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T. Shibue

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Open access Aug 2026

Dissecting context-dependent cancer vulnerabilities using Perturb-seq

It is demonstrated that integrated Perturb-seq experiments spanning diverse contexts enable hypotheses about gene function specific to tissue types or cancer subtypes – suggesting large-scale, genome-wide datasets would offer invaluable insight into the highly context-dependent nature of cancer biology.

Samuel Maffa, Isabella Boyle, Lie Ward et al. · 0 citations
Open access Jul 2026

Direct comparison of CRISPR knockout and interference with Perturb-seq

CRISPR knockout (CRISPRko) and CRISPR interference (CRISPRi) are two workhorse technologies for loss-of-function studies, yet direct comparisons between the two are scant relative to their widespread adoption. Here, we establish benchmarking libraries for Cas9-based CRISPRko and CRISPRi screens using Perturb-seq as the read-out. For both modalities, we observe consistent transcriptional signatures among cells with the same genes perturbed, strong evidence of on-target signal. We also examine tradeoffs between modalities: while CRISPRi guides demonstrate heightened rates of off-target activity, we also observe artifacts stemming from the cellular response to double-stranded breaks with the use of CRISPRko. The libraries and analyses presented here will be a useful benchmarking and de-risking resource for any group preparing for a large-scale Perturb-seq screen.

Laura M Drepanos, Berta Escude Velasco, Abigail J Chase et al. · 1 citation

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