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多维精准医学转录组学工作流程揭示的病毒诱导遗传学,适用于 COVID-19。

Virus-induced genetics revealed by multidimensional precision medicine transcriptional workflow applicable to COVID-19.

机构信息

Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, Michigan.

Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan.

出版信息

Physiol Genomics. 2020 Jun 1;52(6):255-268. doi: 10.1152/physiolgenomics.00045.2020. Epub 2020 May 21.

Abstract

Precision medicine requires the translation of basic biological understanding to medical insights, mainly applied to characterization of each unique patient. In many clinical settings, this requires tools that can be broadly used to identify pathology and risks. Patients often present to the intensive care unit with broad phenotypes, including multiple organ dysfunction syndrome (MODS) resulting from infection, trauma, or other disease processes. Etiology and outcomes are unique to individuals, making it difficult to cohort patients with MODS, but presenting a prime target for testing/developing tools for precision medicine. Using multitime point whole blood (cellular/acellular) total transcriptomics in 27 patients, we highlight the promise of simultaneously mapping viral/bacterial load, cell composition, tissue damage biomarkers, balance between syndromic biology versus environmental response, and unique biological insights in each patient using a single platform measurement. Integration of a transcriptome workflow yielded unexpected insights into the complex interplay between host genetics and viral/bacterial specific mechanisms, highlighted by a unique case of virally induced genetics (VIG) within one of these 27 patients. The power of RNA-Seq to study unique patient biology while investigating environmental contributions can be a critical tool moving forward for translational sciences applied to precision medicine.

摘要

精准医学需要将基础生物学理解转化为医学见解,主要应用于每个独特患者的特征描述。在许多临床环境中,这需要能够广泛用于识别病理和风险的工具。患者经常因感染、创伤或其他疾病过程而以广泛的表型进入重症监护病房,包括多器官功能障碍综合征(MODS)。病因和结果因人而异,使得 MODS 患者难以分组,但为测试/开发精准医学工具提供了主要目标。我们使用 27 名患者的多时间点全血(细胞/无细胞)总转录组学,突出了使用单个平台测量同时映射病毒/细菌载量、细胞组成、组织损伤生物标志物、综合征生物学与环境反应之间平衡以及每个患者独特生物学见解的潜力。转录组学工作流程的整合产生了关于宿主遗传学与病毒/细菌特定机制之间复杂相互作用的意外见解,其中一个 27 名患者中存在病毒诱导遗传学(VIG)的独特案例突出了这一点。RNA-Seq 研究独特患者生物学的同时研究环境贡献的能力可能是推进转化科学应用于精准医学的关键工具。

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