Che-Fan Huang, Michael A Hollas, Aniel Sanchez, Mrittika Bhattacharya, Giang Ho, Ambika Sundaresan, Michael A Caldwell, Xiaoyan Zhao, Ryan Benz, Asim Siddiqui, Neil L Kelleher
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引用次数: 0
Abstract
The dynamic range challenge for the detection of proteins and their proteoforms in human plasma has been well documented. Here, we use the nanoparticle protein corona approach to enrich low-abundance proteins selectively and reproducibly from human plasma and use top-down proteomics to quantify differential enrichment for the 2841 detected proteoforms from 114 proteins. Furthermore, nanoparticle enrichment allowed top-down detection of proteoforms between ∼1 μg/mL and ∼10 pg/mL in absolute abundance, providing up to a 105-fold increase in proteome depth over neat plasma in which only proteoforms from abundant proteins (>1 μg/mL) were detected. The ability to monitor medium and some low-abundant proteoforms through reproducible enrichment significantly extends the applicability of proteoform research by adding depth beyond albumin, immunoglobins, and apolipoproteins to uncover many involved in immunity and cell signaling. As proteoforms carry unique information content relative to peptides, this report opens the door to deeper proteoform sequencing in clinical proteomics of disease or aging cohorts.
期刊介绍:
Journal of Proteome Research publishes content encompassing all aspects of global protein analysis and function, including the dynamic aspects of genomics, spatio-temporal proteomics, metabonomics and metabolomics, clinical and agricultural proteomics, as well as advances in methodology including bioinformatics. The theme and emphasis is on a multidisciplinary approach to the life sciences through the synergy between the different types of "omics".