A fast ranking algorithm for predicting gene functions in biomolecular networks

Ranking genes in functional networks according to a specific biological function is a challenging task raising relevant performance and computational complexity problems. To cope with both these problems we developed a transductive gene ranking method based on kernelized score functions able to fully exploit the topology and the graph structure of biomolecular networks and to capture significant functional relationships between genes. We run the method on a network constructed by integrating multiple biomolecular data sources in the yeast model organism, achieving significantly better results than the compared state-of-the-art network-based algorithms for gene function prediction, and with relevant savings in computational time. The proposed approach is general and fast enough to be in perspective applied to other relevant node ranking problems in large and complex biological networks

Large Scale Ranking and Repositioning of Drugs with Respect to DrugBank Therapeutic Categories

The ranking and prediction of novel therapeutic categories for existing drugs (drug repositioning) is a challenging computational problem involving the analysis of complex chemical and biological networks. In this context we propose a novel semi-supervised learning problem: ranking drugs in integrated bio-chemical networks according to specific DrugBank therapeutic categories. To deal with this challenging problem, we designed a general framework based on bipartite network projections by which homogeneous pharmacological networks can be combined and integrated from heterogeneous and complementary sources of chemical, biomolecular and clinical information. Moreover, we propose a novel method based on kernelized score functions for fast and effective drug ranking in the integrated pharmacological space. Results with 51 therapeutic DrugBank categories involving about 1300 FDA approved drugs show the effectiveness of the proposed approach

Network-based drug ranking and repositioning with respect to DrugBank therapeutic categories

Drug repositioning is a challenging computational problem involving the integration of heterogeneous sources of biomolecular data and the design of label ranking algorithms able to exploit the overall topology of the underlying pharmacological network. In this context, we propose a novel semisupervised drug ranking problem: prioritizing drugs in integrated biochemical networks according to specific DrugBank therapeutic categories. Algorithms for drug repositioning usually perform the inference step into an inhomogeneous similarity space induced by the relationships existing between drugs and a second type of entity (e.g., disease, target, ligand set), thus making unfeasible a drug ranking within a homogeneous pharmacological space. To deal with this problem, we designed a general framework based on bipartite network projections by which homogeneous pharmacological networks can be constructed and integrated from heterogeneous and complementary sources of chemical, biomolecular and clinical information. Moreover, we present a novel algorithmic scheme based on kernelized score functions that adopts both local and global learning strategies to effectively rank drugs in the integrated pharmacological space using different network combination methods. Detailed experiments with more than 80 DrugBank therapeutic categories involving about 1,300 FDA-approved drugs show the effectiveness of the proposed approach

Hierarchical ensemble methods for protein function prediction

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 \u201cflat\u201d 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 \u201cconsensus\u201d 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