Interactions between species introduce spurious associations in microbiome studies

Bibliographic Details
Title: Interactions between species introduce spurious associations in microbiome studies
Authors: Menon, Rajita, Ramanan, Vivek, Korolev, Kirill S.
Source: 2018. PLoS Comput Biol 14(1): e1005939
Publication Year: 2017
Collection: Quantitative Biology
Statistics
Subject Terms: Statistics - Applications, Quantitative Biology - Quantitative Methods
More Details: Microbiota contribute to many dimensions of host phenotype, including disease. To link specific microbes to specific phenotypes, microbiome-wide association studies compare microbial abundances between two groups of samples. Abundance differences, however, reflect not only direct associations with the phenotype, but also indirect effects due to microbial interactions. We found that microbial interactions could easily generate a large number of spurious associations that provide no mechanistic insight. Using techniques from statistical physics, we developed a method to remove indirect associations and applied it to the largest dataset on pediatric inflammatory bowel disease. Our method corrected the inflation of p-values in standard association tests and showed that only a small subset of associations is directly linked to the disease. Direct associations had a much higher accuracy in separating cases from controls and pointed to immunomodulation, butyrate production, and the brain-gut axis as important factors in the inflammatory bowel disease.
Comment: 4 main text figures, 15 supplementary figures (i.e appendix) and 6 supplementary tables. Overall 49 pages including references
Document Type: Working Paper
DOI: 10.1371/journal.pcbi.1005939
Access URL: http://arxiv.org/abs/1708.04577
Accession Number: edsarx.1708.04577
Database: arXiv
More Details
DOI:10.1371/journal.pcbi.1005939