A Zero-Inflated Logistic Normal Multinomial Model for Extracting Microbial Compositions
针对微生物组测序数据中零值过多的问题，提出零膨胀概率主成分分析模型，结合经验贝叶斯方法估计微生物组成，并通过分类变分近似算法实现高效估计。
High throughput sequencing data collected to study the microbiome provide information in the form of relative abundances and should be treated as compositions. Although many approaches including scaling and rarefaction have been proposed for converting raw count data into microbial compositions, most of these methods simply return zero values for zero counts. However, zeros can distort downstream analyses, and they can also pose problems for composition-aware methods. This problem is exacerbated with microbiome abundance data because they are sparse with excessive zeros. In addition to data sparsity, microbial composition estimation depends on other data characteristics such as high dimensionality, over-dispersion, and complex co-occurrence relationships. To address these challenges, we introduce a zero-inflated probabilistic PCA (ZIPPCA) model that accounts for the compositional nature of microbiome data, and propose an empirical Bayes approach to estimate microbial compositions. An efficient iterative algorithm, called classification variational approximation, is developed for carrying out maximum likelihood estimation. Moreover, we study the consistency and asymptotic normality of variational approximation estimator from the perspective of profile M-estimation. Extensive simulations and an application to a dataset from the Human Microbiome Project are presented to compare the performance of the proposed method with that of the existing methods. The method is implemented in R and available at https://github.com/YanyZeng/ZIPPCAlnm. Supplementary materials for this article are available online.