Viral population estimation using pyrosequencing

The diversity of virus populations within single infected hosts presents a major difficulty for the natural immune response as well as for vaccine design and antiviral drug therapy. Recently developed pyrophosphate based sequencing technologies (pyrosequencing) can be used for quantifying this diversity by ultra-deep sequencing of virus samples. We present computational methods for the analysis of such sequence data and apply these techniques to pyrosequencing data obtained from HIV populations within patients harboring drug resistant virus strains. Our main result is the estimation of the population structure of the sample from the pyrosequencing reads. This inference is based on a statistical approach to error correction, followed by a combinatorial algorithm for constructing a minimal set of haplotypes that explain the data. Using this set of explaining haplotypes, we apply a statistical model to infer the frequencies of the haplotypes in the population via an EM algorithm. We demonstrate that pyrosequencing reads allow for effective population reconstruction by extensive simulations and by comparison to 165 sequences obtained directly from clonal sequencing of four independent, diverse HIV populations. Thus, pyrosequencing can be used for cost-effective estimation of the structure of virus populations, promising new insights into viral evolutionary dynamics and disease control strategies.Comment: 23 pages, 13 figure

Learning near-optimal policies with Bellman-residual minimization based fitted policy iteration and a single sample path

We consider the problem of finding a near-optimal policy in continuous space, discounted Markovian Decision Problems given the trajectory of some behaviour policy. We study the policy iteration algorithm where in successive iterations the action-value functions of the intermediate policies are obtained by picking a function from some fixed function set (chosen by the user) that minimizes an unbiased finite-sample approximation to a novel loss function that upper-bounds the unmodified Bellman-residual criterion. The main result is a finite-sample, high-probability bound on the performance of the resulting policy that depends on the mixing rate of the trajectory, the capacity of the function set as measured by a novel capacity concept that we call the VC-crossing dimension, the approximation power of the function set and the discounted-average concentrability of the future-state distribution. To the best of our knowledge this is the first theoretical reinforcement learning result for off-policy control learning over continuous state-spaces using a single trajectory

Let's Get Lade: Robust Estimation of Semiparametric Multiplicative Volatility Models

We investigate a model in which we connect slowly time varying unconditional long-run volatility with short-run conditional volatility whose representation is given as a semi-strong GARCH (1,1) process with heavy tailed errors. We focus on robust estimation of both long-run and short-run volatilities. Our estimation is semiparametric since the long-run volatility is totally unspeci.ed whereas the short-run conditional volatility is a parametric semi-strong GARCH (1,1) process. We propose different robust estimation methods for nonstationary and strictly stationary GARCH parameters with nonparametric long run volatility function. Our estimation is based on a two-step LAD procedure. We establish the relevant asymptotic theory of the proposed estimators. Numerical results lend support to our theoretical results

Nonparametric Beta Kernel Estimator for Long and Short Memory Time Series

In this article we introduces a nonparametric estimator of the spectral density by smoothing the periodogram using beta kernel density. The estimator is proved to be bounded for short memory data and diverges at the origin for long memory data. The convergence in probability of the relative error and Monte Carlo simulations show that the proposed estimator automatically adapts to the long‐ and the short‐range dependency of the process. A cross‐validation procedure is studied in order to select the nuisance parameter of the estimator. Illustrations on historical as well as most recent returns and absolute returns of the S&P500 index show the performance of the beta kernel estimator

Partial Independence in Nonseparable Models

We analyze identification of nonseparable models under three kinds of exogeneity assumptions weaker than full statistical independence. The first is based on quantile independence. Selection on unobservables drives deviations from full independence. We show that such deviations based on quantile independence require non-monotonic and oscillatory propensity scores. Our second and third approaches are based on a distance-from-independence metric, using either a conditional cdf or a propensity score. Under all three approaches we obtain simple analytical characterizations of identified sets for various parameters of interest. We do this in three models: the exogenous regressor model of Matzkin (2003), the instrumental variable model of Chernozhukov and Hansen (2005), and the binary choice model with nonparametric latent utility of Matzkin (1992)

Nonparametric Copula-Based Test for Conditional Independence with Applications to Granger Causality

This article proposes a new nonparametric test for conditional independence that can directly be applied to test for Granger causality. Based on the comparison of copula densities, the test is easy to implement because it does not involve a weighting function in the test statistic, and it can be applied in general settings since there is no restriction on the dimension of the time series data. In fact, to apply the test, only a bandwidth is needed for the nonparametric copula. We prove that the test statistic is asymptotically pivotal under the null hypothesis, establishes local power properties, and motivates the validity of the bootstrap technique that we use in finite sample settings. A simulation study illustrates the size and power properties of the test. We illustrate the practical relevance of our test by considering two empirical applications where we examine the Granger noncausality between financial variables. In a first application and contrary to the general findings in the literature, we provide evidence on two alternative mechanisms of nonlinear interaction between returns and volatilities: nonlinear leverage and volatility feedback effects. This can help better understand the well known asymmetric volatility phenomenon. In a second application, we investigate the Granger causality between stock index returns and trading volume. We find convincing evidence of linear and nonlinear feedback effects from stock returns to volume, but a weak evidence of nonlinear feedback effect from volume to stock returns