Demir, Fatih ORCID: 0000-0002-5744-0205, Kizhakkedathu, Jayachandran N., Rinschen, Markus M. and Huesgen, Pitter F. (2021). MANTI: Automated Annotation of Protein N-Termini for Rapid Interpretation of N-Terminome Data Sets. Anal. Chem., 93 (13). S. 5596 - 5606. WASHINGTON: AMER CHEMICAL SOC. ISSN 1520-6882

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Abstract

Site-specific proteolytic processing is an important, irreversible post-translational protein modification with implications in many diseases. Enrichment of protein N-terminal peptides followed by mass spectrometry-based identification and quantification enables proteome-wide characterization of proteolytic processes and protease substrates but is challenged by the lack of specific annotation tools. A common problem is, for example, ambiguous matches of identified peptides to multiple protein entries in the databases used for identification. We developed MaxQuant Advanced N-termini Interpreter (MANTI), a standalone Perl software with an optional graphical user interface that validates and annotates N-terminal peptides identified by database searches with the popular MaxQuant software package by integrating information from multiple data sources. MANTI utilizes diverse annotation information in a multistep decision process to assign a conservative preferred protein entry for each N-terminal peptide, enabling automated classification according to the likely origin and determines significant changes in N-terminal peptide abundance. Auxiliary R scripts included in the software package summarize and visualize key aspects of the data. To showcase the utility of MANTI, we generated two large-scale TAILS Nterminome data sets from two different animal models of chemically and genetically induced kidney disease, puromycin adenonucleoside-treated rats (PAN), and heterozygous Wilms Tumor protein 1 mice (WT1). MANTI enabled rapid validation and autonomous annotation of >10 000 identified terminal peptides, revealing novel proteolytic proteoforms in 905 and 644 proteins, respectively. Quantitative analysis indicated that proteolytic activities with similar sequence specificity are involved in the pathogenesis of kidney injury and proteinuria in both models, whereas coagulation processes and complement activation were specifically induced after chemical injury.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Demir, FatihUNSPECIFIEDorcid.org/0000-0002-5744-0205UNSPECIFIED
Kizhakkedathu, Jayachandran N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rinschen, Markus M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huesgen, Pitter F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-591751
DOI: 10.1021/acs.analchem.1c00310
Journal or Publication Title: Anal. Chem.
Volume: 93
Number: 13
Page Range: S. 5596 - 5606
Date: 2021
Publisher: AMER CHEMICAL SOC
Place of Publication: WASHINGTON
ISSN: 1520-6882
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
SUBSTRATE-SPECIFICITY; WEB SERVER; IDENTIFICATION; VISUALIZATION; DEGRADATION; ENRICHMENT; PLATFORM; REVEALSMultiple languages
Chemistry, AnalyticalMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/59175

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