G&T-seq: parallel sequencing of the genomes and transcriptomes of single cells

The ability to simultaneously sequence the genome and transcriptome of the same single cell offers
a powerful means to dissect functional genetic heterogeneity at the cellular level. Here we describe
G&T-seq, a method for separating and sequencing genomic DNA and full-length mRNA from single
cells. By applying G&T-seq to over 220 single cells we reveal cellular properties that cannot be
inferred from DNA or RNA sequencing alone, including associations between DNA copy number
variation and gene expression dosage. We further demonstrate the detection of coding interchromosomal
fusions and single nucleotide variants in both the genomes and transcriptomes of
individual cells. G&T-seq enables the study of genotype-phenotype associations in single cells, and
the investigation of DNA cell lineage trees of healthy and diseased tissues with transcriptome inferred
cell types and states.EGA study EGAS00001001204