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

Bettina Mieth, James R.F. Hockley, Nico Görnitz, Marina M.C. Vidovic, Klaus Robert Müller, Alex Gutteridge, Daniel Ziemek

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)


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

Original languageEnglish
Article number20353
JournalScientific reports
Issue number1
Publication statusPublished - 2019 Dec 1

Bibliographical note

Publisher Copyright:
© 2019, The Author(s).

ASJC Scopus subject areas

  • General


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