Next-Generation Proteomics Solutions Set To Accelerate Targeted Therapies

Next-generation proteomics techniques enable scientists to acquire a more comprehensive analysis of the proteome, allowing a deeper understanding of the complex protein networks and pathways involved in biological processes. This enhanced knowledge holds great potential to shed light on disease mechanisms, discover drug targets and identify biomarkers, which can then lead to improved diagnostics, therapeutics and personalized medicine.

Proteomics has bridged the static information provided by genomics of “what could be,” with the context to understand what’s happening in the cells. Switzerland-based Biognosys specializes in next-generation proteomics solutions designed to transform R&D, clinical trials and clinical decision making. The company developed these solutions to provide multi-dimensional insights on protein expression, function and structure at industry-leading speed and scale across all major biological species and sample types.

Technology Networks spoke to Dr. Oliver Rinner, Biognosys’ CEO and co-founder, to understand how the company has demonstrated the capabilities of mass spectrometry (MS)-based proteomics in drug development and discovery, as well as why he feels the industry has reached the tipping point towards MS.

Karen Steward (KS): How have recent advances in proteomics impacted Biognosys and which have been most transformative?

Oliver Rinner (OR): The last decade’s huge progress in analytical capabilities was achieved by improvements in instrumentation, sample preparation protocols and, to a large extent, by advanced software. Before, MS could only scratch the surface and could not access mechanistically relevant lower abundance proteins or modifications, or even subtle structural signals.

Now, we’re seeing an accelerated increase in technical performance, driven by new physical methods like Bruker’s ion-mobility technology and artificial intelligence-based algorithms that enable signal detection performance that had previously been unreachable with classical methods. These advances have set the stage for making proteomics globally accessible.

Empowering research, drug development and clinical decision-making, new technological innovations make the proteome actionable. For example, Biognosys’ label-free discovery proteomics workflow (Hyper Reaction Monitoring or HRM™ technology) enables the analysis of complete proteomes in a data independent acquisition (DIA)-based protein quantification workflow that offers very high proteome coverage with reproducible and precise quantification across many biological samples.

KS: You recently launched Proteoverse^™, could you tell us a bit more about this tool, why it was developed and how it may aid scientists?

OR: At Biognosys, we believe that deep proteome insights hold the key to breakthrough discoveries that transform science for better lives. Proteoverse offers intuitive and interactive data visualization to make proteomics data more accessible, and the identification of actionable biological insights for biomarker and biopharma research easier. It is designed to enable researchers to dig deeper into the data, identify potentially relevant patterns that relate to known mechanisms and formulate new hypotheses in an iterative way.

Proteoverse enhances accessibility to this rich data and provides a wide range of intuitive and interactive data visualization and exploration features. Because we are more than a provider of raw data, our service includes the assistance of proteomics data experts who can handle the complexity of the data sets and judge the analytical validity of specific findings. Customers can get more out of their data by quickly and easily extracting valuable biological insights. This will enable them to advance their research by uncovering the most interesting analytes out of thousands of proteins, exploring their peptide-level structure and examining their biological relevance. The tool will be offered alongside Biognosys’ research services.

We believe that the ability of Proteoverse to bring together subject matter expertise and analytical knowledge in a human interaction will enable researchers to use the data in a meaningful way. Driving interactions between humans is, I believe, the most productive and most satisfying way to advance science.

KS: How might Proteoverse be of help specifically in the oncology space?

OR: Most researchers struggle with data overflow coming from omics data sets. Compared to genomics data, this complexity of data is even more pronounced in the multi-dimensional field of proteomics research. Changes in protein expression, protein modifications or effects that address only subdomains could all be relevant. At the same time, oncology research has uncovered deep disease — or pathway-specific — knowledge about important proteins. So, we have a wealth of functionally relevant data on the one hand that meets deep scientific knowledge of cancer pathways on the other hand. This is why I believe the possibility to contextualize novel functional proteomics insights with already available cancer pathway knowledge in Proteoverse has tremendous potential to advance oncology research.

Additionally, tissue samples are also common in oncology, and these samples work particularly well with MS. Tissue specimens offer a higher concentration of biomarkers at the location of the pathological process, such as cancer, compared to their lower concentration in peripheral blood. They also allow for the capture and characterization of variations in protein expression levels between diseased tissue, such as a tumor, and the corresponding healthy tissue. Our phosphoproteome profiling service offers in-depth, quantitative insights into the kinases, phosphatases and signaling cascades at work in cancer cells, revealing new targets for drug discovery.

Biognosys and Indivumed, precision oncology experts, recently collaborated on a significant project involving the large-scale proteome profiling of colorectal cancer patient biopsies and healthy control tissue. More than 900 tissue samples were analyzed, with each case utilizing only 5–10 mg of tissue. The profiling process involved examining more than 7,000 proteins and 20,000 phospho-peptides. By integrating this comprehensive dataset with Indivumed's multi-omics database, novel insights into key molecules and clinically significant signaling pathways related to colorectal cancer were generated. These findings have the potential to unveil new therapeutic targets and contribute to advancements in precision medicine for the treatment of colorectal cancer.

KS: What most excites you about the current trajectory of Biognosys’ role in cancer research, therapeutic and diagnostic development?

OR: What excites me most is that proteomics is increasingly used not just to perform some black box big data studies, but to understand biological mechanisms and thereby directly impact drug development. In that sense, proteomics becomes highly parallelized biochemistry. I fundamentally believe that only the understanding of biological mechanisms can drive progress in biology. However, classical cell biology had a too narrow view of these mechanisms.

An example is phosphorylation, where many publications focus on a single phosphosite, which creates the impression that proteins have a few important phospho-switches that act in a binary way. By performing global phospho-proteomics, we see that some proteins have dozens of phosphosites, and it became clear that the idea of phosphorylation as a binary switch cannot generally be true. We need new mechanistical models to understand the broader role of phosphorylation in signaling.

Another exciting possibility is the use of MS in structural studies. Structure is the ultimate driver of protein function. Using the limited proteolysis technology that was invented by Prof. Paola Picotti at the Swiss Federal Institute of Technology Zurich (ETH Zürich), now exclusively licensed and further developed by Biognosys, we can start to probe interactions with drugs and proteins or between proteins.

Aside from the analytical technical dimension, the advancement of MS-based proteomics towards clinical applications promises to make impacts beyond early R&D. Proteomics assays enable access to mechanistically relevant pharmacodynamic biomarkers. The field of protein degraders offers an example of the current utilization of MS proteomics assays, and we have recently employed targeted assays in clinical trials.

KS: Technology is advancing rapidly, which can open many R&D opportunities. However, it can also be challenging for research groups to gain access to potentially expensive equipment to evaluate and make decisions on where best to invest their time and money. How do you think companies such as yourselves can help to address this issue? Do you think shared technology centers could be a way forward?

OR: We have recognized from the beginning that, for a technology to thrive and impact scientific and medical progress, it needs to be accessible. By publishing, teaching and providing our software to proteomics users, we have played a significant role in moving the field from a highly technical, largely inaccessible, expert technology towards broad use in academic and industrial labs.

At the same time, I believe that proteomics is fundamentally different from genomics because of its much higher complexity, and therefore it will not follow the same trajectory of next-generation sequencing that can be performed by non-expert lab personnel. Therefore, the ability of researchers to access leading-edge proteomics as an end-to-end service, including the analysis of data, will remain an important part of our mission to provide access to proteomics and, with that capability, impact science.

I expect that we will see a growing number of labs that perform proteomics in-house to some extent but will rely on contract research organizations for additional capacity or to get access to methods, like immunopeptidomics, which they might not have set up internally. Our company can help with both – enabling researchers to get more out of their mass spectrometers, while at the same time giving them the option to use our expertise to perform proteomics studies.

Dr. Oliver Rinner was speaking to Dr. Karen Steward, Senior Science Writer for Technology Networks.