Evaluating a topic model approach for parsing microbiome data structure

Abstract

The increasing availability of microbiome survey data has led to the use of complex machine learning and statistical approaches to measure taxonomic diversity and extract relationships between taxa and their host or environment. However, many approaches inadequately account for the difficulties inherent to microbiome data. These difficulties include (1) insufficient sequencing depth resulting in sparse count data, (2) a large feature space relative to sample space, resulting in data prone to overfitting, (3) library size imbalance, requiring normalization strategies that lead to compositional artifacts, and (4) zero-inflation. Recent work has used probabilistic topics models to more appropriately model microbiome data, but a thorough inspection of just how well topic models capture underlying microbiome signal is lacking. Also, no work has determined whether library size or variance normalization improves model fitting. Here, we assessed a topic model approach on 16S rRNA gene survey data. Through simulation, we show, for small sample sizes, library-size or variance normalization is unnecessary prior to fitting the topic model. In addition, by exploiting topic-to-topic correlations, the topic model successfully captured dynamic time-series behavior of simulated taxonomic subcommunities. Lastly, when the topic model was applied to the David et al. time-series dataset, three distinct gut configurations emerged. However, unlike the David et al. approach, we characterized the events in terms of topics, which captured taxonomic co-occurrence, and posterior uncertainty, which facilitated the interpretation of how the taxonomic configurations evolved over time.