Document Type

Article

Publication Date

7-27-2020

Keywords

JMG, JAXCC

JAX Source

Genome Biol 2020 Jul 27; 21(1):183

PMID

32718323

DOI

https://doi.org/10.1186/s13059-020-02103-2

Abstract

BACKGROUND: Single-cell RNA sequencing is a powerful tool for characterizing cellular heterogeneity in gene expression. However, high variability and a large number of zero counts present challenges for analysis and interpretation. There is substantial controversy over the origins and proper treatment of zeros and no consensus on whether zero-inflated count distributions are necessary or even useful. While some studies assume the existence of zero inflation due to technical artifacts and attempt to impute the missing information, other recent studies argue that there is no zero inflation in scRNA-seq data.

RESULTS: We apply a Bayesian model selection approach to unambiguously demonstrate zero inflation in multiple biologically realistic scRNA-seq datasets. We show that the primary causes of zero inflation are not technical but rather biological in nature. We also demonstrate that parameter estimates from the zero-inflated negative binomial distribution are an unreliable indicator of zero inflation.

CONCLUSIONS: Despite the existence of zero inflation in scRNA-seq counts, we recommend the generalized linear model with negative binomial count distribution, not zero-inflated, as a suitable reference model for scRNA-seq analysis.

Comments

This article is licensed under a Creative Commons Attribution 4.0 International License.

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