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.

Preferential Field Coverage Through Detour-Based Mobility Coordination

Controlling the mobility pattern of mobile nodes (e.g., robots) to monitor a given field is a well-studied problem in sensor networks. In this setup, absolute control over the nodes’ mobility is assumed. Apart from the physical ones, no other constraints are imposed on planning mobility of these nodes. In this paper, we address a more general version of the problem. Specifically, we consider a setting in which mobility of each node is externally constrained by a schedule consisting of a list of locations that the node must visit at particular times. Typically, such schedules exhibit some level of slack, which could be leveraged to achieve a specific coverage distribution of a field. Such a distribution defines the relative importance of different field locations. We define the Constrained Mobility Coordination problem for Preferential Coverage (CMC-PC) as follows: given a field with a desired monitoring distribution, and a number of nodes n, each with its own schedule, we need to coordinate the mobility of the nodes in order to achieve the following two goals: 1) satisfy the schedules of all nodes, and 2) attain the required coverage of the given field. We show that the CMC-PC problem is NP-complete (by reduction to the Hamiltonian Cycle problem). Then we propose TFM, a distributed heuristic to achieve field coverage that is as close as possible to the required coverage distribution. We verify the premise of TFM using extensive simulations, as well as taxi logs from a major metropolitan area. We compare TFM to the random mobility strategy—the latter provides a lower bound on performance. Our results show that TFM is very successful in matching the required field coverage distribution, and that it provides, at least, two-fold query success ratio for queries that follow the target coverage distribution of the field.