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Making Proteomics More Powerful: Building the World’s Largest Synthetic Peptide Spectral Library

Team TFS
Team TFS
shutterstock_349835384Mass spectrometry is proving to be a powerful tool for proteomics – a field that’s helping researchers unravel the inner workings of cells, and could help clinical scientists undertake early diagnosis of rare and complex diseases through the detection of protein biomarkers in the body.

Proteomics researchers are using the high levels of accuracy and throughput offered by the latest mass spectrometry methods and technologies to rapidly identify and quantify proteins within cells, tissues and organisms in order to unlock the treatments of the future.

To help characterize proteins, proteomics approaches often involve comparing the signature mass spectra of digested protein fragments obtained experimentally with predicted peptide spectra generated computationally. But while this method has proven effective for some protein types, it is limited in its ability to accurately identify others, in part due to the sheer number of molecules present in a typical experiment.

Expanding the Proteomics Toolbox

Leading proteomics expert Professor Bernhard Kuster and his group at the Technical University of Munich, Germany, are using the latest Thermo Scientific™ Orbitrap™ mass spectrometry technology to create a powerful proteomics research tool that overcomes this challenge.

This ProteomeTools project aims to build a spectral library of around 1.4 million synthetic peptides that could be employed in a similar way to the reference standards commonly used to identify and quantify molecules in analytical chemistry. This would create the largest spectral library to date for the identification of human proteins using synthetic peptides.

The approach, detailed in a recent paper published in Nature Methods, involved selecting and analyzing more than 333,000 synthetic peptides representing almost all canonical human proteins to generate a collection of synthetic human protein standards.

While previous tools for protein identification may have helped position ourselves on the proteomics ‘map’, this new resource acts as a turn by turn guide to their identification.

Essentially, the library provides researchers with the Orbitrap mass spectral ‘address’ of every protein in the human proteome. This also includes so-called “missing peptides” – those predicted by genomics, but which have yet to be studied experimentally. Such information may help shed light on whether this is due to physical characteristics that make these peptides difficult to detect by mass spectrometry, or whether they are in fact produced by the human body at all.

A Resource That’s Available to All

The researchers used the Thermo Scientific™ Orbitrap Fusion™ Lumos™ Tribrid™ mass spectrometer to generate the synthetic peptide spectra in the database. The ability to analyze the samples using multiple fragmentation methods gave the team greater confidence in the accuracy of their results.

As the spectra will be made available to everyone, researchers around the world will now be able to use the resource to confirm the identities of peptides, even in borderline cases. The tool allows scientists to look up a protein or peptide of interest in cases where the experimental data alone might not be sufficient to elucidate its identity.

Using synthetic peptide standards, the ProteomeTools project aims to fill the gaps in our current ability to study proteins in biological samples, and disseminate this information globally. With these additional resources at their disposal, it’s hoped that researchers will be able to more confidently characterize proteins and deliver improved disease diagnosis and treatment to patients more quickly.

Additional Resources