Journal Article

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

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

2021

Overview

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. Peptide location fingerprinting is a proteomic mass spectrometry tool capable of detecting localised statistically significant changes in peptide yield along the structures of proteins in complex, whole tissue lysates. In this study, peptide location fingerprinting revealed novel biomarker candidates of skin photoageing undetectable by conventional relative quantification.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Aged / ageing / Aging / Analysis / Biomarkers / Biomarkers - chemistry / Care and treatment / Chromatography, Liquid / Collagen / Dermis / Epidermis / Extracellular matrix / Extracellular Matrix - chemistry / Gene expression / Hemidesmosomes - chemistry / Homeostasis / Humans / Identification / Integrins / Keratins - metabolism / Mass spectrometry / Mass spectroscopy / Middle Aged / Original / peptide location fingerprinting / Peptide mapping / Peptide Mapping - methods / Peptides / Peptides - analysis / photoageing / Principal components analysis / Protein Biosynthesis / Protein folding / Proteins / Proteoglycans / Proteome - chemistry / proteomics / Proteomics - methods / Regions / Ribosomal proteins / Scientific imaging / Skin / Skin - chemistry / Skin Aging - radiation effects / Software / Statistical analysis / Tandem Mass Spectrometry / tendon / Versican