DNA Microscopy: Optics-free Spatio-genetic Imaging by a Stand-Alone Chemical Reaction

https://www.sciencedirect.com/science/article/pii/S0092867419305471

Joshua A. Weinstein, Aviv Regev, and Feng Zhang

• The authors develop a novel method of determining spatial localisation of transcripts within the cell through "DNA Microscopy". 
• The method consists, firstly, of randomly tagging individual transcripts or DNA molecules with DNA unique molecular identifiers (UMIs), which are random nucleotide sequences of a particular length. 
• The UMI-concatenated molecules are then amplified through PCR, and diffuse in the cell. UMI tags are designed to contain overhanging complementary regions, such that tagged molecules are subsequently able to bind to another complementary molecule which is in close spatial proximity (called "beacon" and "target" amplicons). Through this process, "unique event identifiers" (UEIs) are generated. The cell can then be lysed, and sequenced through next-generation sequencing.
• The rate at which UMIs bound to a particular molecule concatenate indicates the distance between their points of origin.
• A computational algorithm then decodes molecular proximities from these UEIs to infer the spatial distribution of transcripts at cellular resolution.