Linking Visual Development and Learning to Information Processing: Preattentive and Attentive Brain Dynamics

National Science Foundation (SBE-0354378); Office of Naval Research (N00014-95-1-0657)

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.

Real-Time Spatio-Temporal Query Processing in Mobile Ad-Hoc Sensor Networks

Personal communication devices are increasingly equipped with sensors that are able to collect and locally store information from their environs. The mobility of users carrying such devices, and hence the mobility of sensor readings in space and time, opens new horizons for interesting applications. In particular, we envision a system in which the collective sensing, storage and communication resources, and mobility of these devices could be leveraged to query the state of (possibly remote) neighborhoods. Such queries would have spatio-temporal constraints which must be met for the query answers to be useful. Using a simplified mobility model, we analytically quantify the benefits from cooperation (in terms of the system's ability to satisfy spatio-temporal constraints), which we show to go beyond simple space-time tradeoffs. In managing the limited storage resources of such cooperative systems, the goal should be to minimize the number of unsatisfiable spatio-temporal constraints. We show that Data Centric Storage (DCS), or "directed placement", is a viable approach for achieving this goal, but only when the underlying network is well connected. Alternatively, we propose, "amorphous placement", in which sensory samples are cached locally, and shuffling of cached samples is used to diffuse the sensory data throughout the whole network. We evaluate conditions under which directed versus amorphous placement strategies would be more efficient. These results lead us to propose a hybrid placement strategy, in which the spatio-temporal constraints associated with a sensory data type determine the most appropriate placement strategy for that data type. We perform an extensive simulation study to evaluate the performance of directed, amorphous, and hybrid placement protocols when applied to queries that are subject to timing constraints. Our results show that, directed placement is better for queries with moderately tight deadlines, whereas amorphous placement is better for queries with looser deadlines, and that under most operational conditions, the hybrid technique gives the best compromise.