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Ozols M, Eckersley A, Mellody KT, et al. Peptide location fingerprinting reveals modification-associated biomarker candidates of ageing in human tissue proteomes. Aging Cell. 2021;20(5):e13355doi: 10.1111/acel.13355.
Ozols, M., Eckersley, A., Mellody, K. T., Mallikarjun, V., Warwood, S., O'Cualain, R., Knight, D., Watson, R. E. B., Griffiths, C. E. M., Swift, J., & Sherratt, M. J. (2021). Peptide location fingerprinting reveals modification-associated biomarker candidates of ageing in human tissue proteomes. Aging cell, 20(5), e13355. https://doi.org/10.1111/acel.13355
Ozols, Matiss, et al. "Peptide location fingerprinting reveals modification-associated biomarker candidates of ageing in human tissue proteomes." Aging cell vol. 20,5 (2021): e13355. doi: https://doi.org/10.1111/acel.13355
Ozols M, Eckersley A, Mellody KT, Mallikarjun V, Warwood S, O'Cualain R, Knight D, Watson REB, Griffiths CEM, Swift J, Sherratt MJ. Peptide location fingerprinting reveals modification-associated biomarker candidates of ageing in human tissue proteomes. Aging Cell. 2021 May;20(5):e13355. doi: 10.1111/acel.13355. Epub 2021 Apr 08. PMID: 33830638; PMCID: PMC8135079.
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Aging Cell. 2021 May;20(5):e13355. doi: 10.1111/acel.13355. Epub 2021 Apr 08.

Peptide location fingerprinting reveals modification-associated biomarker candidates of ageing in human tissue proteomes.

Aging cell

Matiss Ozols, Alexander Eckersley, Kieran T Mellody, Venkatesh Mallikarjun, Stacey Warwood, Ronan O'Cualain, David Knight, Rachel E B Watson, Christopher E M Griffiths, Joe Swift, Michael J Sherratt

Affiliations

  1. Division of Cell Matrix Biology & Regenerative Medicine, The University of Manchester, Manchester, UK.
  2. Division of Musculoskeletal & Dermatological Sciences, The University of Manchester, Manchester, UK.
  3. Wellcome Centre for Cell-Matrix Research, The University of Manchester, Manchester, UK.
  4. Biological Mass Spectrometry Core Research Facility, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.
  5. NIHR Manchester Biomedical Research Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.

PMID: 33830638 PMCID: PMC8135079 DOI: 10.1111/acel.13355

Abstract

Although dysfunctional protein homeostasis (proteostasis) is a key factor in many age-related diseases, the untargeted identification of structurally modified proteins remains challenging. Peptide location fingerprinting is a proteomic analysis technique capable of identifying structural modification-associated differences in mass spectrometry (MS) data sets of complex biological samples. A new webtool (Manchester Peptide Location Fingerprinter), applied to photoaged and intrinsically aged skin proteomes, can relatively quantify peptides and map statistically significant differences to regions within protein structures. New photoageing biomarker candidates were identified in multiple pathways including extracellular matrix organisation (collagens and proteoglycans), protein synthesis and folding (ribosomal proteins and TRiC complex subunits), cornification (keratins) and hemidesmosome assembly (plectin and integrin α6β4). Crucially, peptide location fingerprinting uniquely identified 120 protein biomarker candidates in the dermis and 71 in the epidermis which were modified as a consequence of photoageing but did not differ significantly in relative abundance (measured by MS1 ion intensity). By applying peptide location fingerprinting to published MS data sets, (identifying biomarker candidates including collagen V and versican in ageing tendon) we demonstrate the potential of the MPLF webtool for biomarker discovery.

© 2021 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.

Keywords: ageing; biomarkers; mass spectrometry; peptide location fingerprinting; photoageing; proteomics; skin; tendon

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