Removal of false positives in metagenomics-based taxonomy profiling via targeting Type IIB restriction sites.

Removal of false positives in metagenomics-based taxonomy profiling via targeting Type IIB restriction sites.
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DOI:
10.1038/s41467-023-41099-8
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发表时间:
2023-09-01
影响因子:
16.6
通讯作者:
Liu, Yang-Yu
Liu, Yang-Yu
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Sun, Zheng;Liu, Jiang;Zhang, Meng;Wang, Tong;Huang, Shi;Weiss, Scott T.;Liu, Yang-Yu

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准确的物种鉴定和丰度估计对于全宏基因组测序(WMS)数据的解释至关重要。然而,现有的宏基因组分析仪遭受假阳性鉴定,这可能占总鉴定物种的90%以上。在这里,通过利用物种特异性IIB型限制性内切酶消化位点作为参考,而不是通用标记或整个微生物基因组,我们提出了一个宏基因组分析仪,MAP2B(基于IIB型限制性位点的Metabolomic Profiler),以解决这些问题。我们首先说明了使用相对丰度作为确定假阳性的唯一特征的陷阱。然后,我们提出了一个特征集来区分假阳性和真阳性,并使用模拟的CAMI2宏基因组,我们建立了一个假阳性识别模型。通过使用具有不同测序深度和物种丰富度的模拟数据集对宏基因组分析的性能进行基准测试,我们说明了MAP 2B在物种鉴定中优于现有宏基因组分析仪的上级性能。我们使用来自ATCC模拟社区的真实的WMS数据进一步测试了MAP2B的性能,证实了其相对于测序深度的上级精度。最后,通过利用来自IBD队列的WMS数据,我们证明了MAP2B生成的分类特征可以更好地区分IBD并预测代谢组学特征。在这里,利用物种特异性IIB型限制性内切酶消化位点作为参考,而不是通用标记或整个微生物基因组,作者介绍了MAP2B,一种宏基因组分析仪,表明它可以显着消除假阳性鉴定并生成高度准确的分类学分析结果。
Accurate species identification and abundance estimation are critical for the interpretation of whole metagenome sequencing (WMS) data. Yet, existing metagenomic profilers suffer from false-positive identifications, which can account for more than 90% of total identified species. Here, by leveraging species-specific Type IIB restriction endonuclease digestion sites as reference instead of universal markers or whole microbial genomes, we present a metagenomic profiler, MAP2B (MetAgenomic Profiler based on type IIB restriction sites), to resolve those issues. We first illustrate the pitfalls of using relative abundance as the only feature in determining false positives. We then propose a feature set to distinguish false positives from true positives, and using simulated metagenomes from CAMI2, we establish a false-positive recognition model. By benchmarking the performance in metagenomic profiling using a simulation dataset with varying sequencing depth and species richness, we illustrate the superior performance of MAP2B over existing metagenomic profilers in species identification. We further test the performance of MAP2B using real WMS data from an ATCC mock community, confirming its superior precision against sequencing depth. Finally, by leveraging WMS data from an IBD cohort, we demonstrate the taxonomic features generated by MAP2B can better discriminate IBD and predict metabolomic profiles. Here, leveraging species-specific Type IIB restriction endonuclease digestion sites as reference instead of universal markers or whole microbial genomes, the authors introduce MAP2B, a metagenomic profiler, showing it can significantly remove false-positive identification and generate highly accurate taxonomic profiling results.
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