iPACOSE: an iterative algorithm for the estimation of gene regulation networks

In the context of Gaussian Graphical Models (GGMs) with high- dimensional small sample data, we present a simple procedure to esti- mate partial correlations under the constraint that some of them are strictly zero. This method can also be extended to covariance selection. If the goal is to estimate a GGM, our new procedure can be applied to re-estimate the partial correlations after a first graph has been esti- mated in the hope to improve the estimation of non-zero coefficients. In a simulation study, we compare our new covariance selection procedure to existing methods and show that the re-estimated partial correlation coefficients may be closer to the real values in important cases

Use of pre-transformation to cope with outlying values in important candidate genes

Outlying values in predictors often strongly affect the results of statistical analyses in high-dimensional settings. Although they frequently occur with most high-throughput techniques, the problem is often ignored in the literature. We suggest to use a very simple transformation, proposed before in a different context by Royston and Sauerbrei, as an intermediary step between array normalization and high-level statistical analysis. This straightforward univariate transformation identifies extreme values and reduces the influence of outlying values considerably in all further steps of statistical analysis without eliminating the incriminated observation or feature. The use of the transformation and its effects are demonstrated for diverse univariate and multivariate statistical analyses using nine publicly available microarray data sets

Iterative reconstruction of high-dimensional Gaussian Graphical Models based on a new method to estimate partial correlations under constraints.

In the context of Gaussian Graphical Models (GGMs) with high-dimensional small sample data, we present a simple procedure, called PACOSE - standing for PArtial COrrelation SElection - to estimate partial correlations under the constraint that some of them are strictly zero. This method can also be extended to covariance selection. If the goal is to estimate a GGM, our new procedure can be applied to re-estimate the partial correlations after a first graph has been estimated in the hope to improve the estimation of non-zero coefficients. This iterated version of PACOSE is called iPACOSE. In a simulation study, we compare PACOSE to existing methods and show that the re-estimated partial correlation coefficients may be closer to the real values in important cases. Plus, we show on simulated and real data that iPACOSE shows very interesting properties with regards to sensitivity, positive predictive value and stability

SHrinkage Covariance Estimation Incorporating Prior Biological Knowledge with Applications to High-Dimensional Data

In ``-omic data'' analysis, information on the structure of covariates are broadly available either from public databases describing gene regulation processes and functional groups such as the Kyoto encyclopedia of genes and genomes (KEGG), or from statistical analyses -- for example in form of partial correlation estimators. The analysis of transcriptomic data might benefit from the incorporation of such prior knowledge. In this paper we focus on the integration of structured information into statistical analyses in which at least one major step involves the estimation of a (high-dimensional) covariance matrix. More precisely, we revisit the recently proposed ``SHrinkage Incorporating Prior'' (SHIP) covariance estimation method which takes into account the group structure of the covariates, and suggest to integrate the SHIP covariance estimator into various multivariate methods such as linear discriminant analysis (LDA), global analysis of covariance (GlobalANCOVA), and regularized generalized canonical correlation analysis (RGCCA). We demonstrate the use of the resulting new methods based on simulations and discuss the benefit of the integration of prior information through the SHIP estimator. Reproducible R codes are available at http://www.ibe.med.uni-muenchen.de/organisation/mitarbeiter/020_professuren/boulesteix/shipproject/index.html

SHrinkage Covariance Estimation Incorporating Prior Biological Knowledge with Applications to High-Dimensional Data

In ``-omic data'' analysis, information on the structure of covariates are broadly available either from public databases describing gene regulation processes and functional groups such as the Kyoto encyclopedia of genes and genomes (KEGG), or from statistical analyses -- for example in form of partial correlation estimators. The analysis of transcriptomic data might benefit from the incorporation of such prior knowledge. In this paper we focus on the integration of structured information into statistical analyses in which at least one major step involves the estimation of a (high-dimensional) covariance matrix. More precisely, we revisit the recently proposed ``SHrinkage Incorporating Prior'' (SHIP) covariance estimation method which takes into account the group structure of the covariates, and suggest to integrate the SHIP covariance estimator into various multivariate methods such as linear discriminant analysis (LDA), global analysis of covariance (GlobalANCOVA), and regularized generalized canonical correlation analysis (RGCCA). We demonstrate the use of the resulting new methods based on simulations and discuss the benefit of the integration of prior information through the SHIP estimator. Reproducible R codes are available at http://www.ibe.med.uni-muenchen.de/organisation/mitarbeiter/020_professuren/boulesteix/shipproject/index.html

Continuation of Nesterov's Smoothing for Regression with Structured Sparsity in High-Dimensional Neuroimaging

Predictive models can be used on high-dimensional brain images for diagnosis of a clinical condition. Spatial regularization through structured sparsity offers new perspectives in this context and reduces the risk of overfitting the model while providing interpretable neuroimaging signatures by forcing the solution to adhere to domain-specific constraints. Total Variation (TV) enforces spatial smoothness of the solution while segmenting predictive regions from the background. We consider the problem of minimizing the sum of a smooth convex loss, a non-smooth convex penalty (whose proximal operator is known) and a wide range of possible complex, non-smooth convex structured penalties such as TV or overlapping group Lasso. Existing solvers are either limited in the functions they can minimize or in their practical capacity to scale to high-dimensional imaging data. Nesterov's smoothing technique can be used to minimize a large number of non-smooth convex structured penalties but reasonable precision requires a small smoothing parameter, which slows down the convergence speed. To benefit from the versatility of Nesterov's smoothing technique, we propose a first order continuation algorithm, CONESTA, which automatically generates a sequence of decreasing smoothing parameters. The generated sequence maintains the optimal convergence speed towards any globally desired precision. Our main contributions are: To propose an expression of the duality gap to probe the current distance to the global optimum in order to adapt the smoothing parameter and the convergence speed. We provide a convergence rate, which is an improvement over classical proximal gradient smoothing methods. We demonstrate on both simulated and high-dimensional structural neuroimaging data that CONESTA significantly outperforms many state-of-the-art solvers in regard to convergence speed and precision.Comment: 11 pages, 6 figures, accepted in IEEE TMI, IEEE Transactions on Medical Imaging 201

Over-optimism in bioinformatics: an illustration

In statistical bioinformatics research, different optimization mechanisms potentially lead to "over-optimism" in published papers. The present empirical study illustrates these mechanisms through a concrete example from an active research field. The investigated sources of over-optimism include the optimization of the data sets, of the settings, of the competing methods and, most importantly, of the method’s characteristics. We consider a "promising" new classification algorithm that turns out to yield disappointing results in terms of error rate, namely linear discriminant analysis incorporating prior knowledge on gene functional groups through an appropriate shrinkage of the within-group covariance matrix. We quantitatively demonstrate that this disappointing method can artificially seem superior to existing approaches if we "fish for significance”. We conclude that, if the improvement of a quantitative criterion such as the error rate is the main contribution of a paper, the superiority of new algorithms should be validated using "fresh" validation data sets

Incremental-LDI for Multi-View Coding

International audienceThis paper describes an Incremental algorithm for Layer Depth Image construction (I-LDI) from multi-view plus depth data sets. A solution to sampling artifacts is proposed, based on pixel interpolation (inpainting) restricted to isolated unknown pixels. A solution to ghosting artifacts is also proposed, based on a depth discontinuity detection, followed by a local foreground / background classification. We propose a formulation of warping equations which reduces time consumption, specifically for LDI warping. Tests on Breakdancers and Ballet MVD data sets show that extra layers in I-LDI contain only 10% of first layer pixels, compared to 50% for LDI. I-LDI Layers are also more compact, with a less spread pixel distribution, and thus easier to compress than LDI Visual rendering is of similar quality with I-LDI and LDI

Analyse différentielle de puces à ADN. Comparaison entre méthodes wrapper et filter.

13Dans le cadre de données d'expression génétique, nous nous intéressons aux méthodes qui permettent d'identifier les gènes significativement différentiellement exprimés entre deux situations biologiques. Nous allons comparer une méthode classique d'analyse par tests d'hypothèses à des méthodes d'analyse différentielle par régression régularisée. La difficulté de ce genre de jeu de données est la profusion de variables (les gènes) pour assez peu d'individus (les profils d'expression). La stratégie usuelle consiste à mettre en oeuvre autant de tests qu'il y a de variables et de considérer que les variables principales sont celles qui ont la « meilleure »p-value. Une stratégie alternative pourrait consister à choisir de classer les variables non plus en fonction de leur significativité (pour un test), mais plutôt de le classer suivant leur poids dans le modèle régularisé obtenu. Dans la bibliographie, les premières méthodes sont dites filter1, les deuxièmes sont plutôt dites wrapper2. Un bon aperçu de ce que sont les méthodes wrapper et filter est donné dans [9]. Le cadre ressemble à celui de l'apprentissage supervisé, car on dispose de profils d'expression géniques pour si possible l'ensemble du génome d'un organisme, chaque puce appartenant à une classe- situation biologique particulière (par exemple malade vs sain). L'implémentation des méthodes évoquées dans ce rapport a été effectuée sous R [16]

Grouping levels of exposure with same observable effects before class prediction in toxicogenomics.

International audienceGene expression profiling in toxicogenomics is often used to find molecular signature of toxicants. The range of doses chosen in toxicogenomics studies does not always represent all the possible effects on gene expression: several doses of toxicant can lead to the same observable effect on the transcriptome. This makes the problem of dose exposure prediction difficult to address. We propose a strategy allowing to gather the doses with similar effects prior to the computing of a molecular signature. The different gathering of doses are compared with criteria based on likelihood or Monte Carlo Cross Validation. The molecular signature is then determined via a voting algorithm. Experimental results point out that the obtained classifier has better prediction performances than the classifier computed according to the original labeling