Spatial Perturb-seq, so hot right now! With Alexander Nevue

<p>“It's one extra step ahead of a single cell RNA-seq workflow where we can get all the information that we can get from standard Perturb-seq, but we also know the spatial location.”</p><p></p><p>That’s how my guest this week, Arc Institute Senior Scientist Alexander Nevue, describes PerturbSpace, a new method he and his colleagues introduced in a preprint posted to <a rel="noopener noreferrer nofollow" href="https://www.biorxiv.org/content/10.64898/2026.05.25.727765v1" target="_blank"><i>BioRxiv</i></a> May 18. </p><p></p><p>PerturbSpace is the latest method to marry the power of CRISPR-based perturbation screening, where genes across the genome are systematically targeted and the effects of those perturbations are read out in the transcriptome of the cell in which they were made. </p><p></p><p>This juncture of CRISPR-based screening and spatial transcriptomics is one of the hottest areas in molecular biology right now, with nearly 10 different methods published in the last two years, from leading scientists including Genentech’s Aviv Regev; Harvard University’s Xiaowei Zhuang, the inventor of MERFISH and cofounder of Vizen; Yale University’s Rong Fan, and the Broad Institute’s Sami Farhi. </p><p></p><p>Join Alex and me as we discuss the PertubSpace workflow, its advantages and disadvantages compared to other spatial perturb-seq methods, and where he sees the data from these screens making the most impact. </p><p></p><p>Links to other publications of spatial perturbation screening methods with notable authors: </p><p></p><p>PerturbView. Aviv Regev and Erik Lubeck of Genentech.</p><p><a rel="noopener noreferrer nofollow" href="https://www.nature.com/articles/s41587-024-02391-0" target="_blank">https://www.nature.com/articles/s41587-024-02391-0</a></p><p></p><p>Large-scale pooled <i>in vivo </i>CRISPR screening. Jonathan Weissman of MIT and Harvard’s Xiaowei Zhuang, inventor of MERFISH and cofounder of Vizgen.</p><p><a rel="noopener noreferrer nofollow" href="https://www.biorxiv.org/content/10.1101/2024.11.18.624217v3" target="_blank">https://www.biorxiv.org/content/10.1101/2024.11.18.624217v3</a></p><p></p><p><b>SPA</b>tial <b>C</b>ell <b>E</b>xploration (SPACE). Joe Beechem of Bruker/NanoString, in collaboration with Merck.</p><p><a rel="noopener noreferrer nofollow" href="https://www.biorxiv.org/content/10.1101/2025.09.14.675819v2" target="_blank">https://www.biorxiv.org/content/10.1101/2025.09.14.675819v2</a></p><p></p><p>Perturb-DBiT. Rong Fan of Yale University, inventor of DBIT family of methods and cofounder of AtlasXOmics .</p><p><a rel="noopener noreferrer nofollow" href="https://www.researchsquare.com/article/rs-6481967/v1" target="_blank">https://www.researchsquare.com/article/rs-6481967/v1</a></p><p></p><p>CRISPRMap. Jellert Gaublomme of Columbia University, Dan Landau of Weill Cornell Medicine.</p><p><a rel="noopener noreferrer nofollow" href="https://www.nature.com/articles/s41587-024-02386-x" target="_blank">https://www.nature.com/articles/s41587-024-02386-x</a></p><p></p><p>Perturb-FISH. Sami Farhi  of the Broad Institute. </p><p><a rel="noopener noreferrer nofollow" href="https://www.cell.com/cell/fulltext/S0092-8674(25)00197-7" target="_blank">https://www.cell.com/cell/fulltext/S0092-8674(25)00197-7</a></p><p></p><p>NIS-Seq Jonathan L. Schmid-Burgk of University Hospital Bonn.</p><p><a rel="noopener noreferrer nofollow" href="https://www.nature.com/articles/s41587-024-02516-5" target="_blank">https://www.nature.com/articles/s41587-024-02516-5</a></p><p></p><p>Spatial Perturb-Sseq. Wei Leong Chew of A*STAR GIS. <a rel="noopener noreferrer nofollow" href="https://www.nature.com/articles/s41467-026-69677-6" target="_blank">https://www.nature.com/articles/s41467-026-69677-6</a></p><p><br /></p>