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.

Safe Compositional Network Sketches: NetSketch Tool Implementation

Numerous problems exist that can be modeled as traffic through a network in which constraints exist to regulate flow. Vehicular road travel, computer networks, and cloud based resource distribution, among others all have natural representations in this manner. As these networks grow in size and/or complexity, analysis and certification of the safety invariants becomes increasingly costly. The NetSketch formalism introduces a lightweight verification framework that allows for greater scalability than traditional analysis methods. The NetSketch tool was developed to provide the power of this formalism in an easy to use and intuitive user interface.

Graph Wavelets for Spatial Traffic Analysis

A number of problems in network operations and engineering call for new methods of traffic analysis. While most existing traffic analysis methods are fundamentally temporal, there is a clear need for the analysis of traffic across multiple network links — that is, for spatial traffic analysis. In this paper we give examples of problems that can be addressed via spatial traffic analysis. We then propose a formal approach to spatial traffic analysis based on the wavelet transform. Our approach (graph wavelets) generalizes the traditional wavelet transform so that it can be applied to data elements connected via an arbitrary graph topology. We explore the necessary and desirable properties of this approach and consider some of its possible realizations. We then apply graph wavelets to measurements from an operating network. Our results show that graph wavelets are very useful for our motivating problems; for example, they can be used to form highly summarized views of an entire network's traffic load, to gain insight into a network's global traffic response to a link failure, and to localize the extent of a failure event within the network.

Integrated Chest Image Analysis System "BU-MIA"

We introduce "BU-MIA," a Medical Image Analysis system that integrates various advanced chest image analysis methods for detection, estimation, segmentation, and registration. BU-MIA evaluates repeated computed tomography (CT) scans of the same patient to facilitate identification and evaluation of pulmonary nodules for interval growth. It provides a user-friendly graphical user interface with a number of interaction tools for development, evaluation, and validation of chest image analysis methods. The structures that BU-MIA processes include the thorax, lungs, and trachea, pulmonary structures, such as lobes, fissures, nodules, and vessels, and bones, such as sternum, vertebrae, and ribs.

Mining Anomalies Using Traffic Feature Distributions

The increasing practicality of large-scale flow capture makes it possible to conceive of traffic analysis methods that detect and identify a large and diverse set of anomalies. However the challenge of effectively analyzing this massive data source for anomaly diagnosis is as yet unmet. We argue that the distributions of packet features (IP addresses and ports) observed in flow traces reveals both the presence and the structure of a wide range of anomalies. Using entropy as a summarization tool, we show that the analysis of feature distributions leads to significant advances on two fronts: (1) it enables highly sensitive detection of a wide range of anomalies, augmenting detections by volume-based methods, and (2) it enables automatic classification of anomalies via unsupervised learning. We show that using feature distributions, anomalies naturally fall into distinct and meaningful clusters. These clusters can be used to automatically classify anomalies and to uncover new anomaly types. We validate our claims on data from two backbone networks (Abilene and Geant) and conclude that feature distributions show promise as a key element of a fairly general network anomaly diagnosis framework.

Modeling the Java Bytecode Verifier

The Java programming language has been widely described as secure by design. Nevertheless, a number of serious security vulnerabilities have been discovered in Java, particularly in the Bytecode Verifier, a critical component used to verify class semantics before loading is complete. This paper describes a method for representing Java security constraints using the Alloy modeling language. It further describes a system for performing a security analysis on any block of Java bytecodes by converting the bytes into relation initializers in Alloy. Any counterexamples found by the Alloy analyzer correspond directly to insecure code. Analysis of the approach in the context of known security exploits is provided. This type of analysis represents a significant departure from standard malware analysis methods based on signatures or anomaly detection.