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Compressed Perturb-seq: highly efficient screens for regulatory circuits using random composite perturbations

GSE221321 Homo sapiens Expression profiling by high throughput sequencing 4 samples Submitted 2023/01/01 Platform GPL20795
Summary
Pooled CRISPR screens with single-cell RNA-seq readout (Perturb-seq) have emerged as a key technique in functional genomics, but are limited in scale by cost and combinatorial complexity. Here, we reimagine Perturb-seq’s design through the lens of algorithms applied to random, low-dimensional observations. We present compressed Perturb-seq, in which we measure multiple perturbations per cell or multiple cells per droplet, and decompress these measurements by leveraging the sparse structure of regulatory circuits. Applying compressed Perturb-seq to 598 genes in the immune response to bacterial lipopolysaccharide, we achieve the same accuracy as conventional Perturb-seq at 4 to 20-fold reduced cost, with greater power to learn genetic interactions. We identify known and novel regulators of immune responses and uncover evolutionarily constrained genes with downstream targets enriched for immune disease heritability, including many missed by existing GWAS or trans-eQTL studies. Our framework enables new scales of interrogation for a foundational method in functional genomics.
Published in
Compressed Perturb-seq: highly efficient screens for regulatory circuits using random composite perturbations
Yao D, Binan L, Bezney J et al. · bioRxiv : the preprint server for biology 2023 · PMID 36747806 · doi:10.1101/2023.01.23.525200
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Direct links to NCBI, no account and no request form: the whole study as GSE221321_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 4 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA913903 and SRA study SRP413921. Searching any of these in the dataset finder brings you back here.

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