video Abstract. The online version contains supplementary material available at (10.1186/s40168-022-01266-3).
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DOI：
10.1093/bioinformatics/bts342
发表时间：
2012-08-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
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