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David S Clausen

Publications and source records attributed to David S Clausen.

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Modeling complex measurement error in microbiome experiments to estimate relative abundances and detection effects

Accurate estimates of microbial species abundances are needed to advance our understanding of the role that microbiomes play in human and environmental health. However, artificially constructed microbiomes demonstrate that intuitive estimators of microbial relative abundances are biased. To address this, we propose a semiparametric method to estimate relative abundances, species detection effects, and/or cross-sample contamination in microbiome experiments. We show that certain experimental designs result in identifiable model parameters, and we present consistent estimators and asymptotically valid inference procedures. Notably, our procedure can estimate relative abundances on the boundary of the simplex. We demonstrate the utility of the method for comparing experimental protocols, removing cross-sample contamination, and estimating species' detectability.

stat.ME

Estimating Fold Changes from Partially Observed Outcomes with Applications in Microbial Metagenomics

We consider the problem of estimating fold-changes in the expected value of a multivariate outcome observed with unknown sample-specific and category-specific perturbations. This challenge arises in high-throughput sequencing studies of the abundance of microbial taxa because microbes are systematically over- and under-detected relative to their true abundances. Our model admits a partially identifiable estimand, and we establish full identifiability by imposing interpretable parameter constraints. To reduce bias and guarantee the existence of estimators in the presence of sparse observations, we apply an asymptotically negligible and constraint-invariant penalty to our estimating function. We develop a fast coordinate descent algorithm for estimation, and an augmented Lagrangian algorithm for estimation under null hypotheses. We construct a model-robust score test and demonstrate valid inference even for small sample sizes and violated distributional assumptions. The flexibility of the approach and comparisons to related methods are illustrated through a meta-analysis of microbial associations with colorectal cancer.

stat.ME