Figure 1.

General study design comparing two approaches for profiling of apolipoprotein proteoforms. Serum samples of 25 well-phenotyped CARDIA participants were submitted to either reverse-phase LCMS (top)—the traditional top-down-proteomic technique for proteoform quantification9—or IP-SampleStream-MS. The IP-SampleStream-MS approach to proteoform profiling starts from a targeted immunoprecipitation (left). Using magnetic beads and an automated sample-handling platform (Thermo KingFisher), immunoprecipitation is parallelized and automated. Then, samples are transferred to SampleStream for buffer-exchange, concentration, and course filtering based on molecular weight. Each sample is then automatically injected into the MS, allowing for targeted observation of the proteoform profile of different samples in quick succession. Herein, we compared the efficacy and throughput of these two approaches toward characterizing associations between proteoform abundance and phenotype.