Nielson Jessica L, Paquette Jesse, Liu Aiwen W, Guandique Cristian F, Tovar C Amy, Inoue Tomoo, Irvine Karen-Amanda, Gensel John C, Kloke Jennifer, Petrossian Tanya C, Lum Pek Y, Carlsson Gunnar E, Manley Geoffrey T, Young Wise, Beattie Michael S, Bresnahan Jacqueline C, Ferguson Adam R
Department of Neurosurgery, Brain and Spinal Injury Center, University of California, San Francisco, 1001 Potrero Avenue, Building 1, Room 101, San Francisco, California 94143, USA.
Tagb.io, 1 Quartz Way, San Francisco, California 94131, USA.
Nat Commun. 2015 Oct 14;6:8581. doi: 10.1038/ncomms9581.
Data-driven discovery in complex neurological disorders has potential to extract meaningful syndromic knowledge from large, heterogeneous data sets to enhance potential for precision medicine. Here we describe the application of topological data analysis (TDA) for data-driven discovery in preclinical traumatic brain injury (TBI) and spinal cord injury (SCI) data sets mined from the Visualized Syndromic Information and Outcomes for Neurotrauma-SCI (VISION-SCI) repository. Through direct visualization of inter-related histopathological, functional and health outcomes, TDA detected novel patterns across the syndromic network, uncovering interactions between SCI and co-occurring TBI, as well as detrimental drug effects in unpublished multicentre preclinical drug trial data in SCI. TDA also revealed that perioperative hypertension predicted long-term recovery better than any tested drug after thoracic SCI in rats. TDA-based data-driven discovery has great potential application for decision-support for basic research and clinical problems such as outcome assessment, neurocritical care, treatment planning and rapid, precision-diagnosis.
在复杂的神经系统疾病中,数据驱动的发现有潜力从大型、异质性数据集中提取有意义的综合征知识,以提高精准医学的潜力。在此,我们描述了拓扑数据分析(TDA)在从神经创伤-脊髓损伤可视化综合征信息与结果(VISION-SCI)存储库挖掘的临床前创伤性脑损伤(TBI)和脊髓损伤(SCI)数据集中进行数据驱动发现的应用。通过对相互关联的组织病理学、功能和健康结果的直接可视化,TDA在综合征网络中检测到了新的模式,揭示了SCI与同时发生的TBI之间的相互作用,以及未发表的多中心临床前SCI药物试验数据中的有害药物效应。TDA还表明,围手术期高血压比大鼠胸段SCI后任何测试药物都能更好地预测长期恢复情况。基于TDA的数据驱动发现对于基础研究和临床问题(如结果评估、神经重症监护、治疗规划和快速精准诊断)的决策支持具有巨大的潜在应用价值。