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Yufeng Liu

Publications and source records attributed to Yufeng Liu.

67 records · Page 4Linked to original sources

Penalized linear regression with high-dimensional pairwise screening

In variable selection, most existing screening methods focus on marginal effects and ignore dependence between covariates. To improve the performance of selection, we incorporate pairwise effects in covariates for screening and penalization. We achieve this by studying the asymptotic distribution of the maximal absolute pairwise sample correlation among independent covariates. The novelty of the theory is in that the convergence is with respect to the dimensionality $p$, and is uniform with respect to the sample size $n$. Moreover, we obtain an upper bound for the maximal pairwise R squared when regressing the response onto two different covariates. Based on these extreme value results, we propose a screening procedure to detect covariates pairs that are potentially correlated and associated with the response. We further combine the pairwise screening with Sure Independence Screening and develop a new regularized variable selection procedure. Numerical studies show that our method is very competitive in terms of both prediction accuracy and variable selection accuracy.

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Efficient Test-based Variable Selection for High-dimensional Linear Models

Variable selection plays a fundamental role in high-dimensional data analysis. Various methods have been developed for variable selection in recent years. Well-known examples are forward stepwise regression (FSR) and least angle regression (LARS), among others. These methods typically add variables into the model one by one. For such selection procedures, it is crucial to find a stopping criterion that controls model complexity. One of the most commonly used techniques to this end is cross-validation (CV) which, in spite of its popularity, has two major drawbacks: expensive computational cost and lack of statistical interpretation. To overcome these drawbacks, we introduce a flexible and efficient test-based variable selection approach that can be incorporated into any sequential selection procedure. The test, which is on the overall signal in the remaining inactive variables, is based on the maximal absolute partial correlation between the inactive variables and the response given active variables. We develop the asymptotic null distribution of the proposed test statistic as the dimension tends to infinity uniformly in the sample size. We also show that the test is consistent. With this test, at each step of the selection, a new variable is included if and only if the $p$-value is below some pre-defined level. Numerical studies show that the proposed method delivers very competitive performance in terms of variable selection accuracy and computational complexity compared to CV.

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Simultaneous Clustering and Estimation of Heterogeneous Graphical Models

We consider joint estimation of multiple graphical models arising from heterogeneous and high-dimensional observations. Unlike most previous approaches which assume that the cluster structure is given in advance, an appealing feature of our method is to learn cluster structure while estimating heterogeneous graphical models. This is achieved via a high dimensional version of Expectation Conditional Maximization (ECM) algorithm (Meng and Rubin, 1993). A joint graphical lasso penalty is imposed on the conditional maximization step to extract both homogeneity and heterogeneity components across all clusters. Our algorithm is computationally efficient due to fast sparse learning routines and can be implemented without unsupervised learning knowledge. The superior performance of our method is demonstrated by extensive experiments and its application to a Glioblastoma cancer dataset reveals some new insights in understanding the Glioblastoma cancer. In theory, a non-asymptotic error bound is established for the output directly from our high dimensional ECM algorithm, and it consists of two quantities: statistical error (statistical accuracy) and optimization error (computational complexity). Such a result gives a theoretical guideline in terminating our ECM iterations.

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Double Sparsity Kernel Learning with Automatic Variable Selection and Data Extraction

Learning with Reproducing Kernel Hilbert Spaces (RKHS) has been widely used in many scientific disciplines. Because a RKHS can be very flexible, it is common to impose a regularization term in the optimization to prevent overfitting. Standard RKHS learning employs the squared norm penalty of the learning function. Despite its success, many challenges remain. In particular, one cannot directly use the squared norm penalty for variable selection or data extraction. Therefore, when there exists noise predictors, or the underlying function has a sparse representation in the dual space, the performance of standard RKHS learning can be suboptimal. In the literature,work has been proposed on how to perform variable selection in RKHS learning, and a data sparsity constraint was considered for data extraction. However, how to learn in a RKHS with both variable selection and data extraction simultaneously remains unclear. In this paper, we propose a unified RKHS learning method, namely, DOuble Sparsity Kernel (DOSK) learning, to overcome this challenge. An efficient algorithm is provided to solve the corresponding optimization problem. We prove that under certain conditions, our new method can asymptotically achieve variable selection consistency. Simulated and real data results demonstrate that DOSK is highly competitive among existing approaches for RKHS learning.

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Estimating Individualized Treatment Rules for Ordinal Treatments

Precision medicine is an emerging scientific topic for disease treatment and prevention that takes into account individual patient characteristics. It is an important direction for clinical research, and many statistical methods have been recently proposed. One of the primary goals of precision medicine is to obtain an optimal individual treatment rule (ITR), which can help make decisions on treatment selection according to each patient's specific characteristics. Recently, outcome weighted learning (OWL) has been proposed to estimate such an optimal ITR in a binary treatment setting by maximizing the expected clinical outcome. However, for ordinal treatment settings, such as individualized dose finding, it is unclear how to use OWL. In this paper, we propose a new technique for estimating ITR with ordinal treatments. In particular, we propose a data duplication technique with a piecewise convex loss function. We establish Fisher consistency for the resulting estimated ITR under certain conditions, and obtain the convergence and risk bound properties. Simulated examples and two applications to datasets from an irritable bowel problem and a type 2 diabetes mellitus observational study demonstrate the highly competitive performance of the proposed method compared to existing alternatives.

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Stability Enhanced Large-Margin Classifier Selection

Stability is an important aspect of a classification procedure because unstable predictions can potentially reduce users' trust in a classification system and also harm the reproducibility of scientific conclusions. The major goal of our work is to introduce a novel concept of classification instability, i.e., decision boundary instability (DBI), and incorporate it with the generalization error (GE) as a standard for selecting the most accurate and stable classifier. Specifically, we implement a two-stage algorithm: (i) initially select a subset of classifiers whose estimated GEs are not significantly different from the minimal estimated GE among all the candidate classifiers; (ii) the optimal classifier is chosen as the one achieving the minimal DBI among the subset selected in stage (i). This general selection principle applies to both linear and nonlinear classifiers. Large-margin classifiers are used as a prototypical example to illustrate the above idea. Our selection method is shown to be consistent in the sense that the optimal classifier simultaneously achieves the minimal GE and the minimal DBI. Various simulations and real examples further demonstrate the advantage of our method over several alternative approaches.

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Joint Estimation of Multiple Dependent Gaussian Graphical Models with Applications to Mouse Genomics

Gaussian graphical models are widely used to represent conditional dependence among random variables. In this paper, we propose a novel estimator for data arising from a group of Gaussian graphical models that are themselves dependent. A motivating example is that of modeling gene expression collected on multiple tissues from the same individual: here the multivariate outcome is affected by dependencies acting not only at the level of the specific tissues, but also at the level of the whole body; existing methods that assume independence among graphs are not applicable in this case. To estimate multiple dependent graphs, we decompose the problem into two graphical layers: the systemic layer, which affects all outcomes and thereby induces cross- graph dependence, and the category-specific layer, which represents graph-specific variation. We propose a graphical EM technique that estimates both layers jointly, establish estimation consistency and selection sparsistency of the proposed estimator, and confirm by simulation that the EM method is superior to a simple one-step method. We apply our technique to mouse genomics data and obtain biologically plausible results.

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Statistical Significance for Hierarchical Clustering

Cluster analysis has proved to be an invaluable tool for the exploratory and unsupervised analysis of high dimensional datasets. Among methods for clustering, hierarchical approaches have enjoyed substantial popularity in genomics and other fields for their ability to simultaneously uncover multiple layers of clustering structure. A critical and challenging question in cluster analysis is whether the identified clusters represent important underlying structure or are artifacts of natural sampling variation. Few approaches have been proposed for addressing this problem in the context of hierarchical clustering, for which the problem is further complicated by the natural tree structure of the partition, and the multiplicity of tests required to parse the layers of nested clusters. In this paper, we propose a Monte Carlo based approach for testing statistical significance in hierarchical clustering which addresses these issues. The approach is implemented as a sequential testing procedure guaranteeing control of the family-wise error rate. Theoretical justification is provided for our approach, and its power to detect true clustering structure is illustrated through several simulation studies and applications to two cancer gene expression datasets.

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Large-Margin Classification with Multiple Decision Rules

Binary classification is a common statistical learning problem in which a model is estimated on a set of covariates for some outcome indicating the membership of one of two classes. In the literature, there exists a distinction between hard and soft classification. In soft classification, the conditional class probability is modeled as a function of the covariates. In contrast, hard classification methods only target the optimal prediction boundary. While hard and soft classification methods have been studied extensively, not much work has been done to compare the actual tasks of hard and soft classification. In this paper we propose a spectrum of statistical learning problems which span the hard and soft classification tasks based on fitting multiple decision rules to the data. By doing so, we reveal a novel collection of learning tasks of increasing complexity. We study the problems using the framework of large-margin classifiers and a class of piecewise linear convex surrogates, for which we derive statistical properties and a corresponding sub-gradient descent algorithm. We conclude by applying our approach to simulation settings and a magnetic resonance imaging (MRI) dataset from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study.

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IsoDOT Detects Differential RNA-isoform Expression/Usage with respect to a Categorical or Continuous Covariate with High Sensitivity and Specificity

We have developed a statistical method named IsoDOT to assess differential isoform expression (DIE) and differential isoform usage (DIU) using RNA-seq data. Here isoform usage refers to relative isoform expression given the total expression of the corresponding gene. IsoDOT performs two tasks that cannot be accomplished by existing methods: to test DIE/DIU with respect to a continuous covariate, and to test DIE/DIU for one case versus one control. The latter task is not an uncommon situation in practice, e.g., comparing paternal and maternal allele of one individual or comparing tumor and normal sample of one cancer patient. Simulation studies demonstrate the high sensitivity and specificity of IsoDOT. We apply IsoDOT to study the effects of haloperidol treatment on mouse transcriptome and identify a group of genes whose isoform usages respond to haloperidol treatment.

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Significance Analysis for Pairwise Variable Selection in Classification

The goal of this article is to select important variables that can distinguish one class of data from another. A marginal variable selection method ranks the marginal effects for classification of individual variables, and is a useful and efficient approach for variable selection. Our focus here is to consider the bivariate effect, in addition to the marginal effect. In particular, we are interested in those pairs of variables that can lead to accurate classification predictions when they are viewed jointly. To accomplish this, we propose a permutation test called Significance test of Joint Effect (SigJEff). In the absence of joint effect in the data, SigJEff is similar or equivalent to many marginal methods. However, when joint effects exist, our method can significantly boost the performance of variable selection. Such joint effects can help to provide additional, and sometimes dominating, advantage for classification. We illustrate and validate our approach using both simulated example and a real glioblastoma multiforme data set, which provide promising results.

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Local kernel canonical correlation analysis with application to virtual drug screening

Drug discovery is the process of identifying compounds which have potentially meaningful biological activity. A major challenge that arises is that the number of compounds to search over can be quite large, sometimes numbering in the millions, making experimental testing intractable. For this reason computational methods are employed to filter out those compounds which do not exhibit strong biological activity. This filtering step, also called virtual screening reduces the search space, allowing for the remaining compounds to be experimentally tested. In this paper we propose several novel approaches to the problem of virtual screening based on Canonical Correlation Analysis (CCA) and on a kernel-based extension. Spectral learning ideas motivate our proposed new method called Indefinite Kernel CCA (IKCCA). We show the strong performance of this approach both for a toy problem as well as using real world data with dramatic improvements in predictive accuracy of virtual screening over an existing methodology.

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Variable selection for the multicategory SVM via adaptive sup-norm regularization

The Support Vector Machine (SVM) is a popular classification paradigm in machine learning and has achieved great success in real applications. However, the standard SVM can not select variables automatically and therefore its solution typically utilizes all the input variables without discrimination. This makes it difficult to identify important predictor variables, which is often one of the primary goals in data analysis. In this paper, we propose two novel types of regularization in the context of the multicategory SVM (MSVM) for simultaneous classification and variable selection. The MSVM generally requires estimation of multiple discriminating functions and applies the argmax rule for prediction. For each individual variable, we propose to characterize its importance by the supnorm of its coefficient vector associated with different functions, and then minimize the MSVM hinge loss function subject to a penalty on the sum of supnorms. To further improve the supnorm penalty, we propose the adaptive regularization, which allows different weights imposed on different variables according to their relative importance. Both types of regularization automate variable selection in the process of building classifiers, and lead to sparse multi-classifiers with enhanced interpretability and improved accuracy, especially for high dimensional low sample size data. One big advantage of the supnorm penalty is its easy implementation via standard linear programming. Several simulated examples and one real gene data analysis demonstrate the outstanding performance of the adaptive supnorm penalty in various data settings.

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