title: Familial and sporadic idiopathic pulmonary fibrosis: making the diagnosis from peripheral blood.
abstract: BACKGROUND
  Peripheral blood biomarkers might improve diagnostic accuracy for idiopathic pulmonary fibrosis (IPF).
  
  
  RESULTS
  Gene expression profiles were obtained from 89 patients with IPF and 26 normal controls. Samples were stratified according to severity of disease based on pulmonary function. The stratified dataset was split into subsets; two-thirds of the samples were selected to comprise the training set, while one-third was reserved for the validation set. Bayesian probit regression was used on the training set to develop a gene expression model for IPF versus normal. The gene expression model was tested by using it on the validation set to perform class prediction. Unsupervised clustering failed to discriminate between samples of different severity. Therefore, samples of all severities were included in the training and validation sets, in equal proportions. A gene signature model was developed from the training set. The model was built in an iterative fashion with the number of gene features selected to minimize the misclassification error in cross validation. The final model was based on the top 108 discriminating genes in the training set. The signature was successfully applied to the validation set, ROC area under the curve = 0.893, p < 0.0001. Using the optimal threshold (0.74) accurate class predictions were made for 77% of the test cases with sensitivity = 0.70, specificity = 1.00.
  
  
  CONCLUSIONS
  By using Bayesian probit regression to develop a model, we show that it is entirely possible to make a diagnosis of IPF from the peripheral blood with gene signatures.
authors.forename: Eric B
authors.initials: EB
authors.lastname: Meltzer
authors.forename: William T
authors.initials: WT
authors.lastname: Barry
authors.forename: Ivana V
authors.initials: IV
authors.lastname: Yang
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Brown
authors.forename: Marvin I
authors.initials: MI
authors.lastname: Schwarz
authors.forename: Hamish
authors.initials: H
authors.lastname: Patel
authors.forename: Allison
authors.initials: A
authors.lastname: Ashley
authors.forename: Paul W
authors.initials: PW
authors.lastname: Noble
authors.forename: David A
authors.initials: DA
authors.lastname: Schwartz
authors.affiliation: Division of Allergy, Pulmonary, and Critical Care, Vanderbilt University Medical Center, 1313 21st Avenue South, 1105 Oxford House, Nashville, TN, USA. mark.p.steele@vanderbilt.edu.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Steele
mesh_terms: D000368:Aged; D001773:Blood Cells / Q000378:metabolism; D016022:Case-Control Studies; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D015203:Reproducibility of Results; D012720:Severity of Illness Index