TY  - JOUR
AU  - Lange, Philipp F
AU  - Schilling, Oliver
AU  - Huesgen, Pitter F
TI  - Positional proteomics: is the technology ready to study clinical cohorts?
JO  - Expert review of proteomics
VL  - 20
IS  - 12
SN  - 1478-9450
CY  - Abingdon
PB  - Taylor & Francis Group
M1  - DKFZ-2023-02143
SP  - 309-318
PY  - 2023
N1  - 2023 Jul-Dec;20(12):309-318
AB  - Positional proteomics provides proteome-wide information on protein termini and their modifications, uniquely enabling unambiguous identification of site-specific, limited proteolysis. Such proteolytic cleavage irreversibly modifies protein sequences resulting in new proteoforms with distinct protease-generated neo-N and C-termini and altered localization, activity. Mis regulated proteolysis is implicated in a wide variety of human diseases. Protein termini, therefore, constitute a huge, largely unexplored source of specific analytes that provides a deep view into the functional proteome and a treasure trove for biomarkers.We briefly review principal approaches to define protein termini and discuss recent advances in method development. We further highlight the potential of positional proteomics to identify and trace specific proteoforms, with a focus on proteolytic processes altered in disease. Lastly, we discuss current challenges and potential for applying positional proteomics in biomarker and pre-clinical research.Recent developments in positional proteomics have provided significant advances in sensitivity and throughput. In-depth analysis of proteolytic processes in clinical cohorts thus appears feasible in the near future. We argue that this will provide insights into the functional state of the proteome and offer new opportunities to utilize proteolytic processes altered or targeted in disease as specific diagnostic, prognostic and companion biomarkers.
KW  - HUNTER (Other)
KW  - Positional proteomics (Other)
KW  - biomarker (Other)
KW  - degradomics (Other)
KW  - proteoform (Other)
KW  - proteolysis (Other)
KW  - terminomics (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:37869791
DO  - DOI:10.1080/14789450.2023.2272046
UR  - https://inrepo02.dkfz.de/record/284943
ER  -