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  • Poster presentation
  • P-II-0503

Enhancing protein analysis with the confident PTM/Mutation algorithm

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New Technology: AI and Bioinformatics in Mass Spectrometry

Poster

Enhancing protein analysis with the confident PTM/Mutation algorithm

Topic

  • New Technology: AI and Bioinformatics in Mass Spectrometry

Authors

Yandong Zhu (Waterloo / CA), Wenting Li (Waterloo / CA), Zia Rahman (Waterloo / CA), Baozhen Shan (Waterloo / CA)

Abstract

Confident PTM/Mutation is an innovative algorithm designed to enhance the accuracy of protein post-translational modification (PTM) and mutation identification. The importance of accurate PTM and mutation identification in proteomics cannot be overstated. PTM plays crucial roles in regulating protein function, activity, localization, and interaction with other biomolecules. Mutations, on the other hand, can lead to altered protein function and are often implicated in various diseases, including cancer. Understanding these modifications and mutations at a high confidence level is essential for elucidating biological processes and disease mechanisms. Furthermore, reliable identification of PTMs and mutations can aid in the development of targeted therapies and personalized medicine approaches, highlighting the critical need for advanced algorithms like Confident PTM/Mutation in the field of proteomics.

Traditional methods generate extensive lists of potential modifications, many of which lack confident experimental evidence. This excessive output includes numerous unconfident PTMs and mutations, which contaminate the current identification results. This algorithm improves upon conventional methods by incorporating a filtering mechanism based on fragment ion intensity. It requires a consecutive fragment ions series, including the modified position, to exceed a certain intensity threshold for a modification to be considered confident. By focusing on modifications supported by strong ion intensity, the algorithm significantly reduces the number of unconfident PTMs and mutations. Leveraging the premise that higher ion intensity indicates more reliable fragment ion existence, the Confident PTM/Mutation algorithm provides a streamlined and accurate set of modification candidates. This approach enhances the reliability and accuracy of proteomic analysis.

To demonstrate the correctness of the Confident PTM/Mutation algorithm, we applied it to the iPRG 2012 data set for PTM identification. The algorithm successfully reduced the number of reported PTMs from 300 to 16 confident PTMs, all of which have been manually validated. Additionally, we tested the algorithm on the iPRG 2013 data set for mutation identification. Out of 23 peptides, the algorithm confidently identified 6 mutations, while the remaining 17 were also verified manually. These results underscore the algorithm's capability to significantly enhance the accuracy and reliability of PTM and mutation identification in proteomic studies.

In summary, the Confident PTM/Mutation algorithm significantly improves the clarity of results compared to traditional methods without filtering out any important modifications or mutations during proteomic analysis. This advancement ensures that critical PTMs and mutations are identified with high confidence, providing a robust tool for advancing our understanding of protein function and disease mechanisms.

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