Probabilistic inference of biochemical reactions in microbial communities from metagenomic sequences.

Probabilistic inference of biochemical reactions in microbial communities from metagenomic sequences.
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DOI:
10.1371/journal.pcbi.1002981
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发表时间:
2013
影响因子:
4.3
通讯作者:
Tang H
Tang H
中科院分区:
生物学2区
文献类型:
--
作者:
Jiao D;Ye Y;Tang H

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鸟枪式宏基因组学已被应用于各种微生物群落功能的研究。作为这些研究中的关键分析步骤,基于从宏基因组鸟枪序列预测的基因重建生物途径。途径重建提供了对微生物群落功能的深入了解,并可用于比较多个微生物群落。然而,由于基因的功能注释不完善,以及预测的酶与生化反应的分配不明确(例如,某些酶参与多种生物化学反应)。考虑到微生物群落中的代谢功能是由许多酶以协作的方式进行的,我们提出了一种概率采样方法来分析宏基因组数据集中的功能内容,通过在由注释宏基因组定义的整个代谢网络的背景下对催化混杂酶的功能进行采样。我们在环境和人类相关微生物群落的宏基因组数据集上测试了我们的方法。结果表明,我们的方法提供了一个更准确的代表性的代谢活动编码的宏基因组,从而提高了多个微生物群落的比较分析。此外,我们的方法报告了推定反应的可能性分数,这可用于识别反映微生物群落环境适应的重要反应和代谢途径。代谢网络采样的源代码可在http://omics.informatics.indiana.edu/mg/MetaNetSam/上在线获得。我们提出了一种概率抽样方法,从宏基因组鸟枪读数中分析微生物群落中的代谢反应,试图了解微生物群落中的代谢,并将其在多个群落中进行比较。不同于针对一组确定的反应的常规途径重建方法,我们的方法估计每个注释的反应在微生物群落的代谢中发生的可能性,给出鸟枪测序数据。这种概率测量提高了我们对微生物群落中实际代谢的预测,并且可以用于宏基因组数据的比较功能分析。
Shotgun metagenomics has been applied to the studies of the functionality of various microbial communities. As a critical analysis step in these studies, biological pathways are reconstructed based on the genes predicted from metagenomic shotgun sequences. Pathway reconstruction provides insights into the functionality of a microbial community and can be used for comparing multiple microbial communities. The utilization of pathway reconstruction, however, can be jeopardized because of imperfect functional annotation of genes, and ambiguity in the assignment of predicted enzymes to biochemical reactions (e.g., some enzymes are involved in multiple biochemical reactions). Considering that metabolic functions in a microbial community are carried out by many enzymes in a collaborative manner, we present a probabilistic sampling approach to profiling functional content in a metagenomic dataset, by sampling functions of catalytically promiscuous enzymes within the context of the entire metabolic network defined by the annotated metagenome. We test our approach on metagenomic datasets from environmental and human-associated microbial communities. The results show that our approach provides a more accurate representation of the metabolic activities encoded in a metagenome, and thus improves the comparative analysis of multiple microbial communities. In addition, our approach reports likelihood scores of putative reactions, which can be used to identify important reactions and metabolic pathways that reflect the environmental adaptation of the microbial communities. Source code for sampling metabolic networks is available online at http://omics.informatics.indiana.edu/mg/MetaNetSam/. We present a probabilistic sampling approach to profiling metabolic reactions in a microbial community from metagenomic shotgun reads, in an attempt to understand the metabolism within a microbial community and compare them across multiple communities. Different from the conventional pathway reconstruction approaches that aim at a definitive set of reactions, our method estimates how likely each annotated reaction can occur in the metabolism of the microbial community, given the shotgun sequencing data. This probabilistic measure improves our prediction of the actual metabolism in the microbial communities and can be used in the comparative functional analysis of metagenomic data.
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