Next-Generation Protein Sequencing Platform Interrogates Proteins at a Single-Molecule Level

Sequencing the amino acids of single protein molecules has the potential to unlock the proteome and transform drug discovery

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Twenty thousand genes encode twenty thousand parent proteins that, once modified, lead to over a million variants called proteoforms. Proteoforms function—the business end of biology, as Patrick Schneider, PhD, President and COO, Quantum-Si, likes to describe it—can be dynamic as proteins are up- and downregulated and turned on and off with post-translational modifications (PTMs). Identifying and characterizing the vast proteoform population is an immense challenge. GEN spoke to Dr. Schneider to delve into the needs of the proteomics field.

GEN: NGS has opened up the fields of genomics, transcriptomics, metabolomics, and more. What is going on in proteomics?

Schneider: Importantly, next-generation DNA sequencing helped unlock discoveries as they were related to gene mutations or predispositions to certain diseases. This led to early detection of cancer, for example. Now we are at an inflection point where new technologies are required at a single-molecule level and amino acid resolution to understand proteoforms and their effects on health and disease. Quantum-Si’s next-generation protein sequencing platform, PlatinumTM, allows researchers to interrogate proteoforms at a single-molecule level to help understand how they are associated with health and disease.

GEN: Most of the technology used for proteomics appears to be mature. What has delayed new proteomics technology?

Schneider: Some proteomics techniques are decades old, like mass spectrometry and antibody-based targeted methods like ELISAs and Western blots, and they yield a blended average of the proteins in the sample with limited insights to rare events. Emerging technologies that allow interrogation of proteins at the single-molecule level unlock proteoform analysis such as characterizing the on–off switches like phosphorylation. Our big leaps in Platinum technology were the development of a semiconductor consumable that is used to sequence at single-molecule resolution in isolated wells as well as our proprietary technology to identify individual amino acids to sequence the protein.

GEN: How is Quantum-Si kick-starting the widespread adoption of proteomics in basic research?

Quantum-Si’s Platinum™ instrumentSchneider: The first-of-its-kind Platinum next-generation protein sequencing platform provides a simple, convenient, accessible benchtop solution that easily integrates into existing workflows to empower every lab, everywhere, to conduct benchtop proteomics experiments. Our expectation is that every lab studying proteins or or interested in studying proteins, for instance, to complement genomics or transcriptomics data with proteomic insights, needs to have access to Platinum technology to easily identify and characterize proteins. We are building a new protein sequencing category by exploring applications with academic researchers and customers who want to understand what proteins and proteoforms are in their samples. Multiple applications exist for protein sequencing, including protein identification and characterization. As our capabilities expand, we will be spotlighting these new applications through application notes, posters, and presentations at conferences to show the scientific community how to apply the Platinum technology to their specific areas of research and the problems that they are trying to solve.

GEN: What impact will your technology have?

Schneider: We designed the benchtop Platinum to be simple, easy to use, and more accessible than older approaches. There is no need for expensive, complex equipment for basic proteomics analysis. And you do not need a bioinformatics expert to interpret the data. For example, as an alternative to sending protein sample out to a core lab services facility for mass spec identification, researchers can now perform protein identification and characterization in their own labs. Sometimes this is a simple analysis like identifying the protein in a gel band or validating that the antibody reacts to its antigen. Having Platinum in the lab can speed up the iterative loop of research in a cost-effective manner.

GEN: How do you envision the field of proteomics evolving in the next five years?

Schneider: Most drug targets are to proteins and understanding proteoforms is central to the biology of health. Proteomics can lead to new first-in-class medicines by identifying and elucidating new mechanisms of action and the associated proteins and their phosphorylation and other PTM states. Being able to study the changes in proteins that lead to disease and modulating those changes can help create new medicines and have a major impact on human health.


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