Discovery of New Protein Analysis Method to Enable Faster Drug Discoveries, Clinical Analyses
Milwaukee, Nov. 23, 2020 – The study of all proteins in a biological system, or proteomics, enables an unbiased assessment of protein quantities. Proteome analysis is an important tool for clinicians and biologists to build hypotheses about how protein changes associated with disease, which can lead to new therapeutics. Proteomics technology continues to improve, but relatively little data prevents its application to problems that require thousands of samples, such as clinical biomarker discovery or drug discovery.
In an article published in Nature Methods, Jesse G. Meyer, PhD, assistant professor of biochemistry at the Medical College of Wisconsin (MCW), developed a groundbreaking protein analysis technique that enables quantification of proteins in seconds instead of the usual tens of minutes or hours.
“This is a significant breakthrough that will decrease the time required for proteomic analysis, which translates to lower cost per sample,” Dr. Meyer said. “That means we can start thinking about collecting data from thousands of proteomes, which is needed for drug discovery and clinical analyses.”
Due to the complexity of proteins in any biological system, proteomics technology typically relies on separation of proteins pieces called peptides before their analysis. The key advancement of this new proteomic technology is a shift to separate the peptide parts of proteins in the gas phase, instead of the liquid phase, which is achieved in milliseconds.
Preliminary experiments demonstrated that this new method, Direct Infusion – Shotgun Proteome Analysis (DI-SPA), could quantify three to four proteins per second. The researchers showed that the quantitative values from DI-SPA were similar to those from traditional proteomic methods.
To demonstrate its utility, Natalie Niemi, PhD, and Dave Pagliarini, PhD, assistant professor and professor, respectively, at Washington University in Saint Louis, devised experiments testing whether the method could reveal interactions between nutrients, toxin treatments and a genetic mutation. A total of 44 unique conditions were tested, and data was collected from 132 samples in only about four hours. Traditional proteomics methods would require at minimum nearly one week. They found that DI-SPA detected many of the expected proteome remodeling, and that the data could reveal relationships between experimental factors.
“This project is a perfect marriage of technology development, informatics and high throughput screening,” Dr. Meyer said. “The combination of these technologies, and the diverse expertise from everyone involved, produced something greater than the sum of the parts.”
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