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Virus-induced genetics revealed by multidimensional precision medicine transcriptional workflow applicable to COVID-19.
Physiological Genomics ( IF 2.5 ) Pub Date : 2020-05-21 , DOI: 10.1152/physiolgenomics.00045.2020
Jeremy W Prokop 1, 2 , Rama Shankar 1, 2 , Ruchir Gupta 1, 2 , Mara L Leimanis 1, 3 , Derek Nedveck 4 , Katie Uhl 1, 2 , Bin Chen 1, 2 , Nicholas L Hartog 1, 5, 6 , Jason Van Veen 1, 7 , Joshua S Sisco 1, 7 , Olivia Sirpilla 1, 8 , Todd Lydic 9 , Brian Boville 3 , Angel Hernandez 10 , Chi Braunreiter 1, 11 , ChiuYing Cynthia Kuk 1 , Varinder Singh 1, 12 , Joshua Mills 1, 7 , Marc Wegener 13 , Marie Adams 13 , Mary Rhodes 13 , Andre S Bachmann 1 , Wenjing Pan 14 , Miranda L Byrne-Steele 14 , D Casey Smith 14 , Mollye Depinet 14 , Brittany E Brown 14 , Mary Eisenhower 14 , Jian Han 14, 15 , Marcus Haw 16 , Casey Madura 10 , Dominic J Sanfilippo 1, 3 , Laurie H Seaver 1, 17 , Caleb Bupp 1, 17 , Surender Rajasekaran 1, 3, 4
Affiliation  

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.

中文翻译:


适用于 COVID-19 的多维精准医学转录工作流程揭示了病毒诱导的遗传学。



精准医学需要将基本的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,这需要可广泛用于识别病理和风险的工具。重症监护病房的患者通常表现出多种表型,包括由感染、创伤或其他疾病过程引起的多器官功能障碍综合征 (MODS)。病因和结果因人而异,因此很难对 MODS 患者进行分组,但却是测试/开发精准医疗工具的主要目标。在 27 名患者中使用多时间点全血(细胞/非细胞)总转录组学,我们强调了同时绘制病毒/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的平衡以及每位患者独特的生物学见解的前景。使用单一平台测量。转录组工作流程的整合对宿主遗传学和病毒/细菌特异性机制之间复杂的相互作用产生了意想不到的见解,这通过这 27 名患者之一的病毒诱导遗传学 (VIG) 的独特案例得到了强调。 RNA-Seq 能够研究独特的患者生物学,同时调查环境影响,这可能是推动转化科学应用于精准医学的关键工具。
更新日期:2020-05-21
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