TY - JOUR A1 - Mieth, Bettina A1 - Kloft, Marius A1 - Rodriguez, Juan Antonio A1 - Sonnenburg, Soren A1 - Vobruba, Robin A1 - Morcillo-Suarez, Carlos A1 - Farre, Xavier A1 - Marigorta, Urko M. A1 - Fehr, Ernst A1 - Dickhaus, Thorsten A1 - Blanchard, Gilles A1 - Schunk, Daniel A1 - Navarro, Arcadi A1 - Müller, Klaus-Robert T1 - Combining Multiple Hypothesis Testing with Machine Learning Increases the Statistical Power of Genome-wide Association Studies JF - Scientific reports N2 - The standard approach to the analysis of genome-wide association studies (GWAS) is based on testing each position in the genome individually for statistical significance of its association with the phenotype under investigation. To improve the analysis of GWAS, we propose a combination of machine learning and statistical testing that takes correlation structures within the set of SNPs under investigation in a mathematically well-controlled manner into account. The novel two-step algorithm, COMBI, first trains a support vector machine to determine a subset of candidate SNPs and then performs hypothesis tests for these SNPs together with an adequate threshold correction. Applying COMBI to data from a WTCCC study (2007) and measuring performance as replication by independent GWAS published within the 2008-2015 period, we show that our method outperforms ordinary raw p-value thresholding as well as other state-of-the-art methods. COMBI presents higher power and precision than the examined alternatives while yielding fewer false (i.e. non-replicated) and more true (i.e. replicated) discoveries when its results are validated on later GWAS studies. More than 80% of the discoveries made by COMBI upon WTCCC data have been validated by independent studies. Implementations of the COMBI method are available as a part of the GWASpi toolbox 2.0. Y1 - 2016 U6 - https://doi.org/10.1038/srep36671 SN - 2045-2322 VL - 6 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Blanchard, Gilles A1 - Kraemer, Nicole T1 - Convergence rates of Kernel Conjugate Gradient for random design regression JF - Analysis and applications N2 - We prove statistical rates of convergence for kernel-based least squares regression from i.i.d. data using a conjugate gradient (CG) algorithm, where regularization against over-fitting is obtained by early stopping. This method is related to Kernel Partial Least Squares, a regression method that combines supervised dimensionality reduction with least squares projection. Following the setting introduced in earlier related literature, we study so-called "fast convergence rates" depending on the regularity of the target regression function (measured by a source condition in terms of the kernel integral operator) and on the effective dimensionality of the data mapped into the kernel space. We obtain upper bounds, essentially matching known minimax lower bounds, for the L-2 (prediction) norm as well as for the stronger Hilbert norm, if the true regression function belongs to the reproducing kernel Hilbert space. If the latter assumption is not fulfilled, we obtain similar convergence rates for appropriate norms, provided additional unlabeled data are available. KW - Nonparametric regression KW - reproducing kernel Hilbert space KW - conjugate gradient KW - partial least squares KW - minimax convergence rates Y1 - 2016 U6 - https://doi.org/10.1142/S0219530516400017 SN - 0219-5305 SN - 1793-6861 VL - 14 SP - 763 EP - 794 PB - World Scientific CY - Singapore ER - TY - JOUR A1 - Blanchard, Gilles A1 - Flaska, Marek A1 - Handy, Gregory A1 - Pozzi, Sara A1 - Scott, Clayton T1 - Classification with asymmetric label noise: Consistency and maximal denoising JF - Electronic journal of statistics N2 - In many real-world classification problems, the labels of training examples are randomly corrupted. Most previous theoretical work on classification with label noise assumes that the two classes are separable, that the label noise is independent of the true class label, or that the noise proportions for each class are known. In this work, we give conditions that are necessary and sufficient for the true class-conditional distributions to be identifiable. These conditions are weaker than those analyzed previously, and allow for the classes to be nonseparable and the noise levels to be asymmetric and unknown. The conditions essentially state that a majority of the observed labels are correct and that the true class-conditional distributions are "mutually irreducible," a concept we introduce that limits the similarity of the two distributions. For any label noise problem, there is a unique pair of true class-conditional distributions satisfying the proposed conditions, and we argue that this pair corresponds in a certain sense to maximal denoising of the observed distributions. Our results are facilitated by a connection to "mixture proportion estimation," which is the problem of estimating the maximal proportion of one distribution that is present in another. We establish a novel rate of convergence result for mixture proportion estimation, and apply this to obtain consistency of a discrimination rule based on surrogate loss minimization. Experimental results on benchmark data and a nuclear particle classification problem demonstrate the efficacy of our approach. KW - Classification KW - label noise KW - mixture proportion estimation KW - surrogate loss KW - consistency Y1 - 2016 U6 - https://doi.org/10.1214/16-EJS1193 SN - 1935-7524 VL - 10 SP - 2780 EP - 2824 PB - Institute of Mathematical Statistics CY - Cleveland ER - TY - INPR A1 - Blanchard, Gilles A1 - Mücke, Nicole T1 - Optimal rates for regularization of statistical inverse learning problems N2 - We consider a statistical inverse learning problem, where we observe the image of a function f through a linear operator A at i.i.d. random design points X_i, superposed with an additional noise. The distribution of the design points is unknown and can be very general. We analyze simultaneously the direct (estimation of Af) and the inverse (estimation of f) learning problems. In this general framework, we obtain strong and weak minimax optimal rates of convergence (as the number of observations n grows large) for a large class of spectral regularization methods over regularity classes defined through appropriate source conditions. This improves on or completes previous results obtained in related settings. The optimality of the obtained rates is shown not only in the exponent in n but also in the explicit dependence of the constant factor in the variance of the noise and the radius of the source condition set. T3 - Preprints des Instituts für Mathematik der Universität Potsdam - 5 (2016) 5 KW - statistical inverse problem KW - minimax rate KW - kernel method Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-89782 SN - 2193-6943 VL - 5 IS - 5 PB - Universitätsverlag Potsdam CY - Potsdam ER - TY - INPR A1 - Blanchard, Gilles A1 - Delattre, Sylvain A1 - Roquain, Étienne T1 - Testing over a continuum of null hypotheses N2 - We introduce a theoretical framework for performing statistical hypothesis testing simultaneously over a fairly general, possibly uncountably infinite, set of null hypotheses. This extends the standard statistical setting for multiple hypotheses testing, which is restricted to a finite set. This work is motivated by numerous modern applications where the observed signal is modeled by a stochastic process over a continuum. As a measure of type I error, we extend the concept of false discovery rate (FDR) to this setting. The FDR is defined as the average ratio of the measure of two random sets, so that its study presents some challenge and is of some intrinsic mathematical interest. Our main result shows how to use the p-value process to control the FDR at a nominal level, either under arbitrary dependence of p-values, or under the assumption that the finite dimensional distributions of the p-value process have positive correlations of a specific type (weak PRDS). Both cases generalize existing results established in the finite setting, the latter one leading to a less conservative procedure. The interest of this approach is demonstrated in several non-parametric examples: testing the mean/signal in a Gaussian white noise model, testing the intensity of a Poisson process and testing the c.d.f. of i.i.d. random variables. Conceptually, an interesting feature of the setting advocated here is that it focuses directly on the intrinsic hypothesis space associated with a testing model on a random process, without referring to an arbitrary discretization. T3 - Preprints des Instituts für Mathematik der Universität Potsdam - 1 (2012) 1 Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus-56877 ER -