dissecting inflammatory complications in critically injured patients by within-patient gene expression changes a longitudinal clinical genomics study解剖的重伤患者炎症并发症within-patient纵向临床基因组学研究基因表达的变化.pdfVIP

Dissecting Inflammatory Complications in Critically Injured Patients by Within-Patient Gene Expression Changes: A Longitudinal Clinical Genomics Study 1. 1. 2 3 4 Keyur H. Desai , Chuen Seng Tan , Jeffrey T. Leek , Ronald V. Maier , Ronald G. Tompkins , John D. Storey1,5*, and the Inflammation and the Host Response to Injury Large-Scale Collaborative Research Program 1 Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America, 2 Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America, 3 Department of Surgery, Harborview Medical Center, University of Washington, Seattle, Washington, United States of America, 4 Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America, 5 Department of Molecular Biology, Princeton University, Princeton, New Jersey, United States of America Abstract Background: Trauma is the number one killer of individuals 1–44 y of age in the United States. The prognosis and treatment of inflammatory complications in critically injured patients continue to be challenging, with a history of failed clinical trials and poorly understood biology. New approaches are therefore needed to improve our ability to diagnose and treat this clinical condition. Methods and Findings: We conducted a large-scale study on 168 blunt-force trauma patients over 28 d, measuring ,400 clinical variables and longitudinally profiling leukocyte gene expression with ,800 microarrays. Marshall MOF (multiple organ failure) clinical score trajectories were first utilized to organize the patients into five categories o