Search for: All records | NSF Public Access

Note: When clicking on a Digital Object Identifier (DOI) number, you will be taken to an external site maintained by the publisher. Some full text articles may not yet be available without a charge during the embargo (administrative interval).
What is a DOI Number?

Some links on this page may take you to non-federal websites. Their policies may differ from this site.

Proteoform‐Selective Imaging of Tissues Using Mass Spectrometry**

https://doi.org/10.1002/ange.202200721

Yang, Manxi ; Hu, Hang ; Su, Pei ; Thomas, Paul M. ; Camarillo, Jeannie M. ; Greer, Joseph B. ; Early, Bryan P. ; Fellers, Ryan T. ; Kelleher, Neil L. ; Laskin, Julia ( May 2022 , Angewandte Chemie)

Abstract
Unraveling the complexity of biological systems relies on the development of new approaches for spatially resolved proteoform‐specific analysis of the proteome. Herein, we employ nanospray desorption electrospray ionization mass spectrometry imaging (nano‐DESI MSI) for the proteoform‐selective imaging of biological tissues. Nano‐DESI generates multiply charged protein ions, which is advantageous for their structural characterization using tandem mass spectrometry (MS/MS) directly on the tissue. Proof‐of‐concept experiments demonstrate that nano‐DESI MSI combined with on‐tissue top‐down proteomics is ideally suited for the proteoform‐selective imaging of tissue sections. Using rat brain tissue as a model system, we provide the first evidence of differential proteoform expression in different regions of the brain.

more » « less
Proteoform‐Selective Imaging of Tissues Using Mass Spectrometry**

https://doi.org/10.1002/anie.202200721

Yang, Manxi ; Hu, Hang ; Su, Pei ; Thomas, Paul M. ; Camarillo, Jeannie M. ; Greer, Joseph B. ; Early, Bryan P. ; Fellers, Ryan T. ; Kelleher, Neil L. ; Laskin, Julia ( May 2022 , Angewandte Chemie International Edition)

Abstract
Unraveling the complexity of biological systems relies on the development of new approaches for spatially resolved proteoform‐specific analysis of the proteome. Herein, we employ nanospray desorption electrospray ionization mass spectrometry imaging (nano‐DESI MSI) for the proteoform‐selective imaging of biological tissues. Nano‐DESI generates multiply charged protein ions, which is advantageous for their structural characterization using tandem mass spectrometry (MS/MS) directly on the tissue. Proof‐of‐concept experiments demonstrate that nano‐DESI MSI combined with on‐tissue top‐down proteomics is ideally suited for the proteoform‐selective imaging of tissue sections. Using rat brain tissue as a model system, we provide the first evidence of differential proteoform expression in different regions of the brain.

more » « less
The C-Score: A Bayesian Framework to Sharply Improve Proteoform Scoring in High-Throughput Top Down Proteomics

https://doi.org/10.1021/pr401277r

LeDuc, Richard D. ; Fellers, Ryan T. ; Early, Bryan P. ; Greer, Joseph B. ; Thomas, Paul M. ; Kelleher, Neil L. ( July 2014 , Journal of Proteome Research)
Applying Label-Free Quantitation to Top Down Proteomics

https://doi.org/10.1021/ac500395k

Ntai, Ioanna ; Kim, Kyunggon ; Fellers, Ryan T. ; Skinner, Owen S. ; Smith, IV, Archer D. ; Early, Bryan P. ; Savaryn, John P. ; LeDuc, Richard D. ; Thomas, Paul M. ; Kelleher, Neil L. ( May 2014 , Analytical Chemistry)