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Peer-Reviewed Publication
Anal Bioanal Chem2025;417(28):6291-6299.November 1, 2025Journal Article

Next-generation protein sequencing and individual ion mass spectrometry enable complementary analysis of interleukin-6.

Kenneth A Skinner1, Troy D Fisher2, Andrew Lee3, Taojunfeng Su4, Eleonora Forte5, Aniel Sanchez2,6, Michael A Caldwell2,7, Neil L Kelleher8,9,10,11,12
1Quantum-Si Incorporated, Branford, CT, USA.
2Proteomics Center of Excellence, Chemistry of Life Processes Institute, Northwestern University, Evanston, IL, USA.
3Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL, USA.
4Department of Molecular Biosciences, Northwestern University, Evanston, IL, USA.
5Division of Nephrology, Department of Medicine, University of Illinois College of Medicine, Chicago, IL, USA.
6Department of Chemistry, Northwestern University, Evanston, IL, USA.
7Division of Hematology Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
8Proteomics Center of Excellence, Chemistry of Life Processes Institute, Northwestern University, Evanston, IL, USA. n-kelleher@northwestern.edu.
9Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL, USA. n-kelleher@northwestern.edu.
10Department of Molecular Biosciences, Northwestern University, Evanston, IL, USA. n-kelleher@northwestern.edu.
11Division of Hematology Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. n-kelleher@northwestern.edu.
12Department of Chemistry, Northwestern University, Evanston, IL, USA. n-kelleher@northwestern.edu.

Abstract

The vast complexity of the proteome currently overwhelms any single analytical technology in capturing the full spectrum of proteoform diversity. In this study, we evaluated the complementarity of two cutting-edge proteomic technologies-single-molecule protein sequencing and individual ion mass spectrometry-for analyzing recombinant human IL-6 (rhIL-6) at the amino acid, peptide, and intact proteo…

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