Clinically relevant post-translational modification analyses: maturing workflows and bioinformatics tools

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Abstract

Post-translational modifications (PTMs) can occur soon after translation or at any stage in the lifecycle of a given protein, and they may help regulate protein folding, stability, cellular localisation, activity, or the interactions proteins have with other proteins or biomolecular species. PTMs are crucial to our functional understanding of biology, and new quantitative mass spectrometry (MS) and bioinformatics workflows are maturing both in labelled multiplexed and label-free techniques, offering increasing coverage and new opportunities to study human health and disease. Techniques such as Data Independent Acquisition (DIA) are emerging as promising approaches due to their re-mining capability. Many bioinformatics tools have been developed to support the analysis of PTMs by mass spectrometry, from prediction and identifying PTM site assignment, open searches enabling better mining of unassigned mass spectra—many of which likely harbour PTMs—through to understanding PTM associations and interactions. The remaining challenge lies in extracting functional information from clinically relevant PTM studies. This review focuses on canvassing the options and progress of PTM analysis for large quantitative studies, from choosing the platform, through to data analysis, with an emphasis on clinically relevant samples such as plasma and other body fluids, and well-established tools and options for data interpretation.

LanguageEnglish
Article number16
Pages1-30
Number of pages30
JournalInternational Journal of Molecular Sciences
Volume20
Issue number1
DOIs
Publication statusPublished - 1 Jan 2019

Fingerprint

Workflow
Post Translational Protein Processing
Bioinformatics
Computational Biology
Proteins
Mass spectrometry
Protein folding
Body fluids
Ports and harbors
proteins
Labels
Health
Plasmas
Mass Spectrometry
mass spectroscopy
body fluids
harbors
Protein Stability
Protein Folding
Body Fluids

Bibliographical note

Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • Body fluids
  • Clinical samples
  • Post translational modification
  • Ptm
  • Quantitative proteomics

Cite this

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title = "Clinically relevant post-translational modification analyses: maturing workflows and bioinformatics tools",
abstract = "Post-translational modifications (PTMs) can occur soon after translation or at any stage in the lifecycle of a given protein, and they may help regulate protein folding, stability, cellular localisation, activity, or the interactions proteins have with other proteins or biomolecular species. PTMs are crucial to our functional understanding of biology, and new quantitative mass spectrometry (MS) and bioinformatics workflows are maturing both in labelled multiplexed and label-free techniques, offering increasing coverage and new opportunities to study human health and disease. Techniques such as Data Independent Acquisition (DIA) are emerging as promising approaches due to their re-mining capability. Many bioinformatics tools have been developed to support the analysis of PTMs by mass spectrometry, from prediction and identifying PTM site assignment, open searches enabling better mining of unassigned mass spectra—many of which likely harbour PTMs—through to understanding PTM associations and interactions. The remaining challenge lies in extracting functional information from clinically relevant PTM studies. This review focuses on canvassing the options and progress of PTM analysis for large quantitative studies, from choosing the platform, through to data analysis, with an emphasis on clinically relevant samples such as plasma and other body fluids, and well-established tools and options for data interpretation.",
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author = "Dana Pascovici and Wu, {Jemma X.} and McKay, {Matthew J.} and Chitra Joseph and Zainab Noor and Karthik Kamath and Yunqi Wu and Shoba Ranganathan and Vivek Gupta and Mehdi Mirzaei",
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