A unified framework for unconstrained and constrained ordination of microbiome read count data

PLoS One. 2019 Feb 13;14(2):e0205474. doi: 10.1371/journal.pone.0205474. eCollection 2019.

Abstract

Explorative visualization techniques provide a first summary of microbiome read count datasets through dimension reduction. A plethora of dimension reduction methods exists, but many of them focus primarily on sample ordination, failing to elucidate the role of the bacterial species. Moreover, implicit but often unrealistic assumptions underlying these methods fail to account for overdispersion and differences in sequencing depth, which are two typical characteristics of sequencing data. We combine log-linear models with a dispersion estimation algorithm and flexible response function modelling into a framework for unconstrained and constrained ordination. The method is able to cope with differences in dispersion between taxa and varying sequencing depths, to yield meaningful biological patterns. Moreover, it can correct for observed technical confounders, whereas other methods are adversely affected by these artefacts. Unlike distance-based ordination methods, the assumptions underlying our method are stated explicitly and can be verified using simple diagnostics. The combination of unconstrained and constrained ordination in the same framework is unique in the field and facilitates microbiome data exploration. We illustrate the advantages of our method on simulated and real datasets, while pointing out flaws in existing methods. The algorithms for fitting and plotting are available in the R-package RCM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Bacteria / genetics
  • Computer Simulation
  • Data Visualization*
  • Humans
  • Microbiota / genetics*
  • Monte Carlo Method
  • Neoplasms / microbiology
  • RNA, Ribosomal, 16S / genetics

Substances

  • RNA, Ribosomal, 16S

Grants and funding

Stijn Hawinkel was funded by Janssen Pharmaceutical companies of Johnson and Johnson. The funder was kept informed about research progress and provided useful input.