Systematically assessing microbiome-disease associations identifies drivers of inconsistency in metagenomic research.
Systematically assessing microbiome-disease associations identifies drivers of inconsistency in metagenomic research.
复制标题
DOI：
10.1371/journal.pbio.3001556
复制
发表时间：
2022-03
期刊：
影响因子：
9.8
通讯作者：
Patel CJ
中科院分区：
文献类型：
--
作者：
Tierney BT;Tan Y;Yang Z;Shui B;Walker MJ;Kent BM;Kostic AD;Patel CJ
评估人类肠道微生物组与疾病之间的关系需要计算可靠的统计关联。在这里，使用数百万种不同的关联建模策略，我们评估了基于微生物组的疾病指标的一致性或稳健性，用于6种流行和充分研究的表型（15个公共队列和2，343名个体）。我们能够区分分析稳健与非稳健结果。在许多情况下，不同的模型产生了矛盾的协会相同的分类群疾病配对，一些显示正相关，其他负相关。当查询文献中先前报道的581个微生物-疾病关联的子集时，3个分类群中有1个表现出关联符号的实质性不一致。值得注意的是，超过90%的1型糖尿病（T1 D）和2型糖尿病（T2 D）的已发表研究结果在这方面特别不可靠。我们还量化了潜在的混淆因素-测序深度，葡萄糖水平，胆固醇和体重指数，例如-影响关联，分析这些变量如何影响普氏粪杆菌丰度和健康肠道之间的表面相关性。总的来说，我们提出我们的方法作为一种方法，以最大限度地提高信心，优先考虑从微生物组关联研究中出现的发现。人体微生物组与我们健康的许多方面有关，但这些关联中有多少是真正可重现的？这项研究试图通过系统地测试581种已报告为疾病相关的微生物特征的稳健性来解决这个问题。
Evaluating the relationship between the human gut microbiome and disease requires computing reliable statistical associations. Here, using millions of different association modeling strategies, we evaluated the consistency—or robustness—of microbiome-based disease indicators for 6 prevalent and well-studied phenotypes (across 15 public cohorts and 2,343 individuals). We were able to discriminate between analytically robust versus nonrobust results. In many cases, different models yielded contradictory associations for the same taxon–disease pairing, some showing positive correlations and others negative. When querying a subset of 581 microbe–disease associations that have been previously reported in the literature, 1 out of 3 taxa demonstrated substantial inconsistency in association sign. Notably, >90% of published findings for type 1 diabetes (T1D) and type 2 diabetes (T2D) were particularly nonrobust in this regard. We additionally quantified how potential confounders—sequencing depth, glucose levels, cholesterol, and body mass index, for example—influenced associations, analyzing how these variables affect the ostensible correlation between Faecalibacterium prausnitzii abundance and a healthy gut. Overall, we propose our approach as a method to maximize confidence when prioritizing findings that emerge from microbiome association studies. The human microbiome has been associated with many aspects of our health, but how many of these associations are truly reproducible? This study attempts to address this question by systematically testing the robustness of 581 microbial features that have been reported as being disease-associated.
登录
查看更多内容
影响因子：
7.6
作者：
BARON, RM;KENNY, DA
通讯作者：
KENNY, DA
影响因子：
16.6
作者：
Duvallet C;Gibbons SM;Gurry T;Irizarry RA;Alm EJ
通讯作者：
Alm EJ
影响因子：
15.5
作者：
Kim D;Hofstaedter CE;Zhao C;Mattei L;Tanes C;Clarke E;Lauder A;Sherrill-Mix S;Chehoud C;Kelsen J;Conrad M;Collman RG;Baldassano R;Bushman FD;Bittinger K
通讯作者：
Bittinger K
影响因子：
7.7
作者：
Armitage, P
通讯作者：
Armitage, P
影响因子：
17.1
作者：
Goodman, Steven N.;Fanelli, Daniele;Ioannidis, John P. A.
通讯作者：
Ioannidis, John P. A.