Vincent Y. F. Tan

BEYOND ATOPY: MULTIPLE PATTERNS OF SENSITIZATION IN RELATION TO ASTHMA IN A BIRTH COHORT STUDY

RATIONALE The pattern of IgE response (over time or to specific allergens) may reflect different atopic vulnerabilities which are related to the presence of asthma in a fundamentally different way from current definition of atopy. OBJECTIVES To redefine the atopic phenotype by identifying latent structure within a complex dataset, taking into account the timing and type of sensitization to specific allergens, and relating these novel phenotypes to asthma. METHODS In a population-based birth cohort in which multiple skin and IgE tests have been taken throughout childhood, we used a machine learning approach to cluster children into multiple atopic classes in an unsupervised way. We then investigated the relation between these classes and asthma (symptoms, hospitalizations, lung function and airway reactivity). MEASUREMENTS AND MAIN RESULTS A five-class model indicated a complex latent structure, in which children with atopic vulnerability were clustered into four distinct classes (Multiple Early [112/1053, 10.6%]; Multiple Late [171/1053, 16.2%]; Dust Mite [47/1053, 4.5%]; and Non-dust Mite [100/1053, 9.5%]), with a fifth class describing children with No Latent Vulnerability (623/1053, 59.2%). The association with asthma was considerably stronger for Multiple Early compared with other classes and conventionally defined atopy (odds ratio [95% CI]: 29.3 [11.1-77.2] versus 12.4 [4.8-32.2] versus 11.6 [4.8-27.9] for Multiple Early class versus Ever Atopic versus Atopic age 8). Lung function and airway reactivity were significantly poorer among children in Multiple Early class. Cox regression demonstrated a highly significant increase in risk of hospital admissions for wheeze/asthma after age 3 yr only among children in the Multiple Early class (HR 9.2 [3.5-24.0], P < 0.001). CONCLUSIONS IgE antibody responses do not reflect a single phenotype of atopy, but several different atopic vulnerabilities which differ in their relation with asthma presence and severity.

Automatic Relevance Determination in Nonnegative Matrix Factorization with the

This paper addresses the estimation of the latent dimensionality in nonnegative matrix factorization (NMF) with the β-divergence. The β-divergence is a family of cost functions that includes the squared euclidean distance, Kullback-Leibler (KL) and Itakura-Saito (IS) divergences as special cases. Learning the model order is important as it is necessary to strike the right balance between data fidelity and overfitting. We propose a Bayesian model based on automatic relevance determination (ARD) in which the columns of the dictionary matrix and the rows of the activation matrix are tied together through a common scale parameter in their prior. A family of majorization-minimization (MM) algorithms is proposed for maximum a posteriori (MAP) estimation. A subset of scale parameters is driven to a small lower bound in the course of inference, with the effect of pruning the corresponding spurious components. We demonstrate the efficacy and robustness of our algorithms by performing extensive experiments on synthetic data, the swimmer dataset, a music decomposition example, and a stock price prediction task.

(\beta)

ABSTRACT The promiscuous presentation of epitopes by similar HLA class I alleles holds promise for a universal T-cell-based HIV-1 vaccine. However, in some instances, cytotoxic T lymphocytes (CTL) restricted by HLA alleles with similar or identical binding motifs are known to target epitopes at different frequencies, with different functional avidities and with different apparent clinical outcomes. Such differences may be illuminated by the association of similar HLA alleles with distinctive escape pathways. Using a novel computational method featuring phylogenetically corrected odds ratios, we systematically analyzed differential patterns of immune escape across all optimally defined epitopes in Gag, Pol, and Nef in 2,126 HIV-1 clade C-infected adults. Overall, we identified 301 polymorphisms in 90 epitopes associated with HLA alleles belonging to shared supertypes. We detected differential escape in 37 of 38 epitopes restricted by more than one allele, which included 278 instances of differential escape at the polymorphism level. The majority (66 to 97%) of these resulted from the selection of unique HLA-specific polymorphisms rather than differential epitope targeting rates, as confirmed by gamma interferon (IFN-γ) enzyme-linked immunosorbent spot assay (ELISPOT) data. Discordant associations between HLA alleles and viral load were frequently observed between allele pairs that selected for differential escape. Furthermore, the total number of associated polymorphisms strongly correlated with average viral load. These studies confirm that differential escape is a widespread phenomenon and may be the norm when two alleles present the same epitope. Given the clinical correlates of immune escape, such heterogeneity suggests that certain epitopes will lead to discordant outcomes if applied universally in a vaccine.

-Divergence

This monograph presents a unified treatment of single- and multi-user problems in Shannons information theory where we depart from the requirement that the error probability decays asymptotically in the blocklength. Instead, the error probabilities for various problems are bounded above by a non-vanishing constant and the spotlight is shone on achievable coding rates as functions of the growing blocklengths. This represents the study of asymptotic estimates with non-vanishing error probabilities.In Part I, after reviewing the fundamentals of information theory, we discuss Strassens seminal result for binary hypothesis testing where the type-I error probability is non-vanishing and the rate of decay of the type-II error probability with growing number of independent observations is characterized. In Part II, we use this basic hypothesis testing result to develop second- and sometimes, even third-order asymptotic expansions for point-to-point communication. Finally in Part III, we consider network information theory problems for which the second order asymptotics are known. These problems include some classes of channels with random state, the multiple-encoder distributed lossless source coding (Slepian-Wolf) problem and special cases of the Gaussian interference and multiple-access channels. Finally, we discuss avenues for further research.

Widespread Impact of HLA Restriction on Immune Control and Escape Pathways of HIV-1

This paper shows that the logarithm of the ε-error capacity (average error probability) for n uses of a discrete memoryless channel (DMC) is upper bounded by the normal approximation plus a third-order term that does not exceed [ 1/ 2] logn +O(1) if the ε-dispersion of the channel is positive. This matches a lower bound by Y. Polyanskiy (2010) for DMCs with positive reverse dispersion. If the ε-dispersion vanishes, the logarithm of the ε-error capacity is upper bounded by n times the capacity plus a constant term except for a small class of DMCs and ε ≥ [ 1/ 2].

Asymptotic Estimates in Information Theory with Non-Vanishing Error Probabilities

We characterize fundamental limits for the Slepian-Wolf problem, the multiple-access channel and the asymmetric broadcast channel in the finite blocklength setting. For the Slepian-Wolf problem (distributed lossless source coding), we introduce a fundamental quantity known as the entropy dispersion matrix. We show that if this matrix is positive-definite, the optimal rate region under the constraint of a fixed blocklength and non-zero error probability has a curved boundary compared to being polyhedral for the asymptotic Slepian-Wolf scenario. In addition, the entropy dispersion matrix governs the rate of convergence of the non-asymptotic region to the asymptotic one. We develop a general universal achievability procedure for finite blocklength analyses of other network information theory problems such as the multiple-access channel and broadcast channel. We provide inner bounds to these problems using a key result known as the vector rate redundancy theorem which is proved using a multidimensional version of the Berry-Essèen theorem. We show that a so-called information dispersion matrix characterizes these inner bounds.

A Tight Upper Bound for the Third-Order Asymptotics for Most Discrete Memoryless Channels

We consider the scenario in which multiple sensors send spatially correlated data to a fusion center (FC) via independent Rayleigh-fading channels with additive noise. Assuming that the sensor data is sparse in some basis, we show that the recovery of this sparse signal can be formulated as a compressive sensing (CS) problem. To model the scenario in which the sensors operate with intermittently available energy that is harvested from the environment, we propose that each sensor transmits independently with some probability, and adapts the transmit power to its harvested energy. Due to the probabilistic transmissions, the elements of the equivalent sensing matrix are not Gaussian. Besides, since the sensors have different energy harvesting rates and different sensor-to-FC distances, the FC has different receive signal-to-noise ratios (SNRs) for each sensor. This is referred to as the inhomogeneity of SNRs. Thus, the elements of the sensing matrix are also not identically distributed. For this unconventional setting, we provide theoretical guarantees on the number of measurements for reliable and computationally efficient recovery, by showing that the sensing matrix satisfies the restricted isometry property (RIP), under reasonable conditions. We then compute an achievable system delay under an allowable mean-squared-error (MSE). Furthermore, using techniques from large deviations theory, we analyze the impact of inhomogeneity of SNRs on the so-called k-restricted eigenvalues, which governs the number of measurements required for the RIP to hold. We conclude that the number of measurements required for the RIP is not sensitive to the inhomogeneity of SNRs, when the number of sensors n is large and the sparsity of the sensor data (signal) k grows slower than the square root of n. Our analysis is corroborated by extensive numerical results.

On the Dispersions of Three Network Information Theory Problems

As an example of the recently introduced concept of rate of innovation, signals that are linear combinations of a finite number of Diracs per unit time can be acquired by linear filtering followed by uniform sampling. However, in reality, samples are rarely noiseless. In this paper, we introduce a novel stochastic algorithm to reconstruct a signal with finite rate of innovation from its noisy samples. Even though variants of this problem have been approached previously, satisfactory solutions are only available for certain classes of sampling kernels, for example, kernels that satisfy the Strang-Fix condition. In this paper, we consider the infinite-support Gaussian kernel, which does not satisfy the Strang-Fix condition. Other classes of kernels can be employed. Our algorithm is based on Gibbs sampling, a Markov chain Monte Carlo method. Extensive numerical simulations demonstrate the accuracy and robustness of our algorithm.

Wireless Compressive Sensing for Energy Harvesting Sensor Nodes

We consider the problem of high-dimensional Ising (graphical) model selection. We propose a simple algorithm for structure estimation based on the thresholding of the empirical conditional variation distances. We introduce a novel criterion for tractable graph families, where this method is efficient, based on the presence of sparse local separators between node pairs in the underlying graph. For such graphs, the proposed algorithm has a sample complexity of

Estimating Signals With Finite Rate of Innovation From Noisy Samples: A Stochastic Algorithm

n=\Omega(J_{\min}^{-2}\log p)