Discover Protein Variants with Single-molecule Resolution Using Next-Generation Protein Sequencing™
Gain deeper insights to enhance your research through precise detection of protein variants.
Read the Publication
Why Choose Next-Generation Protein Sequencing for protein variant detection?
Examining protein variants is vitally important in biological research and medicine, as even small changes in proteins can significantly impact health and disease. These variants influence a protein’s structure, stability, activity, and interactions, offering insights into their roles in diverse biological processes.
The ProteoVue™ informatics workflow delivers single-molecule resolution for detecting amino acid variants on a benchtop instrument and enables researchers to explore variations undetectable with traditional methods, including single-amino acid substitutions, somatic variations, isobaric variations, and post-translational modifications. Next-Generation Protein Sequencing offers the sensitivity and precision needed to explore proteoforms one amino acid at a time.
Proteoform research is critical in identifying protein variations associated with phenotypic diversity and understanding complex disease mechanisms. Quantum-Si invites researchers and potential collaborators to experience the ProteoVue workflow. Join the community of pioneers seeking deeper understanding and groundbreaking discoveries.
Next-Generation Protein Sequencing enables you to:
Detect amino acid substitutions like SARS CoV-2 Alpha, Delta and Omicron
Distinguish isobaric variations previously unrecognizable by mass spec like isoleucine and leucine
Evaluate amino acid disincorporation events like ubiquitin protein variants
Recognize post-translational modification events with unique kinetic signatures
Next-Generation Protein Sequencing™ to Detect Disease-Relevant Proteoforms
Dr. Gloria Sheynkman of the University of Virginia highlights the importance of detecting protein isoforms for understanding human traits and diseases. She introduces a novel long-read proteogenomics workflow to enhance protein isoform detection. Additionally, she describes how the Platinum® Next-Generation Protein Sequencer™ offers single-molecule protein sequencing technology with high sensitivity and resolution.
Dive in to grasp how Platinum Pro — the Next-Generation Protein Sequencer™ — optimizes protein variant detection with unparalleled precision.
-
Next-Generation Protein Sequencing and individual ion mass spectrometry enable complementary analysis of IL-6 — PREPRINT PUBLICATION
The vast complexity of the proteome currently overwhelms any single analytical technology in capturing the full spectrum of proteoform diversity. In this study, we evaluated the complementarity of two cutting-edge proteomic technologies—single-molecule protein sequencing and individual ion mass spectrometry—for analyzing recombinant human IL-6 (rhIL-6) at the amino acid, peptide, and intact proteoform levels. For single-molecule protein sequencing, we employ the recently released Platinum® instrument. Next-Generation Protein Sequencing™ (NGPS™) on Platinum utilizes cycles of N-terminal amino acid recognizer binding and aminopeptidase cleavage to enable parallelized sequencing of single peptide molecules. We found that NGPS produces single amino acid coverage of multiple key regions of IL-6, including two peptides within helices A and C which harbor residues that reportedly impact IL-6 function. For top-down proteoform evaluation, we use individual ion mass spectrometry (I2MS), a highly parallelized orbitrap-based charge detection MS platform. Single ion detection of gas-phase fragmentation products (I2MS2) gives significant sequence coverage in key regions in IL-6, including two regions within helices B and D that are involved in IL-6 signaling. Together, these complementary technologies deliver a combined 52% sequence coverage, offering a more complete view of IL-6 structural and functional diversity than either technology alone.
This study highlights the synergy of complementary protein detection methods to more comprehensively cover protein segments relevant to biological interactions.
-
Detecting Amino Acid Variants Using Next-Generation Protein Sequencing (NGPS) — PREPRINT PUBLICATION
Next-Generation Protein Sequencing is a single-molecule approach for characterizing protein variants, offering detailed insight into proteoforms and amino acid substitutions not easily discerned by mass spectrometry. The novel data type produced by NGPS, which is based on binding of N-terminal amino acids by fluorescently tagged recognizer proteins, requires the development of new data analysis methods and bioinformatic tools.
Here, we present ProteoVue™, a comprehensive bioinformatics pipeline for Single Amino Acid Variant (SAAV) detection and quantification using the Quantum-Si Platinum NGPS platform.
-
Protein Sequencing With Single-Amino Acid Resolution Discerns Peptides That Discriminate Tropomyosin Proteoforms — PREPRINT PUBLICATION
Protein variants of the same gene–proteoforms–can have high molecular similarity yet exhibit different biological functions. Thus, identifying unique peptides that unambiguously map to proteoforms can provide crucial biological insights. In humans, four human tropomyosin (TPM) genes produce similar proteoforms that can be challenging to distinguish with standard proteomics tools.
Dr. Gloria Sheynkman and her team at the University of Virginia School of Medicine have published a preprint on BioRxiv showcasing the capabilities of the Platinum® Next-Generation Protein Sequencer™ in advancing their research in this complex area of study.
-
Quantum-Si’s Next Generation Protein Sequencing Technology Enables Rapid and Accurate Distinction of Variants of the SARS-CoV-2 Virus — APP NOTE
This application note showcases Quantum-Si’s protein sequencing technology on the Platinum instrument, which enables the rapid and accurate distinction of variants of the SARS-CoV-2 virus based on differences in the amino acid sequence of their Spike proteins. By identifying and tracking these variants, scientists can better understand their impact on public health and develop effective treatments and vaccines.
Download the application note to learn more about this groundbreaking technology.
Focusing on a key mutation, we observed the distinctive kinetic influences on recognizer binding. The clear differences in pulse durations (PD) between the peptides of interest highlight the power of Quantum-Si’s Platinum instrument in differentiating the Alpha variant from the Delta and Omicron variants through a single mutation.
Here we highlight the differentiation of the Omicron variant from the Alpha and Delta variants based on the detection of a single peptide. The capability to identify variant-specific peptides contributes to the accurate and precise distinction of SARS-CoV-2 variants using Quantum-Si’s Platinum instrument.
-
Single-Molecule Protein Sequencing on the Quantum-Si Platform: Advances in Protein and Proteoform Identification and Comparison With Mass Spectrometry — POSTERS
Studies of the proteome would benefit greatly from methods to directly sequence and digitally quantify proteins and detect post-translational modifications with single-molecule sensitivity. Quantum-Si™ has developed the Platinum Next-Generation Protein Sequencing platform to offer a convenient benchtop solution for direct sequencing of single protein molecules with the aim of making protein sequencing accessible to any research lab. Quantum-Si has improved fundamentals of the assay components and platform allowing for increased coverage across the proteome.
- This poster describes these Platinum improvements and how they have resulted in unprecedented read depth and the identification of previously unseen proteins, leading to new insights and greater confidence in protein identification.
-
Platinum Next-Generation Protein Sequencing Advanced Data Analysis — TECHNICAL NOTE
Next-Generation Protein Sequencing (NGPS) on Platinum enables protein identification and characterization with single-molecule and single amino acid resolution in a simple workflow using a benchtop instrument. Platinum Analysis Software workflows make peptide alignment and protein mapping easy to interpret without the need for advanced expertise. The output files from Platinum Analysis Software provide researchers with the opportunity to perform advanced analysis on NGPS data including analysis of amino acid variants and modifications based on kinetic signatures.
- This technical note provides guidance on interpreting results from Primary Analysis and Peptide Alignment Workflows and performing advanced analysis on NGPS data generated by Platinum.
-
Next-Generation Protein Sequencing: Interrogating Proteins with Single-molecule Amino Acid Resolution on Platinum – WEBINARS
Proteins are the workhorses of cells and provide vital insights to cell health and disease function. Immunoassays and mass spectrometry are well established methods for studying proteins and have led to important discoveries in human health and disease. However, these techniques either lack single-molecule resolution to interrogate each individual amino acid residue or require a large investment in equipment and lab space, driving the need for a simple benchtop solution with single-molecule resolution for protein identification and interrogation.
In this webinar, we will explore how next-generation protein sequencing on Platinum works and how it can be used to interrogate proteins with single-molecular amino acid resolution. This new technology utilizes semiconductor chip technology and fluorescently labeled n-terminal amino acid (NAA) recognizers to identify individual amino acids in a protein. The binding kinetics and order of the NAA recognizer signal results in a unique kinetic signature for each amino acid. Aminopeptidases then cleave the n-terminus and expose the next amino acid for binding. This process repeats until each peptide is sequenced.
We will demonstrate how this technology can be used with traditional protein workflows that isolate proteins of interest and interrogate their sequences with single-molecule resolution. Finally, we will discuss the scalability of this technology for advancing our understanding of proteins and offering insights to human health and disease.
Learning Objectives:
- Explore how next-generation protein sequencing works to interrogate amino acid residues
- Understand how next-generation protein sequencing can be used with other lab methods to understand protein biology
- Learn how next-generation protein sequencing can be used to detect amino acid variants with single-molecule resolution
Speakers: Ben Moree, PhD, QSI
Date: December 7, 2023
-
Next-Generation Protein Sequencing Advances Variant Identification — WHITEPAPER
In their quest to fully understand the proteome, researchers face an identification challenge: Distinguishing individual proteins among the 20,000-plus proteins and over 1 million proteoforms in human cells. Now a benchtop sequencer provides easy access to the analytical resolution needed to continue mapping protein variation.
Platinum, the Next-Generation Protein Sequencer, provides unambiguous amino acid detection at single molecule resolution. Learn how it complements existing protein identification techniques, such as mass spectrometry and immunoassays, while providing deeper insights with unprecedented accessibility.
-
Beyond the Genome: Unraveling Protein Variability with Quantum-Si’s Next-generation Protein Sequencing Technology — POSTER
Protein sequencing is a groundbreaking advancement in proteomics that augments genomics and transcriptomics research by providing crucial insights into the functional proteins encoded by the genome. Protein sequencing offers a more complete understanding of cellular processes and disease mechanisms by detecting changes at the protein level, such as post-translational modifications (PTMs), which cannot be captured by genomics data alone. Next-Generation Protein Sequencing (NGPS) on Platinum enables researchers to identify and characterize proteins with single-molecule resolution in a simple workflow and on a benchtop instrument.