Center for Genomic Medicine, Massachusetts General Hospital, 185 Cambridge Street, CPZN 6818, Boston, MA, 02114, USA.
Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
Neurotherapeutics. 2020 Apr;17(2):563-580. doi: 10.1007/s13311-020-00838-1.
Translational genomics represents a broad field of study that combines genome and transcriptome-wide studies in humans and model systems to refine our understanding of human biology and ultimately identify new ways to treat and prevent disease. The approaches to translational genomics can be broadly grouped into two methodologies, forward and reverse genomic translation. Traditional (forward) genomic translation begins with model systems and aims at using unbiased genetic associations in these models to derive insight into biological mechanisms that may also be relevant in human disease. Reverse genomic translation begins with observations made through human genomic studies and refines these observations through follow-up studies using model systems. The ultimate goal of these approaches is to clarify intervenable processes as targets for therapeutic development. In this review, we describe some of the approaches being taken to apply translational genomics to the study of diseases commonly encountered in the neurocritical care setting, including hemorrhagic and ischemic stroke, traumatic brain injury, subarachnoid hemorrhage, and status epilepticus, utilizing both forward and reverse genomic translational techniques. Further, we highlight approaches in the field that could be applied in neurocritical care to improve our ability to identify new treatment modalities as well as to provide important information to patients about risk and prognosis.
转化基因组学代表了一个广泛的研究领域，它将人类和模型系统中的基因组和转录组进行全面研究，以深化我们对人类生物学的理解，并最终确定治疗和预防疾病的新方法。转化基因组学的方法可以大致分为两种方法，正向和反向基因组翻译。传统的（正向）基因组翻译从模型系统开始，旨在利用这些模型中的无偏遗传关联来深入了解可能与人类疾病相关的生物学机制。反向基因组翻译从人类基因组研究中的观察结果开始，并通过使用模型系统进行后续研究来改进这些观察结果。这些方法的最终目标是阐明可干预的过程作为治疗开发的目标。在这篇综述中，我们描述了一些将转化基因组学应用于神经危重症常见疾病研究的方法，包括出血性和缺血性中风、创伤性脑损伤、蛛网膜下腔出血和癫痫持续状态，同时利用正向和反向基因组转化技术。此外，我们强调了该领域中可以应用于神经危重症的方法，以提高我们识别新治疗模式的能力，并为患者提供有关风险和预后的重要信息。
