Infinite factorization of multiple non-parametric views

Combined analysis of multiple data sources has increasing application interest, in particular for distinguishing shared and source-specific aspects. We extend this rationale of classical canonical correlation analysis into a flexible, generative and non-parametric clustering setting, by introducing a novel non-parametric hierarchical mixture model. The lower level of the model describes each source with a flexible non-parametric mixture, and the top level combines these to describe commonalities of the sources. The lower-level clusters arise from hierarchical Dirichlet Processes, inducing an infinite-dimensional contingency table between the views. The commonalities between the sources are modeled by an infinite block model of the contingency table, interpretable as non-negative factorization of infinite matrices, or as a prior for infinite contingency tables. With Gaussian mixture components plugged in for continuous measurements, the model is applied to two views of genes, mRNA expression and abundance of the produced proteins, to expose groups of genes that are co-regulated in either or both of the views. Cluster analysis of co-expression is a standard simple way of screening for co-regulation, and the two-view analysis extends the approach to distinguishing between pre- and post-translational regulation

Robust Bayesian Tensor Factorization with Zero-Inflated Poisson Model and Consensus Aggregation

Tensor factorizations (TF) are powerful tools for the efficient representation and analysis of multidimensional data. However, classic TF methods based on maximum likelihood estimation underperform when applied to zero-inflated count data, such as single-cell RNA sequencing (scRNA-seq) data. Additionally, the stochasticity inherent in TFs results in factors that vary across repeated runs, making interpretation and reproducibility of the results challenging. In this paper, we introduce Zero Inflated Poisson Tensor Factorization (ZIPTF), a novel approach for the factorization of high-dimensional count data with excess zeros. To address the challenge of stochasticity, we introduce Consensus Zero Inflated Poisson Tensor Factorization (C-ZIPTF), which combines ZIPTF with a consensus-based meta-analysis. We evaluate our proposed ZIPTF and C-ZIPTF on synthetic zero-inflated count data and synthetic and real scRNA-seq data. ZIPTF consistently outperforms baseline matrix and tensor factorization methods in terms of reconstruction accuracy for zero-inflated data. When the probability of excess zeros is high, ZIPTF achieves up to $2.4\times$ better accuracy. Additionally, C-ZIPTF significantly improves the consistency and accuracy of the factorization. When tested on both synthetic and real scRNA-seq data, ZIPTF and C-ZIPTF consistently recover known and biologically meaningful gene expression programs

Deep Exponential Families

We describe \textit{deep exponential families} (DEFs), a class of latent variable models that are inspired by the hidden structures used in deep neural networks. DEFs capture a hierarchy of dependencies between latent variables, and are easily generalized to many settings through exponential families. We perform inference using recent "black box" variational inference techniques. We then evaluate various DEFs on text and combine multiple DEFs into a model for pairwise recommendation data. In an extensive study, we show that going beyond one layer improves predictions for DEFs. We demonstrate that DEFs find interesting exploratory structure in large data sets, and give better predictive performance than state-of-the-art models

Deep generative modeling for single-cell transcriptomics.

Single-cell transcriptome measurements can reveal unexplored biological diversity, but they suffer from technical noise and bias that must be modeled to account for the resulting uncertainty in downstream analyses. Here we introduce single-cell variational inference (scVI), a ready-to-use scalable framework for the probabilistic representation and analysis of gene expression in single cells ( https://github.com/YosefLab/scVI ). scVI uses stochastic optimization and deep neural networks to aggregate information across similar cells and genes and to approximate the distributions that underlie observed expression values, while accounting for batch effects and limited sensitivity. We used scVI for a range of fundamental analysis tasks including batch correction, visualization, clustering, and differential expression, and achieved high accuracy for each task