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bioRxiv · 10.1101/2020.07.11.192948

The spatial proteome of the human intervertebral disc reveals architectural changes in health, ageing and degeneration

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 SE Cheah·Danny Chan
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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 genomewide 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, will be valuable references in the field of IVD biology and proteomic analytics.

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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 SE Cheah, Danny Chan. 2020-07-12. The spatial proteome of the human intervertebral disc reveals architectural changes in health, ageing and degeneration. https://doi.org/10.1101/2020.07.11.192948

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