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Angerer, P. ; Fischer, D.S. ; Theis, F.J. ; Scialdone, A. ; Marr, C.

Automatic identification of relevant genes from low-dimensional embeddings of single-cell RNA-seq data.

Bioinformatics 36, 4291-4295 (2020)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold (Paid Option)
MOTIVATION: Dimensionality reduction is a key step in the analysis of single-cell RNA-sequencing data. It produces a low-dimensional embedding for visualization and as a calculation base for downstream analysis. Nonlinear techniques are most suitable to handle the intrinsic complexity of large, heterogeneous single-cell data. However, with no linear relation between gene and embedding coordinate, there is no way to extract the identity of genes driving any cell's position in the low-dimensional embedding, making it difficult to characterize the underlying biological processes. RESULTS: In this article, we introduce the concepts of local and global gene relevance to compute an equivalent of principal component analysis loadings for non-linear low-dimensional embeddings. Global gene relevance identifies drivers of the overall embedding, while local gene relevance identifies those of a defined sub-region. We apply our method to single-cell RNA-seq datasets from different experimental protocols and to different low-dimensional embedding techniques. This shows our method's versatility to identify key genes for a variety of biological processes. AVAILABILITY AND IMPLEMENTATION: To ensure reproducibility and ease of use, our method is released as part of destiny 3.0, a popular R package for building diffusion maps from single-cell transcriptomic data. It is readily available through Bioconductor. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Diffusion Maps; Expression; Reveals
ISSN (print) / ISBN 1367-4803
Zeitschrift Bioinformatics
Quellenangaben Band: 36, Heft: 15, Seiten: 4291-4295 Artikelnummer: , Supplement: ,
Verlag Oxford University Press
Verlagsort Oxford
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Computational Biology (ICB)
Institute of Epigenetics and Stem Cells (IES)
Förderungen DFG
Joachim Herz Stiftung
German research foundation (DFG) fellowship through the Graduate School of Quantitative Biosciences Munich (QBM)