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Strengths and limitations of microarray-based phenotype prediction: lessons learned from the IMPROVER Diagnostic Signature Challenge.

Author(s):

Mario Lauria, Adi L. Tarca, M. Unger, Erhan Bilal, Stephanie Boue, Kushal K. Dey, Julia Hoeng, H. Koeppl, Florian Martin, Pablo Meyer, P. Nandy, Raquel Norel, Manuel Peitsch, Jeremy J. Rice, Roberto Romero, Marja Talikka, Yang Xiang, C. Zechner, Gustavo Stolovitzky
Conference/Journal:

Oxford, England, Bioinformatics, vol. 29, no. 22, pp. 2892-9
Abstract:

MOTIVATION: After more than a decade since microarrays were used to predict phenotype of biological samples, real-life applications for disease screening and identification of patients who would best benefit from treatment are still emerging. The interest of the scientific community in identifying best approaches to develop such prediction models was reaffirmed in a competition style international collaboration called IMPROVER Diagnostic Signature Challenge whose results we describe herein. RESULTS: Fifty-four teams used public data to develop prediction models in four disease areas including multiple sclerosis, lung cancer, psoriasis and chronic obstructive pulmonary disease, and made predictions on blinded new data that we generated. Teams were scored using three metrics that captured various aspects of the quality of predictions, and best performers were awarded. This article presents the challenge results and introduces to the community the approaches of the best overall three performers, as well as an R package that implements the approach of the best overall team. The analyses of model performance data submitted in the challenge as well as additional simulations that we have performed revealed that (i) the quality of predictions depends more on the disease endpoint than on the particular approaches used in the challenge; (ii) the most important modeling factor (e.g. data preprocessing, feature selection and classifier type) is problem dependent; and (iii) for optimal results datasets and methods have to be carefully matched. Biomedical factors such as the disease severity and confidence in diagnostic were found to be associated with the misclassification rates across the different teams. AVAILABILITY: The lung cancer dataset is available from Gene Expression Omnibus (accession, GSE43580). The maPredictDSC R package implementing the approach of the best overall team is available at www.bioconductor.org or http://bioinformaticsprb.med.wayne.edu/.

Year:

2013
Type of Publication:

(01)Article
Supervisor:



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% Autogenerated BibTeX entry
@Article { LauEtal:2013:IFA_4621,
    author={Mario Lauria and Adi L. Tarca and M. Unger and Erhan Bilal and Stephanie Boue and Kushal K. Dey and Julia Hoeng and H. Koeppl and Florian Martin and Pablo Meyer and P. Nandy and Raquel Norel and Manuel
	  Peitsch and Jeremy J. Rice and Roberto Romero and Marja Talikka and Yang Xiang and C. Zechner and Gustavo Stolovitzky},
    title={{Strengths and limitations of microarray-based phenotype
	  prediction: lessons learned from the IMPROVER Diagnostic
	  Signature Challenge.}},
    journal={Bioinformatics},
    year={2013},
    volume={29},
    number={22},
    pages={2892--9},
    month=aug,
    url={http://control.ee.ethz.ch/index.cgi?page=publications;action=details;id=4621}
}
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