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Gene Expression Patterns in Trauma Patients: A Systems Biology Approach
Author(s) -
Srinivasan Seshamalini,
Donohue Duncan E.,
Gautam Aarti,
Conroy Amanda S.,
Nelson Mary F.,
Cohen Mitchell J.,
Hammamieh Rasha,
Jett Marti
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1076.6
Subject(s) - coagulopathy , medicine , biomarker , fold change , myocardial infarction , demographics , thrombelastography , odds ratio , bioinformatics , gene expression , gene , biology , coagulation , genetics , demography , sociology
Coagulopathy in trauma patients is associated with a threefold to fivefold increase in mortality. An initial abnormal coagulation profile, as measured by routine clinical tests such as PT and PTT, increases the odds of dying by 35%–326%. (MacLeod et al. 2003). Yet, the current understanding of the mechanisms underlying the development of coagulopathy following severe injury is extremely limited making its prevention and treatment limited. The aim of this study is to use systems biology approaches to integrate multiple data types including clinical findings, various “‐omics” approaches from the onset of the disease to develop a universal picture of the progression of this hemostatic dysfunction. Adult trauma patients were recruited based on previously published inclusion/exclusion criteria. Blood collection was performed every 2–6 hours for the first 24 hours and daily up to 4 days. Comprehensive demographics, injury, treatment and outcome data was prospectively collected. A temporal change in gene expression was studied using whole genome microarrays which probe 50,000 biological features (Agilent Technologies, CA). 79 samples representing 25 patients were processed and analyzed. A comparison of samples from patients with ISS (Injury Severity Score) below the median of 19 (38 samples) vs. those at or above 19 (n=41) showed significantly higher expression (FDR adjusted moderated t‐test p<.05) for DHX58, which is involved in interferon signaling, and lower expression for MIAT, a known biomarker of myocardial infarction, in samples from high ISS patients. Work is ongoing to fully characterize mRNA expression changes in these patients to better understand the contribution of demographic, clinical, and treatment confounds towards identifying molecular targets with potential utility in informing treatment decisions. DISCLAIMER Research was conducted in compliance with IRB approved human subjects protocol #H7462‐25307‐07A. The views, opinions, and/or findings contained in this report are those of the author(s) and should not be construed as official Department of the Army position, policy, or decision, unless so designated by other official documentation.