A sparse negative binomial mixture model for clustering RNA-seq count data

Abstract

Clustering with variable selection is a challenging yet critical task for modern small-n-large-p data. Existing methods based on sparse Gaussian mixture models or sparse $K$-means provide solutions to continuous data. With the prevalence of RNA-seq technology and lack of count data modeling for clustering, the current practice is to normalize count expression data into continuous measures and apply existing models with a Gaussian assumption. In this article, we develop a negative binomial mixture model with lasso or fused lasso gene regularization to cluster samples (small $n$) with high-dimensional gene features (large $p$). A modified EM algorithm and Bayesian information criterion are used for inference and determining tuning parameters. The method is compared with existing methods using extensive simulations and two real transcriptomic applications in rat brain and breast cancer studies. The result shows the superior performance of the proposed count data model in clustering accuracy, feature selection, and biological interpretation in pathways.

Keywords: Cluster analysis; Feature selection; Gaussian mixture model; Sparse K-means.