Multisample estimation of bacterial composition matrices in metagenomics data

Metagenomics sequencing is routinely applied to quantify bacterial abundances in microbiome studies, where bacterial composition is estimated based on the sequencing read counts. Due to limited sequencing depth and DNA dropouts, many rare bacterial taxa might not be captured in the final sequencing reads, which results in many zero counts. Naive composition estimation using count normalization leads to many zero proportions, which tend to result in inaccurate estimates of bacterial abundance and diversity. This paper takes a multisample approach to estimation of bacterial abundances in order to borrow information across samples and across species. Empirical results from real datasets suggest that the composition matrix over multiple samples is approximately low rank, which motivates a regularized maximum likelihood estimation with a nuclear norm penalty. An efficient optimization algorithm using the generalized accelerated proximal gradient and Euclidean projection onto simplex space is developed. Theoretical upper bounds and the minimax lower bounds of the estimation errors, measured by the Kullback–Leibler divergence and the Frobenius norm, are established. Simulation studies demonstrate that the proposed estimator outperforms the naive estimators. The method is applied to an analysis of a human gut microbiome dataset.

Duke Scholars

Author Anru Zhang Biostatistics & Bioinformatics, Division of Translational Bi ...