Methodological approach from the Best Overall Team in the sbv IMPROVER Diagnostic Signature Challenge

The sbv IMPROVER Diagnostic Signature Challenge used crowdsourcing to identify the best methods to classify clinical samples using transcriptomics data. Participating teams used public microarray data sets to develop prediction models in four disease areas, and then made predictions on blinded test data generated by the organizers. Here we describe the approach of the team for the Perinatology Research Branch (Team PRB; AL Tarca, R Romero), that was awarded the best performing entrant prize out of 54 entrants. The key elements of our approach included: (1) selection of training data sets by trial and error; (2) removal of batch effects by pre-processing the test and training data together; (3) the use of statistical significance and magnitude of change to select biomarkers; and (4) optimization of the number of biomarkers via the cross-validated performance of a simple linear discriminant analysis (LDA) model. Not only were our resulting models ranked consistently high, but they also generated parsimonious signatures of as low as two genes, unlike most of the other top-ranked teams that used hundreds of genes for prediction.