Systematic Molecular Phenotyping: A Path Toward Precision Emergency Medicine?

Abstract

Precision medicine is an emerging approach to disease treatment and prevention that considers variability in patient genes, environment, and lifestyle. However, little has been written about how such research impacts emergency care. Recent advances in analytical techniques have made it possible to characterize patients in a more comprehensive and sophisticated fashion at the molecular level, promising highly individualized diagnosis and treatment. Among these techniques are various systematic molecular phenotyping analyses (e.g., genomics, transcriptomics, proteomics, and metabolomics). Although a number of emergency physicians use such techniques in their research, widespread discussion of these approaches has been lacking in the emergency care literature and many emergency physicians may be unfamiliar with them. In this article, we briefly review the underpinnings of such studies, note how they already impact acute care, discuss areas in which they might soon be applied, and identify challenges in translation to the emergency department (ED). While such techniques hold much promise, it is unclear whether the obstacles to translating their findings to the ED will be overcome in the near future. Such obstacles include validation, cost, turnaround time, user interface, decision support, standardization, and adoption by end-users.

Figure 1

Reproduced with permission from Skibsted et al. Crit Care 2013; 17: 231 and adapted. Numbers denote targets within cellular processes for different systems biology approaches: 1, Genetic analysis and Single Nucleotide Polymorphisms (SNPs) and 2, epigenomics (methylation variable positions) 3, transcriptomics (mRNA); 4, proteomics; and 5, metabolomics; 6, pharmaco-(genomics/metabolomics/proteomics).

Figure 2. A Model for Incorporating Systematic Molecular Phenotyping into Emergency Care

There are multiple potential sources for baseline systematic molecular phenotyping data to be entered into an acute care patient’s electronic health record. During the visit itself, clinical data can be combined with this data to help provide complex decision support. In the future, with more rapid turnaround times, systematic molecular phenotyping might be performed primarily in the ED and incorporated into such systems. Alternatively, patients may arrive with portably stored systematic molecular phenotyping data, or targeted testing of genotypes might be posited based on the patient’s clinical scenario. The results of any testing done in the acute care setting would be retained for future visits, or a patient might have systematic molecular phenotyping done as part of an ED-based public health intervention and stored for future use.

Figure 3

Reproduced from www.genome.gov/sequencingcosts. Direct costs associated with DNA sequencing as reported by the National Human Genome Research Institute’s Genome Sequencing Program. To illustrate the nature of the reductions in costs, this graph shows hypothetical data reflecting Moore's Law, which describes a long-term trend in the computer hardware industry that involves the doubling of 'compute power' every two years. If the costs per genome were to follow Moore’s Law going forward, the cost per genome in the year 2022 would be approximately $100.