Computational identification of clonal cells in single-cell CRISPR screens

Yihan Wang, Shiqi Xie, Daniel Armendariz, Gary C. Hon

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Single-cell CRISPR screens are powerful tools to understand genome function by linking genetic perturbations to transcriptome-wide phenotypes. However, since few cells can be affordably sequenced in these screens, biased sampling of cells could affect data interpretation. One potential source of biased sampling is clonal cell expansion. RESULTS: Here, we identify clonal cells in single cell screens using multiplexed sgRNAs as barcodes. We find that the cells in each clone share transcriptional similarities and bear segmental copy number changes. These analyses suggest that clones are genetically distinct. Finally, we show that the transcriptional similarities of clonally expanded cells contribute to false positives in single-cell CRISPR screens. CONCLUSIONS: Experimental conditions that reduce clonal expansion or computational filtering of clonal cells will improve the reliability of single-cell CRISPR screens.

Original languageEnglish (US)
Pages (from-to)135
Number of pages1
JournalBMC Genomics
Volume23
Issue number1
DOIs
StatePublished - Feb 15 2022

Keywords

  • CRISPR
  • Single-cell CRISPR screens
  • Single-cell genomics

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Fingerprint

Dive into the research topics of 'Computational identification of clonal cells in single-cell CRISPR screens'. Together they form a unique fingerprint.

Cite this