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

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 (ES), 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 single-cell RNA sequencing (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. ES thus provides a powerful approach for maximizing information extraction from high-dimensional datasets such as scRNA-seq data.

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Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interests Sara-Jane Dunn was an employee at Microsoft Research during this study and is currently employed at DeepMind. Microsoft Research provided co-funding for Arthur Radley’s research council studentship and access to computational resources. Neither Microsoft Research nor DeepMind have directed any aspect of the study nor exerted any commercial rights over the results.