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.

Unicast-based Characterization of Network Loss Topologies

Current Internet transport protocols make end-to-end measurements and maintain per-connection state to regulate the use of shared network resources. When a number of such connections share a common endpoint, that endpoint has the opportunity to correlate these end-to-end measurements to better diagnose and control the use of shared resources. A valuable characterization of such shared resources is the "loss topology". From the perspective of a server with concurrent connections to multiple clients, the loss topology is a logical tree rooted at the server in which edges represent lossy paths between a pair of internal network nodes. We develop an end-to-end unicast packet probing technique and an associated analytical framework to: (1) infer loss topologies, (2) identify loss rates of links in an existing loss topology, and (3) augment a topology to incorporate the arrival of a new connection. Correct, efficient inference of loss topology information enables new techniques for aggregate congestion control, QoS admission control, connection scheduling and mirror site selection. Our extensive simulation results demonstrate that our approach is robust in terms of its accuracy and convergence over a wide range of network conditions.

Navite: A Neural Network System For Sensory-Based Robot Navigation

A neural network system, NAVITE, for incremental trajectory generation and obstacle avoidance is presented. Unlike other approaches, the system is effective in unstructured environments. Multimodal inforrnation from visual and range data is used for obstacle detection and to eliminate uncertainty in the measurements. Optimal paths are computed without explicitly optimizing cost functions, therefore reducing computational expenses. Simulations of a planar mobile robot (including the dynamic characteristics of the plant) in obstacle-free and object avoidance trajectories are presented. The system can be extended to incorporate global map information into the local decision-making process.