Pooled genetic screens with image-based profiling.
Russell T WaltonAvtar SinghPaul C BlaineyPublished in: Molecular systems biology (2022)
Spatial structure in biology, spanning molecular, organellular, cellular, tissue, and organismal scales, is encoded through a combination of genetic and epigenetic factors in individual cells. Microscopy remains the most direct approach to exploring the intricate spatial complexity defining biological systems and the structured dynamic responses of these systems to perturbations. Genetic screens with deep single-cell profiling via image features or gene expression programs have the capacity to show how biological systems work in detail by cataloging many cellular phenotypes with one experimental assay. Microscopy-based cellular profiling provides information complementary to next-generation sequencing (NGS) profiling and has only recently become compatible with large-scale genetic screens. Optical screening now offers the scale needed for systematic characterization and is poised for further scale-up. We discuss how these methodologies, together with emerging technologies for genetic perturbation and microscopy-based multiplexed molecular phenotyping, are powering new approaches to reveal genotype-phenotype relationships.
Keyphrases
- single cell
- high throughput
- genome wide
- dna methylation
- rna seq
- gene expression
- copy number
- single molecule
- high resolution
- high speed
- machine learning
- induced apoptosis
- cell proliferation
- clinical trial
- public health
- cell death
- mass spectrometry
- oxidative stress
- randomized controlled trial
- study protocol
- social media
- cell cycle arrest
- health information
- circulating tumor