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Familial and sporadic idiopathic pulmonary fibrosis: making the diagnosis from peripheral blood.

Publication ,  Journal Article
Meltzer, EB; Barry, WT; Yang, IV; Brown, KK; Schwarz, MI; Patel, H; Ashley, A; Noble, PW; Schwartz, DA; Steele, MP
Published in: BMC Genomics
October 16, 2014

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.

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Published In

BMC Genomics

DOI

EISSN

1471-2164

Publication Date

October 16, 2014

Volume

15

Issue

1

Start / End Page

902

Location

England

Related Subject Headings

  • Severity of Illness Index
  • Reproducibility of Results
  • ROC Curve
  • Middle Aged
  • Male
  • Idiopathic Pulmonary Fibrosis
  • Humans
  • Gene Expression Profiling
  • Female
  • Cluster Analysis
 

Citation

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Meltzer, E. B., Barry, W. T., Yang, I. V., Brown, K. K., Schwarz, M. I., Patel, H., … Steele, M. P. (2014). Familial and sporadic idiopathic pulmonary fibrosis: making the diagnosis from peripheral blood. BMC Genomics, 15(1), 902. https://doi.org/10.1186/1471-2164-15-902
Meltzer, Eric B., William T. Barry, Ivana V. Yang, Kevin K. Brown, Marvin I. Schwarz, Hamish Patel, Allison Ashley, Paul W. Noble, David A. Schwartz, and Mark P. Steele. “Familial and sporadic idiopathic pulmonary fibrosis: making the diagnosis from peripheral blood.BMC Genomics 15, no. 1 (October 16, 2014): 902. https://doi.org/10.1186/1471-2164-15-902.
Meltzer EB, Barry WT, Yang IV, Brown KK, Schwarz MI, Patel H, et al. Familial and sporadic idiopathic pulmonary fibrosis: making the diagnosis from peripheral blood. BMC Genomics. 2014 Oct 16;15(1):902.
Meltzer, Eric B., et al. “Familial and sporadic idiopathic pulmonary fibrosis: making the diagnosis from peripheral blood.BMC Genomics, vol. 15, no. 1, Oct. 2014, p. 902. Pubmed, doi:10.1186/1471-2164-15-902.
Meltzer EB, Barry WT, Yang IV, Brown KK, Schwarz MI, Patel H, Ashley A, Noble PW, Schwartz DA, Steele MP. Familial and sporadic idiopathic pulmonary fibrosis: making the diagnosis from peripheral blood. BMC Genomics. 2014 Oct 16;15(1):902.
Journal cover image

Published In

BMC Genomics

DOI

EISSN

1471-2164

Publication Date

October 16, 2014

Volume

15

Issue

1

Start / End Page

902

Location

England

Related Subject Headings

  • Severity of Illness Index
  • Reproducibility of Results
  • ROC Curve
  • Middle Aged
  • Male
  • Idiopathic Pulmonary Fibrosis
  • Humans
  • Gene Expression Profiling
  • Female
  • Cluster Analysis