Dataset Information

Bayesian model selection reveals biological origins of zero inflation in single-cell transcriptomics.

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.

SUBMITTER: Choi K

PROVIDER: S-EPMC7384222 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Bayesian model selection reveals biological origins of zero inflation in single-cell transcriptomics.

Choi Kwangbom K Chen Yang Y Skelly Daniel A DA Churchill Gary A GA

Genome biology 20200727 1

<h4>Background</h4>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 ...[more]

PMID: 32718323

Similar Datasets

Project description:Microorganisms play critical roles in human health and disease. They live in diverse communities in which they interact synergistically or antagonistically. Thus for estimating microbial associations with clinical covariates, such as treatment effects, joint (multivariate) statistical models are preferred. Multivariate models allow one to estimate and exploit complex interdependencies among multiple taxa, yielding more powerful tests of exposure or treatment effects than application of taxon-specific univariate analyses. Analysis of microbial count data also requires special attention because data commonly exhibit zero inflation, i.e., more zeros than expected from a standard count distribution. To meet these needs, we developed a Bayesian variable selection model for multivariate count data with excess zeros that incorporates information on the covariance structure of the outcomes (counts for multiple taxa), while estimating associations with the mean levels of these outcomes. Though there has been much work on zero-inflated models for longitudinal data, little attention has been given to high-dimensional multivariate zero-inflated data modeled via a general correlation structure. Through simulation, we compared performance of the proposed method to that of existing univariate approaches, for both the binary ("excess zero") and count parts of the model. When outcomes were correlated the proposed variable selection method maintained type I error while boosting the ability to identify true associations in the binary component of the model. For the count part of the model, in some scenarios the univariate method had higher power than the multivariate approach. This higher power was at a cost of a highly inflated false discovery rate not observed with the proposed multivariate method. We applied the approach to oral microbiome data from the Pediatric HIV/AIDS Cohort Oral Health Study and identified five (of 44) species associated with HIV infection.

Dataset Information

Bayesian model selection reveals biological origins of zero inflation in single-cell transcriptomics.

Background

Results

Conclusions

Publications

Bayesian model selection reveals biological origins of zero inflation in single-cell transcriptomics.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets