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GPseudoClust: deconvolution of shared pseudo-profiles at single-cell resolution.

Published version
Peer-reviewed

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Authors

Strauss, Magdalena E 
Kirk, Paul DW 
Reid, John E 
Wernisch, Lorenz 

Abstract

MOTIVATION: Many methods have been developed to cluster genes on the basis of their changes in mRNA expression over time, using bulk RNA-seq or microarray data. However, single-cell data may present a particular challenge for these algorithms, since the temporal ordering of cells is not directly observed. One way to address this is to first use pseudotime methods to order the cells, and then apply clustering techniques for time course data. However, pseudotime estimates are subject to high levels of uncertainty, and failing to account for this uncertainty is liable to lead to erroneous and/or over-confident gene clusters. RESULTS: The proposed method, GPseudoClust, is a novel approach that jointly infers pseudotemporal ordering and gene clusters, and quantifies the uncertainty in both. GPseudoClust combines a recent method for pseudotime inference with non-parametric Bayesian clustering methods, efficient Markov Chain Monte Carlo sampling and novel subsampling strategies which aid computation. We consider a broad array of simulated and experimental datasets to demonstrate the effectiveness of GPseudoClust in a range of settings. AVAILABILITY AND IMPLEMENTATION: An implementation is available on GitHub: https://github.com/magStra/nonparametricSummaryPSM and https://github.com/magStra/GPseudoClust. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Description

Keywords

Algorithms, Bayes Theorem, Cluster Analysis, Markov Chains, Single-Cell Analysis

Journal Title

Bioinformatics

Conference Name

Journal ISSN

1367-4803
1367-4811

Volume Title

36

Publisher

Oxford University Press (OUP)