MSACL 2019 US Abstract

Combining MALDI-TOF Serum Profiling and Top-Down Protein Analysis with 21 T FT-ICR Mass Spectrometry for Proteoform Identification

Nathan K. Kaiser (1), Chad R. Weisbrod (2), Lissa C. Anderson (2), Maximillian A. Steers (1), Gary Pestano (1)
(1) Biodesix Inc., Boulder, CO (2) National High Magnetic Field Laboratory, Tallahassee, FL

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Nathan Kaiser (Presenter) Biodesix

Presenter Bio: Currently working as a Sr. Scientist at Biodesix. Previously spent the last 8 years working on High Resolution Mass Spectrometry at the National High Magnetic Field Laboratory.

Relevant Financial Disclosures (within past 24 months) Salary Biodesix Discussing Products? YES, presenter will present educational content related to products/services of one or more ineligible company(ies) listed above. Conflict mitigation IN PROCESS.

Serum profiling of circulating proteins with MALDI-TOF has proven valuable in the development of diagnostic tests. We generated serum protein profiles with MALDI-TOF MS for patients previously diagnosed with lung cancer. Many spectra were averaged to increase sensitivity such that >300 distinct m/z peaks are observed. A subset of three samples were analyzed without any depletion of high abundant proteins prior to analysis by top-down LC-MS with a 21 T FT-ICR mass spectrometer for protein and proteoform identification. Accurate intact protein mass (0.80 ppm RMS error) from the 21 T FT-ICR was used to map identifications back to the MALDI spectra. Results from top-down LC-MS analysis revealed 24 proteins and 57 proteoforms at <1% FDR. With the contribution of identified proteoforms from top-down LC-MS, ~80% of the spectral abundance in the MALDI-TOF spectra are tentatively assigned.