SCSAP SPEAKER SPOTLIGHT
Samouil L. Farhi, Ph.D.
Director, Spatial Technology Platform
Broad Institute
Abstract
Pooled optical screens have enabled the study of cellular interactions, morphology, and dynamics at massive scale, but they have not yet leveraged the power of highly multiplexed, single-cell–resolved transcriptomic readouts to inform molecular pathways. Here, we present Perturb-FISH, which bridges these approaches by combining imaging-based spatial transcriptomics with parallel optical detection of in situ amplified guide RNAs.
We show that Perturb-FISH recovers intracellular effects consistent with Perturb-seq results in a screen of lipopolysaccharide response in cultured monocytes, while also uncovering new intercellular and density-dependent regulation of the innate immune response.
We further pair Perturb-FISH with a functional readout in a screen of autism spectrum disorder risk genes, revealing common calcium activity phenotypes in induced pluripotent stem cell–derived astrocytes, along with their associated genetic interactions and dysregulated molecular pathways.
Finally, we demonstrate that Perturb-FISH can identify neighborhood-dependent perturbation effects in complex tissue by revealing immune–tumor interactions in a xenograft model engrafted with human PBMCs. Perturb-FISH is therefore a broadly applicable method for studying genetic and molecular associations underlying spatial and functional biology at single-cell resolution.
Short Bio
Dr. Sami Farhi is the Director of the Spatial Technology Platform at the Broad Institute of MIT and Harvard. The platform’s goal is to bring next-generation spatial transcriptomics and proteomics approaches to bear on large-scale biological problems. In his parallel research lab, Dr. Farhi focuses on continued technology development and iPS-based screens to understand psychiatric disease using optical methods.
Dr. Farhi joined the Broad Institute in July 2018 after completing his Ph.D. in Chemical Biology at Harvard University, where he developed methods for all-optical neurophysiology. He also holds a B.S. in Chemical Biology from the University of California, Berkeley.
Publications of Interest