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This article is part of the supplement: SNP-SIG 2011: Identification and annotation of SNPs in the context of structure, function and disease

Open Access Proceedings

How to evaluate performance of prediction methods? Measures and their interpretation in variation effect analysis

Mauno Vihinen

Author Affiliations

Institute of Biomedical Technology, FI-33014 University of Tampere, Finland

BioMediTech, Tampere, Finland

Department of Experimental Medical Science, Lund University, SE-221 84 Lund, Sweden

BMC Genomics 2012, 13(Suppl 4):S2  doi:10.1186/1471-2164-13-S4-S2

Published: 18 June 2012

Abstract

Background

Prediction methods are increasingly used in biosciences to forecast diverse features and characteristics. Binary two-state classifiers are the most common applications. They are usually based on machine learning approaches. For the end user it is often problematic to evaluate the true performance and applicability of computational tools as some knowledge about computer science and statistics would be needed.

Results

Instructions are given on how to interpret and compare method evaluation results. For systematic method performance analysis is needed established benchmark datasets which contain cases with known outcome, and suitable evaluation measures. The criteria for benchmark datasets are discussed along with their implementation in VariBench, benchmark database for variations. There is no single measure that alone could describe all the aspects of method performance. Predictions of genetic variation effects on DNA, RNA and protein level are important as information about variants can be produced much faster than their disease relevance can be experimentally verified. Therefore numerous prediction tools have been developed, however, systematic analyses of their performance and comparison have just started to emerge.

Conclusions

The end users of prediction tools should be able to understand how evaluation is done and how to interpret the results. Six main performance evaluation measures are introduced. These include sensitivity, specificity, positive predictive value, negative predictive value, accuracy and Matthews correlation coefficient. Together with receiver operating characteristics (ROC) analysis they provide a good picture about the performance of methods and allow their objective and quantitative comparison. A checklist of items to look at is provided. Comparisons of methods for missense variant tolerance, protein stability changes due to amino acid substitutions, and effects of variations on mRNA splicing are presented.