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Using transfer learning from prior reference knowledge to improve the clustering of single-cell RNA-Seq data.

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Peer-reviewed

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Article

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Authors

Mieth, Bettina 
Hockley, James R F 
Görnitz, Nico 
Vidovic, Marina M-C 
Müller, Klaus-Robert 

Abstract

In many research areas scientists are interested in clustering objects within small datasets while making use of prior knowledge from large reference datasets. We propose a method to apply the machine learning concept of transfer learning to unsupervised clustering problems and show its effectiveness in the field of single-cell RNA sequencing (scRNA-Seq). The goal of scRNA-Seq experiments is often the definition and cataloguing of cell types from the transcriptional output of individual cells. To improve the clustering of small disease- or tissue-specific datasets, for which the identification of rare cell types is often problematic, we propose a transfer learning method to utilize large and well-annotated reference datasets, such as those produced by the Human Cell Atlas. Our approach modifies the dataset of interest while incorporating key information from the larger reference dataset via Non-negative Matrix Factorization (NMF). The modified dataset is subsequently provided to a clustering algorithm. We empirically evaluate the benefits of our approach on simulated scRNA-Seq data as well as on publicly available datasets. Finally, we present results for the analysis of a recently published small dataset and find improved clustering when transferring knowledge from a large reference dataset. Implementations of the method are available at https://github.com/nicococo/scRNA.

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Journal Title

Scientific reports, volume 9, issue 1

Conference Name

Journal ISSN

2045-2322

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