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

Prokop, Jeremy W.; Shankar, Rama; Gupta, Ruchir; Leimanis, Mara L.; Nedveck, Derek; Uhl, Katie; Chen, Bin; Hartog, Nicholas L.; Van Veen, Jason; Sisco, Joshua S.; Sirpilla, Olivia; Lydic, Todd; Boville, Brian; Hernandez, Angel; Braunreiter, Chi; Kuk, ChiuYing Cynthia; Singh, Varinder; Mills, Joshua; Wegener, Marc; Adams, Marie; Rhodes, Mary; Bachmann, Andre S.; Pan, Wenjing; Byrne-Steele, Miranda L.; Smith, D. Casey; Depinet, Mollye; Brown, Brittany E.; Eisenhower, Mary; Han, Jian; Haw, Marcus; Madura, Casey; Sanfilippo, Dominic J.; Seaver, Laurie H.; Bupp, Caleb; Rajasekaran, Surender

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.