ISPTM: an iterative search algorithm for systematic identification of post-translational modifications from complex...

Area of Science:

• Proteomics
• Biochemistry
• Mass Spectrometry

Background:

• Identifying protein post-translational modifications (PTMs) in complex proteomes is challenging.
• Existing methods may not capture the full spectrum of PTMs.

Purpose of the Study:

• To introduce a novel strategy, iterative search for identifying PTMs (ISPTM), for robust PTM identification.
• To evaluate ISPTM's performance on synthetic and complex biological samples.

Main Methods:

• ISPTM employs a basic search followed by iterative searches with limited variable modifications.
• Evaluated on synthetic peptides, protein standards, and mouse nuclear matrix proteins.

Main Results:

• ISPTM identified chemical modifications from sample preparation and biological PTMs activated by Adriamycin.
• Significantly increased MS/MS spectral identification rates and PTM detection sensitivity.
• Provided complementary PTM identification results to established algorithms like InsPecT and MODa.

Conclusions:

• ISPTM is a powerful tool for unbiased and high-confidence identification of diverse PTMs.
• The strategy effectively addresses challenges in PTM discovery from complex proteomic data.