PLATE-Seq for genome-wide regulatory network analysis of high-throughput screens

Erin C. Bush, Forest Ray, Mariano J. Alvarez, Ronald Realubit, Hai Li, Charles Karan, Andrea Califano () and Peter A. Sims ()
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Erin C. Bush: Columbia University Medical Center
Forest Ray: Columbia University Medical Center
Mariano J. Alvarez: Columbia University Medical Center
Ronald Realubit: Columbia University Medical Center
Hai Li: Columbia University Medical Center
Charles Karan: Columbia University Medical Center
Andrea Califano: Columbia University Medical Center
Peter A. Sims: Columbia University Medical Center

Nature Communications, 2017, vol. 8, issue 1, 1-7

Abstract: Abstract Pharmacological and functional genomic screens play an essential role in the discovery and characterization of therapeutic targets and associated pharmacological inhibitors. Although these screens affect thousands of gene products, the typical readout is based on low complexity rather than genome-wide assays. To address this limitation, we introduce pooled library amplification for transcriptome expression (PLATE-Seq), a low-cost, genome-wide mRNA profiling methodology specifically designed to complement high-throughput screening assays. Introduction of sample-specific barcodes during reverse transcription supports pooled library construction and low-depth sequencing that is 10- to 20-fold less expensive than conventional RNA-Seq. The use of network-based algorithms to infer protein activity from PLATE-Seq data results in comparable reproducibility to 30 M read sequencing. Indeed, PLATE-Seq reproducibility compares favorably to other large-scale perturbational profiling studies such as the connectivity map and library of integrated network-based cellular signatures.

Date: 2017
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DOI: 10.1038/s41467-017-00136-z

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