Piphillin: Improved Prediction of Metagenomic Content by Direct Inference from Human Microbiomes.
Piphillin: Improved Prediction of Metagenomic Content by Direct Inference from Human Microbiomes.
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DOI：
10.1371/journal.pone.0166104
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
DeSantis TZ
中科院分区：
文献类型：
--
作者：
Iwai S;Weinmaier T;Schmidt BL;Albertson DG;Poloso NJ;Dabbagh K;DeSantis TZ
临床微生物组的功能分析有助于阐明微生物组扰动可引起患者表型变化的机制。分析微生物组功能能力的直接方法是通过霰弹枪宏基因组学。估计微生物群落功能能力的一种廉价方法是通过收集16S rRNA基因谱，然后间接推断功能基因的丰度。这种推理方法已经在PICRUSt和Tax4Fun软件工具中实现。然而，这些工具有很大的局限性，因为它们依赖于过时的功能数据库和不确定的系统发育树，并且需要非常具体的数据预处理协议。在这里，我们介绍Piphillin，一个简单的算法独立于任何提出的系统发育树，利用现代功能数据库，不需要任何单一的数据预处理协议。当所有三种推断工具与实际的散枪宏基因组学进行评估时，与PICRUSt和Tax4Fun相比，Piphillin在预测人类临床样本中的基因组成方面优于PICRUSt（分别为p<0.01和p<0.001）， Piphillin预测特定基因同源物与疾病关联的能力比PICRUSt提高了15%。从实验动物样本中，没有观察到任何一种工具优于其他工具的性能优势，对于环境样本，所有工具都产生了令人不满意的预测。我们的研究结果表明，使用在Piphillin中实现的直接方法进行功能推断更适合临床生物标本。Piphillin可在http://secondgenome.com/Piphillin公开供学术使用。
Functional analysis of a clinical microbiome facilitates the elucidation of mechanisms by which microbiome perturbation can cause a phenotypic change in the patient. The direct approach for the analysis of the functional capacity of the microbiome is via shotgun metagenomics. An inexpensive method to estimate the functional capacity of a microbial community is through collecting 16S rRNA gene profiles then indirectly inferring the abundance of functional genes. This inference approach has been implemented in the PICRUSt and Tax4Fun software tools. However, those tools have important limitations since they rely on outdated functional databases and uncertain phylogenetic trees and require very specific data pre-processing protocols. Here we introduce Piphillin, a straightforward algorithm independent of any proposed phylogenetic tree, leveraging contemporary functional databases and not obliged to any singular data pre-processing protocol. When all three inference tools were evaluated against actual shotgun metagenomics, Piphillin was superior in predicting gene composition in human clinical samples compared to both PICRUSt and Tax4Fun (p<0.01 and p<0.001, respectively) and Piphillin’s ability to predict disease associations with specific gene orthologs exhibited a 15% increase in balanced accuracy compared to PICRUSt. From laboratory animal samples, no performance advantage was observed for any one of the tools over the others and for environmental samples all produced unsatisfactory predictions. Our results demonstrate that functional inference using the direct method implemented in Piphillin is preferable for clinical biospecimens. Piphillin is publicly available for academic use at http://secondgenome.com/Piphillin.
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