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DIPPER: a spatiotemporal proteomics atlas of human intervertebral discs for exploring ageing and degeneration dynamics
bioRxiv - Systems Biology Pub Date : 2020-11-21 , DOI: 10.1101/2020.07.11.192948
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

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, will be valuable references in the field of IVD biology and proteomic analytics.

中文翻译:

DIPPER:人类椎间盘的时空蛋白质组学图谱,用于探索衰老和变性动力学

椎间盘(IVD)的时空蛋白质组支撑其完整性和功能。我们介绍DIPPER,这是一种深入而全面的IVD蛋白质组学资源,包括来自17个个体的94个全基因组概况。首先,从完整的年轻尸体腰椎IVD的高分辨率空间蛋白质组中获得定义横向和前后轴关键方向趋势的蛋白质模块。他们揭示了监管活动的特定于地区的新颖概况,并显示了在水平和位置匹配的老年尸体椎间盘中潜在的解构路径。机器学习方法预测了一种“水合基质”,它将细胞外基质与MRI强度联系起来。重要的,可以将静态蛋白质组用作点参考,并将其与来自多个临床样品的动态蛋白质组(SILAC /降解组)和转录组数据集成,从而增强鲁棒性和临床相关性。Web界面上可用的数据,发现和方法学将是IVD生物学和蛋白质组学分析领域的宝贵参考。
更新日期:2020-11-22
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