MANTI

MANTI annotates protein N-termini from mass spectrometry-based N-terminome datasets to resolve site-specific proteolytic processing and assign conservative preferred protein entries.

Key Features:

• Integration with MaxQuant: Integrates with MaxQuant output to process identified and quantified N-terminal peptides from mass spectrometry experiments.
• Multistep Decision Process: Employs a multistep decision process that leverages diverse annotation information to assign a conservative preferred protein entry for each identified N-terminal peptide and resolve multiple database matches.
• Automated Classification and Validation: Automates classification of N-terminal peptides according to their likely origin and validates annotations against multiple data sources.
• Quantitative Analysis: Determines significant changes in N-terminal peptide abundance to infer proteolytic activities.
• Visualization: Provides auxiliary R scripts to summarize and visualize key aspects of N-terminome data.
• Implementation: Implemented as standalone Perl software.

Scientific Applications:

• TAILS N-terminome analysis: Applied to generate and annotate large-scale TAILS (Terminal Amine Isotopic Labeling of Substrates) N-terminome datasets from mass spectrometry experiments.
• Kidney disease proteolysis studies: Used on datasets from puromycin adenonucleoside-treated rats and heterozygous Wilms Tumor protein 1 mice to validate and autonomously annotate over 10,000 terminal peptides and discover novel proteolytic proteoforms.

Methodology:

Uses a multistep decision process integrating information from multiple annotation sources to assign a preferred protein entry per N-terminal peptide, classifies peptides by likely origin, validates annotations against data sources, and performs quantitative tests for significant changes in N-terminal peptide abundance; auxiliary R scripts are used for data summarization and visualization.