BASiCS: Bayesian Analysis of Single-Cell Sequencing Data
File(s)
Author(s)
Vallejos, CA
Marioni, JC
Richardson, S
Type
Journal Article
Abstract
Single-cell mRNA sequencing can uncover novel cell-to-cell heterogeneity in gene expression levels in seemingly homogeneous populations of cells. However, these experiments are prone to high levels of unexplained technical noise, creating new challenges for identifying genes that show genuine heterogeneous expression within the population of cells under study. BASiCS (Bayesian Analysis of Single-Cell Sequencing data) is an integrated Bayesian hierarchical model where: (i) cell-specific normalisation constants are estimated as part of the model parameters, (ii) technical variability is quantified based on spike-in genes that are artificially introduced to each analysed cell's lysate and (iii) the total variability of the expression counts is decomposed into technical and biological components. BASiCS also provides an intuitive detection criterion for highly (or lowly) variable genes within the population of cells under study. This is formalised by means of tail posterior probabilities associated to high (or low) biological cell-to-cell variance contributions, quantities that can be easily interpreted by users. We demonstrate our method using gene expression measurements from mouse Embryonic Stem Cells. Cross-validation and meaningful enrichment of gene ontology categories within genes classified as highly (or lowly) variable supports the efficacy of our approach.
Date Issued
2015-06-24
Date Acceptance
2015-05-13
Citation
PLOS Computational Biology, 2015, 11 (6)
ISSN
1553-734X
Publisher
Public Library of Science
Journal / Book Title
PLOS Computational Biology
Volume
11
Issue
6
Copyright Statement
© 2015 Vallejos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
License URL
Subjects
Animals
Bayes Theorem
Computational Biology
Embryonic Stem Cells
Gene Expression Profiling
Mice
Oligonucleotide Array Sequence Analysis
RNA, Messenger
Reproducibility of Results
Single-Cell Analysis
Bioinformatics
06 Biological Sciences
08 Information And Computing Sciences
01 Mathematical Sciences
Publication Status
Published
Article Number
e1004333