Abstract
Motivation
Post-translational modifications (PTMs) on proteins regulate protein structures and functions. A single protein molecule can possess multiple modification sites that can accommodate various PTM types, leading to a variety of different patterns, or combinations of PTMs, on that protein. Different PTM patterns can give rise to distinct biological functions. To facilitate the study of multiple PTMs, top-down mass spectrometry (MS) has proven to be a useful tool to measure the mass of intact proteins, thereby enabling even widely separated PTMs to be assigned to the same protein molecule and allowing determination of how many PTMs are attached to a single protein.
Results
We developed a Python module called MSModDetector that studies PTM patterns from individual ion mass spectrometry (I MS) data. I MS is an intact protein mass spectrometry approach that generates true mass spectra without the need to infer charge states. The algorithm first detects and quantifies mass shifts for a protein of interest and subsequently infers potential PTM patterns using linear programming. The algorithm is evaluated on simulated I MS data and experimental I MS data for the tumor suppressor protein p53. We show that MSModDetector is a useful tool for comparing a protein’s PTM pattern landscape across different conditions. An improved analysis of PTM patterns will enable a deeper understanding of PTM-regulated cellular processes.
Availability
The source code is available at https://github.com/marjanfaizi/MSModDetector together with the scripts used for analyses and to generate the figures presented in this study.
Full Text Availability
The license terms selected by the author(s) for this preprint version do not permit archiving in PMC. The full text is available from the preprint server.
