School of Biosciences, University of Nottingham, Loughborough, LE12 5RD, UK.
School of Science and Technology, Nottingham Trent University, Nottingham, NG11 8NS, UK.
Sci Rep. 2019 Feb 20;9(1):2373. doi: 10.1038/s41598-019-38873-4.
High throughput genomics technologies are applied widely to microbiomes in humans, animals, soil and water, to detect changes in bacterial communities or the genes they carry, between different environments or treatments. We describe a method to test the statistical significance of differences in bacterial population or gene composition, applicable to metagenomic or quantitative polymerase chain reaction data. Our method goes beyond previous published work in being universally most powerful, thus better able to detect statistically significant differences, and through being more reliable for smaller sample sizes. It can also be used for experimental design, to estimate how many samples to use in future experiments, again with the advantage of being universally most powerful. We present three example analyses in the area of antimicrobial resistance. The first is to published data on bacterial communities and antimicrobial resistance genes (ARGs) in the environment; we show that there are significant changes in both ARG and community composition. The second is to new data on seasonality in bacterial communities and ARGs in hooves from four sheep. While the observed differences are not significant, we show that a minimum group size of eight sheep would provide sufficient power to observe significance of similar changes in further experiments. The third is to published data on bacterial communities surrounding rice crops. This is a much larger data set and is used to verify the new method. Our method has broad uses for statistical testing and experimental design in research on changing microbiomes, including studies on antimicrobial resistance.
高通量基因组学技术广泛应用于人类、动物、土壤和水中的微生物组,以检测不同环境或处理条件下细菌群落或其携带基因的变化。我们描述了一种测试细菌种群或基因组成差异的统计显著性的方法,适用于宏基因组或定量聚合酶链反应数据。与之前已发表的工作相比,我们的方法具有普遍最强的优势,因此能够更好地检测到具有统计学意义的差异,并且在样本量较小时更可靠。它还可用于实验设计,以估计在未来实验中使用多少样本,同样具有普遍最强的优势。我们在抗菌药物耐药性领域进行了三个示例分析。第一个是对环境中细菌群落和抗菌药物耐药基因(ARGs)的已发表数据进行分析;我们表明,ARGs 和群落组成都发生了显著变化。第二个是对来自四只绵羊蹄部的细菌群落和 ARGs 季节性的新数据进行分析。虽然观察到的差异没有统计学意义,但我们表明,对于进一步实验中观察到类似变化的显著性,最小的羊群样本量为 8 只将提供足够的能力。第三个是对水稻作物周围细菌群落的已发表数据进行分析。这是一个更大的数据集,用于验证新方法。我们的方法在研究不断变化的微生物组方面,包括抗菌药物耐药性研究,具有广泛的统计检验和实验设计用途。