True Path Rule Hierarchical Ensembles for Genome-Wide Gene Function Prediction

摘要

Gene function prediction is a complex computational problem, characterized by several items: the number of functional classes is large, and a gene may belong to multiple classes; functional classes are structured according to a hierarchy; classes are usually unbalanced, with more negative than positive examples; class labels can be uncertain and the annotations largely incomplete; to improve the predictions, multiple sources of data need to be properly integrated. In this contribution, we focus on the first three items, and, in particular, on the development of a new method for the hierarchical genome-wide and ontology-wide gene function prediction. The proposed algorithm is inspired by the ȁC;true path ruleȁD; (TPR) that governs both the Gene Ontology and FunCat taxonomies. According to this rule, the proposed TPR ensemble method is characterized by a two-way asymmetric flow of information that traverses the graph-structured ensemble: positive predictions for a node influence in a recursive way its ancestors, while negative predictions influence its offsprings. Cross-validated results with the model organism S. Crevisiae, using seven different sources of biomolecular data, and a theoretical analysis of the the TPR algorithm show the effectiveness and the drawbacks of the proposed approach.