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.

Stochastic Refinement of the Visual Hull to Satisfy Photometric and Silhouette Consistency Constraints

An iterative method for reconstructing a 3D polygonal mesh and color texture map from multiple views of an object is presented. In each iteration, the method first estimates a texture map given the current shape estimate. The texture map and its associated residual error image are obtained via maximum a posteriori estimation and reprojection of the multiple views into texture space. Next, the surface shape is adjusted to minimize residual error in texture space. The surface is deformed towards a photometrically-consistent solution via a series of 1D epipolar searches at randomly selected surface points. The texture space formulation has improved computational complexity over standard image-based error approaches, and allows computation of the reprojection error and uncertainty for any point on the surface. Moreover, shape adjustments can be constrained such that the recovered model's silhouette matches those of the input images. Experiments with real world imagery demonstrate the validity of the approach.

Contour Generator Points for Threshold Selection and a Novel Photo-Consistency Measure for Space Carving

Space carving has emerged as a powerful method for multiview scene reconstruction. Although a wide variety of methods have been proposed, the quality of the reconstruction remains highly-dependent on the photometric consistency measure, and the threshold used to carve away voxels. In this paper, we present a novel photo-consistency measure that is motivated by a multiset variant of the chamfer distance. The new measure is robust to high amounts of within-view color variance and also takes into account the projection angles of back-projected pixels. Another critical issue in space carving is the selection of the photo-consistency threshold used to determine what surface voxels are kept or carved away. In this paper, a reliable threshold selection technique is proposed that examines the photo-consistency values at contour generator points. Contour generators are points that lie on both the surface of the object and the visual hull. To determine the threshold, a percentile ranking of the photo-consistency values of these generator points is used. This improved technique is applicable to a wide variety of photo-consistency measures, including the new measure presented in this paper. Also presented in this paper is a method to choose between photo-consistency measures, and voxel array resolutions prior to carving using receiver operating characteristic (ROC) curves.

Basis Token Consistency: A Practical Mechanism for Strong Web Cache Consistency

With web caching and cache-related services like CDNs and edge services playing an increasingly significant role in the modern internet, the problem of the weak consistency and coherence provisions in current web protocols is becoming increasingly significant and drawing the attention of the standards community [LCD01]. Toward this end, we present definitions of consistency and coherence for web-like environments, that is, distributed client-server information systems where the semantics of interactions with resource are more general than the read/write operations found in memory hierarchies and distributed file systems. We then present a brief review of proposed mechanisms which strengthen the consistency of caches in the web, focusing upon their conceptual contributions and their weaknesses in real-world practice. These insights motivate a new mechanism, which we call "Basis Token Consistency" or BTC; when implemented at the server, this mechanism allows any client (independent of the presence and conformity of any intermediaries) to maintain a self-consistent view of the server's state. This is accomplished by annotating responses with additional per-resource application information which allows client caches to recognize the obsolescence of currently cached entities and identify responses from other caches which are already stale in light of what has already been seen. The mechanism requires no deviation from the existing client-server communication model, and does not require servers to maintain any additional per-client state. We discuss how our mechanism could be integrated into a fragment-assembling Content Management System (CMS), and present a simulation-driven performance comparison between the BTC algorithm and the use of the Time-To-Live (TTL) heuristic.

"Networking is IPC": A Guiding Principle to a Better Internet

This position paper outlines a new network architecture, i.e., a style of construction that identifies the objects and how they relate. We do not specify particular protocol implementations or specific interfaces and policies. After all, it should be possible to change protocols in an architecture without changing the architecture. Rather we outline the repeating patterns and structures, and how the proposed model would cope with the challenges faced by today's Internet (and that of the future). Our new architecture is based on the following principle: Application processes communicate via a distributed inter-process communication (IPC) facility. The application processes that make up this facility provide a protocol that implements an IPC mechanism, and a protocol for managing distributed IPC (routing, security and other management tasks). Existing implementation strategies, algorithms, and protocols can be cast and used within our proposed new structure.