Human Proteome Analysis Gets Significant Upgrades

February 1, 2017
Human Proteome Analysis Gets Significant Upgrades
Source: NIH

Proteomics research just got a much-needed boost as a team of scientists led by researchers at the Technical University of Munich (TUM) have reported on the synthesis of a library of more than 330,000 reference peptides representing essentially all canonical proteins of the human proteome. Findings from the new study—published recently in Nature Methods through an article entitled “Building ProteomeTools based on a complete synthetic human proteome”—are a major milestone in the ProteomeTools project, which aims at translating human proteome information into new molecular and digital tools with the potential for use in drug discovery, personalized medicine, and life science research.

"ProteomeTools was started as a collaborative effort bringing together academic and industrial partners to make important contributions to the field of proteomics,” explained senior study investigator and project coordinator Bernhard Küster, Ph.D., chair of proteomics and bioanalytics at TUM. “It is gratifying to see that this work is now producing a wealth of significant results."

In the new study, the researchers report on the synthesis of a synthetic reference peptide library (termed PROPEL for ProteomeTools Peptide Library) representing the majority of proteins within the human proteome. All of the peptides were analyzed by multi-modal liquid chromatography-tandem mass spectrometry (LC-MS/MS), creating a compendium of millions of very high-quality reference spectra (termed PROSPECT for ProteomeTools Spectrum Compendium). The study illustrates the utility of these reagents and data to verify protein identifications from sparse observations and to predict the behavior of peptides during liquid chromatography and tandem mass spectrometry.

The research collaboration of TUM, JPT Peptide Technologies (JPT), SAP, and Thermo Fisher Scientific has made significant quantities of the new data freely available to the scientific community via the data analytics platform ProteomicsDB and the data repository PRIDE (PRoteomics IDEntifications) to enable scientists and to foster collaboration around the globe.

Looking toward the future, the researchers claim that the ProteomeTools project will generate a further one million peptides and corresponding spectra with a focus on splice variants, cancer mutations, and post-translational modifications such as phosphorylation, acetylation, and ubiquitinylation.

With these new resources in hand, ProteomeTools scientists aim to turn the vast amount of molecular information on the human proteome into new reagents, equipment, workflows, assays, and software to enhance the application of proteomics in both science and medicine.

"Representing the human proteome by tandem mass spectra of synthetic peptides alleviates some of the current issues with protein identification and quantification,” Dr. Küster remarked. “The libraries of peptides and spectra now allow us to develop new, and improve upon existing hardware, software, workflows and reagents for proteomics. Making all the data available to the public provides a wonderful opportunity to exploit this resource beyond what a single laboratory can do. We are now reaching out to the community to suggest interesting sets of peptides to make and measure as well as to create LC-MS/MS data on platforms not available to the ProteomeTools consortium."