Probabilistic modeling of bifurcations in single-cell gene expression data using a Bayesian mixture of factor analyzers.

Wellcome Open Research
Kieran R Campbell, Christopher Yau

Abstract

Modeling bifurcations in single-cell transcriptomics data has become an increasingly popular field of research. Several methods have been proposed to infer bifurcation structure from such data, but all rely on heuristic non-probabilistic inference. Here we propose the first generative, fully probabilistic model for such inference based on a Bayesian hierarchical mixture of factor analyzers. Our model exhibits competitive performance on large datasets despite implementing full Markov-Chain Monte Carlo sampling, and its unique hierarchical prior structure enables automatic determination of genes driving the bifurcation process. We additionally propose an Empirical-Bayes like extension that deals with the high levels of zero-inflation in single-cell RNA-seq data and quantify when such models are useful. We apply or model to both real and simulated single-cell gene expression data and compare the results to existing pseudotime methods. Finally, we discuss both the merits and weaknesses of such a unified, probabilistic approach in the context practical bioinformatics analyses.

References

May 20, 2014·Nature Methods·Peter V KharchenkoDavid T Scadden
Nov 4, 2015·Genome Biology·Emma Pierson, Christopher Yau
Apr 8, 2016·Genome Biology·Rhonda Bacher, Christina Kendziorski
May 3, 2016·Nature Biotechnology·Manu SettyDana Pe'er
Jun 19, 2016·Bioinformatics·John E Reid, Lorenz Wernisch
Nov 9, 2016·Nature Biotechnology·Allon WagnerNir Yosef
Dec 25, 2016·Bioinformatics·Kieran R Campbell, Christopher Yau
Jan 24, 2017·Nature Methods·Xiaojie QiuCole Trapnell

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Citations

Jun 21, 2019·PLoS Computational Biology·Lan Huong Nguyen, Susan Holmes
Jun 26, 2018·Bioinformatics·Kieran R Campbell, Christopher Yau
Feb 8, 2019·Biophysics Reviews·Christopher Yau, Kieran Campbell
Jan 21, 2020·Genome Biology·Koki TsuyuzakiItoshi Nikaido
Nov 2, 2017·Briefings in Functional Genomics·Chung-Chau HonMichael J T Stubbington
Jun 20, 2018·BMC Genomics·Kelly StreetSandrine Dudoit
Apr 3, 2019·Nature Biotechnology·Wouter SaelensYvan Saeys
Dec 4, 2019·Nature Methods·Robert A AmezquitaStephanie C Hicks

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Methods Mentioned

BETA
RNA-seq
scRNA-seq

Software Mentioned

DPT
SCDE
MFA
Wishbone
Monocle

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