Journal
ANNALS OF EPIDEMIOLOGY
Volume 26, Issue 5, Pages 336-341Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.annepidem.2016.03.009
Keywords
Microbiome; Control experiments; Rare taxa; Bias; Normalization
Categories
Funding
- NIH [8U54HD080784]
- NIH-NIHMD [2P60MD002256]
- NSF [5100551, DMS-1127914]
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Purpose: In case-control studies of the human microbiome, the goal is to evaluate whether cases differ from controls in the microbiome composition of a particular body habitat and which taxa are responsible for the differences. These studies leverage sequencing technology and spectroscopy that provide new measurements of the microbiome. Methods: Three challenges in conducting reproducible microbiome research using a case-control design are compensating for differences in observed and actual microbial community composition, detecting rare taxa in microbial communities, and choosing properly powered analysis methods. The significance of each challenge, evaluation of commonly held views, analysis of unanswered questions, and suggestions of strategies for solutions are discussed. Results: Understanding the effects of these choices on case-control analyses has been underappreciated, with an implicit assumption that further advances in technology will address all the current shortcomings. Conclusions: It is recommended that research on the human microbiome include positive and negative control experiments to provide insight into bias, contamination, and technical variation. Research protocols such as these may afford a better opportunity to make quantitative and qualitative adjustments to data, thereby reducing the risk of falsely positive results, increasing power to discover true disease determinants, and enhancing interpretation across studies. (C) 2016 Elsevier Inc. All rights reserved.
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