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

Adi L. Tarca, Mario Lauria, Michael Unger, Erhan Bilal, Stephanie Boue, Kushal Kumar Dey, Julia Hoeng, Heinz Koeppl, Florian Martin, Pablo Meyer, Preetam Nandy, Raquel Norel, Manuel Peitsch, Jeremy J. Rice, Roberto Romero, Gustavo Stolovitzky, Marja Talikka, Yang Xiang, Christoph Zechner

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2892-2899
Number of pages8
JournalBioinformatics
Volume29
Issue number22
DOIs
StatePublished - Nov 15 2013

ASJC Scopus subject areas

  • Statistics and Probability
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Computational Theory and Mathematics
  • Computational Mathematics

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    Tarca, A. L., Lauria, M., Unger, M., Bilal, E., Boue, S., Dey, K. K., Hoeng, J., Koeppl, H., Martin, F., Meyer, P., Nandy, P., Norel, R., Peitsch, M., Rice, J. J., Romero, R., Stolovitzky, G., Talikka, M., Xiang, Y., & Zechner, C. (2013). Strengths and limitations of microarray-based phenotype prediction: Lessons learned from the IMPROVER Diagnostic Signature Challenge. Bioinformatics, 29(22), 2892-2899. https://doi.org/10.1093/bioinformatics/btt492