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.

Collocation Games and Their Application to Distributed Resource Management

We introduce Collocation Games as the basis of a general framework for modeling, analyzing, and facilitating the interactions between the various stakeholders in distributed systems in general, and in cloud computing environments in particular. Cloud computing enables fixed-capacity (processing, communication, and storage) resources to be offered by infrastructure providers as commodities for sale at a fixed cost in an open marketplace to independent, rational parties (players) interested in setting up their own applications over the Internet. Virtualization technologies enable the partitioning of such fixed-capacity resources so as to allow each player to dynamically acquire appropriate fractions of the resources for unencumbered use. In such a paradigm, the resource management problem reduces to that of partitioning the entire set of applications (players) into subsets, each of which is assigned to fixed-capacity cloud resources. If the infrastructure and the various applications are under a single administrative domain, this partitioning reduces to an optimization problem whose objective is to minimize the overall deployment cost. In a marketplace, in which the infrastructure provider is interested in maximizing its own profit, and in which each player is interested in minimizing its own cost, it should be evident that a global optimization is precisely the wrong framework. Rather, in this paper we use a game-theoretic framework in which the assignment of players to fixed-capacity resources is the outcome of a strategic "Collocation Game". Although we show that determining the existence of an equilibrium for collocation games in general is NP-hard, we present a number of simplified, practically-motivated variants of the collocation game for which we establish convergence to a Nash Equilibrium, and for which we derive convergence and price of anarchy bounds. In addition to these analytical results, we present an experimental evaluation of implementations of some of these variants for cloud infrastructures consisting of a collection of multidimensional resources of homogeneous or heterogeneous capacities. Experimental results using trace-driven simulations and synthetically generated datasets corroborate our analytical results and also illustrate how collocation games offer a feasible distributed resource management alternative for autonomic/self-organizing systems, in which the adoption of a global optimization approach (centralized or distributed) would be neither practical nor justifiable.

A Neural Model of 3D Shape-From-Texture: Multiple-Scale Filtering, Boundary Grouping, and Surface Filling-In

A neural model is presented of how cortical areas V1, V2, and V4 interact to convert a textured 2D image into a representation of curved 3D shape. Two basic problems are solved to achieve this: (1) Patterns of spatially discrete 2D texture elements are transformed into a spatially smooth surface representation of 3D shape. (2) Changes in the statistical properties of texture elements across space induce the perceived 3D shape of this surface representation. This is achieved in the model through multiple-scale filtering of a 2D image, followed by a cooperative-competitive grouping network that coherently binds texture elements into boundary webs at the appropriate depths using a scale-to-depth map and a subsequent depth competition stage. These boundary webs then gate filling-in of surface lightness signals in order to form a smooth 3D surface percept. The model quantitatively simulates challenging psychophysical data about perception of prolate ellipsoids (Todd and Akerstrom, 1987, J. Exp. Psych., 13, 242). In particular, the model represents a high degree of 3D curvature for a certain class of images, all of whose texture elements have the same degree of optical compression, in accordance with percepts of human observers. Simulations of 3D percepts of an elliptical cylinder, a slanted plane, and a photo of a golf ball are also presented.