ClonoCluster: A method for using clonal origin to inform transcriptome clustering

Lee P. Richman, Yogesh Goyal, Connie L. Jiang, Arjun Raj*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Clustering cells based on their high-dimensional profiles is an important data reduction process by which researchers infer distinct cellular states. The advent of cellular barcoding, however, provides an alternative means by which to group cells: by their clonal origin. We developed ClonoCluster, a computational method that combines both clone and transcriptome information to create hybrid clusters that weight both kinds of data with a tunable parameter. We generated hybrid clusters across six independent datasets and found that ClonoCluster generated qualitatively different clusters in all cases. The markers of these hybrid clusters were different but had equivalent fidelity to transcriptome-only clusters. The genes most strongly associated with the rearrangements in hybrid clusters were ribosomal function and extracellular matrix genes. We also developed the complementary tool Warp Factor that incorporates clone information in popular 2D visualization techniques like UMAP. Integrating ClonoCluster and Warp Factor revealed biologically relevant markers of cell identity.

Original languageEnglish (US)
Article number100247
JournalCell Genomics
Volume3
Issue number2
DOIs
StatePublished - Feb 8 2023

Keywords

  • Bioinformatics
  • clonality
  • clustering
  • lineage tracing
  • single cell

ASJC Scopus subject areas

  • Genetics
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)

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