eLife (Dec 2020)

DIPPER, a spatiotemporal proteomics atlas of human intervertebral discs for exploring ageing and degeneration dynamics

  • Vivian Tam,
  • Peikai Chen,
  • Anita Yee,
  • Nestor Solis,
  • Theo Klein,
  • Mateusz Kudelko,
  • Rakesh Sharma,
  • Wilson CW Chan,
  • Christopher M Overall,
  • Lisbet Haglund,
  • Pak C Sham,
  • Kathryn Song Eng Cheah,
  • Danny Chan

DOI
https://doi.org/10.7554/eLife.64940
Journal volume & issue
Vol. 9

Abstract

Read online

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 (http://www.sbms.hku.hk/dclab/DIPPER/), will be valuable references in the field of IVD biology and proteomic analytics.

Keywords