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.

Approximately Uniform Random Sampling in Sensor Networks

Recent work in sensor databases has focused extensively on distributed query problems, notably distributed computation of aggregates. Existing methods for computing aggregates broadcast queries to all sensors and use in-network aggregation of responses to minimize messaging costs. In this work, we focus on uniform random sampling across nodes, which can serve both as an alternative building block for aggregation and as an integral component of many other useful randomized algorithms. Prior to our work, the best existing proposals for uniform random sampling of sensors involve contacting all nodes in the network. We propose a practical method which is only approximately uniform, but contacts a number of sensors proportional to the diameter of the network instead of its size. The approximation achieved is tunably close to exact uniform sampling, and only relies on well-known existing primitives, namely geographic routing, distributed computation of Voronoi regions and von Neumann's rejection method. Ultimately, our sampling algorithm has the same worst-case asymptotic cost as routing a point-to-point message, and thus it is asymptotically optimal among request/reply-based sampling methods. We provide experimental results demonstrating the effectiveness of our algorithm on both synthetic and real sensor topologies.

Fusion Artmap: A Neural Network Architecture for Multi-Channel Data Fusion and Classification

Fusion ARTMAP is a self-organizing neural network architecture for multi-channel, or multi-sensor, data fusion. Single-channel Fusion ARTMAP is functionally equivalent to Fuzzy ART during unsupervised learning and to Fuzzy ARTMAP during supervised learning. The network has a symmetric organization such that each channel can be dynamically configured to serve as either a data input or a teaching input to the system. An ART module forms a compressed recognition code within each channel. These codes, in turn, become inputs to a single ART system that organizes the global recognition code. When a predictive error occurs, a process called paraellel match tracking simultaneously raises vigilances in multiple ART modules until reset is triggered in one of them. Parallel match tracking hereby resets only that portion of the recognition code with the poorest match, or minimum predictive confidence. This internally controlled selective reset process is a type of credit assignment that creates a parsimoniously connected learned network. Fusion ARTMAP's multi-channel coding is illustrated by simulations of the Quadruped Mammal database.

A Distributed Outstar Network for Spatial Pattern Learning

The distributed outstar, a generalization of the outstar neural network for spatial pattern learning, is introduced. In the outstar, signals from a source node cause weights to learn and recall arbitrary patterns across a target field of nodes. The distributed outstar replaces the outstar source node with a source field of arbitrarily many nodes, whose activity pattern may be arbitrarily distributed or compressed. Learning proceeds according to a principle of atrophy due to disuse, whereby a path weight decreases in joint proportion to the transmitted path signal and the degree of disuse of the target node. During learning, the total signal to a target node converges toward that node's activity level. Weight changes at a node are apportioned according to the distributed pattern of converging signals. Three synaptic transmission functions, by a product rule, a capacity rule, and a threshold rule, are examined for this system. The three rules are computationally equivalent when source field activity is maximally compressed, or winner-take-all. When source field activity is distributed, catastrophic forgetting may occur. Only the threshold rule solves this problem. Analysis of spatial pattern learning by distributed codes thereby leads to the conjecture that the unit of long-term memory in such a system is an adaptive threshold, rather than the multiplicative path weight widely used in neural models.

Neural Pattern Recognition With Multi-Scale Pyramidal Coding and Selective Attention

A new neural network architecture for spatial patttern recognition using multi-scale pyramida1 coding is here described. The network has an ARTMAP structure with a new class of ART-module, called Hybrid ART-module, as its front-end processor. Hybrid ART-module, which has processing modules corresponding to each scale channel of multi-scale pyramid, employs channels of finer scales only if it is necesssary to discriminate a pattern from others. This process is effected by serial match tracking. Also the parallel match tracking is used to select the spatial location having most salient feature and limit its attention to that part.

A Neural Network Model of Speech Acquisition and Motor Equivalent Speech Production

This article describes a neural network model that addresses the acquisition of speaking skills by infants and subsequent motor equivalent production of speech sounds. The model learns two mappings during a babbling phase. A phonetic-to-orosensory mapping specifies a vocal tract target for each speech sound; these targets take the form of convex regions in orosensory coordinates defining the shape of the vocal tract. The babbling process wherein these convex region targets are formed explains how an infant can learn phoneme-specific and language-specific limits on acceptable variability of articulator movements. The model also learns an orosensory-to-articulatory mapping wherein cells coding desired movement directions in orosensory space learn articulator movements that achieve these orosensory movement directions. The resulting mapping provides a natural explanation for the formation of coordinative structures. This mapping also makes efficient use of redundancy in the articulator system, thereby providing the model with motor equivalent capabilities. Simulations verify the model's ability to compensate for constraints or perturbations applied to the articulators automatically and without new learning and to explain contextual variability seen in human speech production.

Fuzzy ARTMAP: A Neural Network Architecture for Incremental Supervised Learning of Analog Multidimensional Maps

A new neural network architecture is introduced for incremental supervised learning of recognition categories and multidimensional maps in response to arbitrary sequences of analog or binary input vectors. The architecture, called Fuzzy ARTMAP, achieves a synthesis of fuzzy logic and Adaptive Resonance Theory (ART) neural networks by exploiting a close formal similarity between the computations of fuzzy subsethood and ART category choice, resonance, and learning. Fuzzy ARTMAP also realizes a new Minimax Learning Rule that conjointly minimizes predictive error and maximizes code compression, or generalization. This is achieved by a match tracking process that increases the ART vigilance parameter by the minimum amount needed to correct a predictive error. As a result, the system automatically learns a minimal number of recognition categories, or "hidden units", to met accuracy criteria. Category proliferation is prevented by normalizing input vectors at a preprocessing stage. A normalization procedure called complement coding leads to a symmetric theory in which the MIN operator (Λ) and the MAX operator (v) of fuzzy logic play complementary roles. Complement coding uses on-cells and off-cells to represent the input pattern, and preserves individual feature amplitudes while normalizing the total on-cell/off-cell vector. Learning is stable because all adaptive weights can only decrease in time. Decreasing weights correspond to increasing sizes of category "boxes". Smaller vigilance values lead to larger category boxes. Improved prediction is achieved by training the system several times using different orderings of the input set. This voting strategy can also be used to assign probability estimates to competing predictions given small, noisy, or incomplete training sets. Four classes of simulations illustrate Fuzzy ARTMAP performance as compared to benchmark back propagation and genetic algorithm systems. These simulations include (i) finding points inside vs. outside a circle; (ii) learning to tell two spirals apart; (iii) incremental approximation of a piecewise continuous function; and (iv) a letter recognition database. The Fuzzy ARTMAP system is also compared to Salzberg's NGE system and to Simpson's FMMC system.

Received signal strength in large-scale wireless relay sensor network: a stochastic ray approach

The authors consider a point percolation lattice representation of a large-scale wireless relay sensor network (WRSN) deployed in a cluttered environment. Each relay sensor corresponds to a grid point in the random lattice and the signal sent by the source is modelled as an ensemble of photons that spread in the space, which may 'hit' other sensors and are 'scattered' around. At each hit, the relay node forwards the received signal to its nearest neighbour through direction-selective relaying. The authors first derive the distribution that a relay path reaches a prescribed location after undergoing certain number of hops. Subsequently, a closed-form expression of the average received signal strength (RSS) at the destination can be computed as the summation of all signal echoes' energy. Finally, the effect of the anomalous diffusion exponent ß on the mean RSS in a WRSN is studied, for which it is found that the RSS scaling exponent e is given by (3ß-1)/ß. The results would provide useful insight into the design and deployment of large-scale WRSNs in future. © 2011 The Institution of Engineering and Technology.

Exploring statistical and population aspects of network complexity

The characterization and the definition of the complexity of objects is an important but very difficult problem that attracted much interest in many different fields. In this paper we introduce a new measure, called network diversity score (NDS), which allows us to quantify structural properties of networks. We demonstrate numerically that our diversity score is capable of distinguishing ordered, random and complex networks from each other and, hence, allowing us to categorize networks with respect to their structural complexity. We study 16 additional network complexity measures and find that none of these measures has similar good categorization capabilities. In contrast to many other measures suggested so far aiming for a characterization of the structural complexity of networks, our score is different for a variety of reasons. First, our score is multiplicatively composed of four individual scores, each assessing different structural properties of a network. That means our composite score reflects the structural diversity of a network. Second, our score is defined for a population of networks instead of individual networks. We will show that this removes an unwanted ambiguity, inherently present in measures that are based on single networks. In order to apply our measure practically, we provide a statistical estimator for the diversity score, which is based on a finite number of samples.

Constructing random matrices to represent real ecosystems

Models of complex systems with n components typically have order n² parameters because each component can potentially interact with every other. When it is impractical to measure these parameters, one may choose random parameter values and study the emergent statistical properties at the system level. Many influential results in theoretical ecology have been derived from two key assumptions: that species interact with random partners at random intensities and that intraspecific competition is comparable between species. Under these assumptions, community dynamics can be described by a community matrix that is often amenable to mathematical analysis. We combine empirical data with mathematical theory to show that both of these assumptions lead to results that must be interpreted with caution. We examine 21 empirically derived community matrices constructed using three established, independent methods. The empirically derived systems are more stable by orders of magnitude than results from random matrices. This consistent disparity is not explained by existing results on predator-prey interactions. We investigate the key properties of empirical community matrices that distinguish them from random matrices. We show that network topology is less important than the relationship between a species’ trophic position within the food web and its interaction strengths. We identify key features of empirical networks that must be preserved if random matrix models are to capture the features of real ecosystems.

Network signatures based on gene pair expression ratios improve classification and the analysis of muscle-invasive urothelial cancer

Urothelial cancer (UC) is highly recurrent and can progress from non-invasive (NMIUC) to a more aggressive muscle-invasive (MIUC) subtype that invades the muscle tissue layer of the bladder. We present a proof of principle study that network-based features of gene pairs can be used to improve classifier performance and the functional analysis of urothelial cancer gene expression data. In the first step of our procedure each individual sample of a UC gene expression dataset is inflated by gene pair expression ratios that are defined based on a given network structure. In the second step an elastic net feature selection procedure for network-based signatures is applied to discriminate between NMIUC and MIUC samples. We performed a repeated random subsampling cross validation in three independent datasets. The network signatures were characterized by a functional enrichment analysis and studied for the enrichment of known cancer genes. We observed that the network-based gene signatures from meta collections of proteinprotein interaction (PPI) databases such as CPDB and the PPI databases HPRD and BioGrid improved the classification performance compared to single gene based signatures. The network based signatures that were derived from PPI databases showed a prominent enrichment of cancer genes (e.g., TP53, TRIM27 and HNRNPA2Bl). We provide a novel integrative approach for large-scale gene expression analysis for the identification and development of novel diagnostical targets in bladder cancer. Further, our method allowed to link cancer gene associations to network-based expression signatures that are not observed in gene-based expression signatures.

MicroRNA–mRNA interaction network using TSK-type recurrent neural fuzzy network

MicroRNAs are short non-coding RNAs that can regulate gene expression during various crucial cell processes such as differentiation, proliferation and apoptosis. Changes in expression profiles of miRNA play an important role in the development of many cancers, including CRC. Therefore, the identification of cancer related miRNAs and their target genes are important for cancer biology research. In this paper, we applied TSK-type recurrent neural fuzzy network (TRNFN) to infer miRNA–mRNA association network from paired miRNA, mRNA expression profiles of CRC patients. We demonstrated that the method we proposed achieved good performance in recovering known experimentally verified miRNA–mRNA associations. Moreover, our approach proved successful in identifying 17 validated cancer miRNAs which are directly involved in the CRC related pathways. Targeting such miRNAs may help not only to prevent the recurrence of disease but also to control the growth of advanced metastatic tumors. Our regulatory modules provide valuable insights into the pathogenesis of cancer

An efficient scheme for the evaluation of coding performance of high speed links incorporating joint error behaviour based on Monte Carlo Method

While channel coding is a standard method of improving a system’s energy efficiency in digital communications, its practice does not extend to high-speed links. Increasing demands in network speeds are placing a large burden on the energy efficiency of high-speed links and render the benefit of channel coding for these systems a timely subject. The low error rates of interest and the presence of residual intersymbol interference (ISI) caused by hardware constraints impede the analysis and simulation of coded high-speed links. Focusing on the residual ISI and combined noise as the dominant error mechanisms, this paper analyses error correlation through concepts of error region, channel signature, and correlation distance. This framework provides a deeper insight into joint error behaviours in high-speed links, extends the range of statistical simulation for coded high-speed links, and provides a case against the use of biased Monte Carlo methods in this setting

Static Pricing for a Network Service Provider

This article studies the static pricing problem of a network service provider who has a fixed capacity and faces different types of customers (classes). Each type of customers can have its own capacity constraint but it is assumed that all classes have the same resource requirement. The provider must decide a static price for each class. The customer types are characterized by their arrival process, with a price-dependant arrival rate, and the random time they remain in the system. Many real-life situations could fit in this framework, for example an Internet provider or a call center, but originally this problem was thought for a company that sells phone-cards and needs to set the price-per-minute for each destination. Our goal is to characterize the optimal static prices in order to maximize the provider's revenue. We note that the model here presented, with some slight modifications and additional assumptions can be used in those cases when the objective is to maximize social welfare.

TU Graz: Course: 707.000 Web Science and Web Technology: Lecture 6: Network Evolution and Process

In this class, we will discuss the nature of network evolution and some selected network processes. We will discuss graph generation algorithms that generate networks with different interesting characteristics. Optional : The Structure and Function of Complex Networks (chapter 8), M.E.J. Newman, SIAM Review 45 167--256 (2003); Optional: Emergence of Scaling in Random Networks, A.L. Barabasi and R. Albert, Science 286, 509 (1999)