title: Sequencing thousands of single-cell genomes with combinatorial indexing.
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.
authors.affiliation: Department of Molecular &Medical Genetics, Oregon Health &Science University, Portland, Oregon, USA.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Vitak
authors.affiliation: Department of Molecular &Medical Genetics, Oregon Health &Science University, Portland, Oregon, USA.|Program in Molecular &Cellular Biosciences, Oregon Health &Science University, Portland, Oregon, USA.
authors.forename: Kristof A
authors.identifier: 0000-0002-4869-7957
authors.initials: KA
authors.lastname: Torkenczy
authors.affiliation: Department of Molecular &Medical Genetics, Oregon Health &Science University, Portland, Oregon, USA.|Program in Molecular &Cellular Biosciences, Oregon Health &Science University, Portland, Oregon, USA.|Oregon National Primate Research Center, Beaverton, Oregon, USA.
authors.forename: Jimi L
authors.initials: JL
authors.lastname: Rosenkrantz
authors.affiliation: Department of Molecular &Medical Genetics, Oregon Health &Science University, Portland, Oregon, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Fields
authors.affiliation: Advanced Research Group, Illumina Inc., San Diego, California, USA.
authors.forename: Lena
authors.initials: L
authors.lastname: Christiansen
authors.affiliation: Department of Cell, Developmental &Cancer Biology, Oregon Health &Science University, Portland, Oregon, USA.|Knight Cancer Institute, Portland, Oregon, USA.
authors.forename: Melissa H
authors.initials: MH
authors.lastname: Wong
authors.affiliation: Department of Molecular &Medical Genetics, Oregon Health &Science University, Portland, Oregon, USA.|Oregon National Primate Research Center, Beaverton, Oregon, USA.|Department of Behavioral Neurosciences, Oregon Health &Science University, Portland, Oregon, USA.|Knight Cardiovascular Institute, Portland, Oregon, USA.
authors.forename: Lucia
authors.initials: L
authors.lastname: Carbone
authors.affiliation: Advanced Research Group, Illumina Inc., San Diego, California, USA.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Steemers
authors.affiliation: Department of Molecular &Medical Genetics, Oregon Health &Science University, Portland, Oregon, USA.|Knight Cardiovascular Institute, Portland, Oregon, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Adey
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000818:Animals; D045744:Cell Line, Tumor; D002874:Chromosome Mapping / Q000379:methods*; D056915:DNA Copy Number Variations / Q000235:genetics*; D005625:Frontal Lobe / Q000166:cytology*; D015723:Gene Library; D015894:Genome, Human / Q000235:genetics; D006367:HeLa Cells; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008253:Macaca mulatta; D010190:Pancreatic Neoplasms / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods*; D059010:Single-Cell Analysis / Q000379:methods*