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Computational approaches to identify sites of phosphorylation
  • Alex Joyce,
  • Brian Searle
Alex Joyce
The Ohio State University Medical Center
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Brian Searle
The Ohio State University Medical Center

Corresponding Author:[email protected]

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Abstract

Due to their oftentimes ambiguous nature, phosphopeptide positional isomers can present challenges in bottom-up mass spectrometry-based workflows as search engine scores alone are often not enough to confidently distinguish them. Additional scoring algorithms can remedy this by providing confidence metrics in addition to these search results, reducing ambiguity. Here we describe challenges to interpreting phosphoproteomics data and review several different approaches to determine sites of phosphorylation for both data-dependent and data-independent acquisition-based workflows. Finally, we discuss open questions regarding neutral losses, gas-phase rearrangement, and false localization rate estimation experienced by both types of acquisition workflows and best practices for managing ambiguity in phosphosite determination.
15 Jun 2023Submitted to PROTEOMICS
15 Jun 2023Review(s) Completed, Editorial Evaluation Pending
15 Jun 2023Submission Checks Completed
15 Jun 2023Assigned to Editor
15 Jun 2023Reviewer(s) Assigned
09 Aug 2023Editorial Decision: Revise Minor
07 Oct 2023Review(s) Completed, Editorial Evaluation Pending
07 Oct 20231st Revision Received
09 Oct 2023Editorial Decision: Accept