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A Scalable, Multiplexed Assay for Decoding GPCR-Ligand Interactions with RNA Sequencing

This repository supports the papers found here or bioRxiv

G protein-coupled receptors (GPCRs) are central to how mammalian cells sense and respond to chemicals. Mammalian olfactory receptors (ORs), the largest family of GPCRs, mediate the sense of smell through activation by small molecules, though for most bonafide ligands, they have not been identified. Here, we introduce a platform to screen large chemical panels against multiplexed GPCR libraries using next-generation sequencing of barcoded genetic reporters in stably engineered human cell lines. We mapped 39 mammalian ORs against 181 odorants and identified 79 interactions that have not been reported to our knowledge, including ligands for 15 previously orphaned receptors. This multiplexed receptor assay allows the cost-effective mapping of large chemical libraries to receptor repertoires at scale.

Getting Started

To run the standard data analysis for this project and produce the graphs in the paper, run OlfactionCodeToPublish.Rmd in the /SelfContainedR folder.

To run the chemicals through the autoencoder created by Gómez-Bombarelli et al. . . .

Prerequisites

What things you need to install the software and how to install them

Contributing

Versioning

Authors

Eric M. Jones*, Rishi Jajoo*, Daniel Cancilla1, Nathan B. Lubock, Jeff Wang, Megan Satyadi, Rocky Cheung, Claire de March, Hiroaki Matsunami, Sriram Kosuri

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