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

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.

Precision Medicine and Public Health: New Challenges for Effective and Sustainable Health

“…Precision medicine, also known as personalized or stratified medicine, is an emerging paradigm in disease diagnosis, prevention, and treatment [ 131 , 132 ], aiming at targeted treatments tailored to patient characteristics, which include not only biomarkers, but also individual, social, and economic factors [ 133 ]. This represents a novel strategy to rapidly identify, in a noninvasive way, an altered biology and to discern the pathways in individuals suffering from a disease, thereby guiding the most appropriate therapy [ 134 , 135 ]. The approach has as its cornerstone the recent advances in omics sciences, molecular biology, and bioinformatics that support the evaluation and treatment of disorders, focusing on four main principles: prediction—anticipating the disease occurrence based on risk factors, lifestyles, and social determinants; prevention—delaying the disease’s evolution before the initial manifestations and once it has settled; personalization—adapting the best therapeutic strategy by analyzing genetic, molecular, and individual factors; and participation—involving biomedical research, academic institutions, health professionals, and the patient [ 131 ].…”

The Feasibility of Studying Metabolites in PICU Multi-Organ Dysfunction Syndrome Patients Over an 8-day Course Using An Untargeted Approach

“…After IRB approval, a short-term longitudinal design was adopted at Helen DeVos Children's Hospital (2016-062-SH/HDVCH). Samples were collected under the protocol and study design [10][11][12] in a quaternary-care, urban, pediatric hospital in Western, Michigan. In brief, patients who were identified as having MODS were enrolled, 24 in total, with an additional 4 sedation-control patients.…”

“…We have previously described the current cohort of patients for patient whole blood transcriptomics [10,11], and plasma lipidome [12]. This has revealed a complex biology in a heterogenous patient population with a non-uniform patient response to treatments over an 8-day course (stabilization and recovery phases) of illness during a PICU admission.…”

“…This has revealed a complex biology in a heterogenous patient population with a non-uniform patient response to treatments over an 8-day course (stabilization and recovery phases) of illness during a PICU admission. Complimentary to these previously reported analytic modalities from whole blood [10][11][12], the aim of this current report was two-fold: 1) to characterize total blood plasma metabolites (polar, charged) using an untargeted approach, 2) to determine change in metabolites over an 8-day PICU course. There is a gap in our understanding of the complex interaction between pediatric critical illness, specifically multi-organ dysfunction syndrome (MODS) [13] (affecting twenty percent of PICU admissions [14], resulting in ten times the mortality rate [15]), and their respective blood metabolites.…”

Controlled trials needed to prove efficacy and safety of convalescent plasma therapy in coronavirus disease 2019

“…RNA sequencing has the advantage to tease out unique and complex interplay between the host and virus, moving toward precision medicine. 5 Further advantages of RNA sequencing is the ability to get robust data with a smaller number of patients, allowing for quicker turnaround of actionable data in the midst of a pandemic. Comparing transcriptomic data with serial cytokine profiles and flow cytometry in the setting of a placebo-controlled randomized trial will allow detailed immunologic description of changes likely attributable to convalescent plasma therapy on a cellular level.…”