Comprehensive evaluation of methods for differential expression analysis of metatranscriptomics data.
Comprehensive evaluation of methods for differential expression analysis of metatranscriptomics data.
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DOI：
10.1093/bib/bbad279
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发表时间：
2023-09-20
影响因子：
9.5
通讯作者：
中科院分区：
文献类型：
--
作者：
了解人类微生物组的功能很重要，但专门用于微生物基因表达的统计方法（即元转录组学）的发展仍处于起步阶段。许多目前采用的差异表达分析方法已被设计用于不同的数据类型，并没有在元转录组学设置进行评估。为了解决这一差距，我们对元转录组学数据的10种差异分析方法进行了全面评估和基准测试。我们使用了真实的和模拟数据的组合来评估以下方法的性能（即I型错误、错误发现率和灵敏度）：对数正态（LN）、对数β（LB）、MAST、DESeq 2、宏基因组Seq、ANCOM-BC、LEfSe、ALDEx 2、Kruskal-Wallis和两部分Kruskal-Wallis。该模拟由参加儿童牙病研究（幼儿龋齿，ECC）的300名学龄前儿童的龈上生物膜微生物组数据提供信息，而验证则来自ECC研究和炎症性肠病研究的另外两个数据集。LB检验在小样本和大样本中均显示出最高的灵敏度，并合理控制了I型误差。实际上，MAST受到膨胀的I类错误的阻碍。在ECC研究中应用LN和LB测试后，我们发现由产乳酸的弯曲杆菌携带的基因C8 PHV 7和C8 PEV 7与儿童牙病的关联最强。这一全面的模型评价提供了实用的指导，选择适当的方法，严格的差异表达的元转录组学分析。选择最佳方法可以增加检测真实信号的可能性，同时最大限度地减少声称错误信号的机会。
Understanding the function of the human microbiome is important but the development of statistical methods specifically for the microbial gene expression (i.e. metatranscriptomics) is in its infancy. Many currently employed differential expression analysis methods have been designed for different data types and have not been evaluated in metatranscriptomics settings. To address this gap, we undertook a comprehensive evaluation and benchmarking of 10 differential analysis methods for metatranscriptomics data. We used a combination of real and simulated data to evaluate performance (i.e. type I error, false discovery rate and sensitivity) of the following methods: log-normal (LN), logistic-beta (LB), MAST, DESeq2, metagenomeSeq, ANCOM-BC, LEfSe, ALDEx2, Kruskal–Wallis and two-part Kruskal–Wallis. The simulation was informed by supragingival biofilm microbiome data from 300 preschool-age children enrolled in a study of childhood dental disease (early childhood caries, ECC), whereas validations were sought in two additional datasets from the ECC study and an inflammatory bowel disease study. The LB test showed the highest sensitivity in both small and large samples and reasonably controlled type I error. Contrarily, MAST was hampered by inflated type I error. Upon application of the LN and LB tests in the ECC study, we found that genes C8PHV7 and C8PEV7, harbored by the lactate-producing Campylobacter gracilis, had the strongest association with childhood dental disease. This comprehensive model evaluation offers practical guidance for selection of appropriate methods for rigorous analyses of differential expression in metatranscriptomics. Selection of an optimal method increases the possibility of detecting true signals while minimizing the chance of claiming false ones.
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影响因子：
16.6
作者：
Nearing JT;Douglas GM;Hayes MG;MacDonald J;Desai DK;Allward N;Jones CMA;Wright RJ;Dhanani AS;Comeau AM;Langille MGI
通讯作者：
Langille MGI
影响因子：
12.3
作者：
Mallick H;Ma S;Franzosa EA;Vatanen T;Morgan XC;Huttenhower C
通讯作者：
Huttenhower C
影响因子：
11
作者：
Duran-Pinedo, Ana E.;Chen, Tsute;Frias-Lopez, Jorge
通讯作者：
Frias-Lopez, Jorge
微生物组成的分析：归一化和差异丰度分析的综述。
影响因子：
9.2
作者：
Lin H;Peddada SD
通讯作者：
Peddada SD
影响因子：
3.3
作者：
Iraola G;Pérez R;Naya H;Paolicchi F;Pastor E;Valenzuela S;Calleros L;Velilla A;Hernández M;Morsella C
通讯作者：
Morsella C