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PAGA: graph abstraction reconciles clustering with trajectory inference through a topology preserving map of single cells

Genome biology · 2019 · Vol. 20(1) · pp. 59–59
F. Alexander WolfFiona HameyMireya PlassJordi SolanaJoakim S. DahlinBerthold GöttgensNikolaus RajewskyLukas M. SimonFabian J. Theis

Abstract

Single-cell RNA-seq quantifies biological heterogeneity across both discrete cell types and continuous cell transitions. Partition-based graph abstraction (PAGA) provides an interpretable graph-like map of the arising data manifold, based on estimating connectivity of manifold partitions ( https://github.com/theislab/paga ). PAGA maps preserve the global topology of data, allow analyzing data at different resolutions, and result in much higher computational efficiency of the typical exploratory data analysis workflow. We demonstrate the method by inferring structure-rich cell maps with consistent topology across four hematopoietic datasets, adult planaria and the zebrafish embryo and benchmark computational performance on one million neurons.

Single-cell and spatial transcriptomicsCell Image Analysis TechniquesAdvanced Fluorescence Microscopy TechniquesTheoretical computer scienceCluster analysisComputer scienceBiologyGraphTopology (electrical circuits)WorkflowData miningNonlinear dimensionality reductionInference

MeSH terms

AlgorithmsAnimalsComputer GraphicsEmbryo, NonmammalianHematopoietic Stem CellsHumansPlanariansReference StandardsSoftwareZebrafishSequence Analysis, RNAGene Expression Regulation, DevelopmentalComputational BiologySingle-Cell AnalysisHigh-Throughput Nucleotide Sequencing

Funding

  • Deutsches Zentrum für Herz-Kreislaufforschung
  • Cancer Research UK
  • Deutsche Forschungsgemeinschaft
  • Vetenskapsrådet
  • National Institutes of Health
  • Medical Research Council
  • Cambridge Institute for Medical Research, University of Cambridge
  • National Institute of Diabetes and Digestive and Kidney Diseases
Citations
1,749
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67.84
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References
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Nature Biotechnology · 2015 · 7,447 citations
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Proceedings of the National Academy of Sciences · 2006 · 12,046 citations
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eLife · 2017 · 2,286 citations
SCANPY: large-scale single-cell gene expression data analysis
Genome biology · 2018 · 8,867 citations
Deep generative modeling for single-cell transcriptomics
Nature Methods · 2018 · 2,493 citations
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