Quantitative Analysis of Single Nucleotide Polymorphisms within Copy Number Variation

Background Single nucleotide polymorphisms (SNPs) have been used extensively in genetics and epidemiology studies. Traditionally, SNPs that did not pass the Hardy-Weinberg equilibrium (HWE) test were excluded from these analyses. Many investigators have addressed possible causes for departure from HWE, including genotyping errors, population admixture and segmental duplication. Recent large-scale surveys have revealed abundant structural variations in the human genome, including copy number variations (CNVs). This suggests that a significant number of SNPs must be within these regions, which may cause deviation from HWE. Results We performed a Bayesian analysis on the potential effect of copy number variation, segmental duplication and genotyping errors on the behavior of SNPs. Our results suggest that copy number variation is a major factor of HWE violation for SNPs with a small minor allele frequency, when the sample size is large and the genotyping error rate is 0~1%. Conclusions Our study provides the posterior probability that a SNP falls in a CNV or a segmental duplication, given the observed allele frequency of the SNP, sample size and the significance level of HWE testing.

Stochastic Mesh-Based Multiview Reconstruction

A method for reconstruction of 3D polygonal models from multiple views is presented. The method uses sampling techniques to construct a texture-mapped semi-regular polygonal mesh of the object in question. Given a set of views and segmentation of the object in each view, constructive solid geometry is used to build a visual hull from silhouette prisms. The resulting polygonal mesh is simplified and subdivided to produce a semi-regular mesh. Regions of model fit inaccuracy are found by projecting the reference images onto the mesh from different views. The resulting error images for each view are used to compute a probability density function, and several points are sampled from it. Along the epipolar lines corresponding to these sampled points, photometric consistency is evaluated. The mesh surface is then pulled towards the regions of higher photometric consistency using free-form deformations. This sampling-based approach produces a photometrically consistent solution in much less time than possible with previous multi-view algorithms given arbitrary camera placement.

A Bayesian Approach for TCP to Distinguish Congestion from Wireless Losses

(This Technical Report revises TR-BUCS-2003-011) The Transmission Control Protocol (TCP) has been the protocol of choice for many Internet applications requiring reliable connections. The design of TCP has been challenged by the extension of connections over wireless links. In this paper, we investigate a Bayesian approach to infer at the source host the reason of a packet loss, whether congestion or wireless transmission error. Our approach is "mostly" end-to-end since it requires only one long-term average quantity (namely, long-term average packet loss probability over the wireless segment) that may be best obtained with help from the network (e.g. wireless access agent).Specifically, we use Maximum Likelihood Ratio tests to evaluate TCP as a classifier of the type of packet loss. We study the effectiveness of short-term classification of packet errors (congestion vs. wireless), given stationary prior error probabilities and distributions of packet delays conditioned on the type of packet loss (measured over a larger time scale). Using our Bayesian-based approach and extensive simulations, we demonstrate that congestion-induced losses and losses due to wireless transmission errors produce sufficiently different statistics upon which an efficient online error classifier can be built. We introduce a simple queueing model to underline the conditional delay distributions arising from different kinds of packet losses over a heterogeneous wired/wireless path. We show how Hidden Markov Models (HMMs) can be used by a TCP connection to infer efficiently conditional delay distributions. We demonstrate how estimation accuracy is influenced by different proportions of congestion versus wireless losses and penalties on incorrect classification.

Ergodicity and Mixing Rate of One-Dimensional Cellular Automata

One-and two-dimensional cellular automata which are known to be fault-tolerant are very complex. On the other hand, only very simple cellular automata have actually been proven to lack fault-tolerance, i.e., to be mixing. The latter either have large noise probability ε or belong to the small family of two-state nearest-neighbor monotonic rules which includes local majority voting. For a certain simple automaton L called the soldiers rule, this problem has intrigued researchers for the last two decades since L is clearly more robust than local voting: in the absence of noise, L eliminates any finite island of perturbation from an initial configuration of all 0's or all 1's. The same holds for a 4-state monotonic variant of L, K, called two-line voting. We will prove that the probabilistic cellular automata Kε and Lε asymptotically lose all information about their initial state when subject to small, strongly biased noise. The mixing property trivially implies that the systems are ergodic. The finite-time information-retaining quality of a mixing system can be represented by its relaxation time Relax(⋅), which measures the time before the onset of significant information loss. This is known to grow as (1/ε)^c for noisy local voting. The impressive error-correction ability of L has prompted some researchers to conjecture that Relax(Lε) = 2^(c/ε). We prove the tight bound 2^(c1log^21/ε) ＜ Relax(Lε) ＜ 2^(c2log^21/ε) for a biased error model. The same holds for Kε. Moreover, the lower bound is independent of the bias assumption. The strong bias assumption makes it possible to apply sparsity/renormalization techniques, the main tools of our investigation, used earlier in the opposite context of proving fault-tolerance.

An Information Theoretic Framework for Field Monitoring Using Autonomously Mobile Sensors

We consider a mobile sensor network monitoring a spatio-temporal field. Given limited cache sizes at the sensor nodes, the goal is to develop a distributed cache management algorithm to efficiently answer queries with a known probability distribution over the spatial dimension. First, we propose a novel distributed information theoretic approach in which the nodes locally update their caches based on full knowledge of the space-time distribution of the monitored phenomenon. At each time instant, local decisions are made at the mobile nodes concerning which samples to keep and whether or not a new sample should be acquired at the current location. These decisions account for minimizing an entropic utility function that captures the average amount of uncertainty in queries given the probability distribution of query locations. Second, we propose a different correlation-based technique, which only requires knowledge of the second-order statistics, thus relaxing the stringent constraint of having a priori knowledge of the query distribution, while significantly reducing the computational overhead. It is shown that the proposed approaches considerably improve the average field estimation error by maintaining efficient cache content. It is further shown that the correlation-based technique is robust to model mismatch in case of imperfect knowledge of the underlying generative correlation structure.

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.

Fuzzy ARTMAP, Slow Learning and Probability Estimation

A nonparametric probability estimation procedure using the fuzzy ARTMAP neural network is here described. Because the procedure does not make a priori assumptions about underlying probability distributions, it yields accurate estimates on a wide variety of prediction tasks. Fuzzy ARTMAP is used to perform probability estimation in two different modes. In a 'slow-learning' mode, input-output associations change slowly, with the strength of each association computing a conditional probability estimate. In 'max-nodes' mode, a fixed number of categories are coded during an initial fast learning interval, and weights are then tuned by slow learning. Simulations illustrate system performance on tasks in which various numbers of clusters in the set of input vectors mapped to a given class.

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.

Fast Learning VIEWNET Architectures for Recognizing 3-D Objects from Multiple 2-D Views

The recognition of 3-D objects from sequences of their 2-D views is modeled by a family of self-organizing neural architectures, called VIEWNET, that use View Information Encoded With NETworks. VIEWNET incorporates a preprocessor that generates a compressed but 2-D invariant representation of an image, a supervised incremental learning system that classifies the preprocessed representations into 2-D view categories whose outputs arc combined into 3-D invariant object categories, and a working memory that makes a 3-D object prediction by accumulating evidence from 3-D object category nodes as multiple 2-D views are experienced. The simplest VIEWNET achieves high recognition scores without the need to explicitly code the temporal order of 2-D views in working memory. Working memories are also discussed that save memory resources by implicitly coding temporal order in terms of the relative activity of 2-D view category nodes, rather than as explicit 2-D view transitions. Variants of the VIEWNET architecture may also be used for scene understanding by using a preprocessor and classifier that can determine both What objects are in a scene and Where they are located. The present VIEWNET preprocessor includes the CORT-X 2 filter, which discounts the illuminant, regularizes and completes figural boundaries, and suppresses image noise. This boundary segmentation is rendered invariant under 2-D translation, rotation, and dilation by use of a log-polar transform. The invariant spectra undergo Gaussian coarse coding to further reduce noise and 3-D foreshortening effects, and to increase generalization. These compressed codes are input into the classifier, a supervised learning system based on the fuzzy ARTMAP algorithm. Fuzzy ARTMAP learns 2-D view categories that are invariant under 2-D image translation, rotation, and dilation as well as 3-D image transformations that do not cause a predictive error. Evidence from sequence of 2-D view categories converges at 3-D object nodes that generate a response invariant under changes of 2-D view. These 3-D object nodes input to a working memory that accumulates evidence over time to improve object recognition. ln the simplest working memory, each occurrence (nonoccurrence) of a 2-D view category increases (decreases) the corresponding node's activity in working memory. The maximally active node is used to predict the 3-D object. Recognition is studied with noisy and clean image using slow and fast learning. Slow learning at the fuzzy ARTMAP map field is adapted to learn the conditional probability of the 3-D object given the selected 2-D view category. VIEWNET is demonstrated on an MIT Lincoln Laboratory database of l28x128 2-D views of aircraft with and without additive noise. A recognition rate of up to 90% is achieved with one 2-D view and of up to 98.5% correct with three 2-D views. The properties of 2-D view and 3-D object category nodes are compared with those of cells in monkey inferotemporal cortex.

Vector Associative Maps: Unsupervised Real-time Error-based Learning and Control of Movement Trajectories

This article describes neural network models for adaptive control of arm movement trajectories during visually guided reaching and, more generally, a framework for unsupervised real-time error-based learning. The models clarify how a child, or untrained robot, can learn to reach for objects that it sees. Piaget has provided basic insights with his concept of a circular reaction: As an infant makes internally generated movements of its hand, the eyes automatically follow this motion. A transformation is learned between the visual representation of hand position and the motor representation of hand position. Learning of this transformation eventually enables the child to accurately reach for visually detected targets. Grossberg and Kuperstein have shown how the eye movement system can use visual error signals to correct movement parameters via cerebellar learning. Here it is shown how endogenously generated arm movements lead to adaptive tuning of arm control parameters. These movements also activate the target position representations that are used to learn the visuo-motor transformation that controls visually guided reaching. The AVITE model presented here is an adaptive neural circuit based on the Vector Integration to Endpoint (VITE) model for arm and speech trajectory generation of Bullock and Grossberg. In the VITE model, a Target Position Command (TPC) represents the location of the desired target. The Present Position Command (PPC) encodes the present hand-arm configuration. The Difference Vector (DV) population continuously.computes the difference between the PPC and the TPC. A speed-controlling GO signal multiplies DV output. The PPC integrates the (DV)·(GO) product and generates an outflow command to the arm. Integration at the PPC continues at a rate dependent on GO signal size until the DV reaches zero, at which time the PPC equals the TPC. The AVITE model explains how self-consistent TPC and PPC coordinates are autonomously generated and learned. Learning of AVITE parameters is regulated by activation of a self-regulating Endogenous Random Generator (ERG) of training vectors. Each vector is integrated at the PPC, giving rise to a movement command. The generation of each vector induces a complementary postural phase during which ERG output stops and learning occurs. Then a new vector is generated and the cycle is repeated. This cyclic, biphasic behavior is controlled by a specialized gated dipole circuit. ERG output autonomously stops in such a way that, across trials, a broad sample of workspace target positions is generated. When the ERG shuts off, a modulator gate opens, copying the PPC into the TPC. Learning of a transformation from TPC to PPC occurs using the DV as an error signal that is zeroed due to learning. This learning scheme is called a Vector Associative Map, or VAM. The VAM model is a general-purpose device for autonomous real-time error-based learning and performance of associative maps. The DV stage serves the dual function of reading out new TPCs during performance and reading in new adaptive weights during learning, without a disruption of real-time operation. YAMs thus provide an on-line unsupervised alternative to the off-line properties of supervised error-correction learning algorithms. YAMs and VAM cascades for learning motor-to-motor and spatial-to-motor maps are described. YAM models and Adaptive Resonance Theory (ART) models exhibit complementary matching, learning, and performance properties that together provide a foundation for designing a total sensory-cognitive and cognitive-motor autonomous system.

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.

An Integrated Neural Network-Event-Related Potentials Model of Temporal and Probability Context Effects on Event Categorization

We present a neural network that adapts and integrates several preexisting or new modules to categorize events in short term memory (STM), encode temporal order in working memory, evaluate timing and probability context in medium and long term memory. The model shows how processed contextual information modulates event recognition and categorization, focal attention and incentive motivation. The model is based on a compendium of Event Related Potentials (ERPs) and behavioral results either collected by the authors or compiled from the classical ERP literature. Its hallmark is, at the functional level, the interplay of memory registers endowed with widely different dynamical ranges, and at the structural level, the attempt to relate the different modules to known anatomical structures.