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Unsupervised generative and graph representation learning for modelling cell differentiation.

Accepted version
Peer-reviewed

Type

Article

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Authors

Bica, Ioana 
Andrés-Terré, Helena 
Liò, Pietro 

Abstract

Using machine learning techniques to build representations from biomedical data can help us understand the latent biological mechanism of action and lead to important discoveries. Recent developments in single-cell RNA-sequencing protocols have allowed measuring gene expression for individual cells in a population, thus opening up the possibility of finding answers to biomedical questions about cell differentiation. In this paper, we explore unsupervised generative neural methods, based on the variational autoencoder, that can model cell differentiation by building meaningful representations from the high dimensional and complex gene expression data. We use disentanglement methods based on information theory to improve the data representation and achieve better separation of the biological factors of variation in the gene expression data. In addition, we use a graph autoencoder consisting of graph convolutional layers to predict relationships between single-cells. Based on these models, we develop a computational framework that consists of methods for identifying the cell types in the dataset, finding driver genes for the differentiation process and obtaining a better understanding of relationships between cells. We illustrate our methods on datasets from multiple species and also from different sequencing technologies.

Description

Keywords

Animals, Cell Differentiation, Datasets as Topic, Gene Expression, Humans, Machine Learning, Models, Biological, Models, Statistical, RNA-Seq

Journal Title

Sci Rep

Conference Name

Journal ISSN

2045-2322
2045-2322

Volume Title

10

Publisher

Springer Science and Business Media LLC

Rights

All rights reserved
Sponsorship
European Research Council (677501)
Medical Research Council (MC_PC_12009)
Medical Research Council (MC_PC_17230)