DIPPER, a spatiotemporal proteomics atlas of human intervertebral discs for exploring ageing and degeneration dynamics.
Vivian TamPeikai ChenAnita YeeNestor SolisTheo KleinMateusz KudelkoRakesh SharmaWilson Cw ChanChristopher M OverallLisbet HaglundPak C ShamKathryn Song Eng CheahDanny ChanPublished in: eLife (2020)
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.
Keyphrases
- extracellular matrix
- big data
- genome wide
- machine learning
- single cell
- high resolution
- label free
- electronic health record
- minimally invasive
- endothelial cells
- mass spectrometry
- dna methylation
- artificial intelligence
- rna seq
- ultrasound guided
- magnetic resonance imaging
- gene expression
- transcription factor
- high intensity
- induced pluripotent stem cells
- protein protein
- middle aged
- data analysis
- pluripotent stem cells
- human health
- high glucose
- risk assessment
- diffusion weighted imaging
- liquid chromatography