Contact map prediction using a large-scale ensemble of rule sets and the fusion of multiple predicted structural features

Abstract

Motivation: The prediction of a protein’s contact map has become in recent years, a crucial stepping stone for the prediction of the com-plete 3D structure of a protein. In this article, we describe a method-ology for this problem that was shown to be successful in CASP8 and CASP9. The methodology is based on (i) the fusion of the prediction of a variety of structural aspects of protein residues, (ii) an ensemble strategy used to facilitate the training process and (iii) a rule-based machine learning system from which we can extract human-readable explanations of the predictor and derive useful information about the contact map representation. Results: The main part of the evaluation is the comparison against the sequence-based contact prediction methods from CASP9, where our method presented the best rank in five out of the six evaluated met-rics. We also assess the impact of the size of the ensemble used in our predictor to show the trade-off between performance and training time of our method. Finally, we also study the rule sets generated by our machine learning system. From this analysis, we are able to estimate the contribution of the attributes in our representation and how these interact to derive contact predictions