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Theory for High-Throughput Genetic Interaction Screening
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DOI：10.1021/acssynbio.2c00627.png)
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Systematic, genome-scalegenetic screens have been instrumentalfor elucidating genotype-phenotype relationships, but approachesfor probing genetic interactions have been limited to at most & SIM;100pre-selected gene combinations in mammalian cells. Here, we introducea theory for high-throughput genetic interaction screens. The theoryextends our recently developed Multiplexing using Spectral Imagingand Combinatorics (MuSIC) approach to propose & SIM;10(5) spectrally unique, genetically encoded MuSIC barcodes from 18 currentlyavailable fluorescent proteins. Simulation studies based on constraintsimposed by spectral flow cytometry equipment suggest that geneticinteraction screens at the human genome-scale may be possible if MuSICbarcodes can be paired to guide RNAs. While experimental testing ofthis theory awaits, it offers transformative potential for geneticperturbation technology and knowledge of genetic function. More broadly,the availability of a genome-scale spectral barcode library for non-destructiveidentification of single cells could find more widespread applicationssuch as traditional genetic screening and high-dimensional lineagetracing.
Keyword:
fluorescence
genetic screening
barcodes
genetic interactionscreening
spectral flow cytometry
simulations
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