Sequencing thousands of single-cell genomes with combinatorial indexing

Sarah A. Vitak, Kristof A. Torkenczy, Jimi L. Rosenkrantz, Andrew J. Fields, Lena Christiansen, Melissa Wong, Lucia Carbone, Frank J. Steemers, Andrew Adey

63 Scopus citations

Abstract

Single-cell genome sequencing has proven valuable for the detection of somatic variation, particularly in the context of tumor evolution. Current technologies suffer from high library construction costs, which restrict the number of cells that can be assessed and thus impose limitations on the ability to measure heterogeneity within a tissue. Here, we present single-cell combinatorial indexed sequencing (SCI-seq) as a means of simultaneously generating thousands of low-pass single-cell libraries for detection of somatic copy-number variants. We constructed libraries for 16,698 single cells from a combination of cultured cell lines, primate frontal cortex tissue and two human adenocarcinomas, and obtained a detailed assessment of subclonal variation within a pancreatic tumor.

Original languageEnglish (US)
Pages (from-to)302-308
Number of pages7
JournalNature Methods
Volume14
Issue number3
DOIs
Publication statusPublished - Feb 28 2017

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Biology
  • Biochemistry
  • Cell Biology

Cite this

Vitak, S. A., Torkenczy, K. A., Rosenkrantz, J. L., Fields, A. J., Christiansen, L., Wong, M., ... Adey, A. (2017). Sequencing thousands of single-cell genomes with combinatorial indexing. Nature Methods, 14(3), 302-308. https://doi.org/10.1038/nmeth.4154