RT Journal
A1 Sanders, Ashley D.
A1 Hills, Mark
A1 Porubský, David
A1 Guryev, Victor
A1 Falconer, Ester
A1 Lansdorp, Peter M.
T1 Characterizing polymorphic inversions in human genomes by single-cell sequencing
JF Genome Research 
JO Genome Research 
YR 2016 
FD November 01 
VO 26 
IS 11 
SP 1575 
OP 1587 
DO 10.1101/gr.201160.115 
UL http://genome.cshlp.org/content/26/11/1575.abstract 
AB Identifying genomic features that differ between individuals and cells can help uncover the functional variants that drive phenotypes and disease susceptibilities. For this, single-cell studies are paramount, as it becomes increasingly clear that the contribution of rare but functional cellular subpopulations is important for disease prognosis, management, and progression. Until now, studying these associations has been challenged by our inability to map structural rearrangements accurately and comprehensively. To overcome this, we coupled single-cell sequencing of DNA template strands (Strand-seq) with custom analysis software to rapidly discover, map, and genotype genomic rearrangements at high resolution. This allowed us to explore the distribution and frequency of inversions in a heterogeneous cell population, identify several polymorphic domains in complex regions of the genome, and locate rare alleles in the reference assembly. We then mapped the entire genomic complement of inversions within two unrelated individuals to characterize their distinct inversion profiles and built a nonredundant global reference of structural rearrangements in the human genome. The work described here provides a powerful new framework to study structural variation and genomic heterogeneity in single-cell samples, whether from individuals for population studies or tissue types for biomarker discovery.