Development of clinical phenotypes and biological profiles via proteomic analysis of trauma patients
Jotaro Tachino,
Hisatake Matsumoto,
Fuminori Sugihara,
Shigeto Seno,
Daisuke Okuzaki,
Tetsuhisa Kitamura,
Sho Komukai,
Yoshiyuki Kido,
Takashi Kojima,
Yuki Togami,
Yusuke Katayama,
Yuko Nakagawa,
Hiroshi Ogura
Affiliations
Jotaro Tachino
Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine
Hisatake Matsumoto
Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine
Fuminori Sugihara
Core Instrumentation Facility, Immunology Frontier Research Center and Research Institute for Microbial Diseases, Osaka University
Shigeto Seno
Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University
Daisuke Okuzaki
Genome Information Research Center, Research Institute for Microbial Disease, Osaka University
Tetsuhisa Kitamura
Division of Environmental Medicine and Population Sciences, Department of Social and Environmental Medicine, Osaka University Graduate School of Medicine
Sho Komukai
Division of Biomedical Statistics, Department of Integrated Medicine, Graduate School of Medicine, Osaka University
Yoshiyuki Kido
Cybermedia Center, Osaka University
Takashi Kojima
Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine
Yuki Togami
Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine
Yusuke Katayama
Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine
Yuko Nakagawa
Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine
Hiroshi Ogura
Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine
Abstract Background Trauma is a heterogeneous condition, and specific clinical phenotypes may identify target populations that could benefit from certain treatment strategies. In this retrospective study, we determined clinical phenotypes and identified new target populations of trauma patients and their treatment strategies. Methods We retrospectively analyzed datasets from the Japan Trauma Data Bank and determined trauma death clinical phenotypes using statistical machine learning techniques and evaluation of biological profiles. Results The analysis included 71,038 blunt trauma patients [median age, 63 (interquartile range [IQR], 40–78) years; 45,479 (64.0%) males; median Injury Severity Score, 13 (IQR, 9–20)], and the derivation and validation cohorts included 42,780 (60.2%) and 28,258 (39.8%) patients, respectively. Of eight derived phenotypes (D-1–D-8), D-8 (n = 2178) had the highest mortality (48.6%) with characteristic severely disturbed consciousness and was further divided into four phenotypes: D-8α, multiple trauma in the young (n = 464); D-8β, head trauma with lower body temperature (n = 178); D-8γ, severe head injury in the elderly (n = 957); and D-8δ, multiple trauma, with higher predicted mortality than actual mortality (n = 579). Phenotype distributions were comparable in the validation cohort. Biological profile analysis of 90 trauma patients revealed that D-8 exhibited excessive inflammation, including enhanced acute inflammatory response, dysregulated complement activation pathways, and impaired coagulation, including downregulated coagulation and platelet degranulation pathways, compared with other phenotypes. Conclusions We identified clinical phenotypes with high mortality, and the evaluation of the molecular pathogenesis underlying these clinical phenotypes suggests that lethal trauma may involve excessive inflammation and coagulation disorders.
