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Entropy sorting of single cell RNA sequencing data reveals the inner cell mass in the human pre-implantation embryo

Accepted version
Peer-reviewed

Type

Article

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Authors

Radley, Arthur 
Smith, Austin 
Dunn, Sara-Jane 
Corujo-Simon, Elena 
Nichols, Jennifer 

Abstract

A major challenge in single cell gene expression analysis is to discern meaningful cellular heterogeneity from technical or biological noise. To address this challenge, we present Entropy Sorting, a mathematical framework that distinguishes genes indicative of cell identity. ES achieves this in an unsupervised manner by quantifying if observed correlations between features are more likely to have occurred due to random chance versus a dependent relationship, without the need for any user defined significance threshold. On synthetic data we demonstrate the removal of noisy signals to reveal a higher resolution of gene expression patterns than commonly used feature selection methods. We then apply ES to human pre-implantation embryo scRNA-seq data. Previous studies failed to unambiguously identify early inner cell mass (ICM), suggesting that the human embryo may diverge from the mouse paradigm. In contrast, ES resolves the ICM and reveals sequential lineage bifurcations as in the classical model. Entropy sorting thus provides a powerful approach for maximising information extraction from high dimensional datasets such as scRNA-seq data.

Description

Keywords

feature selection, human embryo inner cell mass, single-cell RNA sequencing, Humans, Animals, Mice, Entropy, Blastocyst, Embryonic Development, Embryo, Mammalian, Sequence Analysis, RNA, Single-Cell Analysis, Gene Expression Profiling

Journal Title

Stem Cell Reports

Conference Name

Journal ISSN

2213-6711
2213-6711

Volume Title

Publisher

Elsevier
Sponsorship
BBSRC (1943266)
Biotechnology and Biological Sciences Research Council (1943266)
Biotechnology and Biological Sciences Research Council (2489150)
Biotechnology and Biological Sciences Research Council (BB/P021573/1)
Biotechnology and Biological Sciences Research Council (BB/T007044/2)
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2023-06-30 14:02:58
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2022-09-26 23:30:31
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