Project should provide treasure-trove of molecular information on human protein and lead to development of new biomarkers for use in clinical laboratory tests and personalized medicine

Human proteins provide clinical laboratories and anatomic pathology groups with a rich source of biomarkers used in medical tests and personalized medicine. Pathologists, therefore, should take note of a major milestone achieved by researchers from the Technical University of Munich (TUM) that moves science closer to developing a way to understand the complete human proteome.

Scientists participating in the ProteomeTools project have announced the synthesis of a library of more than 330,000 peptides representing essentially all canonical proteins of the human proteome.

Translating Human Proteome into Molecular and Digital Tools

The ProteomeTools project is “a joint effort of TUM, JPT Peptide Technologies, SAP SE, and Thermo Fisher Scientific … dedicated to translating the human proteome into molecular and digital tools for drug discovery, personalized medicine, and life science research.” Over the course of the project, 1.4 million synthetic peptides covering essentially all human gene products will be synthesized and analyzed using multimodal liquid chromatography-tandem mass spectrometry (LC-MS/MS).

ProteomeTools published their first paper, “Building ProteomeTools Based on a Complete Synthetic Human Proteome,” which detailed their work in Nature Methods.

“ProteomeTools was started as a collaborative effort bringing together academic and industrial partners to make important contributions to the field of proteomics. It is gratifying to see that this work is now producing a wealth of significant results,” stated TUM researcher Bernhard Kuster, PhD, one of the leaders of the effort and senior author on the Nature Methods paper, in a TUM news release.

Thousands of New Biomarkers for Clinical Laboratories, and More!

Kuster discussed the significance of the consortium’s work in an article published in Genome Web, which described ProteomeTools as “a resource that provides the proteomics community with a set of established standards against which it can compare experimental data.”

“In proteomics today, we are doing everything by inference,” Kuster stated to Genome Web. “We have a tandem mass spectrum and we use a computer algorithm to match it to a peptide sequence that [is generated] in silico to simulate what their spectrum might look like without us actually knowing what it looks like. That is a very fundamental problem.”

Bernhard Kuster, PhD

Bernhard Kuster, PhD (above center), of the Technical University of Munich (TUM), led a team of researchers from the ProteomeTools project who completed a tandem mass spectrometry analysis of more than 330,000 synthetic tryptic peptides representing essentially all of the canonical human gene products. The resource eventually will cover all one million peptides. (Photo copyright: Andreas Heddergott/TUM.)

In the Genome Web article, Kuster provides an example of how researchers could use the information developed by ProteomeTools, noting it could be useful for confirming peptide identification in borderline cases. “Because the spectra for these synthetic peptides are available to everyone, you could look up a protein or peptide ID that you find exciting, but where the [experimental] data might not totally convince you as to whether it is true or not,” he explained.

Kuster also states that he believes the resource has the potential to allow “the field to move away from conventional database searching methods toward a spectral matching approach.”

The TUM news release notes 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.” The end result could be a treasure-trove of molecular information on the human proteome and development of thousands of new biomarkers for clinical use for therapeutic drugs, and more.

“Representing the human proteome by tandem mass spectra of synthetic peptides alleviates some of the current issues with protein identification and quantification. 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,” Kuster stated in the TUM news release.

All data from the ProteomeTools project is available at the ProteomeXchange Consortium. Pathologists and clinical laboratory professionals working to develop new assays will find it to be a valuable resource.

—Andrea Downing Peck

Related Information:

Researchers Build Complete Synthetic Human Proteome

Building Proteome Tools Based on a Complete Synthetic Human Proteome

Milestone for the Analysis of Human Proteomes