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.

Asynchronous Auction for Distributed Nonlinear Resource Allocation Problem

Resource Allocation Problems (RAPs) are concerned with the optimal allocation of resources to tasks. Problems in fields such as search theory, statistics, finance, economics, logistics, sensor & wireless networks fit this formulation. In literature, several centralized/synchronous algorithms have been proposed including recently proposed auction algorithm, RAP Auction. Here we present asynchronous implementation of RAP Auction for distributed RAPs.

On the Stable Paths Problem and a Restricted Variant

Interdomain routing on the Internet is performed using route preference policies specified independently, and arbitrarily by each Autonomous System in the network. These policies are used in the border gateway protocol (BGP) by each AS when selecting next-hop choices for routes to each destination. Conflicts between policies used by different ASs can lead to routing instabilities that, potentially, cannot be resolved no matter how long BGP is run. The Stable Paths Problem (SPP) is an abstract graph theoretic model of the problem of selecting nexthop routes for a destination. A stable solution to the problem is a set of next-hop choices, one for each AS, that is compatible with the policies of each AS. In a stable solution each AS has selected its best next-hop given that the next-hop choices of all neighbors are fixed. BGP can be viewed as a distributed algorithm for solving SPP. In this report we consider the stable paths problem, as well as a family of restricted variants of the stable paths problem, which we call F stable paths problems. We show that two very simple variants of the stable paths problem are also NP-complete. In addition we show that for networks with a DAG topology, there is an efficient centralized algorithm to solve the stable paths problem, and that BGP always efficiently converges to a stable solution on such networks.

Reliable Cellular Automata with Self-Organization

In a probabilistic cellular automaton in which all local transitions have positive probability, the problem of keeping a bit of information for more than a constant number of steps is nontrivial, even in an infinite automaton. Still, there is a solution in 2 dimensions, and this solution can be used to construct a simple 3-dimensional discrete-time universal fault-tolerant cellular automaton. This technique does not help much to solve the following problems: remembering a bit of information in 1 dimension; computing in dimensions lower than 3; computing in any dimension with non-synchronized transitions. Our more complex technique organizes the cells in blocks that perform a reliable simulation of a second (generalized) cellular automaton. The cells of the latter automaton are also organized in blocks, simulating even more reliably a third automaton, etc. Since all this (a possibly infinite hierarchy) is organized in "software", it must be under repair all the time from damage caused by errors. A large part of the problem is essentially self-stabilization recovering from a mess of arbitrary-size and content caused by the faults. The present paper constructs an asynchronous one-dimensional fault-tolerant cellular automaton, with the further feature of "self-organization". The latter means that unless a large amount of input information must be given, the initial configuration can be chosen to be periodical with a small period.

Determining Acceptance Possibility for a Quantum Computation is Hard for the Polynomial Hierarchy

It is shown that determining whether a quantum computation has a non-zero probability of accepting is at least as hard as the polynomial time hierarchy. This hardness result also applies to determining in general whether a given quantum basis state appears with nonzero amplitude in a superposition, or whether a given quantum bit has positive expectation value at the end of a quantum computation. This result is achieved by showing that the complexity class NQP of Adleman, Demarrais, and Huang, a quantum analog of NP, is equal to the counting class coC=P.

The Cache Inference Problem and its Application to Content and Request Routing

In many networked applications, independent caching agents cooperate by servicing each other's miss streams, without revealing the operational details of the caching mechanisms they employ. Inference of such details could be instrumental for many other processes. For example, it could be used for optimized forwarding (or routing) of one's own miss stream (or content) to available proxy caches, or for making cache-aware resource management decisions. In this paper, we introduce the Cache Inference Problem (CIP) as that of inferring the characteristics of a caching agent, given the miss stream of that agent. While CIP is insolvable in its most general form, there are special cases of practical importance in which it is, including when the request stream follows an Independent Reference Model (IRM) with generalized power-law (GPL) demand distribution. To that end, we design two basic "litmus" tests that are able to detect LFU and LRU replacement policies, the effective size of the cache and of the object universe, and the skewness of the GPL demand for objects. Using extensive experiments under synthetic as well as real traces, we show that our methods infer such characteristics accurately and quite efficiently, and that they remain robust even when the IRM/GPL assumptions do not hold, and even when the underlying replacement policies are not "pure" LFU or LRU. We exemplify the value of our inference framework by considering example applications.

Anisotropic Interpolation on Graphs: The Combinatorial Dirichlet Problem

The combinatorial Dirichlet problem is formulated, and an algorithm for solving it is presented. This provides an effective method for interpolating missing data on weighted graphs of arbitrary connectivity. Image processing examples are shown, and the relation to anistropic diffusion is discussed.

Large-Scale Neural Systems for Vision and Cognition

— Consideration of how people respond to the question What is this? has suggested new problem frontiers for pattern recognition and information fusion, as well as neural systems that embody the cognitive transformation of declarative information into relational knowledge. In contrast to traditional classification methods, which aim to find the single correct label for each exemplar (This is a car), the new approach discovers rules that embody coherent relationships among labels which would otherwise appear contradictory to a learning system (This is a car, that is a vehicle, over there is a sedan). This talk will describe how an individual who experiences exemplars in real time, with each exemplar trained on at most one category label, can autonomously discover a hierarchy of cognitive rules, thereby converting local information into global knowledge. Computational examples are based on the observation that sensors working at different times, locations, and spatial scales, and experts with different goals, languages, and situations, may produce apparently inconsistent image labels, which are reconciled by implicit underlying relationships that the network’s learning process discovers. The ARTMAP information fusion system can, moreover, integrate multiple separate knowledge hierarchies, by fusing independent domains into a unified structure. In the process, the system discovers cross-domain rules, inferring multilevel relationships among groups of output classes, without any supervised labeling of these relationships. In order to self-organize its expert system, the ARTMAP information fusion network features distributed code representations which exploit the model’s intrinsic capacity for one-to-many learning (This is a car and a vehicle and a sedan) as well as many-to-one learning (Each of those vehicles is a car). Fusion system software, testbed datasets, and articles are available from http://cns.bu.edu/techlab.

A Memory Model for Concept Hierarchy Representation and Commonsense Reasoning

Most associative memory models perform one level mapping between predefined sets of input and output patterns1 and are unable to represent hierarchical knowledge. Complex AI systems allow hierarchical representation of concepts, but generally do not have learning capabilities. In this paper, a memory model is proposed which forms concept hierarchy by learning sample relations between concepts. All concepts are represented in a concept layer. Relations between a concept and its defining lower level concepts, are chunked as cognitive codes represented in a coding layer. By updating memory contents in the concept layer through code firing in the coding layer, the system is able to perform an important class of commonsense reasoning, namely recognition and inheritance.

A Fuzzy ARTMAP Nonparametric Probability Estimator For Nonstationary Pattern Recognition Problem

An incremental, nonparametric probability estimation procedure using the fuzzy ARTMAP neural network is introduced. In slow-learning mode, fuzzy ARTMAP searches for patterns of data on which to build ever more accurate estimates. In max-nodes mode, the network initially learns a fixed number of categories, and weights are then adjusted gradually.

A Solution of the Figure-ground Problem for Biological Vision

A neural network model of 3-D visual perception and figure-ground separation by visual cortex is introduced. The theory provides a unified explanation of how a 2-D image may generate a 3-D percept; how figures pop-out from cluttered backgrounds; how spatially sparse disparity cues can generate continuous surface representations at different perceived depths; how representations of occluded regions can be completed and recognized without usually being seen; how occluded regions can sometimes be seen during percepts of transparency; how high spatial frequency parts of an image may appear closer than low spatial frequency parts; how sharp targets are detected better against a figure and blurred targets are detector better against a background; how low spatial frequency parts of an image may be fused while high spatial frequency parts are rivalrous; how sparse blue cones can generate vivid blue surface percepts; how 3-D neon color spreading, visual phantoms, and tissue contrast percepts are generated; how conjunctions of color-and-depth may rapidly pop-out during visual search. These explanations arise derived from an ecological analysis of how monocularly viewed parts of an image inherit the appropriate depth from contiguous binocularly viewed parts, as during DaVinci stereopsis. The model predicts the functional role and ordering of multiple interactions within and between the two parvocellular processing streams that join LGN to prestriate area V4. Interactions from cells representing larger scales and disparities to cells representing smaller scales and disparities are of particular importance.