ArticleNature methods2024
Multiplexed profiling of intracellular protein abundance, activity, interactions and druggability with LABEL-seq.
Article in Nature methods, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Combining multiplexed functional data to improve variant classification.Genome medicine · 2026Article
- A scalable approach to resolving variants of uncertain significance.bioRxiv : the preprint server for biology · 2026Article
- Dosa: A method to covalently barcode proteins for high-throughput biochemistry.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Multiplex design and discovery of proximity handles for programmable proteome editing.bioRxiv : the preprint server for biology · 2025Article
- Dosa: A method to covalently barcode proteins for high throughput biochemistry.bioRxiv : the preprint server for biology · 2025Article
- Identification of positions in human aldolase a that are neutral for apparent KArchives of biochemistry and biophysics · 2024Article
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3 authors.
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Abstract
Here we describe labeling with barcodes and enrichment for biochemical analysis by sequencing (LABEL-seq), an assay for massively parallel profiling of pooled protein variants in human cells. By leveraging the intracellular self-assembly of an RNA-binding domain (RBD) with a stable, variant-encoding RNA barcode, LABEL-seq facilitates the direct measurement of protein properties and functions using simple affinity enrichments of RBD protein fusions, followed by high-throughput sequencing of co-enriched barcodes. Measurement of ~20,000 variant effects for ~1,600 BRaf variants revealed that variation at positions frequently mutated in cancer minimally impacted intracellular abundance but could dramatically alter activity, protein-protein interactions and druggability. Integrative analysis identified networks of positions with similar biochemical roles and enabled modeling of variant effects on cell proliferation and small molecule-promoted degradation. Thus, LABEL-seq enables direct measurement of multiple biochemical properties in a native cellular context, providing insights into protein function, disease mechanisms and druggability.
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