Unsupervised generative and graph representation learning for modelling cell differentiation

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 individu...

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Autores principales: Ioana Bica, Helena Andrés-Terré, Ana Cvejic, Pietro Liò
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Lenguaje:EN
Publicado: Nature Portfolio 2020
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Acceso en línea:https://doaj.org/article/dfe3326beb63483f91402dc5465d9cf2
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spelling oai:doaj.org-article:dfe3326beb63483f91402dc5465d9cf22021-12-02T17:40:46ZUnsupervised generative and graph representation learning for modelling cell differentiation10.1038/s41598-020-66166-82045-2322https://doaj.org/article/dfe3326beb63483f91402dc5465d9cf22020-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-66166-8https://doaj.org/toc/2045-2322Abstract 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.Ioana BicaHelena Andrés-TerréAna CvejicPietro LiòNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-13 (2020)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Ioana Bica
Helena Andrés-Terré
Ana Cvejic
Pietro Liò
Unsupervised generative and graph representation learning for modelling cell differentiation
description 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.
format article
author Ioana Bica
Helena Andrés-Terré
Ana Cvejic
Pietro Liò
author_facet Ioana Bica
Helena Andrés-Terré
Ana Cvejic
Pietro Liò
author_sort Ioana Bica
title Unsupervised generative and graph representation learning for modelling cell differentiation
title_short Unsupervised generative and graph representation learning for modelling cell differentiation
title_full Unsupervised generative and graph representation learning for modelling cell differentiation
title_fullStr Unsupervised generative and graph representation learning for modelling cell differentiation
title_full_unstemmed Unsupervised generative and graph representation learning for modelling cell differentiation
title_sort unsupervised generative and graph representation learning for modelling cell differentiation
publisher Nature Portfolio
publishDate 2020
url https://doaj.org/article/dfe3326beb63483f91402dc5465d9cf2
work_keys_str_mv AT ioanabica unsupervisedgenerativeandgraphrepresentationlearningformodellingcelldifferentiation
AT helenaandresterre unsupervisedgenerativeandgraphrepresentationlearningformodellingcelldifferentiation
AT anacvejic unsupervisedgenerativeandgraphrepresentationlearningformodellingcelldifferentiation
AT pietrolio unsupervisedgenerativeandgraphrepresentationlearningformodellingcelldifferentiation
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