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Register a new userMulti-sample estimation of centered log-ratio matrix in microbiome studies
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Yezheng Li
Publication date
2021
fields
Mathematical Statistics
and research's language is
English
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In microbiome studies, one of the ways of studying bacterial abundances is to estimate bacterial composition based on the sequencing read counts. Various transformations are then applied to such compositional data for downstream statistical analysis, among which the centered log-ratio (clr) transformation is most commonly used. 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 makes clr transformation infeasible. This paper proposes a multi-sample approach to estimation of the clr matrix directly in order to borrow information across samples and across species. Empirical results from real datasets suggest that the clr 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 is developed. Theoretical upper bounds of the estimation errors and of its corresponding singular subspace errors are established. Simulation studies demonstrate that the proposed estimator outperforms the naive estimators. The method is analyzed on Gut Microbiome dataset and the American Gut project.
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Metagenomics sequencing is routinely applied to quantify bacterial abundances in microbiome studies, where the 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 multi-sample approach to the estimation of bacterial abundances in order to borrow information across samples and across species. Empirical results from real data sets 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. The 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.
Shape-constrained density estimation is an important topic in mathematical statistics. We focus on densities on $mathbb{R}^d$ that are log-concave, and we study geometric properties of the maximum likelihood estimator (MLE) for weighted samples. Cule, Samworth, and Stewart showed that the logarithm of the optimal log-concave density is piecewise linear and supported on a regular subdivision of the samples. This defines a map from the space of weights to the set of regular subdivisions of the samples, i.e. the face poset of their secondary polytope. We prove that this map is surjective. In fact, every regular subdivision arises in the MLE for some set of weights with positive probability, but coarser subdivisions appear to be more likely to arise than finer ones. To quantify these results, we introduce a continuous version of the secondary polytope, whose dual we name the Samworth body. This article establishes a new link between geometric combinatorics and nonparametric statistics, and it suggests numerous open problems.
We present local biplots, a an extension of the classic principal components biplot to multi-dimensional scaling. Noticing that principal components biplots have an interpretation as the Jacobian of a map from data space to the principal subspace, we define local biplots as the Jacobian of the analogous map for multi-dimensional scaling. In the process, we show a close relationship between our local biplot axes, generalized Euclidean distances, and generalized principal components. In simulations and real data we show how local biplots can shed light on what variables or combinations of variables are important for the low-dimensional embedding provided by multi-dimensional scaling. They give particular insight into a class of phylogenetically-informed distances commonly used in the analysis of microbiome data, showing that different variants of these distances can be interpreted as implicitly smoothing the data along the phylogenetic tree and that the extent of this smoothing is variable.
The odds ratio (OR) is a widely used measure of the effect size in observational research. ORs reflect statistical association between a binary outcome, such as the presence of a health condition, and a binary predictor, such as an exposure to a pollutant. Statistical significance and interval estimates are often computed for the logarithm of OR, ln(OR), and depend on the asymptotic standard error of ln(OR). For a sample of size N, the standard error can be written as a ratio of sigma over square root of N, where sigma is the population standard deviation of ln(OR). The ratio of ln(OR) over sigma is a standardized effect size. Unlike correlation, that is another familiar standardized statistic, the standardized ln(OR) cannot reach values of minus one or one. We find that its maximum possible value is given by the Laplace Limit Constant, (LLC=0.6627...), that appears as a condition in solutions to Kepler equation -- one of the central equations in celestial mechanics. The range of the standardized ln(OR) is bounded by minus LLC to LLC, reaching its maximum for ln(OR)~4.7987. This range has implications for analysis of epidemiological associations, affecting the behavior of the reasonable prior distribution for the standardized ln(OR).
Let X_1, ..., X_n be independent and identically distributed random vectors with a log-concave (Lebesgue) density f. We first prove that, with probability one, there exists a unique maximum likelihood estimator of f. The use of this estimator is attractive because, unlike kernel density estimation, the method is fully automatic, with no smoothing parameters to choose. Although the existence proof is non-constructive, we are able to reformulate the issue of computation in terms of a non-differentiable convex optimisation problem, and thus combine techniques of computational geometry with Shors r-algorithm to produce a sequence that converges to the maximum likelihood estimate. For the moderate or large sample sizes in our simulations, the maximum likelihood estimator is shown to provide an improvement in performance compared with kernel-based methods, even when we allow the use of a theoretical, optimal fixed bandwidth for the kernel estimator that would not be available in practice. We also present a real data clustering example, which shows that our methodology can be used in conjunction with the Expectation--Maximisation (EM) algorithm to fit finite mixtures of log-concave densities. An R version of the algorithm is available in the package LogConcDEAD -- Log-Concave Density Estimation in Arbitrary Dimensions.
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