Introduction to bioimaging-based spatial multi-omic novel methods

Abstract

Background: Spatial multi-omics are demonstrated to be a powerful method to assist researchers on genetic studies. In this review, bioimaging-based spatial multi-omics techniques such as seqFISH+, merFISH, integrated DNA seqFISH+, DNA merFISH, and MINA are introduced along with each technique’s probe design, development, and imaging processes.

Results: seqFISH employed 4–5 fluorophores to barcode and conducted multiple rounds of hybridization, in order that mRNA can be identified through color-coding. seqFISH+ added 60 pseudo-color and distributed them equally into three channels to enhance imaging power, in order that i.e., 24,000 genes can be imaged in total. merFISH utilized 4 out 16 Hamming distance to innovatively provide a robust error-detecting method. MINA, a methodology combining merFISH (multiplexed error-robust fluorescence in situ hybridization) and chromosomal tracing, enabled multiplexed genomic architecture imaged in mammalian single cells. Optical reconstruction of chromatin architecture (ORCA) a method that could conduct DNA path tracing in nanoscale manner with kilobase resolution, an FISH variation that improved genetic resolution, enable high-precision fiducial registration and sequential imaging, and utilized Oligopaint probe to hybridize the short genomic region ranging from 2 to 10 kilobase. ORCA then prescribes these short section primary probes with individual barcodes to attach fluorophore and to be imaged.

Conclusion: This review concentrated on providing a comprehensive overview for these spatial-multi-omics techniques with the intention on helping researchers on selecting appropriate technique for their research.

Graphical abstract

Keywords

FISH / multiplex FISH / super-resolution imaging / gene regulation

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