PT  - JOURNAL ARTICLE
AU  - Joshua G. Harrison
AU  - W. John Calder
AU  - Vivaswat Shastry
AU  - C. Alex Buerkle
TI  - Dirichlet-multinomial modelling outperforms alternatives for analysis of microbiome and other ecological count data
AID  - 10.1101/711317
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 711317
4099  - http://biorxiv.org/content/early/2019/12/01/711317.short
4100  - http://biorxiv.org/content/early/2019/12/01/711317.full
AB  - Molecular ecology regularly requires the analysis of count data that reflect the relative abundance of features of a composition (e.g., taxa in a community, gene transcripts in a tissue). The sampling process that generates these data can be modeled using the multinomial distribution. Replicate multinomial samples inform the relative abundances of features in an underlying Dirichlet distribution. These distributions together form a hierarchical model for relative abundances among replicates and sampling groups. This type of Dirichlet-multinomial modelling (DMM) has been described previously, but its benefits and limitations are largely untested. With simulated data, we quantified the ability of DMM to detect differences in proportions between treatment and control groups, and compared the efficacy of three computational methods to implement DMM—Hamiltonian Monte Carlo (HMC), variational inference (VI), and Gibbs Markov chain Monte Carlo. We report that DMM was better able to detect shifts in relative abundances than analogous analytical tools, while identifying an acceptably low number of false positives. Among methods for implementing DMM, HMC provided the most accurate estimates of relative abundances, and VI was the most computationally efficient. The sensitivity of DMM was exemplified through analysis of previously published data describing lung microbiomes. We report that DMM identified several potentially pathogenic, bacterial taxa as more abundant in the lungs of children who aspirated foreign material during swallowing; these differences went undetected with different statistical approaches. Our results suggest that DMM has strong potential as a statistical method to guide inference in molecular ecology.