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A generic method for assignment of reliability scores applied to solvent accessibility predictions

Bent Petersen1, Thomas Nordahl Petersen1, Pernille Andersen12, Morten Nielsen1 and Claus Lundegaard1*

Author affiliations

1 Center for Biological Sequence Analysis – CBS, Department of Systems Biology, Kemitorvet 208, Technical University of Denmark – DTU, DK-2800 Lyngby, Denmark

2 Centre for Medical Parasitology – CMP, CSS Building 22, University of Copenhagen, DK-1014 Copenhagen, Denmark

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Citation and License

BMC Structural Biology 2009, 9:51  doi:10.1186/1472-6807-9-51

Published: 31 July 2009



Estimation of the reliability of specific real value predictions is nontrivial and the efficacy of this is often questionable. It is important to know if you can trust a given prediction and therefore the best methods associate a prediction with a reliability score or index. For discrete qualitative predictions, the reliability is conventionally estimated as the difference between output scores of selected classes. Such an approach is not feasible for methods that predict a biological feature as a single real value rather than a classification. As a solution to this challenge, we have implemented a method that predicts the relative surface accessibility of an amino acid and simultaneously predicts the reliability for each prediction, in the form of a Z-score.


An ensemble of artificial neural networks has been trained on a set of experimentally solved protein structures to predict the relative exposure of the amino acids. The method assigns a reliability score to each surface accessibility prediction as an inherent part of the training process. This is in contrast to the most commonly used procedures where reliabilities are obtained by post-processing the output.


The performance of the neural networks was evaluated on a commonly used set of sequences known as the CB513 set. An overall Pearson's correlation coefficient of 0.72 was obtained, which is comparable to the performance of the currently best public available method, Real-SPINE. Both methods associate a reliability score with the individual predictions. However, our implementation of reliability scores in the form of a Z-score is shown to be the more informative measure for discriminating good predictions from bad ones in the entire range from completely buried to fully exposed amino acids. This is evident when comparing the Pearson's correlation coefficient for the upper 20% of predictions sorted according to reliability. For this subset, values of 0.79 and 0.74 are obtained using our and the compared method, respectively. This tendency is true for any selected subset.