2025/02/08 by Peter Chovanec, Yi Yin · 1 voice
Biochemistry, Genetics and Molecular Biology · #Cancer Genomics and Diagnostics #Epigenetics and DNA Methylation #Single-cell and spatial transcriptomics
paper · pdf · doi:10.1093/nar/gkaf101
openalex publication_date 2025/02/08 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31
Single-cell combinatorial indexing (sci) methods have addressed major limitations of throughput and cost for many single-cell modalities. With the incorporation of linear amplification and three-level barcoding in our suite of methods called sci-L3, we further addressed the limitations of uniformity in single-cell genome amplification. Here, we build on the generalizability of sci-L3 by extending it to template strand sequencing (sci-L3-Strand-seq), genome conformation capture (sci-L3-Hi-C), and the joint profiling of RNA and chromatin accessibility (sci-L3-RNA/ATAC). We demonstrate the ease of adapting sci-L3 to these new modalities by only requiring a single-step modification of the original protocol. As a proof of principle, we show our ability to detect sister chromatid exchanges, genome compartmentalization, and cell state-specific features in thousands of single cells. We anticipate sci-L3 to be compatible with additional modalities, including DNA methylation (sci-MET) and chromatin-associated factors (CUT&Tag), and ultimately enable a multi-omics readout of them.