DIPPER, a spatiotemporal proteomics atlas of human intervertebral discs for exploring ageing and degeneration dynamics
- The University of Hong Kong, Hong Kong
- University of British Columbia, Canada
- McGill University, Canada
- The University of Hong Kong, China
Abstract
The spatiotemporal proteome of the intervertebral disc (IVD) underpins its integrity and function. We present DIPPER, a deep and comprehensive IVD proteomic resource comprising 94 genome-wide profiles from 17 individuals. To begin with, protein modules defining key directional trends spanning the lateral and anteroposterior axes were derived from high-resolution spatial proteomes of intact young cadaveric lumbar IVDs. They revealed novel region-specific profiles of regulatory activities, and displayed potential paths of deconstruction in the level- and location-matched aged cadaveric discs. Machine learning methods predicted a 'hydration matrisome' that connects extracellular matrix with MRI intensity. Importantly, the static proteome used as point-references can be integrated with dynamic proteome (SILAC/degradome) and transcriptome data from multiple clinical samples, enhancing robustness and clinical relevance. The data, findings and methodology, available on a web interface (www.sbms.hku.hk/dclab/DIPPER), will be valuable references in the field of IVD biology and proteomic analytics.
Data availability
The mass spectrometry proteomics raw data have been deposited to the ProteomeXchange Consortium via the PRIDE repository with the following dataset identifiers for cadaver samples (PXD017774), SILAC samples (PXD018193), and degradome samples (PXD018298000). The RAW data for the transcriptome data has been deposited on NCBI GEO with accession number GSE147383.
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The degradome of the human intervertebral discPRIDE database, PXD018298.
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A proteomic architectural landscape of the healthy and aging human intervertebral discPRIDE database, PXD017740.
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Actively synthesised proteins in human intervertebral discPRIDE database, PXD018193.
Article and author information
Author details
Kathryn Song Eng Cheah
Funding
Research Grants Council, University Grants Committee (E-HKU703/18)
- Danny Chan
Research Grants Council, University Grants Committee (T12-708/12N)
- Kathryn Song Eng Cheah
Research Grants Council, University Grants Committee (AoE/M-04/04)
- Kathryn Song Eng Cheah
Ministry of Science and Technology of the People's Republic of China ((973") (2014CB942900)")
- Danny Chan
Canadian Institutes of Health Research (FDN-148408)
- Christopher M Overall
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Subburaman Mohan, Loma Linda University, United States
Ethics
Human subjects: Ethics Statement: Clinical specimens were obtained with approval by the Institutional Review Board (references UW13-576 and EC 1516-00 11/01/2001) and with informed consent in accordance with the Helsinki Declaration of 1975 (revision 1983)
Version history
- Received: November 16, 2020
- Accepted: December 30, 2020
- Accepted Manuscript published: December 31, 2020 (version 1)
- Accepted Manuscript updated: January 26, 2021 (version 2)
- Version of Record published: February 2, 2021 (version 3)
Copyright
© 2020, Tam et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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DIPPER, a spatiotemporal proteomics atlas of human intervertebral discs for exploring ageing and degeneration dynamics
eLife 9:e64940.
https://doi.org/10.7554/eLife.64940
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