3D mapping and accelerated super-resolution imaging of the human genome using in situ sequencing.
IF: 47.990
Cited by: 91


There is a need for methods that can image chromosomes with genome-wide coverage, as well as greater genomic and optical resolution. We introduce OligoFISSEQ, a suite of three methods that leverage fluorescence in situ sequencing (FISSEQ) of barcoded Oligopaint probes to enable the rapid visualization of many targeted genomic regions. Applying OligoFISSEQ to human diploid fibroblast cells, we show how four rounds of sequencing are sufficient to produce 3D maps of 36 genomic targets across six chromosomes in hundreds to thousands of cells, implying a potential to image thousands of targets in only five to eight rounds of sequencing. We also use OligoFISSEQ to trace chromosomes at finer resolution, following the path of the X chromosome through 46 regions, with separate studies showing compatibility of OligoFISSEQ with immunocytochemistry. Finally, we combined OligoFISSEQ with OligoSTORM, laying the foundation for accelerated single-molecule super-resolution imaging of large swaths of, if not entire, human genomes.


Spatial Genomics

MeSH terms

Chromosome Painting
Genome, Human
Oligonucleotide Array Sequence Analysis
Oligonucleotide Probes
Physical Chromosome Mapping


Nguyen, Huy Q
Chattoraj, Shyamtanu
Castillo, David
Nguyen, Son C
Nir, Guy
Lioutas, Antonios
Hershberg, Elliot A
Martins, Nuno M C
Reginato, Paul L
Hannan, Mohammed
Beliveau, Brian J
Church, George M
Daugharthy, Evan R
Marti-Renom, Marc A
Wu, C-Ting

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