2025 Proteomics Breakthroughs

Proteomics—a term first coined in the mid-1990s—refers to the study of the complete set of proteins expressed in a cell, tissue, or organism. In contrast to genomics and transcriptomics, proteomics is particularly well-suited for capturing dynamic events, including such things as protein degradation and post-translational modifications. While proteomics has generally lagged behind genomics in scale and throughput, rapid technological advances are narrowing that gap. To explore the latest breakthroughs, GEN spoke with five companies at the forefront of proteomic innovation.

Proteomics and blockbuster drugs

Chief Scientific Advisor

Novo Nordisk

Lotte Bjerre Knudsen, DMSc is chief scientific advisor at Novo Nordisk, the company behind the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide sold under the brand names Ozempic, Rybelsus, and Wegovy. She has studied the GLP-1 hormone and its effects for 35 years and is a co-inventor of liraglutide, Novo Nordisk’s first GLP-1 receptor agonist.

Bjerre Knudsen highlights a 2025 article in Nature Medicine investigating the effects of semaglutide on the circulating proteome in two Phase III trials (called STEP 1 and STEP 2) in overweight participants with and without type 2 diabetes.1

From the proteomics perspective, the researchers chose to use the SomaScan affinity-based platform (Standard BioTools) due to the abundance of published literature utilizing this technology, including studies with large cohorts. “Mass spectrometry and Olink [an alternate affinity-based platform, now part of Thermo Fisher] are great,” she adds. “However, with the SomaScan, it was a little bit easier to see how to compare this with other datasets.”

Ultimately, she was not surprised by proteomics results suggesting beneficial effects for several organs—including the liver, pancreas, brain, and intestines.

“We also see a lot of things that were not unexpected but interesting,” she adds. For instance, semaglutide tended to lower the abundance of proteins associated with substance use disorder, fibromyalgia, neuropathic pain, and depression.

Do these proteomics results imply that GLP-1 agonists can now be used to treat addiction? “Saying that you can say everything about addiction based on a blood sample is a crude measure,” she warns.

Bjerre Knudsen also worries that the benefits of GLP-1 drugs for certain indications are being exaggerated. She advises patients to talk to their doctors before making any health-related decisions regarding this class of drugs. “Take the dose that is prescribed. It is a medicine, so you need to follow the label,” she says.

In addition to obesity and diabetes, another 2025 proteomics study in Nature Medicine documents how semaglutide improves circulating markers in animals with chronic liver disease.2

Finally, Novo Nordisk is compiling a third set of proteomics data associated with the ongoing SELECT trial, which is investigating the effect of semaglutide in 17,000 overweight participants without diabetes. Bjerre Knudsen notes that both proteomics and genomics data are now available for about half of the patients.

What is the advantage of pairing genomics and proteomics? “With proteomics, you cannot get to causality. There can be many reasons why proteins are moving in the same or opposite direction,” she notes. “But if you have genetics, you can also get to causality.”

Proteomics brought to the benchtop

Meredith L. Carpenter, PhD, head of scientific affairs at Quantum-Si, explains that several major challenges exist in developing new proteomics tools. To begin with, proteins, unlike DNA, cannot be amplified. “That means that proteomics methods must allow for the analysis of small amounts of material,” she notes.

Another challenge is that proteins can span a very broad range of concentrations, making for a complex mixture. Finally, proteins contain not only the basic 20 amino acids, but also hundreds of different post-translational modifications that can affect their biological function. “Quantum-Si has considered all of these challenges as it has built out its technology roadmap,” says Carpenter.

In contrast, Quantum-Si’s single-molecule protein sequencer—called Platinum® Pro—can be easily operated on a laboratory benchtop. “We provide everything that is needed to perform sample preparation, sequencing, and analysis, with no special expertise needed,” she notes.

The instrument determines the identity and order of amino acids making up a given protein. Proteins are first enzymatically digested into peptides, which are then analyzed on sequencing chips within millions of tiny wells. The sequencing process involves fluorescently labeled protein recognizers that bind to each amino acid on the peptide and identify it.

Carpenter emphasizes that by providing single-molecule, single-amino acid resolution, the Platinum Pro produces a completely different set of data from either mass spectrometry or targeted approaches, such as Olink and SomaScan. “Depending on the application, this can allow for increased sensitivity, specificity, or both,” she adds.

As was the case in genomic analysis, Carpenter anticipates that benchtop protein sequencing will become a workhorse in bringing protein sequencing to local laboratories.

The benefits of mass spectrometry

Can Ozbal, PhD, Founder and CEO of Momentum Biotechnologies, stresses that tremendous advances have been made in the field of mass spectrometry-based proteomics. For instance, he notes that it is now possible to obtain entire cell or tissue proteomes with only 15 to 30 minutes of instrument time.

Importantly, mass spectrometry can comprehensively characterize the proteins in a sample without the need for specific experimental targets. “With mass spectrometry, we do not need to know up front what we seek to measure—the mass spectrometer will tell us,” Ozbal notes.

Another benefit of mass spectrometry-based proteomics is high accuracy, with the overwhelming majority of proteins in a given sample being correctly identified, he notes. Finally, mass spectrometry is quantitative, so it can accurately and precisely measure protein levels in a cell, tissue, or plasma sample.

Ozbal notes that most of Momentum’s clients are biotech and pharma companies interested in how their drugs interact with proteins in cells and tissues. The company’s suite of assays enables the analysis of many important protein properties—such as abundance, subcellular localization, and protein turnover, which can be pharmacologically modulated or exploited.

Finally, mass spectrometry is an ideal method for quantifying post-translational modifications to proteins—such as phosphorylation, ubiquitination, or glycosylation—with high accuracy, precision, and sensitivity.

Advancing spatial proteomics

Charlotte Stadler, PhD, associate professor and co-director of the Spatial Biology Platform at SciLifeLab, explains how spatial proteomics enables the exploration of protein expression in cells and tissues while maintaining sample integrity.

Stadler’s group focuses on imaging-based approaches that map protein expression directly in intact tissue sections, down to the level of individual cells. “This spatial information is key to understanding cellular functions and disease processes,” she notes.

Although antibody-based imaging has been used in biology for over a century, researchers are now able to visualize dozens of proteins in the same sample. “This leap is possible thanks to new multiplexing solutions that overcome the spectral limitations of fluorescent dyes,” she notes.

Her lab utilizes various platforms—including the Phenocycler Fusion platform from Akoya Biosciences and the Lunaphore COMET—that rely on antibodies to target proteins using a fluorescent readout.

Stadler’s lab also collaborates closely with the Human Protein Atlas, which provides access to a near proteome-wide collection of high-quality antibodies. “The Human Protein Atlas is a resource that maps the location of proteins within human cells,” notes Mathias Uhlén, professor and director of the Human Protein Atlas program at SciLifeLab, as well as a founding director of SciLifeLab.

Uhlén notes that the Human Protein Atlas can visualize proteins across 32 different organelles and subcellular structures. “This helps researchers understand which genes are expressed and where in the cell their protein products function,” he notes.

Meanwhile, Stadler’s lab is applying spatial proteomics to identify optimal treatments for cohorts of patients with urothelial carcinoma. While targeted therapies, such as antibody-drug conjugates, have shown promising response rates

for this disease, they are not suitable for every individual.

“Therefore, more targeted and advanced diagnostic tests are needed to choose the right therapy for each patient,” notes Stadler. “Spatial proteomics can provide that information.”

Advancing large-scale proteomics

David Peoples, chief financial and business officer of Ultima Genomics, notes how improvements in technology are enabling large-scale proteomics studies. “One of the most exciting developments in the field is the increasing feasibility of running proteomics at a population scale,” he notes.

Peoples highlights how Ultima Genomics is supporting the Regeneron Genetics Center’s large-scale proteomics project, which involves 200,000 samples from the Geisinger Health Study. The company is also supporting the analysis of 600,000 samples associated with the U.K. Biobank Pharma Proteomics Project.

“The goal is to uncover associations between protein levels, genetics, and disease phenotypes,” he notes. By linking these data to longitudinal clinical records, researchers can identify novel biomarkers, clarify disease mechanisms, and uncover potential therapeutic targets. Large-scale proteomics may also become a foundational tool for precision medicine, according to Peoples.

The Regeneron team is using the Olink Explore HT platform to quantify protein targets in blood serum samples. Ultima’s UG 100 sequencing platform then reads out DNA barcodes that represent protein counts. “Ultima provides the high-throughput, cost-efficient sequencing readout that turns Olink’s assay results into digital data,” notes Peoples.

Ultima’s UG 100 platform is a novel short-read sequencing system designed to increase throughput, reduce costs, and facilitate scalability. Instead of conventional flow cells, the system utilizes a large open surface area supported by a silicon wafer, which supports massively parallel sequencing reactions. The system also utilizes spin-dispense fluidics, continuous rotary imaging with high-speed cameras, and machine learning-driven base calling.

“You have already done the hard work, which is to collect, store, and document these valuable samples,” notes Peoples. “Why make sacrifices in terms of the biological data you collect from these samples?”

References

• Maretty L, Gill D, Simonsen L, et al. Proteomic changes upon treatment with semaglutide in individuals with obesity. Nat Med. 2025;31(1):267-277. doi: 10.1038/s41591-024-03355-2.
• Jara M, Norlin J, Kjær MS, et al. Nat Med. Modulation of metabolic, inflammatory and fibrotic pathways by semaglutide in metabolic dysfunction-associated steatohepatitis. 2025. doi: 10.1038/s41591-025-03799-0. Online ahead of print.