Rapid mass spectrometric conversion of tissue biopsy samples into permanent quantitative digital proteome maps

Nature Medicine
Tiannan GuoRuedi Aebersold

Abstract

Clinical specimens are each inherently unique, limited and nonrenewable. Small samples such as tissue biopsies are often completely consumed after a limited number of analyses. Here we present a method that enables fast and reproducible conversion of a small amount of tissue (approximating the quantity obtained by a biopsy) into a single, permanent digital file representing the mass spectrometry (MS)-measurable proteome of the sample. The method combines pressure cycling technology (PCT) and sequential window acquisition of all theoretical fragment ion spectra (SWATH)-MS. The resulting proteome maps can be analyzed, re-analyzed, compared and mined in silico to detect and quantify specific proteins across multiple samples. We used this method to process and convert 18 biopsy samples from nine patients with renal cell carcinoma into SWATH-MS fragment ion maps. From these proteome maps we detected and quantified more than 2,000 proteins with a high degree of reproducibility across all samples. The measured proteins clearly distinguished tumorous kidney tissues from healthy tissues and differentiated distinct histomorphological kidney cancer subtypes.

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Citations

Jan 31, 2016·Genome Medicine·Charles AuffrayMatthias Schwab
Nov 7, 2015·Molecular Biology of the Cell·Hannes L RöstRuedi Aebersold
Jan 12, 2016·Clinical Proteomics·Christopher A CrutchfieldDaniel W Chan
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Feb 13, 2019·Scientific Data·Peter BlattmannRuedi Aebersold

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Datasets Mentioned

BETA
PXD000672

Methods Mentioned

BETA
biopsy
biopsies

Software Mentioned

FileConverter
iProphet
MS
OpenMS
PCT
ProteinInference
PeptideProphet
aLFQ R - package
Trans
! Tandem

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