Rosetta is one of the leading algorithms for protein structure prediction today. It is a Monte Carlo energy minimization method requiring many random restarts to find structures with low energy. In this paper we present a resampling technique for structure prediction of small alpha/beta proteins using Rosetta. From an initial roundof Rosetta sampling, we learn properties of the energy landscape that guide a subsequent round of sampling toward lower-energy structures. Rather than attempt to fit the full energy landscape, we use feature selection methods--both L1-regularized linear regression and decision trees--to identify structural features that give rise to low energy. We then enrich these structural features in the second sampling round. Results are presented across a benchmark set of nine small alpha/beta proteinsdemonstrating that our methods seldom impair, and frequently improve, Rosetta's performance.

We study the distribution of the adaptive LASSO estimator (Zou (2006)) in finite samples as well as in the large-sample limit. The large-sample distributions are derived both for the case where the adaptive LASSO estimator is tuned to perform conservative model selection as well as for the case where the tuning results in consistent model selection. We show that the finite-sample as well as the large-sample distributions are typically highly non-normal, regardless of the choice of the tuning parameter. The uniform convergence rate is also obtained, and is shown to be slower than $n^{-1/2}$ in case the estimator is tuned to perform consistent model selection. In particular, these results question the statistical relevance of the `oracle' property of the adaptive LASSO estimator established in Zou (2006). Moreover, we also provide an impossibility result regarding the estimation of the distribution function of the adaptive LASSO estimator.The theoretical results, which are obtained for a regression model with orthogonal design, are complemented by a Monte Carlo study using non-orthogonal regressors.

Regression is a very important method in engineering and science for the estimation of the dependencies between two or more variables on the basis of some given sample points. The best known regression method is certainly the parametric regression technique after Legendre and Gauss, which minimizes the squared error between a model - often a polynom - and the samples. The least squares method is fast and well suitable for strongly linearly correlated data, but seldom appropriate for high-dimensional problems with difficult, unknown, and nonlinear dependencies. For these problems, nonparametric regression techniques - like kernel or Nadaraya-Watson regression methods - are more suitable (Nadaraya [1964], Watson [1964]).

Many complex disease syndromes such as asthma consist of a large number of highly related, rather than independent, clinical phenotypes, raising a new technical challenge in identifying genetic variations associated simultaneously with correlated traits. In this study, we propose a new statistical framework called graph-guided fused lasso (GFlasso) to address this issue in a principled way. Our approach explicitly represents the dependency structure among the quantitative traits as a network, and leverages this trait network to encode structured regularizations in a multivariate regression model over the genotypes and traits, so that the genetic markers that jointly influence subgroups of highly correlated traits can be detected with high sensitivity and specificity. While most of the traditional methods examined each phenotype independently and combined the results afterwards, our approach analyzes all of the traits jointly in a single statistical method, and borrow information across correlated phenotypes to discover the genetic markers that perturbe a subset of correlated triats jointly rather than a single trait. Using simulated datasets based on the HapMap consortium data and an asthma dataset, we compare the performance of our method with the single-marker analysis, and other sparse regression methods such as the ridge regression and the lasso that do not use any structural information in the traits. Our results show that there is a significant advantage in detecting the true causal SNPs when we incorporate the correlation pattern in traits using our proposed methods.

For supervised and unsupervised learning, positive definite kernels allow to use large and potentially infinite dimensional feature spaces with a computational cost that only depends on the number of observations. This is usually done through the penalization of predictor functions by Euclidean or Hilbertian norms. In this paper, we explore penalizing by sparsity-inducing norms such as the l1-norm or the block l1-norm. We assume that the kernel decomposes into a large sum of individual basis kernels which can be embedded in a directed acyclic graph; we show that it is then possible to perform kernel selection through a hierarchical multiple kernel learning framework, in polynomial time in the number of selected kernels. This framework is naturally applied to non linear variable selection; our extensive simulations on synthetic datasets and datasets from the UCI repository show that efficiently exploring the large feature space through sparsity-inducing norms leads to state-of-the-art predictive performance.

It has been widely observed that there is no single "dominant" SAT solver; instead, different solvers perform best on different instances. Rather than following the traditional approach of choosing the best solver for a given class of instances, we advocate making this decision online on a per-instance basis. Building on previous work, we describe SATzilla, an automated approach for constructing per-instance algorithm portfolios for SAT that use so-called empirical hardness models to choose among their constituent solvers. This approach takes as input a distribution of problem instances and a set of component solvers, and constructs a portfolio optimizing a given objective function (such as mean runtime, percent of instances solved, or score in a competition). The excellent performance of SATzilla was independently verified in the 2007 SAT Competition, where our SATzilla07 solvers won three gold, one silver and one bronze medal. In this article, we go well beyond SATzilla07 by making the portfolio construction scalable and completely automated, and improving it by integrating local search solvers as candidate solvers, by predicting performance score instead of runtime, and by using hierarchical hardness models that take into account different types of SAT instances. We demonstrate the effectiveness of these new techniques in extensive experimental results on data sets including instances from the most recent SAT competition.

This work concerns estimation of multidimensional nonlinear regression models using multilayer perceptron (MLP). The main problem with such model is that we have to know the covariance matrix of the noise to get optimal estimator. however we show that, if we choose as cost function the logarithm of the determinant of the empirical error covariance matrix, we get an asymptotically optimal estimator.

In this paper we consider the problem of grouped variable selection in high-dimensional regression using $\ell_1-\ell_q$ regularization ($1\leq q \leq \infty$), which can be viewed as a natural generalization of the $\ell_1-\ell_2$ regularization (the group Lasso). The key condition is that the dimensionality $p_n$ can increase much faster than the sample size $n$, i.e. $p_n \gg n$ (in our case $p_n$ is the number of groups), but the number of relevant groups is small. The main conclusion is that many good properties from $\ell_1-$regularization (Lasso) naturally carry on to the $\ell_1-\ell_q$ cases ($1 \leq q \leq \infty$), even if the number of variables within each group also increases with the sample size. With fixed design, we show that the whole family of estimators are both estimation consistent and variable selection consistent under different conditions. We also show the persistency result with random design under a much weaker condition. These results provide a unified treatment for the whole family of estimators ranging from $q=1$ (Lasso) to $q=\infty$ (iCAP), with $q=2$ (group Lasso)as a special case. When there is no group structure available, all the analysis reduces to the current results of the Lasso estimator ($q=1$).

Recent research has studied the role of sparsity in high dimensional regression and signal reconstruction, establishing theoretical limits for recovering sparse models from sparse data. This line of work shows that $\ell_1$-regularized least squares regression can accurately estimate a sparse linear model from $n$ noisy examples in $p$ dimensions, even if $p$ is much larger than $n$. In this paper we study a variant of this problem where the original $n$ input variables are compressed by a random linear transformation to $m \ll n$ examples in $p$ dimensions, and establish conditions under which a sparse linear model can be successfully recovered from the compressed data. A primary motivation for this compression procedure is to anonymize the data and preserve privacy by revealing little information about the original data. We characterize the number of random projections that are required for $\ell_1$-regularized compressed regression to identify the nonzero coefficients in the true model with probability approaching one, a property called ``sparsistence.'' In addition, we show that $\ell_1$-regularized compressed regression asymptotically predicts as well as an oracle linear model, a property called ``persistence.'' Finally, we characterize the privacy properties of the compression procedure in information-theoretic terms, establishing upper bounds on the mutual information between the compressed and uncompressed data that decay to zero.

Multinomial logistic regression provides the standard penalised maximumlikelihood solution to multi-class pattern recognition problems. More recently, the development of sparse multinomial logistic regression models has found application in text processing and microarray classification, where explicit identification of the most informative features is of value. In this paper, we propose a sparse multinomial logistic regression method, in which the sparsity arises from the use of a Laplace prior, but where the usual regularisation parameter is integrated out analytically. Evaluation over a range of benchmark datasets reveals this approach results in similar generalisation performance to that obtained using cross-validation, but at greatly reduced computational expense.