Frank J Steemers | Search bioRxiv

bioRxiv2016

Massively multiplex single-cell Hi-C

We present combinatorial single cell Hi-C, a novel method that leverages combinatorial cellular indexing to measure chromosome conformation in large numbers of single cells. In this proof-of-concept, we generate and sequence combinatorial single cell Hi-C libraries for two mouse and four human cell types, comprising a total of 9,316 single cells across 5 experiments. We demonstrate the utility of single-cell Hi-C data in separating different cell types, identify previously uncharacterized cell-to-cell heterogeneity in the conformational properties of mammalian chromosomes, and demonstrate that combinatorial indexing is a generalizable molecular strategy for single-cell genomics.

Genomics↗

bioRxiv2016

Construction of thousands of single cell genome sequencing libraries using combinatorial indexing

Single cell genome sequencing has proven to be a valuable tool for the detection of somatic variation, particularly in the context of tumor evolution and neuronal heterogeneity. Current technologies suffer from high per-cell library construction costs which restrict the number of cells that can be assessed, thus imposing limitations on the ability to quantitatively measure genomic 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 the purpose of somatic copy number variant detection. In total, we constructed libraries for 16,698 single cells from a combination of cultured cell lines, frontal cortex tissue from Macaca mulatta, and two human adenocarcinomas. This novel technology provides the opportunity for low-cost, deep characterization of somatic copy number variation in single cells, providing a foundational knowledge across both healthy and diseased tissues.

Genomics↗