articleCell SystemsJun 1, 2017HYBRID OA

An Optimized Shotgun Strategy for the Rapid Generation of Comprehensive Human Proteomes

University of Copenhagen · Novo Nordisk Foundation · +1 more institution

PubMed
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Abstract

This study investigates the challenge of comprehensively cataloging the complete human proteome from a single-cell type using mass spectrometry (MS)-based shotgun proteomics. We modify a classical two-dimensional high-resolution reversed-phase peptide fractionation scheme and optimize a protocol that provides sufficient peak capacity to saturate the sequencing speed of modern MS instruments. This strategy enables the deepest proteome of a human single-cell type to date, with the HeLa proteome sequenced to a depth of ∼584,000 unique peptide sequences and ∼14,200 protein isoforms (∼12,200 protein-coding genes). This depth is comparable with next-generation RNA sequencing and enables the identification of…

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