Table of Contents
ISRN Bioinformatics
Volume 2014 (2014), Article ID 901419, 34 pages
Review Article

Hierarchical Ensemble Methods for Protein Function Prediction

AnacletoLab-Dipartimento di Informatica, Università degli Studi di Milano, Via Comelico 39, 20135 Milano, Italy

Received 2 February 2014; Accepted 25 February 2014; Published 5 May 2014

Academic Editors: T. Can and T. R. Hvidsten

Copyright © 2014 Giorgio Valentini. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Protein function prediction is a complex multiclass multilabel classification problem, characterized by multiple issues such as the incompleteness of the available annotations, the integration of multiple sources of high dimensional biomolecular data, the unbalance of several functional classes, and the difficulty of univocally determining negative examples. Moreover, the hierarchical relationships between functional classes that characterize both the Gene Ontology and FunCat taxonomies motivate the development of hierarchy-aware prediction methods that showed significantly better performances than hierarchical-unaware “flat” prediction methods. In this paper, we provide a comprehensive review of hierarchical methods for protein function prediction based on ensembles of learning machines. According to this general approach, a separate learning machine is trained to learn a specific functional term and then the resulting predictions are assembled in a “consensus” ensemble decision, taking into account the hierarchical relationships between classes. The main hierarchical ensemble methods proposed in the literature are discussed in the context of existing computational methods for protein function prediction, highlighting their characteristics, advantages, and limitations. Open problems of this exciting research area of computational biology are finally considered, outlining novel perspectives for future research.