title: Identification and interpretation of longitudinal gene expression changes in trauma.
abstract: BACKGROUND
  The relationship between leukocyte gene expression and recovery of respiratory function after injury may provide information on the etiology of multiple organ dysfunction.
  
  
  OBJECTIVE
  To find a list of genes for which expression after injury predicts respiratory recovery, and to identify which networks and pathways characterize these genes.
  
  
  METHODS
  Blood was sampled at 12 hours and at 1, 4, 7, 21 and 28 days from 147 patients who had been admitted to the hospital after blunt trauma. Leukocyte gene expression was measured using Affymetrix oligonucleotide arrays. A linear model, fit to each probe-set expression value, was used to impute the gene expression trajectory over the entire follow-up period. The proportional hazards model score test was used to calculate the statistical significance of each probe-set trajectory in predicting respiratory recovery. A list of genes was determined such that the expected proportion of false positive results was less than 10%. These genes were compared to the Gene Ontology for 'response to stimulus' and, using Ingenuity software, were mapped into networks and pathways.
  
  
  RESULTS
  The median time to respiratory recovery was 6 days. There were 170 probe-sets representing 135 genes that were found to be related to respiratory recovery. These genes could be mapped to nine networks. Two known pathways that were activated were antigen processing and presentation and JAK-signaling.
  
  
  CONCLUSIONS
  The examination of the relationship of gene expression over time with a patient's clinical course can provide information which may be useful in determining the mechanism of recovery or lack of recovery after severe injury.
authors.affiliation: Pfizer Inc., New York, New York, United States of America. Natasa.Rajicic@pfizer.com
authors.forename: Natasa
authors.initials: N
authors.lastname: Rajicic
authors.forename: Joseph
authors.initials: J
authors.lastname: Cuschieri
authors.forename: Dianne M
authors.initials: DM
authors.lastname: Finkelstein
authors.forename: Carol L
authors.initials: CL
authors.lastname: Miller-Graziano
authors.forename: Douglas
authors.initials: D
authors.lastname: Hayden
authors.forename: Lyle L
authors.initials: LL
authors.lastname: Moldawer
authors.forename: Ernest
authors.initials: E
authors.lastname: Moore
authors.forename: Grant
authors.initials: G
authors.lastname: O'Keefe
authors.forename: Kimberly
authors.initials: K
authors.lastname: Pelik
authors.forename: H Shaw
authors.initials: HS
authors.lastname: Warren
authors.forename: David A
authors.initials: DA
authors.lastname: Schoenfeld
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000209:etiology / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D013997:Time Factors; D014947:Wounds and Injuries / Q000378:metabolism*