Mass Spec Platforms
Critical to using mass spectrometry platforms for biomarker development is the need to progress from the general profiling of proteins to the targeting of specific protein panels, Randall W. Nelson, Ph.D., research professor and director of the molecular biosignatures analysis unit at The Biodesign Institute, Arizona State University.
The value of such a targeted approach, Dr. Nelson observed, lies in the ability to differentiate microheterogeneity in the proteins under investigation—variation in the chemical structure of the amino acid sequence of a protein that does not produce a major change in its properties such as gene, translational, and posttranslational modifications—and to generate data on only the specific molecular determinants relevant to disease. His talk focused on using targeted mass spectrometric immunoassays to investigate human plasma and urinary proteins in healthy and disease cohorts.
Dr. Nelson’s group uses mass spectrometry to identify biomarkers by looking for specific variances in proteins, characterizing them one by one. Plasma protein is increasingly their area of interest.
While Dr. Nelson served as the president, CEO, and founder at Intrinsic Bioprobes, the company adopted a strategy by looking at routine proteins in more detail and identified post-translational modifications, point mutations, variants, and truncations that defined the proteome. These variants, in turn, provide information that can be used to design targeted diagnostic assays, stratify patients in clinical trials, monitor patients more effectively, and facilitate pharmacokinetic studies by following in vivo changes of therapeutic proteins.
Dr. Nelson shared results with the conference illustrating the ability to detect low level protein variants relevant to type 2 diabetes, and how these findings are subsequently used to develop advanced assays for disease diagnosis and monitoring. Currently, these assays are out of R&D and being used in CLIA labs. Dr. Nelson forsees diagnostic use within the next 5–10 years.