Integration of relational and hierarchical network information for protein function prediction

BACKGROUND:In the current climate of high-throughput computational biology, the inference of a protein's function from related measurements, such as protein-protein interaction relations, has become a canonical task. Most existing technologies pursue this task as a classification problem, on a term-by-term basis, for each term in a database, such as the Gene Ontology (GO) database, a popular rigorous vocabulary for biological functions. However, ontology structures are essentially hierarchies, with certain top to bottom annotation rules which protein function predictions should in principle follow. Currently, the most common approach to imposing these hierarchical constraints on network-based classifiers is through the use of transitive closure to predictions.RESULTS:We propose a probabilistic framework to integrate information in relational data, in the form of a protein-protein interaction network, and a hierarchically structured database of terms, in the form of the GO database, for the purpose of protein function prediction. At the heart of our framework is a factorization of local neighborhood information in the protein-protein interaction network across successive ancestral terms in the GO hierarchy. We introduce a classifier within this framework, with computationally efficient implementation, that produces GO-term predictions that naturally obey a hierarchical 'true-path' consistency from root to leaves, without the need for further post-processing.CONCLUSION:A cross-validation study, using data from the yeast Saccharomyces cerevisiae, shows our method offers substantial improvements over both standard 'guilt-by-association' (i.e., Nearest-Neighbor) and more refined Markov random field methods, whether in their original form or when post-processed to artificially impose 'true-path' consistency. Further analysis of the results indicates that these improvements are associated with increased predictive capabilities (i.e., increased positive predictive value), and that this increase is consistent uniformly with GO-term depth. Additional in silico validation on a collection of new annotations recently added to GO confirms the advantages suggested by the cross-validation study. Taken as a whole, our results show that a hierarchical approach to network-based protein function prediction, that exploits the ontological structure of protein annotation databases in a principled manner, can offer substantial advantages over the successive application of 'flat' network-based methods.

Authenticated Index Structures for Aggregation Queries in Outsourced Databases

In an outsourced database system the data owner publishes information through a number of remote, untrusted servers with the goal of enabling clients to access and query the data more efficiently. As clients cannot trust servers, query authentication is an essential component in any outsourced database system. Clients should be given the capability to verify that the answers provided by the servers are correct with respect to the actual data published by the owner. While existing work provides authentication techniques for selection and projection queries, there is a lack of techniques for authenticating aggregation queries. This article introduces the first known authenticated index structures for aggregation queries. First, we design an index that features good performance characteristics for static environments, where few or no updates occur to the data. Then, we extend these ideas and propose more involved structures for the dynamic case, where the database owner is allowed to update the data arbitrarily. Our structures feature excellent average case performance for authenticating queries with multiple aggregate attributes and multiple selection predicates. We also implement working prototypes of the proposed techniques and experimentally validate the correctness of our ideas.

Information Fusion and Hierarchical Knowledge Discovery by ARTMAP Neural Networks

Mapping novel terrain from sparse, complex data often requires the resolution of conflicting information from sensors working at different times, locations, and scales, and from experts with different goals and situations. Information fusion methods help resolve inconsistencies in order to distinguish correct from incorrect answers, as when evidence variously suggests that an object's class is car, truck, or airplane. The methods developed here consider a complementary problem, supposing that information from sensors and experts is reliable though inconsistent, as when evidence suggests that an objects class is car, vehicle, or man-made. Underlying relationships among objects are assumed to be unknown to the automated system of the human user. The ARTMAP information fusion system uses distributed code representations that exploit the neural network's capacity for one-to-many learning in order to produce self-organizing expert systems that discover hierarchial knowledge structures. The system infers multi-level relationships among groups of output classes, without any supervised labeling of these relationships. The procedure is illustrated with two image examples.

Self-Organizing Information Fusion and Hierarchical Knowledge Discovery: A New Framework Using Artmap Neural Networks

Classifying novel terrain or objects from sparse, complex data may require the resolution of conflicting information from sensors woring at different times, locations, and scales, and from sources with different goals and situations. Information fusion methods can help resolve inconsistencies, as when eveidence variously suggests that and object's class is car, truck, or airplane. The methods described her address a complementary problem, supposing that information from sensors and experts is reliable though inconsistent, as when evidence suggests that an object's class is car, vehicle, and man-made. Underlying relationships among classes are assumed to be unknown to the autonomated system or the human user. The ARTMAP information fusion system uses distributed code representations that exploit the neural network's capacity for one-to-many learning in order to produce self-organizing expert systems that discover hierachical knowlege structures. The fusion system infers multi-level relationships among groups of output classes, without any supervised labeling of these relationships. The procedure is illustrated with two image examples, but is not limited to image domain.