Figure 3 describes the process by which the informatics core selects constituent information from core data sources, and links in together in a deidentified IRB approved research database for complex statistical analysis.click to view
Our long-term vision is to foster hypothesis-based and translational research around the human metabolic/physiologic response to injury and/or critical illness. The purpose is three-fold: to improve understanding of biologic processes after trauma or critical illness; to foster translational research, bringing the bench to the bedside; and, to encourage interaction and communication within the Institution and throughout the trauma community.
Our Genetics and Computation Core is supported by NIH and DOD funding. We postulate that the routine identification of the stress genotype, coupled with covariates of the stress environment (shock, injury severity, comorbidities) and identification of the stress phenotype, will allow the introduction of strategies that personalize therapy and improve outcome. Our conceptual framework is:
Classically, phenotype is defined as observable characteristics (demographic, anatomic and behavioral) which result from the expression of an individual's genotype. We believe that host factors, in general, and genetic factors, in particular, are under-appreciated components of injury outcome. The population contains genetic variations (polymorphisms) which, under normal circumstances, are masked. They are not pathologic and have no impact on an organism's ability to function in non-stress states. In the stress state, such as multisystem trauma, these polymorphisms are exposed and result in differing outcomes among patients. We call this concept 'the stress genotype'.
In conjunction with the Division of Trauma Orthopedics, we have funding to look at the problem of heterotopic ossification, a complication which has close to a 60% penetration rate in military casualties with high velocity blast injury. Using the paradigm outlined above the equation become simple:
Over the past decade, advances in genetic technology have been applied to many disciplines in medicine. In trauma, the process is difficult because the disease is common and the phenotype, and its interaction with the stress environment, is profoundly complex. We hypothesize that a few critical pathways largely determine the host response following trauma. Variation in the genetic composition of these critical pathways (the stress genotype) affects their function, alters the stress response and can dramatically affect patient outcome (stress phenotype).
The stress environment is highly variable; introducing numerous confounders to the genetic signal. These confounders are both patient-based (age, injury characteristics, concomitant injuries and co-morbidities, and differences in therapy - pharmacologic and surgical) and system-based (quality of care and clinical variation inherent to the practice of individual physicians). Practice variability in our Trauma Center is obviated by a care delivery structure that aggregates trauma patients in the hands of a small number of physicians practicing under standardized evidence-based protocols.
To ensure the integrity of the genetic signal, one must confront the challenges of simultaneously measuring the confounders of the stress environment and the stress phenotype. The solution requires a robust information management system capable of dense data collection on individual patients and the aggregation of this data to populations of patients. Our existing research Core infrastructure was developed to achieve just this goal.